Genetic Association Analysis of Common Variants in FOXO3 Related to Longevity in a Chinese Population

PubMed Central

Yan, Dongjing; Liao, Xiaoping; Wang, Xianshou; Fu, Yunxin; Cai, Wangwei

2016-01-01

Recent studies suggested that forkhead box class O3 (FOXO3) functions as a key regulator for the insulin/insulin-like growth factor-1signaling pathway that influence aging and longevity. This study aimed to comprehensively elucidate the association of common genetic variants in FOXO3 with human longevity in a Chinese population. Eighteen single-nucleotide polymorphisms (SNPs) in FOXO3 were successfully genotyped in 616 unrelated long-lived individuals and 846 younger controls. No nominally significant effects were found. However, when stratifying by gender, four SNPs (rs10499051, rs7762395, rs4946933 and rs3800230) previously reported to be associated with longevity and one novel SNP (rs4945815) showed significant association with male longevity (P-values: 0.007–0.032), but all SNPs were not associated with female longevity. Correspondingly, males carrying the G-G-T-G haplotype of rs10499051, rs7762395, rs4945815 and rs3800230 tended to have longer lifespan than those carrying the most common haplotype A-G-C-T (odds ratio = 2.36, 95% confidence interval = 1.20–4.63, P = 0.013). However, none of the associated SNPs and haplotype remained significant after Bonferroni correction. In conclusion, our findings revealed that the FOXO3 variants we tested in our population of Chinese men and women were associated with longevity in men only. None of these associations passed Bonferroni correction. Bonferroni correction is very stringent for association studies. We therefore believe the effects of these nominally significant variants on human longevity will be confirmed by future studies. PMID:27936216

Spatio-Temporal Variation of Longevity Clusters and the Influence of Social Development Level on Lifespan in a Chinese Longevous Area (1982–2010)

PubMed Central

Qin, Jian; Xia, Tianlong; Li, You; Liang, Xue; Wei, Peng; Long, Bingshuang; Lei, Mingzhi; Wei, Xiao; Tang, Xianyan; Zhang, Zhiyong

2017-01-01

The study aims to determine the spatial and temporal variation of a longevous region and explore the correlation between longevity and socioeconomic development. Population data at the township level were obtained from the last four population censuses (1982–2010). Five main lifespan indicators and the Human Development Index (HDI) were calculated. Getis-Ord G*, Gravity modeling, and Pearson’s r between lifespan indicators and HDI were applied. In this study, a stable longevous gathering area was discovered in Hechi during different periods. Under the influence of social and economic development, more longevous areas appeared. However, the effects of genetic and natural environmental factors on longevity were always dominant in this remote and mountainous city. Furthermore, longevity indicators lacked any significant correlation with life expectancy. No significant positive correlation was detected between lifespan indicators and HDI. Thus, we conclude that lifespan indicators can determine the spatial distribution and variation pattern of longevity from multiple dimensions. The geographical scope of longevity in Hechi City is gradually expanding, and significant spatial clustering was detected in southwestern, southern, and eastern parts of Hechi. This study also found that social economic development is likely to have a certain impact on new longevous areas, but their role on extreme longevity is not significant. PMID:28753971

Effects of several environmental factors on longevity and health of the human population of Zhongxiang, Hubei, China.

PubMed

Lv, Jinmei; Wang, Wuyi; Krafft, Thomas; Li, Yonghua; Zhang, Fengying; Yuan, Fuqing

2011-11-01

Increasing human health and longevity is of global interest. Environmental, genetic, and stochastic factors all affect longevity. Among these factors, the environment is extremely important. To investigate the relationship between the environment and longevity, we studied the environment in Zhongxiang (China), where the inhabitants commonly have long life spans. Air was analyzed for negative oxygen ions, SO2, and inhalable particles, while drinking water and rice were analyzed for macro- and micro-elements. The air quality in this area was determined to be grade I with high negative oxygen ion content and low SO2 and inhalable particle contents. Apart from Fe, Mn, and F, all tested elements and the pH were within national standards and World Health Organization guidelines. The percentage of long-lived people in the area was closely related to the macro- and micro-element contents of their staple food, rice. The elements in rice could be classified into three categories according to their effect on longevity: Sr, Ca, Al, Mo, and Se, which were positively correlated with longevity; Fe, Mn, Zn, Cr, P, Mg, and K, which had a weak effect on local longevity, and Cu and Ba, which had a negative effect on longevity.

Review and meta-analysis of genetic polymorphisms associated with exceptional human longevity.

PubMed

Revelas, Mary; Thalamuthu, Anbupalam; Oldmeadow, Christopher; Evans, Tiffany-Jane; Armstrong, Nicola J; Kwok, John B; Brodaty, Henry; Schofield, Peter R; Scott, Rodney J; Sachdev, Perminder S; Attia, John R; Mather, Karen A

2018-06-08

Many factors contribute to exceptional longevity, with genetics playing a significant role. However, to date, genetic studies examining exceptional longevity have been inconclusive. This comprehensive review seeks to determine the genetic variants associated with exceptional longevity by undertaking meta-analyses. Meta-analyses of genetic polymorphisms previously associated with exceptional longevity (85+) were undertaken. For each variant, meta-analyses were performed if there were data from at least three independent studies available, including two unpublished additional cohorts. Five polymorphisms, ACE rs4340, APOE ε2/3/4, FOXO3A rs2802292, KLOTHO KL-VS and IL6 rs1800795 were significantly associated with exceptional longevity, with the pooled effect sizes (odds ratios) ranging from 0.42 (APOE ε4) to 1.45 (FOXO3A males). In general, the observed modest effect sizes of the significant variants suggest many genes of small influence play a role in exceptional longevity, which is consistent with results for other polygenic traits. Our results also suggest that genes related to cardiovascular health may be implicated in exceptional longevity. Future studies should examine the roles of gender and ethnicity and carefully consider study design, including the selection of appropriate controls. Copyright © 2018. Published by Elsevier B.V.

Comparative study of physico-chemical parameters of drinking water from some longevity and non-longevity areas of China.

PubMed

Du, Yajun; Luo, Kunli; Hussain, Rahib

2017-06-01

There is an obvious regional longevity phenomenon in China and many longevity counties are located in South China. This study was carried out to find the characteristics of elemental contents of drinking water in longevity areas in South China and the differences to non-longevity areas in China. A total of 128 drinking water samples were collected from longevity areas in South China (n = 40), non-longevity areas in South China (n = 74) and non-longevity areas in North China (n = 14) and 46 parameters of water were determined or calculated. The results showed that drinking water in longevity areas of South China had a high ratio of sum concentration of essential micro-elements in sum concentration of micro-elements (SCME) and a low ratio of sum concentration of hazardous micro-elements in SCME. The concentration of total hardness (TH) and strontium in drinking water was 157.82 mg/L and 82.1 μg/L, respectively, and they were 14.61 mg/L, 7.45 μg/L and 291.69 mg/L, 748.65 μg/L in the non-longevity areas of South and North China, respectively. The study concluded that drinking water containing 157.82 mg/L TH and 82.1 μg/L strontium in South China may be optimum to human health.

Predictors of Exceptional Longevity: Effects of Early-Life and Midlife Conditions, and Familial Longevity.

PubMed

Gavrilov, Leonid A; Gavrilova, Natalia S

Knowledge of strong predictors of mortality and longevity is very important for actuarial science and practice. Earlier studies found that parental characteristics as well as early-life conditions and midlife environment play a significant role in survival to advanced ages. However, little is known about the simultaneous effects of these three factors on longevity. This ongoing study attempts to fill this gap by comparing centenarians born in the United States in 1890-1891 with peers born in the same years who died at age 65. The records for centenarians and controls were taken from computerized family histories, which were then linked to 1900 and 1930 U.S. censuses. As a result of this linkage procedure, 765 records of confirmed centenarians and 783 records of controls were obtained. Analysis with multivariate logistic regression found the existence of both general and gender-specific predictors of human longevity. General predictors common for men and women are paternal and maternal longevity. Gender-specific predictors of male longevity are occupation as a farmer at age 40, Northeastern region of birth in the United States, and birth in the second half of year. A gender-specific predictor of female longevity is the availability of radio in the household according to the 1930 U.S. census. Given the importance of familial longevity as an independent predictor of survival to advanced ages, we conducted a comparative study of biological and nonbiological relatives of centenarians using a larger sample of 1,945 validated U.S. centenarians born in 1880-1895. We found that male gender of centenarian has a significant positive effect on survival of adult male relatives (brothers and fathers) but not female blood relatives. Life span of centenarian siblings-in-law is lower compared to life span of centenarian siblings and does not depend on centenarian gender. Wives of male centenarians (who share lifestyle and living conditions) have a significantly better survival compared to wives of centenarians' brothers. This finding demonstrates an important role of shared familial environment and lifestyle in human longevity. The results of this study suggest that familial background, some early-life conditions and midlife characteristics play an important role in longevity.

Who Are the Okinawans? Ancestry, Genome Diversity, and Implications for the Genetic Study of Human Longevity From a Geographically Isolated Population

PubMed Central

Hsueh, Wen-Chi; He, Qimei; Willcox, D. Craig; Nievergelt, Caroline M.; Donlon, Timothy A.; Kwok, Pui-Yan; Suzuki, Makoto; Willcox, Bradley J.

2014-01-01

Isolated populations have advantages for genetic studies of longevity from decreased haplotype diversity and long-range linkage disequilibrium. This permits smaller sample sizes without loss of power, among other utilities. Little is known about the genome of the Okinawans, a potential population isolate, recognized for longevity. Therefore, we assessed genetic diversity, structure, and admixture in Okinawans, and compared this with Caucasians, Chinese, Japanese, and Africans from HapMap II, genotyped on the same Affymetrix GeneChip Human Mapping 500K array. Principal component analysis, haplotype coverage, and linkage disequilibrium decay revealed a distinct Okinawan genome—more homogeneity, less haplotype diversity, and longer range linkage disequilibrium. Population structure and admixture analyses utilizing 52 global reference populations from the Human Genome Diversity Cell Line Panel demonstrated that Okinawans clustered almost exclusively with East Asians. Sibling relative risk (λs) analysis revealed that siblings of Okinawan centenarians have 3.11 times (females) and 3.77 times (males) more likelihood of centenarianism. These findings suggest that Okinawans are genetically distinct and share several characteristics of a population isolate, which are prone to develop extreme phenotypes (eg, longevity) from genetic drift, natural selection, and population bottlenecks. These data support further exploration of genetic influence on longevity in the Okinawans. PMID:24444611

Uric acid, an important antioxidant contributing to survival in termites

PubMed Central

Tasaki, Eisuke; Sakurai, Hiroki; Nitao, Masaru; Matsuura, Kenji; Iuchi, Yoshihito

2017-01-01

Reactive oxygen species (ROS) are generated spontaneously in all organisms and cause oxidative damage to biomolecules when present in excess. Accumulated oxidative damage accelerates aging; enhanced antioxidant capacity may be a positive factor for longevity. Recently, numerous studies of aging and longevity have been performed using short-lived animals, however, longevity mechanisms remain unknown. Here we show that a termite Reticulitermes speratus that is thought to be long-lived eusocial insect than other solitary insects uses large quantities of uric acid as an antioxidant against ROS. We demonstrated that the accumulation of uric acid considerably increases the free radical-scavenging activity and resistance against ultraviolet-induced oxidative stress in laboratory-maintained termites. In addition, we found that externally administered uric acid aided termite survival under highly oxidative conditions. The present data demonstrates that in addition to nutritional and metabolic roles, uric acid is an essential antioxidant for survival and contributes significantly to longevity. Uric acid also plays important roles in primates but causes gout when present in excess in humans. Further longevity studies of long-lived organisms may provide important breakthroughs with human health applications. PMID:28609463

[How long can a life be? Longevity not a matter for health care alone; today a host of companies would lure us with remedies said to postpone aging].

PubMed

Werkö, Lars

2003-02-27

Studies of changes in longevity address two main questions. Firstly, why does life expectancy vary in different parts of the western world? Secondly, what are the prospects of human longevity: a life span of no more than 85-90 years on average, or the possibility of reaching much higher ages? The study of longevity and its relation to changes in social circumstances, health care and the number of available general practitioners might be of importance for health care planning. Sweden has a special responsibility to use its unique system of health statistics for such studies. The increase in longevity has inspired many scientists to try to commercialize the results of their studies in various models, and to sell products that are supposed to prolong life. "Science of longevity medicine" is a concept from which serious researchers want to distance themselves.

A novel generalized normal distribution for human longevity and other negatively skewed data.

PubMed

Robertson, Henry T; Allison, David B

2012-01-01

Negatively skewed data arise occasionally in statistical practice; perhaps the most familiar example is the distribution of human longevity. Although other generalizations of the normal distribution exist, we demonstrate a new alternative that apparently fits human longevity data better. We propose an alternative approach of a normal distribution whose scale parameter is conditioned on attained age. This approach is consistent with previous findings that longevity conditioned on survival to the modal age behaves like a normal distribution. We derive such a distribution and demonstrate its accuracy in modeling human longevity data from life tables. The new distribution is characterized by 1. An intuitively straightforward genesis; 2. Closed forms for the pdf, cdf, mode, quantile, and hazard functions; and 3. Accessibility to non-statisticians, based on its close relationship to the normal distribution.

A Novel Generalized Normal Distribution for Human Longevity and other Negatively Skewed Data

PubMed Central

Robertson, Henry T.; Allison, David B.

2012-01-01

Negatively skewed data arise occasionally in statistical practice; perhaps the most familiar example is the distribution of human longevity. Although other generalizations of the normal distribution exist, we demonstrate a new alternative that apparently fits human longevity data better. We propose an alternative approach of a normal distribution whose scale parameter is conditioned on attained age. This approach is consistent with previous findings that longevity conditioned on survival to the modal age behaves like a normal distribution. We derive such a distribution and demonstrate its accuracy in modeling human longevity data from life tables. The new distribution is characterized by 1. An intuitively straightforward genesis; 2. Closed forms for the pdf, cdf, mode, quantile, and hazard functions; and 3. Accessibility to non-statisticians, based on its close relationship to the normal distribution. PMID:22623974

The effect of drinking water quality on the health and longevity of people-A case study in Mayang, Hunan Province, China

NASA Astrophysics Data System (ADS)

Lu, J.; Yuan, F.

2017-08-01

Drinking water is an important source for trace elements intake into human body. Thus, the drinking water quality has a great impact on people’s health and longevity. This study aims to study the relationship between drinking water quality and human health and longevity. A longevity county Mayang in Hunan province, China was chosen as the study area. The drinking water and hair of local centenarians were collected and analyzed the chemical composition. The drinking water is weak alkaline and rich in the essential trace elements. The daily intakes of Ca, Cu, Fe, Se, Sr from drinking water for residents in Mayang were much higher than the national average daily intake from beverage and water. There was a positive correlation between Ni and Pb in drinking water and Ni and Pb in hair. There were significant correlations between Cu, K in drinking water and Ba, Ca, Mg, Sr in the hair at the 0.01 level. The concentrations of Mg, Sr, Se in drinking water showed extremely significant positive relation with two centenarian index 100/80% and 100/90% correlation. Essential trace elements in drinking water can be an important factor for local health and longevity.

Predictors of Exceptional Longevity: Effects of Early-Life Childhood Conditions, Midlife Environment and Parental Characteristics.

PubMed

Gavrilov, Leonid A; Gavrilova, Natalia S

Knowledge of strong predictors of mortality and longevity is very important for actuarial science and practice. Earlier studies found that parental characteristics as well as early-life conditions and midlife environment play a significant role in survival to advanced ages. However, little is known about the simultaneous effects of these three factors on longevity. This ongoing study attempts to fill this gap by comparing centenarians born in the United States in 1890-91 with peers born in the same years who died at age 65. The records for centenarians and controls were taken from computerized family histories, which were then linked to 1900 and 1930 U.S. censuses. As a result of this linkage procedure, 765 records of confirmed centenarians and 783 records of controls were obtained. Analysis with multivariate logistic regression found that parental longevity and some midlife characteristics proved to be significant predictors of longevity while the role of childhood conditions was less important. More centenarians were born in the second half of the year compared to controls, suggesting early origins of longevity. We found the existence of both general and gender-specific predictors of human longevity. General predictors common for men and women are paternal and maternal longevity. Gender-specific predictors of male longevity are the farmer occupation at age 40, Northeastern region of birth in the United States and birth in the second half of year. A gender-specific predictor of female longevity is surprisingly the availability of radio in the household according to the 1930 U.S. census. Given the importance of familial longevity as an independent predictor of survival to advanced ages, we conducted a comparative study of biological and nonbiological relatives of centenarians using a larger sample of 1,945 validated U.S. centenarians born in 1880-95. We found that male gender of centenarian has significant positive effect on survival of adult male relatives (brothers and fathers) but not female blood relatives. Life span of centenarian siblings-in-law is lower compared to life span of centenarian siblings and does not depend on centenarian gender. Wives of male centenarians (who share lifestyle and living conditions) have a significantly better survival compared to wives of centenarians' brothers. This finding demonstrates an important role of shared familial environment and lifestyle in human longevity. The results of this study suggest that familial background, early-life conditions and midlife characteristics play an important role in longevity.

Predictors of Exceptional Longevity: Effects of Early-Life Childhood Conditions, Midlife Environment and Parental Characteristics

PubMed Central

Gavrilov, Leonid A.; Gavrilova, Natalia S.

2014-01-01

Knowledge of strong predictors of mortality and longevity is very important for actuarial science and practice. Earlier studies found that parental characteristics as well as early-life conditions and midlife environment play a significant role in survival to advanced ages. However, little is known about the simultaneous effects of these three factors on longevity. This ongoing study attempts to fill this gap by comparing centenarians born in the United States in 1890–91 with peers born in the same years who died at age 65. The records for centenarians and controls were taken from computerized family histories, which were then linked to 1900 and 1930 U.S. censuses. As a result of this linkage procedure, 765 records of confirmed centenarians and 783 records of controls were obtained. Analysis with multivariate logistic regression found that parental longevity and some midlife characteristics proved to be significant predictors of longevity while the role of childhood conditions was less important. More centenarians were born in the second half of the year compared to controls, suggesting early origins of longevity. We found the existence of both general and gender-specific predictors of human longevity. General predictors common for men and women are paternal and maternal longevity. Gender-specific predictors of male longevity are the farmer occupation at age 40, Northeastern region of birth in the United States and birth in the second half of year. A gender-specific predictor of female longevity is surprisingly the availability of radio in the household according to the 1930 U.S. census. Given the importance of familial longevity as an independent predictor of survival to advanced ages, we conducted a comparative study of biological and nonbiological relatives of centenarians using a larger sample of 1,945 validated U.S. centenarians born in 1880–95. We found that male gender of centenarian has significant positive effect on survival of adult male relatives (brothers and fathers) but not female blood relatives. Life span of centenarian siblings-in-law is lower compared to life span of centenarian siblings and does not depend on centenarian gender. Wives of male centenarians (who share lifestyle and living conditions) have a significantly better survival compared to wives of centenarians' brothers. This finding demonstrates an important role of shared familial environment and lifestyle in human longevity. The results of this study suggest that familial background, early-life conditions and midlife characteristics play an important role in longevity. PMID:25664346

Haplotype-based identification of a microsomal transfer protein marker associated with the human lifespan

PubMed Central

Geesaman, Bard J.; Benson, Erica; Brewster, Stephanie J.; Kunkel, Louis M.; Blanché, Hélène; Thomas, Gilles; Perls, Thomas T.; Daly, Mark J.; Puca, Annibale A.

2003-01-01

We previously reported a genomewide linkage study for human longevity using 308 long-lived individuals (LLI) (centenarians or near-centenarians) in 137 sibships and identified statistically significant linkage within chromosome 4 near microsatellite D4S1564. This interval spans 12 million bp and contains ≈50 putative genes. To identify the specific gene and gene variants impacting lifespan, we performed a haplotype-based fine-mapping study of the interval. The resulting genetic association study identified a haplotype marker within microsomal transfer protein as a modifier of human lifespan. This same variant was tested in a second cohort of LLI from France, and although the association was not replicated, there was evidence for statistical distortion in the form of Hardy–Weinberg disequilibrium. Microsomal transfer protein has been identified as the rate-limiting step in lipoprotein synthesis and may affect longevity by subtly modulating this pathway. This study provides proof of concept for the feasibility of using the genomes of LLI to identify genes impacting longevity. PMID:14615589

Predictors of Exceptional Longevity: Effects of Early-Life and Midlife Conditions, and Familial Longevity

PubMed Central

Gavrilov, Leonid A.; Gavrilova, Natalia S.

2015-01-01

Knowledge of strong predictors of mortality and longevity is very important for actuarial science and practice. Earlier studies found that parental characteristics as well as early-life conditions and midlife environment play a significant role in survival to advanced ages. However, little is known about the simultaneous effects of these three factors on longevity. This ongoing study attempts to fill this gap by comparing centenarians born in the United States in 1890–1891 with peers born in the same years who died at age 65. The records for centenarians and controls were taken from computerized family histories, which were then linked to 1900 and 1930 U.S. censuses. As a result of this linkage procedure, 765 records of confirmed centenarians and 783 records of controls were obtained. Analysis with multivariate logistic regression found the existence of both general and gender-specific predictors of human longevity. General predictors common for men and women are paternal and maternal longevity. Gender-specific predictors of male longevity are occupation as a farmer at age 40, Northeastern region of birth in the United States, and birth in the second half of year. A gender-specific predictor of female longevity is the availability of radio in the household according to the 1930 U.S. census. Given the importance of familial longevity as an independent predictor of survival to advanced ages, we conducted a comparative study of biological and nonbiological relatives of centenarians using a larger sample of 1,945 validated U.S. centenarians born in 1880–1895. We found that male gender of centenarian has a significant positive effect on survival of adult male relatives (brothers and fathers) but not female blood relatives. Life span of centenarian siblings-in-law is lower compared to life span of centenarian siblings and does not depend on centenarian gender. Wives of male centenarians (who share lifestyle and living conditions) have a significantly better survival compared to wives of centenarians’ brothers. This finding demonstrates an important role of shared familial environment and lifestyle in human longevity. The results of this study suggest that familial background, some early-life conditions and midlife characteristics play an important role in longevity. PMID:26412963

Selection bias in studies of human reproduction-longevity trade-offs.

PubMed

Helle, Samuli

2017-12-13

A shorter lifespan as a potential cost of high reproductive effort in humans has intrigued researchers for more than a century. However, the results have been inconclusive so far and despite strong theoretical expectations we do not currently have compelling evidence for the longevity costs of reproduction. Using Monte Carlo simulation, it is shown here that a common practice in human reproduction-longevity studies using historical data (the most relevant data sources for this question), the omission of women who died prior to menopausal age from the analysis, results in severe underestimation of the potential underlying trade-off between reproduction and lifespan. In other words, assuming that such a trade-off is expressed also during reproductive years, the strength of the trade-off between reproduction and lifespan is progressively weakened when women dying during reproductive ages are sequentially and non-randomly excluded from the analysis. In cases of small sample sizes (e.g. few hundreds of observations), this selection bias by reducing statistical power may even partly explain the null results commonly found in this field. Future studies in this field should thus apply statistical approaches that account for or avoid selection bias in order to recover reliable effect size estimates between reproduction and longevity. © 2017 The Author(s).

FOXO Transcriptional Factors and Long-Term Living

PubMed Central

Rashid, Rehana; Muneer, Saiqa; Hasan, Syed Muhammad Farid

2017-01-01

Several pathologies such as neurodegeneration and cancer are associated with aging, which is affected by many genetic and environmental factors. Healthy aging conceives human longevity, possibly due to carrying the defensive genes. For instance, FOXO (forkhead box O) genes determine human longevity. FOXO transcription factors are involved in the regulation of longevity phenomenon via insulin and insulin-like growth factor signaling. Only one FOXO gene (FOXO DAF-16) exists in invertebrates, while four FOXO genes, that is, FOXO1, FOXO3, FOXO4, and FOXO6 are found in mammals. These four transcription factors are involved in the multiple cellular pathways, which regulate growth, stress resistance, metabolism, cellular differentiation, and apoptosis in mammals. However, the accurate mode of longevity by FOXO factors is unclear until now. This article describes briefly the existing knowledge that is related to the role of FOXO factors in human longevity. PMID:28894507

Older age becomes common late in human evolution

PubMed Central

Caspari, Rachel; Lee, Sang-Hee

2004-01-01

Increased longevity, expressed as number of individuals surviving to older adulthood, represents one of the ways the human life history pattern differs from other primates. We believe it is a critical demographic factor in the development of human culture. Here, we examine when changes in longevity occurred by assessing the ratio of older to younger adults in four hominid dental samples from successive time periods, and by determining the significance of differences in these ratios. Younger and older adult status is assessed by wear seriation of each sample. Whereas there is significant increased longevity between all groups, indicating a trend of increased adult survivorship over the course of human evolution, there is a dramatic increase in longevity in the modern humans of the Early Upper Paleolithic. We believe that this great increase contributed to population expansions and cultural innovations associated with modernity. PMID:15252198

Countervailing effects of income, air pollution, smoking, and obesity on aging and life expectancy: population-based study of U.S. Counties.

PubMed

Allen, Ryan T; Hales, Nicholas M; Baccarelli, Andrea; Jerrett, Michael; Ezzati, Majid; Dockery, Douglas W; Pope, C Arden

2016-08-12

Income, air pollution, obesity, and smoking are primary factors associated with human health and longevity in population-based studies. These four factors may have countervailing impacts on longevity. This analysis investigates longevity trade-offs between air pollution and income, and explores how relative effects of income and air pollution on human longevity are potentially influenced by accounting for smoking and obesity. County-level data from 2,996 U.S. counties were analyzed in a cross-sectional analysis to investigate relationships between longevity and the four factors of interest: air pollution (mean 1999-2008 PM2.5), median income, smoking, and obesity. Two longevity measures were used: life expectancy (LE) and an exceptional aging (EA) index. Linear regression, generalized additive regression models, and bivariate thin-plate smoothing splines were used to estimate the benefits of living in counties with higher incomes or lower PM2.5. Models were estimated with and without controls for smoking, obesity, and other factors. Models which account for smoking and obesity result in substantially smaller estimates of the effects of income and pollution on longevity. Linear regression models without these two variables estimate that a $1,000 increase in median income (1 μg/m(3) decrease in PM2.5) corresponds to a 27.39 (33.68) increase in EA and a 0.14 (0.12) increase in LE, whereas models that control for smoking and obesity estimate only a 12.32 (20.22) increase in EA and a 0.07 (0.05) increase in LE. Nonlinear models and thin-plate smoothing splines also illustrate that, at higher levels of income, the relative benefits of the income-pollution tradeoff changed-the benefit of higher incomes diminished relative to the benefit of lower air pollution exposure. Higher incomes and lower levels of air pollution both correspond with increased human longevity. Adjusting for smoking and obesity reduces estimates of the benefits of higher income and lower air pollution exposure. This adjustment also alters the tradeoff between income and pollution: increases in income become less beneficial relative to a fixed reduction in air pollution-especially at higher levels of income.

Does renal ageing affect survival?

PubMed

Razzaque, M Shawkat

2007-10-01

The effects of ageing on progressive deterioration of renal function, both in human and experimental animals, are described elsewhere, but the effect of renal damage on overall survival and longevity is not yet clearly established. The wild-type animals of various genetic backgrounds, fed with regular diet, overtime develop severe age-associated nephropathy, that include but not limited to inflammatory cell infiltration, glomerulosclerosis, and tubulointerstitial fibrosis. Such renal damage significantly reduces their survival. Reducing renal damage, either by caloric restriction or by suppressing growth hormone (GH)/insulin-like growth factor-1 (IGF-1) activity could significantly enhance the longevity of these animals. Available survival studies using experimental animals clearly suggest that kidney pathology is one of the important non-neoplastic lesions that could affect overall survival, and that restoration of renal function by preventing kidney damage could significantly extend longevity. Careful long-term studies are needed to determine the human relevance of these experimental studies.

Demographic, genetic and phenotypic characteristics of centenarians in Italy: Focus on gender differences.

PubMed

Montesanto, Alberto; De Rango, Francesco; Pirazzini, Chiara; Guidarelli, Giulia; Domma, Filippo; Franceschi, Claudio; Passarino, Giuseppe

2017-07-01

An impressive and coherent series of epidemiological data from different populations (New England Americans, Mormons, Ashkenazi Jewish, Icelandic, Okinawan Japanese, Italians) suggests that long-lived subjects able to reach the extreme limits of human life, such as centenarians and supercentenarians, represent an extraordinary and informative model to identify the mechanisms responsible for healthy aging and human longevity. In most studies, genetic, demographic and phenotypic characteristics of longevity are discussed separately. However, longevity is a very complex trait due to the complicated interactions of numerous genetic and environmental factors. It is therefore necessary to analyse centenarians with a multidimensional approach, trying to consider different aspects simultaneously. In this review we will focus on Italian centenarians, who have been extensively studied for many years with different approaches, in order to show their peculiarities and the emerging data from the studies carried out on this exceptional population. Copyright © 2017 Elsevier B.V. All rights reserved.

Variations of the angiotensin II type 1 receptor gene are associated with extreme human longevity.

PubMed

Benigni, Ariela; Orisio, Silvia; Noris, Marina; Iatropoulos, Paraskevas; Castaldi, Davide; Kamide, Kei; Rakugi, Hiromi; Arai, Yasumichi; Todeschini, Marta; Ogliari, Giulia; Imai, Enyu; Gondo, Yasuyuki; Hirose, Nobuyoshi; Mari, Daniela; Remuzzi, Giuseppe

2013-06-01

Longevity phenotype in humans results from the influence of environmental and genetic factors. Few gene polymorphisms have been identified so far with a modest effect on lifespan leaving room for the search of other players in the longevity game. It has been recently demonstrated that targeted disruption of the mouse homolog of the human angiotensin II type 1 receptor (AT1R) gene (AGTR1) translates into marked prolongation of animal lifespan (Benigni et al., J Clin Invest 119(3):524-530, 2009). Based on the above study in mice, here we sought to search for AGTR1 variations associated to reduced AT1 receptor protein levels and to prolonged lifespan in humans. AGTR1 was sequenced in 173 Italian centenarians and 376 younger controls. A novel non-synonymous mutation was detected in a centenarian. Two polymorphisms in AGTR1 promoter, rs422858 and rs275653, in complete linkage disequilibrium, were significantly associated with the ability to attain extreme old age. We then replicated the study of rs275653 in a large independent cohort of Japanese origin (598 centenarians and semi-supercentenarians, 422 younger controls) and indeed confirmed its association with exceptional old age. In combined analyses, rs275653 was associated to extreme longevity either at recessive model (P = 0.007, odds ratio (OR) 3.57) or at genotype level (P = 0.015). Significance was maintained after correcting for confounding factors. Fluorescence activated cell sorting analysis revealed that subjects homozygous for the minor allele of rs275653 had less AT1R-positive peripheral blood polymorphonuclear cells. Moreover, rs275653 was associated to lower blood pressure in centenarians. These findings highlight the role of AGTR1 as a possible candidate among longevity-enabling genes.

Glycomics and glycoproteomics focused on aging and age-related diseases--Glycans as a potential biomarker for physiological alterations.

PubMed

Miura, Yuri; Endo, Tamao

2016-08-01

Since glycosylation depends on glycosyltransferases, glycosidases, and sugar nucleotide donors, it is susceptible to the changes associated with physiological and pathological conditions. Therefore, alterations in glycan structures may be good targets and biomarkers for monitoring health conditions. Since human aging and longevity are affected by genetic and environmental factors such as diseases, lifestyle, and social factors, a scale that reflects various environmental factors is required in the study of human aging and longevity. We herein focus on glycosylation changes elucidated by glycomic and glycoproteomic studies on aging, longevity, and age-related diseases including cognitive impairment, diabetes mellitus, and frailty. We also consider the potential of glycan structures as biomarkers and/or targets for monitoring physiological and pathophysiological changes. Glycan structures are altered in age-related diseases. These glycans and glycoproteins may be involved in the pathophysiology of these diseases and, thus, be useful diagnostic markers. Age-dependent changes in N-glycans have been reported previously in cohort studies, and characteristic N-glycans in extreme longevity have been proposed. These findings may lead to a deeper understanding of the mechanisms underlying aging as well as the factors influencing longevity. Alterations in glycosylation may be good targets and biomarkers for monitoring health conditions, and be applicable to studies on age-related diseases and healthy aging. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of blood type and blood handling on feeding success, longevity and egg production in the body louse, Pediculus humanus humanus.

PubMed

Mumcuoglu, K Y; Danilevich, M; Zelig, O; Grinbaum, H; Friger, M; Meinking, T L

2011-03-01

The effects of feeding different types of human blood to human body lice, Pediculus humanus humanus L. (Phthiraptera: Pediculidae), on feeding success, longevity and numbers of eggs laid were investigated using an artificial blood-feeding system in the laboratory. No significant differences were found between lice fed on different human blood types for any of the parameters tested. However, when lice were fed on human blood of one blood type followed immediately by a different blood type, they took significantly smaller bloodmeals, their longevity was reduced and they laid fewer eggs per female than control lice that had been fed twice on the same human blood type. When lice were fed human blood that had been stored for 1-26 weeks, the quantity of blood taken, the proportion of lice that became fully engorged and lice longevity diminished gradually as the storage time of the blood increased, but there was no effect of storage time on the mean number of eggs laid per female. However, lice would not feed on 26-week-old blood. The type of anticoagulant used had a significant effect on the proportion fed, longevity and number of eggs laid per female. Generally, EDTA (ethylenediaminetetraacetic acid)-treated blood reduced longevity and the number of eggs laid per female to a greater degree than heparinized or citrated blood. Lice fed on rabbit blood took significantly larger amounts of blood, lived longer and laid a higher mean number of eggs per female than lice fed on human blood. © 2010 The Authors. Medical and Veterinary Entomology © 2010 The Royal Entomological Society.

Replication of an association of variation in the FOXO3A gene with human longevity using both case–control and longitudinal data

PubMed Central

Soerensen, Mette; Dato, Serena; Christensen, Kaare; McGue, Matt; Stevnsner, Tinna; Bohr, Vilhelm A.; Christiansen, Lene

2010-01-01

Summary Genetic variation in FOXO3A has previously been associated with human longevity. Studies published so far have been case–control studies and hence vulnerable to bias introduced by cohort effects. In this study we extended the previous findings in the cohorts of oldest old Danes (the Danish 1905 cohort, N = 1089) and middle-aged Danes (N = 736), applying a longitudinal study design as well as the case–control study design. Fifteen SNPs were chosen in order to cover the known common variation in FOXO3A. Comparing SNP frequencies in the oldest old with middle-aged individuals, we found association (after correction for multiple testing) of eight SNPs; 4 (rs13217795, rs2764264, rs479744, and rs9400239) previously reported to be associated with longevity and four novel SNPs (rs12206094, rs13220810, rs7762395, and rs9486902 (corrected P-values 0.001–0.044). Moreover, we found association of the haplotypes TAC and CAC of rs9486902, rs10499051, and rs12206094 (corrected P-values: 0.01–0.03) with longevity. Finally, we here present data applying a longitudinal study design; when using follow-up survival data on the oldest old in a longitudinal analysis, we found no SNPs to remain significant after the correction for multiple testing (Bonferroni correction). Hence, our results support and extent the proposed role of FOXO3A as a candidate longevity gene for survival from younger ages to old age, yet not during old age. PMID:20849522

Is extreme climate or moderate climate more conducive to longevity in China?

NASA Astrophysics Data System (ADS)

Huang, Yi; Rosenberg, Mark; Wang, Yingli

2018-02-01

Climate is closely related to human longevity. In China, there are many climate types. According to national population censuses from 1982 to 2000, most provinces with a high ratio of centenarians are located in western and northwestern China far from the sea; these areas are characterized by a dry, cold climate, very high altitude, very high daily temperature range, strong winds, and partial hypoxia. Meanwhile, provinces with a high ratio of nonagenarians from 1982 to 2000 are located in southern China near the sea. Previous studies have attributed the high ratio of centenarians in western and northwestern China to the extreme local climate. However, centenarians in these areas decreased greatly in 2010, whereas residents in southern China frequently reached 90 to 100 years old in 2010. This study aims to explain this strange phenomenon and find whether extreme climate in Tibetan plateau and northwestern China or moderate climate in southern China is more conducive to longevity. The study found that mortality rate in Tibetan plateau is much higher than southern China, then a population evolution experiment was proposed to compare longevity indicators between low mortality rate and high mortality rate and shows that longevity indicators will decrease in the near future and increase above their original levels after several decades when the mortality rate is decreased. Results of this study show individuals in northwestern China do not live as long as those in eastern and southern China. A moderate climate is more conducive to longevity than extreme climate in China. The longevity of a region should be judged by long-term longevity indicators.

Is extreme climate or moderate climate more conducive to longevity in China?

PubMed

Huang, Yi; Rosenberg, Mark; Wang, Yingli

2018-06-01

Climate is closely related to human longevity. In China, there are many climate types. According to national population censuses from 1982 to 2000, most provinces with a high ratio of centenarians are located in western and northwestern China far from the sea; these areas are characterized by a dry, cold climate, very high altitude, very high daily temperature range, strong winds, and partial hypoxia. Meanwhile, provinces with a high ratio of nonagenarians from 1982 to 2000 are located in southern China near the sea. Previous studies have attributed the high ratio of centenarians in western and northwestern China to the extreme local climate. However, centenarians in these areas decreased greatly in 2010, whereas residents in southern China frequently reached 90 to 100 years old in 2010. This study aims to explain this strange phenomenon and find whether extreme climate in Tibetan plateau and northwestern China or moderate climate in southern China is more conducive to longevity. The study found that mortality rate in Tibetan plateau is much higher than southern China, then a population evolution experiment was proposed to compare longevity indicators between low mortality rate and high mortality rate and shows that longevity indicators will decrease in the near future and increase above their original levels after several decades when the mortality rate is decreased. Results of this study show individuals in northwestern China do not live as long as those in eastern and southern China. A moderate climate is more conducive to longevity than extreme climate in China. The longevity of a region should be judged by long-term longevity indicators.

Is extreme climate or moderate climate more conducive to longevity in China?

NASA Astrophysics Data System (ADS)

Huang, Yi; Rosenberg, Mark; Wang, Yingli

2018-06-01

Climate is closely related to human longevity. In China, there are many climate types. According to national population censuses from 1982 to 2000, most provinces with a high ratio of centenarians are located in western and northwestern China far from the sea; these areas are characterized by a dry, cold climate, very high altitude, very high daily temperature range, strong winds, and partial hypoxia. Meanwhile, provinces with a high ratio of nonagenarians from 1982 to 2000 are located in southern China near the sea. Previous studies have attributed the high ratio of centenarians in western and northwestern China to the extreme local climate. However, centenarians in these areas decreased greatly in 2010, whereas residents in southern China frequently reached 90 to 100 years old in 2010. This study aims to explain this strange phenomenon and find whether extreme climate in Tibetan plateau and northwestern China or moderate climate in southern China is more conducive to longevity. The study found that mortality rate in Tibetan plateau is much higher than southern China, then a population evolution experiment was proposed to compare longevity indicators between low mortality rate and high mortality rate and shows that longevity indicators will decrease in the near future and increase above their original levels after several decades when the mortality rate is decreased. Results of this study show individuals in northwestern China do not live as long as those in eastern and southern China. A moderate climate is more conducive to longevity than extreme climate in China. The longevity of a region should be judged by long-term longevity indicators.

RNA Editing Genes Associated with Extreme Old Age in Humans and with Lifespan in C. elegans

PubMed Central

Puca, Annibale; Solovieff, Nadia; Kojima, Toshio; Wang, Meng C.; Melista, Efthymia; Meltzer, Micah; Fischer, Sylvia E. J.; Andersen, Stacy; Hartley, Stephen H.; Sedgewick, Amanda; Arai, Yasumichi; Bergman, Aviv; Barzilai, Nir; Terry, Dellara F.; Riva, Alberto; Anselmi, Chiara Viviani; Malovini, Alberto; Kitamoto, Aya; Sawabe, Motoji; Arai, Tomio; Gondo, Yasuyuki; Steinberg, Martin H.; Hirose, Nobuyoshi; Atzmon, Gil; Ruvkun, Gary; Baldwin, Clinton T.; Perls, Thomas T.

2009-01-01

Background The strong familiality of living to extreme ages suggests that human longevity is genetically regulated. The majority of genes found thus far to be associated with longevity primarily function in lipoprotein metabolism and insulin/IGF-1 signaling. There are likely many more genetic modifiers of human longevity that remain to be discovered. Methodology/Principal Findings Here, we first show that 18 single nucleotide polymorphisms (SNPs) in the RNA editing genes ADARB1 and ADARB2 are associated with extreme old age in a U.S. based study of centenarians, the New England Centenarian Study. We describe replications of these findings in three independently conducted centenarian studies with different genetic backgrounds (Italian, Ashkenazi Jewish and Japanese) that collectively support an association of ADARB1 and ADARB2 with longevity. Some SNPs in ADARB2 replicate consistently in the four populations and suggest a strong effect that is independent of the different genetic backgrounds and environments. To evaluate the functional association of these genes with lifespan, we demonstrate that inactivation of their orthologues adr-1 and adr-2 in C. elegans reduces median survival by 50%. We further demonstrate that inactivation of the argonaute gene, rde-1, a critical regulator of RNA interference, completely restores lifespan to normal levels in the context of adr-1 and adr-2 loss of function. Conclusions/Significance Our results suggest that RNA editors may be an important regulator of aging in humans and that, when evaluated in C. elegans, this pathway may interact with the RNA interference machinery to regulate lifespan. PMID:20011587

Relationships among Environment, Climate, and Longevity in China

PubMed Central

Huang, Yi; Rosenberg, Mark; Hou, Lingli; Hu, Mengjin

2017-01-01

Human longevity is influenced by environment and nutrition. We considered environmental and nutritional factors relating to longevity in Chinese cities. We found higher 85+/65+ distribution ratios, indicating enhanced longevity, in the coastal and southern regions of China. These areas also featured higher humidity, low standard deviation of monthly temperature, higher levels of selenium (Se) distribution in soil, and greater sea fish consumption. Moderate climate is more conducive to longevity, however, there is no significant difference in longevity between different sub-climatic types within moderate climate; the relation between humidity and longevity is not always positive, the relation between altitude and longevity is not always negative. Nutritional factors like Se and omega-3 fatty acids contained in sea fish were crucial to longevity. In contrast, the consumption of meat and freshwater fish were less related to longevity. Taken together, humidity, altitude, and per capita sea fish consumption, when evaluated via geographically weighted regression, explained 66% and 68% of longevity among Chinese individuals in 2000 and 2010, respectively. Other factors require further discussion. PMID:28991186

Relationships among Environment, Climate, and Longevity in China.

PubMed

Huang, Yi; Rosenberg, Mark; Hou, Lingli; Hu, Mengjin

2017-10-08

Human longevity is influenced by environment and nutrition. We considered environmental and nutritional factors relating to longevity in Chinese cities. We found higher 85+/65+ distribution ratios, indicating enhanced longevity, in the coastal and southern regions of China. These areas also featured higher humidity, low standard deviation of monthly temperature, higher levels of selenium (Se) distribution in soil, and greater sea fish consumption. Moderate climate is more conducive to longevity, however, there is no significant difference in longevity between different sub-climatic types within moderate climate; the relation between humidity and longevity is not always positive, the relation between altitude and longevity is not always negative. Nutritional factors like Se and omega-3 fatty acids contained in sea fish were crucial to longevity. In contrast, the consumption of meat and freshwater fish were less related to longevity. Taken together, humidity, altitude, and per capita sea fish consumption, when evaluated via geographically weighted regression, explained 66% and 68% of longevity among Chinese individuals in 2000 and 2010, respectively. Other factors require further discussion.

Economic level and human longevity: Spatial and temporal variations and correlation analysis of per capita GDP and longevity indicators in China.

PubMed

Wang, Shaobin; Luo, Kunli; Liu, Yonglin; Zhang, Shixi; Lin, Xiaoxu; Ni, Runxiang; Tian, Xinglei; Gao, Xing

2015-01-01

We show the variation of longevity indicators in China during the past 60 years and its correlation patterns with per capita GDP (GDPpc) both at provincial and inner-provincial level. Population data from six national population censuses in China (1953-2010) at provincial level and in several typical provinces in 2010 at county-level were selected. Four main longevity indicators were calculated. Pearson's r and distributed lags time series analysis between longevity indicators and GDPpc were conducted. The results show that Guangxi and Hainan Provinces maintain relatively high long-lived population (population over the age of 90) across various population censuses. The distributions of the population over the age of 80 and life expectancy are significantly affected by both contemporaneous and historical GDPpc at provincial level. However, areas of high long-lived population (over the age of 90) exhibit continuously stable features that lack any significant correlation with GDPpc both at provincial and inner-provincial level. Our results indicate a mixed distribution pattern of several longevity indexes and different relation to GDPpc. It shows consistent trend with Preston curve, that is, economic conditions may have limited influence on human longevity, especially for those who live longer than 90 years old. This study suggests that the economic development may favor the local residents to have access to live as old as 80 years old, but it is still difficult for most residents to reach the level of centenarians. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Longevity health sciences and mental health as future medicine.

PubMed

Riga, Sorin; Riga, Dan; Mihailescu, Alexandra; Motoc, Daniela; Mos, Liana; Schneider, Francisc

2010-06-01

Longevity health sciences and mental health are fields of public health and of preventive and integrative medicine. The antagonism between health construction and human pathology is substantiated by two opposite fundamental pathways: the health-longevity tetrad versus the aging-disease cascade. It is necessary that the current paradigm of contemporary medicine be replaced by the advanced paradigm of future medicine. A societal cost-benefit rate is decisive for health-longevity promotion. This is why the WHO public health strategy keeps forwarding the societal medical target into the global health-longevity field.

How the Effects of Aging and Stresses of Life Are Integrated in Mortality Rates: Insights for Genetic Studies of Human Health and Longevity

PubMed Central

Yashin, Anatoliy I.; Arbeev, Konstantin G.; Arbeeva, Liubov S.; Wu, Deqing; Akushevich, Igor; Kovtun, Mikhail; Yashkin, Arseniy; Kulminski, Alexander; Culminskaya, Irina; Stallard, Eric; Li, Miaozhu; Ukraintseva, Svetlana V.

2015-01-01

Background Increasing proportions of elderly individuals in developed countries combined with substantial increases in related medical expenditures make the improvement of the health of the elderly a high priority today. If the process of aging by individuals is a major cause of age related health declines then postponing aging could be an efficient strategy for improving the health of the elderly. Implementing this strategy requires a better understanding of genetic and non-genetic connections among aging, health, and longevity. Data and methods We review progress and problems in research areas whose development may contribute to analyses of such connections. These include genetic studies of human aging and longevity, the heterogeneity of populations with respect to their susceptibility to disease and death, forces that shape age patterns of human mortality, secular trends in mortality decline, and integrative mortality modeling using longitudinal data. Results The dynamic involvement of genetic factors in (i) morbidity/mortality risks, (ii) responses to stresses of life, (iii) multi-morbidities of many elderly individuals, (iv) trade-offs for diseases, (v) genetic heterogeneity, and (vi) other relevant aging-related health declines, underscores the need for a comprehensive, integrated approach to analyze the genetic connections for all of the above aspects of aging-related changes. Conclusion The dynamic relationships among aging, health, and longevity traits would be better understood if one linked several research fields within one conceptual framework that allowed for efficient analyses of available longitudinal data using the wealth of available knowledge about aging, health, and longevity already accumulated in the research field. PMID:26280653

Viewpoint: A Contributory Role of Shell Ginger (Alpinia zerumbet) for Human Longevity in Okinawa, Japan?

PubMed Central

Teschke, Rolf

2018-01-01

The longevity of the population in the Okinawa Islands of Japan has been ascribed to genetic factors and the traditional Okinawa cuisine, which is low in calories and high in plant content. This diet includes shell ginger (Alpinia zerumbet (Pers.) B.L. Burtt & R.M. Sm) of the ginger family (Zingiberaceae). Due to its local popularity, Alpinia zerumbet has become the subject of a good deal of study at the University of the Ryukyus in Okinawa. Personal local experience and review of the literature now suggest that culinary shell ginger may contribute to longevity among the population in Okinawa. This is supported by its abundant phytochemical content, with antioxidant and anti-obesity properties. The major bioactive phytochemicals are dihydro-5,6-dehydrokawain (DDK; 80–410 mg g−1 fresh weight), 5,6-dehydrokawain (DK; ≤100 mg g−1), and essential oils, phenols, phenolic acids, and fatty acids (≤150 mg g−1 each). Further, Alpinia zerumbet extends the lifespan in animals by 22.6%. In conclusion, culinary shell ginger may significantly contribute to human longevity in Okinawa. PMID:29385084

Genetics and epigenetics of aging and longevity

PubMed Central

Moskalev, Alexey A; Aliper, Alexander M; Smit-McBride, Zeljka; Buzdin, Anton; Zhavoronkov, Alex

2014-01-01

Evolutionary theories of aging predict the existence of certain genes that provide selective advantage early in life with adverse effect on lifespan later in life (antagonistic pleiotropy theory) or longevity insurance genes (disposable soma theory). Indeed, the study of human and animal genetics is gradually identifying new genes that increase lifespan when overexpressed or mutated: gerontogenes. Furthermore, genetic and epigenetic mechanisms are being identified that have a positive effect on longevity. The gerontogenes are classified as lifespan regulators, mediators, effectors, housekeeping genes, genes involved in mitochondrial function, and genes regulating cellular senescence and apoptosis. In this review we demonstrate that the majority of the genes as well as genetic and epigenetic mechanisms that are involved in regulation of longevity are highly interconnected and related to stress response. PMID:24603410

Are reproductive and somatic senescence coupled in humans? Late, but not early, reproduction correlated with longevity in historical Sami women

PubMed Central

Helle, Samuli; Lummaa, Virpi; Jokela, Jukka

2005-01-01

Evolutionary theory of senescence emphasizes the importance of intense selection on early reproduction owing to the declining force of natural selection with age that constrains lifespan. In humans, recent studies have, however, suggested that late-life mortality might be more closely related to late rather than early reproduction, although the role of late reproduction on fitness remains unclear. We examined the association between early and late reproduction with longevity in historical post-reproductive Sami women. We also estimated the strength of natural selection on early and late reproduction using path analysis, and the effect of reproductive timing on offspring survival to adulthood and maternal risk of dying at childbirth. We found that natural selection favoured both earlier start and later cessation of reproduction, and higher total fe cundity. Maternal age at childbirth was not related to offspring or maternal survival. Interestingly, females who produced their last offspring at advanced age also lived longest, while age at first reproduction and total fecundity were unrelated to female longevity. Our results thus suggest that reproductive and somatic senescence may have been coupled in these human populations, and that selection could have favoured late reproduction. We discuss alternative hypotheses for the mechanisms which might have promoted the association between late reproduction and longevity. PMID:15875567

Characteristic glycopeptides associated with extreme human longevity identified through plasma glycoproteomics.

PubMed

Miura, Yuri; Hashii, Noritaka; Ohta, Yuki; Itakura, Yoko; Tsumoto, Hiroki; Suzuki, Junya; Takakura, Daisuke; Abe, Yukiko; Arai, Yasumichi; Toyoda, Masashi; Kawasaki, Nana; Hirose, Nobuyoshi; Endo, Tamao

2018-06-01

Glycosylation is highly susceptible to changes of the physiological conditions, and accordingly, is a potential biomarker associated with several diseases and/or longevity. Semi-supercentenarians (SSCs; older than 105 years) are thought to be a model of human longevity. Thus, we performed glycoproteomics using plasma samples of SSCs, and identified proteins and conjugated N-glycans that are characteristic of extreme human longevity. Plasma proteins from Japanese semi-supercentenarians (SSCs, 106-109 years), aged controls (70-88 years), and young controls (20-38 years) were analysed by using lectin microarrays and liquid chromatography/mass spectrometry (LC/MS). Peak area ratios of glycopeptides to corresponding normalising peptides were subjected to orthogonal projections to latent structures discriminant analysis (OPLS-DA). Furthermore, plasma levels of clinical biomarkers were measured. We found two lectins such as Phaseolus vulgaris, and Erythrina cristagalli (ECA), of which protein binding were characteristically increased in SSCs. Peak area ratios of ECA-enriched glycopeptides were successfully discriminated between SSCs and controls using OPLS-DA, and indicated that tri-antennary and sialylated N-glycans of haptoglobin at Asn207 and Asn211 sites were characterized in SSCs. Sialylated glycans of haptoglobin are a potential biomarker of several diseases, such as hepatocellular carcinoma, liver cirrhosis, and IgA-nephritis. However, the SSCs analysed here did not suffer from these diseases. Tri-antennary and sialylated N-glycans on haptoglobin at the Asn207 and Asn211 sites were abundant in SSCs and characteristic of extreme human longevity. We found abundant glycans in SSCs, which may be associated with human longevity. Copyright © 2018 Elsevier B.V. All rights reserved.

The pursuit of longevity - the bringer of peace to the middle East.

PubMed

Stambler, Ilia

2014-01-01

Despite the common apprehensions regarding the aging population, this work aims to argue, on both deontological and utilitarian moral grounds, that any increase in general life-expectancy will be beneficial for the Middle East, countering the common fears associated with this increase. A set of ethical arguments concerning increasing longevity is presented, from both the deontological and utilitarian perspective. A wide selection of economic, psychological, demographic and epidemiological literature and databases is analyzed to determine common correlates of extended longevity. On the deontological grounds, the value of extended longevity is derived from the value of life preservation, regardless of its term. On the utilitarian grounds, the value of extended longevity is demonstrated by its correlation with further human values, such as education level and intellectual activity, economic prosperity, equality, solidarity and peacefulness. With the common apprehensions of stagnation and scarcity due to life extension found wanting, the pursuit of longevity by the population can be seen as a cross-cultural and cross-generational good. Though the current study mainly refers to sources and data relevant to the Middle East, a similar pro-longevity argument can be also made for other cultural contexts. In view of its numerous benefits, normatively, the goal of longevity should be set clearly and openly by the society, and actively pursued, or at least discussed, in academia, the political system and broader public.

Pollution and contamination of the domestic environment leading to detrimental, long run and possible irreversible effects upon human and animal health and longevity

NASA Technical Reports Server (NTRS)

1975-01-01

Negative impacts of industrial waste disposal into the domestic environment affect human and animal health and longevity, destruct the ecosystem, and accumulate potential harmful substances in the food chain leading to disease and genetic defects in the population.

Association between Longevity and Element Levels in Food and Drinking Water of Typical Chinese Longevity Area.

PubMed

Hao, Z; Liu, Y; Li, Y; Song, W; Yu, J; Li, H; Wang, W

2016-01-01

To carrying out an integrated analysis on regional environment and human health in China and to detect the association between longevity and daily element intake from food and drinking water. Cross-sectional study. All the 18 cities and counties in Hainan Province. The distribution of elderly population and longevity indexes at a county level in Hainan Province were investigated. Quality of food and drinking water in Hainan was evaluated by comparing the chemical elements with National Standards. In addition, the association between element concentrations in food and water and longevity was examined using spearman's rank correlation. The proportion of elderly people is higher in the northern part of the province compared with southern counties. Food contributes a greater proportion of daily element intake than drinking water. Compared with the National Standards, reaching rates for elements were over 85% for both food and drinking water. There was a positive correlation between daily intake of Cu, Se, and Zn from food and water and aging and longevity indexes, and a negative correlation between Pb intake and these indexes. The quality of food and water in Hainan Province are good and that, compared with water, food is a more important source of trace elements. An appropriate supply of Cu, Se, and Zn is important, whereas excessive intake of Pb should be avoided. The findings also provide basic data to support further studies on regional variations in longevity and their relationship to diet and drinking water.

The Longevity Consortium: Harnessing diverse approaches to understand the genetic basis of human longevity and healthy aging. An introduction to a series of articles.

PubMed

Kahn, Arnold

2011-04-01

The Longevity Consortium is a multi-investigator, multi-institutional research group focused on identifying the genetic variants that regulate human lifespan and healthy aging. The text that follows is an introduction to a series of seven articles prepared by Consortium investigators that represent a profile of planned and ongoing research and up-to-date reviews of topics of major interest to biogerontologists and others scientists and clinicians interested in ageing research. Copyright © 2010 Elsevier B.V. All rights reserved.

Biodemography of Exceptional Longevity: Early-life and Mid-life predictors of Human Longevity

PubMed Central

Gavrilov, Leonid A.; Gavrilova, Natalia S.

2011-01-01

Effects of early-life and middle-life conditions on exceptional longevity are explored in this study using two matched case-control studies. The first study compares 198 validated centenarians born in the United States in 1890-1893 to their shorter-lived siblings. Family histories of centenarians were reconstructed and exceptional longevity validated using early U.S. censuses, Social Security Administration Death Master File, state death indexes, online genealogies and other supplementary data resources. Siblings born to young mothers (<25 years) had significantly higher chances to live to 100 compared to siblings born to older mothers (odds ratio = 2.03, 95% CI = 1.33 - 3.11, P = 0.001) while paternal age and birth order were not associated with exceptional longevity. The second study explores whether people living to 100 and beyond are any different in physical characteristics at young age from their shorter-lived peers. A random representative sample of 240 men born in 1887 and survived to age 100 was selected from the US Social Security Administration database and linked to the US WWI civil draft registration cards collected in 1917 when these men were 30 years old. These validated centenarians were then compared to randomly selected controls matched by calendar year of birth, race and place of draft registration in 1917. It was found that ‘stout’ body build (being in the heaviest 15% of population) was negatively associated with survival to age 100 years. Farmer occupation and large number of children (4+) at age 30 increased the chances of exceptional longevity. Detailed description of dataset development, data cleaning procedure and validation of exceptional longevity is provided for both studies. These results demonstrate that matched case-control design is a useful approach in exploring effects of early-life conditions and middle-life characteristics on exceptional longevity. PMID:22582891

Genetic association of FOXO1A and FOXO3A with longevity trait in Han Chinese populations

PubMed Central

Li, Yang; Wang, Wen-Jing; Cao, Huiqing; Lu, Jiehua; Wu, Chong; Hu, Fang-Yuan; Guo, Jian; Zhao, Ling; Yang, Fan; Zhang, Yi-Xin; Li, Wei; Zheng, Gu-Yan; Cui, Hanbin; Chen, Xiaomin; Zhu, Zhiming; He, Hongbo; Dong, Birong; Mo, Xianming; Zeng, Yi; Tian, Xiao-Li

2009-01-01

FOXO1A and FOXO3A are two members of the FoxO family. FOXO3A has recently been linked to human longevity in Japanese, German and Italian populations. Here we tested the genetic contribution of FOXO1A and FOXO3A to the longevity phenotype in Han Chinese population. Six tagging SNPs from FOXO1A and FOXO3A were selected and genotyped in 1817 centenarians and younger individuals. Two SNPs of FOXO1A were found to be associated with longevity in women (P = 0.01–0.005), whereas all three SNPs of FOXO3A were associated with longevity in both genders (P = 0.005–0.001). One SNP from FOXO1A was found not to be associated with longevity. In haplotype association tests, the OR (95% CI) for haplotypes TTG and CCG of FOXO1A in association with female longevity were 0.72 (0.58–0.90) and 1.38 (1.08–1.76), P = 0.0033 and 0.0063, respectively. The haplotypes of FOXO3A were associated with longevity in men [GTC: OR (95% CI) = 0.67 (0.51–0.86), P = 0.0014; CGT: OR (95% CI) = 1.48 (1.12–1.94), P = 0.0035] and in women [GTC: OR (95% CI) = 0.75 (0.60–0.94), P = 0.0094; CGT: OR (95% CI) = 1.47 (1.16–1.86), P = 0.0009]. The haplotype association tests were validated by permutation analysis. The association of FOXO1A with female longevity was replicated in 700 centenarians and younger individuals that were sampled geographically different from the original population. Thus, we demonstrate that, unlike FOXO3A, FOXO1A is more closely associated with human female longevity, suggesting that the genetic contribution to longevity trait may be affected by genders. PMID:19793722

Human longevity is influenced by many genetic variants: evidence from 75,000 UK Biobank participants

PubMed Central

Pilling, Luke C.; Atkins, Janice L.; Bowman, Kirsty; Jones, Samuel E.; Tyrrell, Jessica; Beaumont, Robin N.; Ruth, Katherine S.; Tuke, Marcus A.; Yaghootkar, Hanieh; Wood, Andrew R.; Freathy, Rachel M.; Murray, Anna; Weedon, Michael N.; Xue, Luting; Lunetta, Kathryn; Murabito, Joanne M.; Harries, Lorna W.; Robine, Jean-Marie; Brayne, Carol; Kuchel, George A.; Ferrucci, Luigi; Frayling, Timothy M.; Melzer, David

2016-01-01

Variation in human lifespan is 20 to 30% heritable in twins but few genetic variants have been identified. We undertook a Genome Wide Association Study (GWAS) using age at death of parents of middle-aged UK Biobank participants of European decent (n=75,244 with father's and/or mother's data, excluding early deaths). Genetic risk scores for 19 phenotypes (n=777 proven variants) were also tested. In GWAS, a nicotine receptor locus (CHRNA3, previously associated with increased smoking and lung cancer) was associated with fathers' survival. Less common variants requiring further confirmation were also identified. Offspring of longer lived parents had more protective alleles for coronary artery disease, systolic blood pressure, body mass index, cholesterol and triglyceride levels, type-1 diabetes, inflammatory bowel disease and Alzheimer's disease. In candidate analyses, variants in the TOMM40/APOE locus were associated with longevity, but FOXO variants were not. Associations between extreme longevity (mother >=98 years, fathers >=95 years, n=1,339) and disease alleles were similar, with an additional association with HDL cholesterol (p=5.7×10-3). These results support a multiple protective factors model influencing lifespan and longevity (top 1% survival) in humans, with prominent roles for cardiovascular-related pathways. Several of these genetically influenced risks, including blood pressure and tobacco exposure, are potentially modifiable. PMID:27015805

The challenges in moving from ageing to successful longevity.

PubMed

Kolovou, Genovefa; Barzilai, Nir; Caruso, Calogero; Sikora, Ewa; Capri, Miriam; Tzanetakou, Irene P; Bilianou, Helen; Avery, Peter; Katsiki, Niki; Panotopoulos, George; Franceschi, Claudio; Benetos, Athanase; Mikhailidis, Dimitri P

2014-01-01

During the last decades survival has significantly improved and centenarians are becoming a fast-growing group of the population. Human life span is mainly dependent on environmental and genetic factors. Favourable modifications of lifestyle factors (e.g. physical activity, diet and not smoking) and healthcare (e.g. effective vascular disease prevention) have also increased human life span. Genetic factors contribute to the variation of human life span by around 25%, which is believed to be more profound after 85 years of age. It is likely that multiple factors influence life span and we need answers to questions such as: 1) What does it take to reach 100?, 2) Do centenarians have better health during their lifespan compared with contemporaries who died at a younger age?, 3) Do centenarians have protective modifications of body composition, fat distribution and energy expenditure, maintain high physical and cognitive function, and sustained engagement in social and productive activities?, 4) Do centenarians have genes which contribute to longevity?, 5) Do centenarians benefit from epigenetic phenomena?, 6) Is it possible to influence the transgenerational epigenetic inheritance (epigenetic memory) which leads to longevity?, 7) Is the influence of nutrigenomics important for longevity?, 8) Do centenarians benefit more from drug treatment, particularly in primary prevention?, and, 9) Are there any potential goals for drug research? Many definitions of successful ageing have been proposed, but at present there is no consensus definition. Such definitions may need to differentiate between "Longevity Syndrome" and "Exceptional Longevity".

Human longevity is characterised by high thyroid stimulating hormone secretion without altered energy metabolism.

PubMed

Jansen, S W; Akintola, A A; Roelfsema, F; van der Spoel, E; Cobbaert, C M; Ballieux, B E; Egri, P; Kvarta-Papp, Z; Gereben, B; Fekete, C; Slagboom, P E; van der Grond, J; Demeneix, B A; Pijl, H; Westendorp, R G J; van Heemst, D

2015-06-19

Few studies have included subjects with the propensity to reach old age in good health, with the aim to disentangle mechanisms contributing to staying healthier for longer. The hypothalamic-pituitary-thyroid (HPT) axis maintains circulating levels of thyroid stimulating hormone (TSH) and thyroid hormone (TH) in an inverse relationship. Greater longevity has been associated with higher TSH and lower TH levels, but mechanisms underlying TSH/TH differences and longevity remain unknown. The HPT axis plays a pivotal role in growth, development and energy metabolism. We report that offspring of nonagenarians with at least one nonagenarian sibling have increased TSH secretion but similar bioactivity of TSH and similar TH levels compared to controls. Healthy offspring and spousal controls had similar resting metabolic rate and core body temperature. We propose that pleiotropic effects of the HPT axis may favour longevity without altering energy metabolism.

Three dimensions of the survival curve: horizontalization, verticalization, and longevity extension.

PubMed

Cheung, Siu Lan Karen; Robine, Jean-Marie; Tu, Edward Jow-Ching; Caselli, Graziella

2005-05-01

Three dimensions of the survival curve have been developed: (1) "horizontalization," which corresponds to how long a cohort and how many survivors can live before aging-related deaths significantly decrease the proportion of survivors; (2) "verticalization," which corresponds to how concentrated aging-related ("normal") deaths are around the modal age at death (M); and (3) "longevity extension," which corresponds to how far the highest normal life durations can exceed M. Our study shows that the degree of horizontalization increased relatively less than the degree of verticalization in Hong Kong from 1976 to 2001. After age normalization, the highest normal life durations moved closer to M, implying that the increase in human longevity is meeting some resistance.

Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity.

PubMed

Joshi, Peter K; Pirastu, Nicola; Kentistou, Katherine A; Fischer, Krista; Hofer, Edith; Schraut, Katharina E; Clark, David W; Nutile, Teresa; Barnes, Catriona L K; Timmers, Paul R H J; Shen, Xia; Gandin, Ilaria; McDaid, Aaron F; Hansen, Thomas Folkmann; Gordon, Scott D; Giulianini, Franco; Boutin, Thibaud S; Abdellaoui, Abdel; Zhao, Wei; Medina-Gomez, Carolina; Bartz, Traci M; Trompet, Stella; Lange, Leslie A; Raffield, Laura; van der Spek, Ashley; Galesloot, Tessel E; Proitsi, Petroula; Yanek, Lisa R; Bielak, Lawrence F; Payton, Antony; Murgia, Federico; Concas, Maria Pina; Biino, Ginevra; Tajuddin, Salman M; Seppälä, Ilkka; Amin, Najaf; Boerwinkle, Eric; Børglum, Anders D; Campbell, Archie; Demerath, Ellen W; Demuth, Ilja; Faul, Jessica D; Ford, Ian; Gialluisi, Alessandro; Gögele, Martin; Graff, MariaElisa; Hingorani, Aroon; Hottenga, Jouke-Jan; Hougaard, David M; Hurme, Mikko A; Ikram, M Arfan; Jylhä, Marja; Kuh, Diana; Ligthart, Lannie; Lill, Christina M; Lindenberger, Ulman; Lumley, Thomas; Mägi, Reedik; Marques-Vidal, Pedro; Medland, Sarah E; Milani, Lili; Nagy, Reka; Ollier, William E R; Peyser, Patricia A; Pramstaller, Peter P; Ridker, Paul M; Rivadeneira, Fernando; Ruggiero, Daniela; Saba, Yasaman; Schmidt, Reinhold; Schmidt, Helena; Slagboom, P Eline; Smith, Blair H; Smith, Jennifer A; Sotoodehnia, Nona; Steinhagen-Thiessen, Elisabeth; van Rooij, Frank J A; Verbeek, André L; Vermeulen, Sita H; Vollenweider, Peter; Wang, Yunpeng; Werge, Thomas; Whitfield, John B; Zonderman, Alan B; Lehtimäki, Terho; Evans, Michele K; Pirastu, Mario; Fuchsberger, Christian; Bertram, Lars; Pendleton, Neil; Kardia, Sharon L R; Ciullo, Marina; Becker, Diane M; Wong, Andrew; Psaty, Bruce M; van Duijn, Cornelia M; Wilson, James G; Jukema, J Wouter; Kiemeney, Lambertus; Uitterlinden, André G; Franceschini, Nora; North, Kari E; Weir, David R; Metspalu, Andres; Boomsma, Dorret I; Hayward, Caroline; Chasman, Daniel; Martin, Nicholas G; Sattar, Naveed; Campbell, Harry; Esko, Tōnu; Kutalik, Zoltán; Wilson, James F

2017-10-13

Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents' survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan.Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan.

Decreased epigenetic age of PBMCs from Italian semi-supercentenarians and their offspring.

PubMed

Horvath, Steve; Pirazzini, Chiara; Bacalini, Maria Giulia; Gentilini, Davide; Di Blasio, Anna Maria; Delledonne, Massimo; Mari, Daniela; Arosio, Beatrice; Monti, Daniela; Passarino, Giuseppe; De Rango, Francesco; D'Aquila, Patrizia; Giuliani, Cristina; Marasco, Elena; Collino, Sebastiano; Descombes, Patrick; Garagnani, Paolo; Franceschi, Claudio

2015-12-01

Given the dramatic increase in ageing populations, it is of great importance to understand the genetic and molecular determinants of healthy ageing and longevity. Semi-supercentenarians (subjects who reached an age of 105-109 years) arguably represent the gold standard of successful human ageing because they managed to avoid or postpone the onset of major age-related diseases. Relatively few studies have looked at epigenetic determinants of extreme longevity in humans. Here we test whether families with extreme longevity are epigenetically distinct from controls according to an epigenetic biomarker of ageing which is known as "epigenetic clock". We analyze the DNA methylation levels of peripheral blood mononuclear cells (PBMCs) from Italian families constituted of 82 semi-supercentenarians (mean age: 105.6 ± 1.6 years), 63 semi-supercentenarians' offspring (mean age: 71.8 ± 7.8 years), and 47 age-matched controls (mean age: 69.8 ± 7.2 years). We demonstrate that the offspring of semi-supercentenarians have a lower epigenetic age than age-matched controls (age difference=5.1 years, p=0.00043) and that centenarians are younger (8.6 years) than expected based on their chronological age. By contrast, no significant difference could be observed for estimated blood cell counts (such as naïve or exhausted cytotoxic T cells or helper T cells). Future studies will be needed to replicate these findings in different populations and to extend them to other tissues. Overall, our results suggest that epigenetic processes might play a role in extreme longevity and healthy human ageing.

Decreased epigenetic age of PBMCs from Italian semi-supercentenarians and their offspring

PubMed Central

Horvath, Steve; Pirazzini, Chiara; Bacalini, Maria Giulia; Gentilini, Davide; Di Blasio, Anna Maria; Delledonne, Massimo; Mari, Daniela; Arosio, Beatrice; Monti, Daniela; Passarino, Giuseppe; De Rango, Francesco; D'Aquila, Patrizia; Giuliani, Cristina; Marasco, Elena; Collino, Sebastiano; Descombes, Patrick; Garagnani, Paolo; Franceschi, Claudio

2015-01-01

Given the dramatic increase in ageing populations, it is of great importance to understand the genetic and molecular determinants of healthy ageing and longevity. Semi-supercentenarians (subjects who reached an age of 105-109 years) arguably represent the gold standard of successful human ageing because they managed to avoid or postpone the onset of major age-related diseases. Relatively few studies have looked at epigenetic determinants of extreme longevity in humans. Here we test whether families with extreme longevity are epigenetically distinct from controls according to an epigenetic biomarker of ageing which is known as “epigenetic clock”. We analyze the DNA methylation levels of peripheral blood mononuclear cells (PBMCs) from Italian families constituted of 82 semi-supercentenarians (mean age: 105.6 ± 1.6 years), 63 semi-supercentenarians' offspring (mean age: 71.8 ± 7.8 years), and 47 age-matched controls (mean age: 69.8 ± 7.2 years). We demonstrate that the offspring of semi-supercentenarians have a lower epigenetic age than age-matched controls (age difference=5.1 years, p=0.00043) and that centenarians are younger (8.6 years) than expected based on their chronological age. By contrast, no significant difference could be observed for estimated blood cell counts (such as naïve or exhausted cytotoxic T cells or helper T cells). Future studies will be needed to replicate these findings in different populations and to extend them to other tissues. Overall, our results suggest that epigenetic processes might play a role in extreme longevity and healthy human ageing. PMID:26678252

How Much Is Enough in a Perfect World? Cultural Variation in Ideal Levels of Happiness, Pleasure, Freedom, Health, Self-Esteem, Longevity, and Intelligence.

PubMed

Hornsey, Matthew J; Bain, Paul G; Harris, Emily A; Lebedeva, Nadezhda; Kashima, Emiko S; Guan, Yanjun; González, Roberto; Chen, Sylvia Xiaohua; Blumen, Sheyla

2018-06-01

The maximization principle-that people aspire to the highest possible level of something good if all practical constraints are removed-is a common yet untested assumption about human nature. We predict that in holistic cultures-where contradiction, change, and context are emphasized-ideal states of being for the self will be more moderate than in other cultures. In two studies ( Ns = 2,392 and 6,239), we asked this question: If participants could choose their ideal level of happiness, pleasure, freedom, health, self-esteem, longevity, and intelligence, what level would they choose? Consistent with predictions, results showed that maximization was less pronounced in holistic cultures; members of holistic cultures aspired to less happiness, pleasure, freedom, health, self-esteem, longevity, and IQ than did members of other cultures. In contrast, no differences emerged on ideals for society. The studies show that the maximization principle is not a universal aspect of human nature and that there are predictable cultural differences in people's notions of perfection.

Immunochip analysis identifies association of the RAD50/IL13 region with human longevity.

PubMed

Flachsbart, Friederike; Ellinghaus, David; Gentschew, Liljana; Heinsen, Femke-Anouska; Caliebe, Amke; Christiansen, Lene; Nygaard, Marianne; Christensen, Kaare; Blanché, Hélène; Deleuze, Jean-François; Derbois, Céline; Galan, Pilar; Büning, Carsten; Brand, Stephan; Peters, Anette; Strauch, Konstantin; Müller-Nurasyid, Martina; Hoffmann, Per; Nöthen, Markus M; Lieb, Wolfgang; Franke, Andre; Schreiber, Stefan; Nebel, Almut

2016-06-01

Human longevity is characterized by a remarkable lack of confirmed genetic associations. Here, we report on the identification of a novel locus for longevity in the RAD50/IL13 region on chromosome 5q31.1 using a combined European sample of 3208 long-lived individuals (LLI) and 8919 younger controls. First, we performed a large-scale association study on 1458 German LLI (mean age 99.0 years) and 6368 controls (mean age 57.2 years) by targeting known immune-associated loci covered by the Immunochip. The analysis of 142 136 autosomal single nucleotide polymorphisms (SNPs) revealed an Immunochip-wide significant signal (PI mmunochip  = 7.01 × 10(-9) ) for the SNP rs2075650 in the TOMM40/APOE region, which has been previously described in the context of human longevity. To identify novel susceptibility loci, we selected 15 markers with PI mmunochip  < 5 × 10(-4) for replication in two samples from France (1257 LLI, mean age 102.4 years; 1811 controls, mean age 49.1 years) and Denmark (493 LLI, mean age 96.2 years; 740 controls, mean age 63.1 years). The association at SNP rs2706372 replicated in the French study collection and showed a similar trend in the Danish participants and was also significant in a meta-analysis of the combined French and Danish data after adjusting for multiple testing. In a meta-analysis of all three samples, rs2706372 reached a P-value of PI mmunochip+Repl  = 5.42 × 10(-7) (OR = 1.20; 95% CI = 1.12-1.28). SNP rs2706372 is located in the extended RAD50/IL13 region. RAD50 seems a plausible longevity candidate due to its involvement in DNA repair and inflammation. Further studies are needed to identify the functional variant(s) that predispose(s) to a long and healthy life. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Gut Microbiota and Extreme Longevity.

PubMed

Biagi, Elena; Franceschi, Claudio; Rampelli, Simone; Severgnini, Marco; Ostan, Rita; Turroni, Silvia; Consolandi, Clarissa; Quercia, Sara; Scurti, Maria; Monti, Daniela; Capri, Miriam; Brigidi, Patrizia; Candela, Marco

2016-06-06

The study of the extreme limits of human lifespan may allow a better understanding of how human beings can escape, delay, or survive the most frequent age-related causes of morbidity, a peculiarity shown by long-living individuals. Longevity is a complex trait in which genetics, environment, and stochasticity concur to determine the chance to reach 100 or more years of age [1]. Because of its impact on human metabolism and immunology, the gut microbiome has been proposed as a possible determinant of healthy aging [2, 3]. Indeed, the preservation of host-microbes homeostasis can counteract inflammaging [4], intestinal permeability [5], and decline in bone and cognitive health [6, 7]. Aiming at deepening our knowledge on the relationship between the gut microbiota and a long-living host, we provide for the first time the phylogenetic microbiota analysis of semi-supercentenarians, i.e., 105-109 years old, in comparison to adults, elderly, and centenarians, thus reconstructing the longest available human microbiota trajectory along aging. We highlighted the presence of a core microbiota of highly occurring, symbiotic bacterial taxa (mostly belonging to the dominant Ruminococcaceae, Lachnospiraceae, and Bacteroidaceae families), with a cumulative abundance decreasing along with age. Aging is characterized by an increasing abundance of subdominant species, as well as a rearrangement in their co-occurrence network. These features are maintained in longevity and extreme longevity, but peculiarities emerged, especially in semi-supercentenarians, describing changes that, even accommodating opportunistic and allochthonous bacteria, might possibly support health maintenance during aging, such as an enrichment and/or higher prevalence of health-associated groups (e.g., Akkermansia, Bifidobacterium, and Christensenellaceae). Copyright © 2016 Elsevier Ltd. All rights reserved.

Genetic variants linked to education predict longevity

PubMed Central

Marioni, Riccardo E.; Ritchie, Stuart J.; Joshi, Peter K.; Hagenaars, Saskia P.; Fischer, Krista; Adams, Mark J.; Hill, W. David; Davies, Gail; Nagy, Reka; Amador, Carmen; Läll, Kristi; Metspalu, Andres; Liewald, David C.; Wilson, James F.; Hayward, Caroline; Esko, Tõnu; Porteous, David J.; Gale, Catharine R.; Deary, Ian J.

2016-01-01

Educational attainment is associated with many health outcomes, including longevity. It is also known to be substantially heritable. Here, we used data from three large genetic epidemiology cohort studies (Generation Scotland, n = ∼17,000; UK Biobank, n = ∼115,000; and the Estonian Biobank, n = ∼6,000) to test whether education-linked genetic variants can predict lifespan length. We did so by using cohort members’ polygenic profile score for education to predict their parents’ longevity. Across the three cohorts, meta-analysis showed that a 1 SD higher polygenic education score was associated with ∼2.7% lower mortality risk for both mothers (total ndeaths = 79,702) and ∼2.4% lower risk for fathers (total ndeaths = 97,630). On average, the parents of offspring in the upper third of the polygenic score distribution lived 0.55 y longer compared with those of offspring in the lower third. Overall, these results indicate that the genetic contributions to educational attainment are useful in the prediction of human longevity. PMID:27799538

Genetic variants linked to education predict longevity.

PubMed

Marioni, Riccardo E; Ritchie, Stuart J; Joshi, Peter K; Hagenaars, Saskia P; Okbay, Aysu; Fischer, Krista; Adams, Mark J; Hill, W David; Davies, Gail; Nagy, Reka; Amador, Carmen; Läll, Kristi; Metspalu, Andres; Liewald, David C; Campbell, Archie; Wilson, James F; Hayward, Caroline; Esko, Tõnu; Porteous, David J; Gale, Catharine R; Deary, Ian J

2016-11-22

Educational attainment is associated with many health outcomes, including longevity. It is also known to be substantially heritable. Here, we used data from three large genetic epidemiology cohort studies (Generation Scotland, n = ∼17,000; UK Biobank, n = ∼115,000; and the Estonian Biobank, n = ∼6,000) to test whether education-linked genetic variants can predict lifespan length. We did so by using cohort members' polygenic profile score for education to predict their parents' longevity. Across the three cohorts, meta-analysis showed that a 1 SD higher polygenic education score was associated with ∼2.7% lower mortality risk for both mothers (total n deaths = 79,702) and ∼2.4% lower risk for fathers (total n deaths = 97,630). On average, the parents of offspring in the upper third of the polygenic score distribution lived 0.55 y longer compared with those of offspring in the lower third. Overall, these results indicate that the genetic contributions to educational attainment are useful in the prediction of human longevity.

Hormonal regulation of longevity in mammals

PubMed Central

Brown-Borg, Holly M.

2007-01-01

Multiple biological and environmental factors impact the life span of an organism. The endocrine system is a highly integrated physiological system in mammals that regulates metabolism, growth, reproduction, and response to stress, among other functions. As such, this pervasive entity has a major influence on aging and longevity. The growth hormone, insulin-like growth factor-1 and insulin pathways have been at the forefront of hormonal control of aging research in the last few years. Other hormones, including those from the thyroid and reproductive system have also been studied in terms of life span regulation. The relevance of these hormones to human longevity remains to be established, however the evidence from other species including yeast, nematodes, and flies suggest that evolutionarily well-conserved mechanisms are at play and the endocrine system is a key determinant. PMID:17360245

Paraoxonase-1 (PON1) rs662 Polymorphism and Its Association with Serum Lipid Levels and Longevity in the Bama Zhuang Population.

PubMed

Li, You; Liang, Guiyun; Shi, Liwei; Liang, Xue; Long, Bingshuang; Qin, Jian; Zhang, Zhiyong

2016-12-27

BACKGROUND The present study was performed to identify the association of PON1 rs662 polymorphism with serum lipid levels and human longevity in the Bama Zhuang population. MATERIAL AND METHODS PON1 genotypes were determined by Taqman SNP Genotyping Assays in 110 long-lived inhabitants (longevity group, aged 90-110 years), 110 healthy inhabitants in Bama County (control 1 group, aged 43-82 years) and 110 healthy inhabitants in Nandan County (control 2 group, aged 28-82 years) without family history of longevity. RESULTS BMI (body mass index) and TG (serum total triglyceride) level were lower in the longevity group than in the two control groups, while the contents of serum LDL-c (low-density lipoprotein cholesterol) and HDL-c (high-density lipoprotein cholesterol) and the levels of SBP (systolic blood pressure) and DBP (diastolic blood pressure) in the longevity group were higher than in the two control groups (p<0.01). Significant differences in the frequencies of three genotypes (GG, AG, and AA) were observed between the longevity group and control 2 group (χ²=15.190, p=0.001). The minor allele frequency (MAF) of rs662 was significantly higher in the longevity group than in the two control groups. The levels of HDL-c in the longevity group were different among the three genotypes (p<0.05). The levels of TG for GG and GG+AG genotypes were significantly different, while the levels of TC (total cholesterol) and HDL-c for AG and GG+AG genotypes were significantly different among the three groups (p<0.05). Serum lipid parameters were correlated with several environmental factors, including age, gender, DBP, SBP, and BMI. The association of PON1 rs662 polymorphism and serum lipid levels was different among the three groups. CONCLUSIONS PON1 polymorphism might be one of the genetic factors of longevity in the Bama Zhuang population. The PON1 rs662 SNP (single nucleotide polymorphism) was associated with serum HDL-c levels in the longevity group.

Proton magnetic resonance spectroscopy shows lower intramyocellular lipid accumulation in middle-aged subjects predisposed to familial longevity.

PubMed

Wijsman, C A; van Opstal, A M; Kan, H E; Maier, A B; Westendorp, R G J; Slagboom, P E; Webb, A G; Mooijaart, S P; van Heemst, D

2012-02-01

Families predisposed to longevity show enhanced glucose tolerance and skeletal muscle insulin sensitivity compared with controls, independent of body composition and physical activity. Intramyocellular lipid (IMCL) accumulation in skeletal muscle has been associated with insulin resistance. Here, we assessed whether subjects enriched for familial longevity have lower IMCL levels. We determined IMCL levels in 48 subjects from the Leiden Longevity Study, comprising 24 offspring of nonagenarian siblings and 24 partners thereof as control subjects. IMCL levels were assessed noninvasively using short echo time proton magnetic resonance spectroscopy ((1)H-MRS) of the tibialis anterior muscle with a 7 Tesla human MR scanner. IMCL levels were calculated relative to the total creatine (tCr) CH3 signal. Physical activity was assessed using the International Physical Activity Questionnaire (IPAQ). After correction for age, sex, BMI, and physical activity, offspring of long-lived nonagenarian siblings tended to show lower IMCL levels compared with controls (IMCL/tCr: 3.1 ± 0.5 vs. 4.5 ± 0.5, respectively, P = 0.051). In a pairwise comparison, this difference reached statistical significance (P = 0.038). We conclude that offspring of nonagenarian siblings predisposed to longevity show lower IMCL levels compared with environmentally matched control subjects. Future research should focus on assessing what mechanisms may explain the lower IMCL levels in familial longevity.

Association of FOXO3A variation with human longevity confirmed in German centenarians

PubMed Central

Flachsbart, Friederike; Caliebe, Amke; Kleindorp, Rabea; Blanché, Hélène; von Eller-Eberstein, Huberta; Nikolaus, Susanna; Schreiber, Stefan; Nebel, Almut

2009-01-01

The human forkhead box O3A gene (FOXO3A) encodes an evolutionarily conserved key regulator of the insulin–IGF1 signaling pathway that is known to influence metabolism and lifespan in model organisms. A recent study described 3 SNPs in the FOXO3A gene that were statistically significantly associated with longevity in a discovery sample of long-lived men of Japanese ancestry [Willcox et al. (2008) Proc Natl Acad Sci USA 105:13987–13992]. However, this finding required replication in an independent population. Here, we have investigated 16 known FOXO3A SNPs in an extensive collection of 1,762 German centenarians/nonagenarians and younger controls and provide evidence that polymorphisms in this gene were indeed associated with the ability to attain exceptional old age. The FOXO3A association was considerably stronger in centenarians than in nonagenarians, highlighting the importance of centenarians for genetic longevity research. Our study extended the initial finding observed in Japanese men to women and indicates that both genders were likely to be equally affected by variation in FOXO3A. Replication in a French centenarian sample generated a trend that supported the previous results. Our findings confirmed the initial discovery in the Japanese sample and indicate FOXO3A as a susceptibility gene for prolonged survival in humans. PMID:19196970

Healthy Aging: Is Smaller Better?

PubMed Central

Bartke, Andrzej

2014-01-01

A recent report of virtually complete protection from diabetes and cancer in a population of people with hereditary dwarfism revived interest in elucidating the relationships between growth, adult body size, age-related disease and longevity. In many species, smaller individuals outlive those that are larger and a similar relationship was shown in studies of various human populations. Adult body size is strongly dependent on the actions of growth hormone (GH) and the absence of GH or GH receptor in mice leads to a remarkable extension of longevity. Many mechanisms that may account for, or contribute to, this association have been identified. It is suggested that modest modifications of the diet at different ages may extend human healthspan and lifespan by reducing levels of hormones that stimulate growth. PMID:22261798

Midlife muscle strength and human longevity up to age 100 years: a 44-year prospective study among a decedent cohort.

PubMed

Rantanen, Taina; Masaki, Kamal; He, Qimei; Ross, G Webster; Willcox, Bradley J; White, Lon

2012-06-01

We studied prospectively the midlife handgrip strength, living habits, and parents' longevity as predictors of length of life up to becoming a centenarian. The participants were 2,239 men from the Honolulu Heart Program/Honolulu-Asia Aging Study who were born before the end of June 1909 and who took part in baseline physical assessment in 1965-1968, when they were 56-68 years old. Deaths were followed until the end of June 2009 for 44 years with complete ascertainment. Longevity was categorized as centenarian (≥100 years, n = 47), nonagenarian (90-99 years, n = 545), octogenarian (80-89 years, n = 847), and ≤79 years (n = 801, reference). The average survival after baseline was 20.8 years (SD = 9.62). Compared with people who died at the age of ≤79 years, centenarians belonged 2.5 times (odds ratio (OR) = 2.52, 95% confidence interval (CI) = 1.23-5.10) more often to the highest third of grip strength in midlife, were never smokers (OR = 5.75 95% CI = 3.06-10.80), had participated in physical activity outside work (OR = 1.13 per daily hour, 95% CI = 1.02-1.25), and had a long-lived mother (≥80 vs. ≤60 years, OR = 2.3, 95% CI = 1.06-5.01). Associations for nonagenarians and octogenarians were parallel, but weaker. Multivariate modeling showed that mother's longevity and offspring's grip strength operated through the same or overlapping pathway to longevity. High midlife grip strength and long-lived mother may indicate resilience to aging, which, combined with healthy lifestyle, increases the probability of extreme longevity.

Biological processes modulating longevity across primates: a phylogenetic genome-phenome analysis.

PubMed

Muntané, Gerard; Farré, Xavier; Antonio Rodríguez, Juan; Pegueroles, Cinta; Hughes, David A; de Magalhães, João Pedro; Gabaldón, Toni; Navarro, Arcadi

2018-05-21

Aging is a complex process affecting different species and individuals in different ways. Comparing genetic variation across species with their aging phenotypes will help understanding the molecular basis of aging and longevity. Although most studies on aging have so far focused on short-lived model organisms, recent comparisons of genomic, transcriptomic, and metabolomic data across lineages with different lifespans are unveiling molecular signatures associated with longevity. Here, we examine the relationship between genomic variation and maximum lifespan (MLS) across primate species. We used two different approaches. First, we searched for parallel amino acid mutations that co-occur with increases in longevity across the primate linage. Twenty-five such amino acid variants were identified, several of which have been previously reported by studies with different experimental setups and in different model organisms. The genes harboring these mutations are mainly enriched in functional categories such as Wound Healing, Blood Coagulation and Cardiovascular Disorders. We demonstrate that these pathways are highly enriched for pleiotropic effects, as predicted by the Antagonistic Pleiotropy (AP) theory of aging. A second approach was focused on changes in rates of protein evolution across the primate phylogeny. Using the Phylogenetic Generalized Least Squares (PGLS) we show that some genes exhibit strong correlations between their evolutionary rates and longevity-associated traits. These include genes in the Sphingosine 1-phosphate pathway, PI3K signaling and the Thrombin/protease-activated receptor pathway, among other cardiovascular processes. Together, these results shed light into human senescence patterns and underscore the power of comparative genomics to identify pathways related to aging and longevity.

Whole genome sequences of a male and female supercentenarian, ages greater than 114 years.

PubMed

Sebastiani, Paola; Riva, Alberto; Montano, Monty; Pham, Phillip; Torkamani, Ali; Scherba, Eugene; Benson, Gary; Milton, Jacqueline N; Baldwin, Clinton T; Andersen, Stacy; Schork, Nicholas J; Steinberg, Martin H; Perls, Thomas T

2011-01-01

Supercentenarians (age 110+ years old) generally delay or escape age-related diseases and disability well beyond the age of 100 and this exceptional survival is likely to be influenced by a genetic predisposition that includes both common and rare genetic variants. In this report, we describe the complete genomic sequences of male and female supercentenarians, both age >114 years old. We show that: (1) the sequence variant spectrum of these two individuals' DNA sequences is largely comparable to existing non-supercentenarian genomes; (2) the two individuals do not appear to carry most of the well-established human longevity enabling variants already reported in the literature; (3) they have a comparable number of known disease-associated variants relative to most human genomes sequenced to-date; (4) approximately 1% of the variants these individuals possess are novel and may point to new genes involved in exceptional longevity; and (5) both individuals are enriched for coding variants near longevity-associated variants that we discovered through a large genome-wide association study. These analyses suggest that there are both common and rare longevity-associated variants that may counter the effects of disease-predisposing variants and extend lifespan. The continued analysis of the genomes of these and other rare individuals who have survived to extremely old ages should provide insight into the processes that contribute to the maintenance of health during extreme aging.

Whole Genome Sequences of a Male and Female Supercentenarian, Ages Greater than 114 Years

PubMed Central

Sebastiani, Paola; Riva, Alberto; Montano, Monty; Pham, Phillip; Torkamani, Ali; Scherba, Eugene; Benson, Gary; Milton, Jacqueline N.; Baldwin, Clinton T.; Andersen, Stacy; Schork, Nicholas J.; Steinberg, Martin H.; Perls, Thomas T.

2012-01-01

Supercentenarians (age 110+ years old) generally delay or escape age-related diseases and disability well beyond the age of 100 and this exceptional survival is likely to be influenced by a genetic predisposition that includes both common and rare genetic variants. In this report, we describe the complete genomic sequences of male and female supercentenarians, both age >114 years old. We show that: (1) the sequence variant spectrum of these two individuals’ DNA sequences is largely comparable to existing non-supercentenarian genomes; (2) the two individuals do not appear to carry most of the well-established human longevity enabling variants already reported in the literature; (3) they have a comparable number of known disease-associated variants relative to most human genomes sequenced to-date; (4) approximately 1% of the variants these individuals possess are novel and may point to new genes involved in exceptional longevity; and (5) both individuals are enriched for coding variants near longevity-associated variants that we discovered through a large genome-wide association study. These analyses suggest that there are both common and rare longevity-associated variants that may counter the effects of disease-predisposing variants and extend lifespan. The continued analysis of the genomes of these and other rare individuals who have survived to extremely old ages should provide insight into the processes that contribute to the maintenance of health during extreme aging. PMID:22303384

DRD4 genotype predicts longevity in mouse and human.

PubMed

Grady, Deborah L; Thanos, Panayotis K; Corrada, Maria M; Barnett, Jeffrey C; Ciobanu, Valentina; Shustarovich, Diana; Napoli, Anthony; Moyzis, Alexandra G; Grandy, David; Rubinstein, Marcelo; Wang, Gene-Jack; Kawas, Claudia H; Chen, Chuansheng; Dong, Qi; Wang, Eric; Volkow, Nora D; Moyzis, Robert K

2013-01-02

Longevity is influenced by genetic and environmental factors. The brain's dopamine system may be particularly relevant, since it modulates traits (e.g., sensitivity to reward, incentive motivation, sustained effort) that impact behavioral responses to the environment. In particular, the dopamine D4 receptor (DRD4) has been shown to moderate the impact of environments on behavior and health. We tested the hypothesis that the DRD4 gene influences longevity and that its impact is mediated through environmental effects. Surviving participants of a 30-year-old population-based health survey (N = 310; age range, 90-109 years; the 90+ Study) were genotyped/resequenced at the DRD4 gene and compared with a European ancestry-matched younger population (N = 2902; age range, 7-45 years). We found that the oldest-old population had a 66% increase in individuals carrying the DRD4 7R allele relative to the younger sample (p = 3.5 × 10(-9)), and that this genotype was strongly correlated with increased levels of physical activity. Consistent with these results, DRD4 knock-out mice, when compared with wild-type and heterozygous mice, displayed a 7-9.7% decrease in lifespan, reduced spontaneous locomotor activity, and no lifespan increase when reared in an enriched environment. These results support the hypothesis that DRD4 gene variants contribute to longevity in humans and in mice, and suggest that this effect is mediated by shaping behavioral responses to the environment.

Human longevity and common variations in the LMNA gene: a meta-analysis

PubMed Central

Conneely, Karen N.; Capell, Brian C.; Erdos, Michael R.; Sebastiani, Paola; Solovieff, Nadia; Swift, Amy J.; Baldwin, Clinton T.; Budagov, Temuri; Barzilai, Nir; Atzmon, Gil; Puca, Annibale A.; Perls, Thomas T.; Geesaman, Bard J.; Boehnke, Michael; Collins, Francis S.

2012-01-01

Summary A mutation in the LMNA gene is responsible for the most dramatic form of premature aging, Hutchinson-Gilford progeria syndrome (HGPS). Several recent studies have suggested that protein products of this gene might have a role in normal physiological cellular senescence. To explore further LMNA's possible role in normal aging, we genotyped 16 SNPs over a span of 75.4 kb of the LMNA gene on a sample of long-lived individuals (US Caucasians with age ≥95 years, N=873) and genetically matched younger controls (N=443). We tested all common non-redundant haplotypes (frequency ≥ 0.05) based on subgroups of these 16 SNPs for association with longevity. The most significant haplotype, based on 4 SNPs, remained significant after adjustment for multiple testing (OR = 1.56, P=2.5×10−5, multiple-testing-adjusted P=0.0045). To attempt to replicate these results, we genotyped 3448 subjects from four independent samples of long-lived individuals and control subjects from 1) the New England Centenarian Study (NECS) (N=738), 2) the Southern Italian Centenarian Study (SICS) (N=905), 3) France (N=1103), and 4) the Einstein Ashkenazi Longevity Study (N=702). We replicated the association with the most significant haplotype from our initial analysis in the NECS sample (OR = 1.60, P=0.0023), but not in the other three samples (P>.15). In a meta-analysis combining all five samples, the best haplotype remained significantly associated with longevity after adjustment for multiple testing in the initial and follow-up samples (OR = 1.18, P=7.5×10−4, multiple-testing-adjusted P=0.037). These results suggest that LMNA variants may play a role in human lifespan. PMID:22340368

Intellectual maturity and longevity: late-blooming composers and writers live longer than child prodigies

PubMed Central

Hafkamp, Maurits P.J.; Slaets, Joris P.J.; van Bodegom, David

2017-01-01

Life history theory links human physical and sexual development to longevity. However, there have been no studies on the association of intellectual development with longevity. This observational study investigates the relationship between the onset of intellectual maturity and lifespan through the life histories of composers and creative writers, whose intellectual development can be gauged through their compositions and writings. In these groups we model the relationship between the age at first creative work, and age at death using multilevel regression, adjusting for sex, date of birth, and nationality. Historical biographical records on 1110 musical composers and 1182 creative writers, born in the period 1400 AD through 1915 AD, were obtained from the Oxford Companion to Music and the Oxford Companion to English Literature. Composers and creative writers lived, respectively 0.16 (p = 0.02) and 0.18 (p < 0.01) years longer for each later year of age at first work. When completion of the first creative work is interpreted as a proxy for the onset of intellectual maturity in composers and creative writers, our findings indicate that a later onset of intellectual maturity is associated with higher longevity. PMID:28562321

Intellectual maturity and longevity: late-blooming composers and writers live longer than child prodigies.

PubMed

Hafkamp, Maurits P J; Slaets, Joris P J; van Bodegom, David

2017-05-30

Life history theory links human physical and sexual development to longevity. However, there have been no studies on the association of intellectual development with longevity. This observational study investigates the relationship between the onset of intellectual maturity and lifespan through the life histories of composers and creative writers, whose intellectual development can be gauged through their compositions and writings. In these groups we model the relationship between the age at first creative work, and age at death using multilevel regression, adjusting for sex, date of birth, and nationality. Historical biographical records on 1110 musical composers and 1182 creative writers, born in the period 1400 AD through 1915 AD, were obtained from the Oxford Companion to Music and the Oxford Companion to English Literature. Composers and creative writers lived, respectively 0.16 ( p = 0.02) and 0.18 ( p < 0.01) years longer for each later year of age at first work. When completion of the first creative work is interpreted as a proxy for the onset of intellectual maturity in composers and creative writers, our findings indicate that a later onset of intellectual maturity is associated with higher longevity.

Understanding the Natural and Socioeconomic Factors behind Regional Longevity in Guangxi, China: Is the Centenarian Ratio a Good Enough Indicator for Assessing the Longevity Phenomenon?

PubMed

Deng, Qucheng; Wei, Yongping; Zhao, Yan; Han, Xuerong; Yin, Juan

2018-05-08

Despite a number of longevity indicators having been used in previous longevity studies, few studies have critically evaluated whether these indicators are suitable to assess the regional longevity level. In addition, an increasing number of studies have attempted to determine the influence of socioeconomic and natural factors on regional longevity, but only certain factors were considered. This study aims to bridge this gap by determining the relationship between the 7 longevity indicators and selecting 24 natural and socioeconomic indicators in 109 selected counties and urban districts in Guangxi, China. This study has applied spatial analysis and geographically weighted regression as the main research methods. The seven longevity indicators here refer to centenarian ratio, longevity index, longevity level, aging tendency, 80⁺ ratio, 90⁺ ratio, and 95⁺ ratio. Natural indicators in this study mainly refer to atmospheric pressure, temperature, difference in temperature, humidity, rainfall, radiation, water vapor, and altitude. Socioeconomic indicators can be categorized into those related to economic status, education, local infrastructure, and health care facilities. The results show that natural factors such as the difference in temperature and altitude, along with socioeconomic factors such as GDP, might be the most significant contributors to the longevity of people aged 60⁻90 years in Guangxi. The longevity index and longevity level are useful supplementary indexes to the centenarian ratio for assessing the regional longevity.

Sasang Constitutional Medicine and Traditional Chinese Medicine: A Comparative Overview

PubMed Central

Yoo, Junghee; Lee, Euiju; Kim, Chungmi; Lee, Junhee; Lixing, Lao

2012-01-01

Sasang constitutional medicine (SCM) is a holistic typological constitution medicine which balances psychological, social, and physical aspects of an individual to achieve wellness and increase longevity. SCM has the qualities of preventative medicine, as it emphasizes daily health management based on constitutionally differentiated regimens and self-cultivation of the mind and body. This review's goal is to establish a fundamental understanding of SCM and to provide a foundation for further study. It compares the similarities and differences of philosophical origins, perspectives on the mind (heart), typological systems, pathology, and therapeutics between SCM and traditional Chinese medicine (TCM). TCM is based on the Taoist view of the universe and humanity. The health and longevity of an individual depends on a harmonious relationship with the universe. On the other hand, SCM is based on the Confucian view of the universe and humanity. SCM focuses on the influence of human affairs on the psyche, physiology, and pathology. PMID:21941592

Opposing impacts on healthspan and longevity by limiting dietary selenium in Telomere Dysfunctional mice

USDA-ARS?s Scientific Manuscript database

Selenium (Se) is an essential trace element essential for optimal health. We investigated the role of Se in longevity and healthspan in a mouse model of healthy aging in humans with short telomeres. Telomere shortening is associated with aging, mortality and aging-related diseases. We found that whi...

Quantifying Intrinsic and Extrinsic Contributions to Human Longevity: Application of a Two-Process Vitality Model to the Human Mortality Database.

PubMed

Sharrow, David J; Anderson, James J

2016-12-01

The rise in human life expectancy has involved declines in intrinsic and extrinsic mortality processes associated, respectively, with senescence and environmental challenges. To better understand the factors driving this rise, we apply a two-process vitality model to data from the Human Mortality Database. Model parameters yield intrinsic and extrinsic cumulative survival curves from which we derive intrinsic and extrinsic expected life spans (ELS). Intrinsic ELS, a measure of longevity acted on by intrinsic, physiological factors, changed slowly over two centuries and then entered a second phase of increasing longevity ostensibly brought on by improvements in old-age death reduction technologies and cumulative health behaviors throughout life. The model partitions the majority of the increase in life expectancy before 1950 to increasing extrinsic ELS driven by reductions in environmental, event-based health challenges in both childhood and adulthood. In the post-1950 era, the extrinsic ELS of females appears to be converging to the intrinsic ELS, whereas the extrinsic ELS of males is approximately 20 years lower than the intrinsic ELS.

Quantifying Intrinsic and Extrinsic Contributions to Human Longevity: Application of a Two-Process Vitality Model to the Human Mortality Database

PubMed Central

Anderson, James J.

2016-01-01

The rise in human life expectancy has involved declines in intrinsic and extrinsic mortality processes associated, respectively, with senescence and environmental challenges. To better understand the factors driving this rise, we apply a two-process vitality model to data from the Human Mortality Database. Model parameters yield intrinsic and extrinsic cumulative survival curves from which we derive intrinsic and extrinsic expected life spans (ELS). Intrinsic ELS, a measure of longevity acted on by intrinsic, physiological factors, changed slowly over two centuries and then entered a second phase of increasing longevity ostensibly brought on by improvements in old-age death reduction technologies and cumulative health behaviors throughout life. The model partitions the majority of the increase in life expectancy before 1950 to increasing extrinsic ELS driven by reductions in environmental, event-based health challenges in both childhood and adulthood. In the post-1950 era, the extrinsic ELS of females appears to be converging to the intrinsic ELS, whereas the extrinsic ELS of males is approximately 20 years lower than the intrinsic ELS. PMID:27837429

Characterization of the Hypothalamic-Pituitary-Adrenal-Axis in Familial Longevity under Resting Conditions.

PubMed

Jansen, Steffy W; Roelfsema, Ferdinand; Akintola, Abimbola A; Oei, Nicole Y; Cobbaert, Christa M; Ballieux, Bart E; van der Grond, Jeroen; Westendorp, Rudi G; Pijl, Hanno; van Heemst, Diana

2015-01-01

The hypothalamic-pituitary-adrenal (HPA)-axis is the most important neuro-endocrine stress response system of our body which is of critical importance for survival. Disturbances in HPA-axis activity have been associated with adverse metabolic and cognitive changes. Humans enriched for longevity have less metabolic and cognitive disturbances and therefore diminished activity of the HPA axis may be a potential candidate mechanism underlying healthy familial longevity. Here, we compared 24-h plasma ACTH and serum cortisol concentration profiles and different aspects of the regulation of the HPA-axis in offspring from long-lived siblings, who are enriched for familial longevity and age-matched controls. Case-control study within the Leiden Longevity study cohort consisting of 20 middle-aged offspring of nonagenarian siblings (offspring) together with 18 partners (controls). During 24 h, venous blood was sampled every 10 minutes for determination of circulatory ACTH and cortisol concentrations. Deconvolution analysis, cross approximate entropy analysis and ACTH-cortisol-dose response modeling were used to assess, respectively, ACTH and cortisol secretion parameters, feedforward and feedback synchrony and adrenal gland ACTH responsivity. Mean (95% Confidence Interval) basal ACTH secretion was higher in male offspring compared to male controls (645 (324-1286) ngl/L/24 h versus 240 (120-477) ng/L/24 h, P = 0.05). Other ACTH and cortisol secretion parameters did not differ between offspring and controls. In addition, no significant differences in feedforward and feedback synchrony and adrenal gland ACTH responsivity were observed between groups. These results suggest that familial longevity is not associated with major differences in HPA-axis activity under resting conditions, although modest, sex-specific differences may exist between groups that might be clinically relevant.

Genome-Wide Analysis of Germline Signaling Genes Regulating Longevity and Innate Immunity in the Nematode Pristionchus pacificus

PubMed Central

Sommer, Ralf J.

2012-01-01

Removal of the reproductive system of many animals including fish, flies, nematodes, mice and humans can increase lifespan through mechanisms largely unknown. The abrogation of the germline in Caenorhabditis elegans increases longevity by 60% due to a signal emitted from the somatic gonad. Apart from increased longevity, germline-less C. elegans is also resistant to other environmental stressors such as feeding on bacterial pathogens. However, the evolutionary conservation of this pathogen resistance, its genetic basis and an understanding of genes involved in producing this extraordinary survival phenotype are currently unknown. To study these evolutionary aspects we used the necromenic nematode Pristionchus pacificus, which is a genetic model system used in comparison to C. elegans. By ablation of germline precursor cells and subsequent feeding on the pathogen Serratia marcescens we discovered that P. pacificus shows remarkable resistance to bacterial pathogens and that this response is evolutionarily conserved across the Genus Pristionchus. To gain a mechanistic understanding of the increased resistance to bacterial pathogens and longevity in germline-ablated P. pacificus we used whole genome microarrays to profile the transcriptional response comparing germline ablated versus un-ablated animals when fed S. marcescens. We show that lipid metabolism, maintenance of the proteasome, insulin signaling and nuclear pore complexes are essential for germline deficient phenotypes with more than 3,300 genes being differentially expressed. In contrast, gene expression of germline-less P. pacificus on E. coli (longevity) and S. marcescens (immunity) is very similar with only 244 genes differentially expressed indicating that longevity is due to abundant gene expression also involved in immunity. By testing existing mutants of Ppa-DAF-16/FOXO and the nuclear hormone receptor Ppa-DAF-12 we show a conserved function of both genes in resistance to bacterial pathogens and longevity. This is the first study to show that the influence of the reproductive system on extending lifespan and innate immunity is conserved in evolution. PMID:22912581

Anti-photoaging potential of propolis extract in UVB-irradiated human dermal fibroblasts through increasing the expression of FOXO3A and NGF genes.

PubMed

Ebadi, Parimah; Fazeli, Mehdi

2017-11-01

Propolis is a resinous compound that has been widely used in folk medicine. Different biological activities and therapeutic applications of propolis have been studied before. However, the effects of propolis on longevity-associated genes expression in the prevention of skin photoaging still remained unclear. Therefore in this study the protective effects of propolis on the expressions of two longevity-associated genes, FOXO3A and NGF genes, against UVB-induced photoaging in human dermal fibroblasts (HDF) were investigated. Propolis extract demonstrated a concentration-dependent free radical scavenging activity that was determined by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay. Also, Folin-Ciocalteu method was used to measure the total phenolic content of the extract. The viability of HDF cells was decreased gradually with increasing UVB radiation doses and 248mJ/cm 2 was selected as the sub-cytotoxic dose. Pre-treatment with propolis extract increased the viability of UVB-irradiated human dermal fibroblasts and decreased the number of β-galactosidase positive cells as senescent cells among them. It also increased the expression of FOXO3A and NGF genes in irradiated and non-irradiated cells. Consequently, these findings suggest that propolis extract has anti-photoaging potential and this property, in addition to its strong antioxidant activity, may be due to its effects on upregulation of longevity-associated genes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Longevity candidate genes and their association with personality traits in the elderly

PubMed Central

Luciano, Michelle; Lopez, Lorna M.; de Moor, Marleen H.M.; Harris, Sarah E.; Davies, Gail; Nutile, Teresa; Krueger, Robert F.; Esko, Tõnu; Schlessinger, David; Toshiko, Tanaka; Derringer, Jaime L.; Realo, Anu; Hansell, Narelle K.; Pergadia, Michele L.; Pesonen, Anu-Katriina; Sanna, Serena; Terracciano, Antonio; Madden, Pamela A.F.; Penninx, Brenda; Spinhoven, Philip; Hartman, Catherine; Oostra, Ben A.; Janssens, A. Cecile J.W.; Eriksson, Johan G; Starr, John M.; Cannas, Alessandra; Ferrucci, Luigi; Metspalu, Andres; Wright, Margeret J.; Heath, Andrew C.; van Duijn, Cornelia M.; Bierut, Laura J.; Raikkonen, Katri; Martin, Nicholas G.; Ciullo, Marina; Rujescu, Dan; Boomsma, Dorret I.; Deary, Ian J.

2013-01-01

Human longevity and personality traits are both heritable and are consistently linked at the phenotypic level. We test the hypothesis that candidate genes influencing longevity in lower organisms are associated with variance in the five major dimensions of human personality (measured by the NEO-FFI and IPIP inventories) plus related mood states of anxiety and depression. Seventy single nucleotide polymorphisms (SNPs) in six brain expressed, longevity candidate genes (AFG3L2, FRAP1, MAT1A, MAT2A, SYNJ1 and SYNJ2) were typed in over one thousand 70-year old participants from the Lothian Birth Cohort of 1936 (LBC1936). No SNPs were associated with the personality and psychological distress traits at a Bonferroni corrected level of significance (p < 0.0002), but there was an over-representation of nominally significant (p < 0.05) SNPs in the synaptojanin-2 (SYNJ2) gene associated with agreeableness and symptoms of depression. Eight SNPs which showed nominally significant association across personality measurement instruments were tested in an extremely large replication sample of 17 106 participants. SNP rs350292, in SYNJ2, was significant: the minor allele was associated with an average decrease in NEO agreeableness scale scores of 0.25 points, and 0.67 points in the restricted analysis of elderly cohorts (most aged > 60 years). Because we selected a specific set of longevity genes based on functional genomics findings, further research on other longevity gene candidates is warranted to discover whether they are relevant candidates for personality and psychological distress traits. PMID:22213687

Chemical qualities of water that contribute to human health in a positive way

USGS Publications Warehouse

Hopps, Howard C.

1986-01-01

The emphasis on harmful substances that may occur in potable waters has almost obscured the fact that important beneficial constituents are commonly present.The chemical substances in water that make positive contributions to human health act mainly in two ways: (i) nutritionally, by supplying essential macro and micro elements that the diet (excluding water) may not provide in adequate amounts (for example, Mg, I and Zn); and (ii) by providing macro and micro elements that inhibit the absorption and/or effects of toxic elements such as Hg, Pb and Cd. Specific examples of these beneficial effects will be given, also examples of harmful effects on health that may result from excessive intake of these ordinarily beneficial elements.Because concentrations of the essential macro and micro elements that occur in natural, potable waters vary greatly, depending upon their source, geographic considerations are very important in any studies attempting to relate water quality to health. In this context, the inverse relationship between hard water and cardiovascular disease will be discussed. Specific data relating hardness and Mg and Ca content of potable waters to specific geographic regions of the U.S.A. will be presented. These data show a strong positive correlation between low Mg content and decreased longevity, and between high Ca and Mg content and increased longevity. In the regions considered, increased longevity correlates strongly with decreased cardiovascular mortality, and the decreased longevity with increased cardiovascular mortality.

DRD4 genotype predicts longevity in mouse and human

PubMed Central

Grady, Deborah L.; Thanos, Panayotis K.; Corrada, Maria M.; Barnett, Jeffrey C.; Ciobanu, Valentina; Shustarovich, Diana; Napoli, Anthony; Moyzis, Alexandra G.; Grandy, David; Rubinstein, Marcelo; Wang, Gene-Jack; H.Kawas, Claudia; Chen, Chuansheng; Dong, Qi; Wang, Eric; Volkow, Nora D.; Moyzis, Robert K.

2013-01-01

Longevity is influenced by genetic and environmental factors. The brain's dopamine system may be particularly relevant, since it modulates traits (e.g., sensitivity to reward, incentive motivation, sustained effort) that impact behavioral responses to the environment. In particular, the dopamine D4 receptor (DRD4) has been shown to moderate the impact of environments on behavior and health. We tested the hypothesis that the DRD4 gene influences longevity and that its impact is mediated through environmental effects. Surviving participants of a 30 year-old population-based health survey (N=310, age range 90–109; the 90+ Study) were genotyped/resequenced at the DRD4 gene, and compared to a European ancestry-matched younger population (N=2902, age range 7–45). We found that the oldest-old population had a 66% increase in individuals carrying the DRD4 7R allele relative to the younger sample (p=3.5 × 10−9), and that this genotype was strongly correlated with increased levels of physical activity. Consistent with these results, DRD4 knockout mice, when compared to wild-type and heterozygous mice, displayed a 7–9.7% decrease in lifespan, reduced spontaneous locomotor activity, and no lifespan increase when reared in an enriched environment. These results support the hypothesis that DRD4 gene variants contribute to longevity in humans and in mice, and suggest that this effect is mediated by shaping behavioral responses to the environment. PMID:23283341

The Development of Brazilian Municipalities Flooded by Hydropower Plants

NASA Astrophysics Data System (ADS)

Araujo, N.; Moretto, E. M.; Roquetti, D. R.; Beduschi, L. C.; Praia, A.; Pulice, S.; Albiach, E.; Athayde, S.

2016-12-01

Hydropower plants cause negative environmental impacts during the phases of construction and operation. On the other hand, there is a general assumption that these projects also induce local development of the affected places, since there is a great influx of social and financial capital brought locally, especially during the construction phase the relationship between hydropower plant implementation s and local development has been controversial in the Environmental Impact Assessment field, and there is no empirical evidence showing how hydroelectric dam construction affects local development. Considering municipal development as a kind of local development and operationalizing the concept of human development by adopting income, longevity and education dimensions defined by Amartya Sen, this study aimed to verify empirical evidences regarding the role of hydropower plants in human development of their flooded municipalities in Brazil. For this, we considered 134 hydroelectric plants and correspondent 641 flooded municipalities, for which 155 human development indicators were obtained for the period of 2000 to 2010. Results obtained from statistical correlation analysis and their assumption tests showed that increases in the municipal flooded area and increases in the period of flooding - to which a given municipality is submitted - were associated with lower performances of human development indicators. Specifically, increases in social inequality, poverty and lower performances of longevity and education were detected for the flooded municipalities. We also found that the financial compensation was associated with better performance of municipal income and lower performances of education and longevity. Finally, approaching the growth poles theory of François Perroux and the productive linkages theory of Albert Hirschman, we suggest that the size of the flooded areas, the flooding period and the financial compensation may lead to an enclave situation in municipalities flooded by hydropower plants, considering issues of education and longevity. Furthermore, it is likely that the labor force, investments and financial compensation inputs brought by these projects to the local municipalities are not strong enough to reverse this enclave scenario.

The Human Ageing Genomic Resources: online databases and tools for biogerontologists

PubMed Central

de Magalhães, João Pedro; Budovsky, Arie; Lehmann, Gilad; Costa, Joana; Li, Yang; Fraifeld, Vadim; Church, George M.

2009-01-01

Summary Ageing is a complex, challenging phenomenon that will require multiple, interdisciplinary approaches to unravel its puzzles. To assist basic research on ageing, we developed the Human Ageing Genomic Resources (HAGR). This work provides an overview of the databases and tools in HAGR and describes how the gerontology research community can employ them. Several recent changes and improvements to HAGR are also presented. The two centrepieces in HAGR are GenAge and AnAge. GenAge is a gene database featuring genes associated with ageing and longevity in model organisms, a curated database of genes potentially associated with human ageing, and a list of genes tested for their association with human longevity. A myriad of biological data and information is included for hundreds of genes, making GenAge a reference for research that reflects our current understanding of the genetic basis of ageing. GenAge can also serve as a platform for the systems biology of ageing, and tools for the visualization of protein-protein interactions are also included. AnAge is a database of ageing in animals, featuring over 4,000 species, primarily assembled as a resource for comparative and evolutionary studies of ageing. Longevity records, developmental and reproductive traits, taxonomic information, basic metabolic characteristics, and key observations related to ageing are included in AnAge. Software is also available to aid researchers in the form of Perl modules to automate numerous tasks and as an SPSS script to analyse demographic mortality data. The Human Ageing Genomic Resources are available online at http://genomics.senescence.info. PMID:18986374

Longevity of Self-etch Dentin Bonding Adhesives Compared to Etch-and-rinse Dentin Bonding Adhesives: A Systematic Review.

PubMed

Masarwa, Nader; Mohamed, Ahmed; Abou-Rabii, Iyad; Abu Zaghlan, Rawan; Steier, Liviu

2016-06-01

A systematic review and meta-analysis were performed to compare longevity of Self-Etch Dentin Bonding Adhesives to Etch-and-Rinse Dentin Bonding Adhesives. The following databases were searched for PubMed, MEDLINE, Web of Science, CINAHL, the Cochrane Library complemented by a manual search of the Journal of Adhesive Dentistry. The MESH keywords used were: "etch and rinse," "total etch," "self-etch," "dentin bonding agent," "bond durability," and "bond degradation." Included were in-vitro experimental studies performed on human dental tissues of sound tooth structure origin. The examined Self-Etch Bonds were of two subtypes; Two Steps and One Step Self-Etch Bonds, while Etch-and-Rinse Bonds were of two subtypes; Two Steps and Three Steps. The included studies measured micro tensile bond strength (μTBs) to evaluate bond strength and possible longevity of both types of dental adhesives at different times. The selected studies depended on water storage as the aging technique. Statistical analysis was performed for outcome measurements compared at 24 h, 3 months, 6 months and 12 months of water storage. After 24 hours (p-value = 0.051), 3 months (p-value = 0.756), 6 months (p-value=0.267), 12 months (p-value=0.785) of water storage self-etch adhesives showed lower μTBs when compared to the etch-and-rinse adhesives, but the comparisons were statistically insignificant. In this study, longevity of Dentin Bonds was related to the measured μTBs. Although Etch-and-Rinse bonds showed higher values at all times, the meta-analysis found no difference in longevity of the two types of bonds at the examined aging times. Copyright © 2016 Elsevier Inc. All rights reserved.

Demographics of human supercentenarians and the implications for longevity medicine.

PubMed

Coles, L Stephen

2004-06-01

Demographers have forecast that there are going to be a great many more older adults in the next few decades. This will have great implications for longevity medicine. The Gerontology Research Group, affiliated with the UCLA School of Medicine, has compiled and maintained a Table of Worldwide Living Supercentenarians (persons 110 years or older) for the last 4 years, shedding important light on the biological limits of human morbidity and mortality and providing a realistic perspective on the problem of long-term interventions that can reasonably be achieved in the near future.

Small nucleoli are a cellular hallmark of longevity

PubMed Central

Tiku, Varnesh; Jain, Chirag; Raz, Yotam; Nakamura, Shuhei; Heestand, Bree; Liu, Wei; Späth, Martin; Suchiman, H. Eka. D.; Müller, Roman-Ulrich; Slagboom, P. Eline; Partridge, Linda; Antebi, Adam

2017-01-01

Animal lifespan is regulated by conserved metabolic signalling pathways and specific transcription factors, but whether these pathways affect common downstream mechanisms remains largely elusive. Here we show that NCL-1/TRIM2/Brat tumour suppressor extends lifespan and limits nucleolar size in the major C. elegans longevity pathways, as part of a convergent mechanism focused on the nucleolus. Long-lived animals representing distinct longevity pathways exhibit small nucleoli, and decreased expression of rRNA, ribosomal proteins, and the nucleolar protein fibrillarin, dependent on NCL-1. Knockdown of fibrillarin also reduces nucleolar size and extends lifespan. Among wildtype C. elegans, individual nucleolar size varies, but is highly predictive for longevity. Long-lived dietary restricted fruit flies and insulin-like-peptide mutants exhibit small nucleoli and fibrillarin expression, as do long-lived dietary restricted and IRS1 knockout mice. Furthermore, human muscle biopsies from individuals who underwent modest dietary restriction coupled with exercise also display small nucleoli. We suggest that small nucleoli are a cellular hallmark of longevity and metabolic health conserved across taxa. PMID:28853436

Small nucleoli are a cellular hallmark of longevity.

PubMed

Tiku, Varnesh; Jain, Chirag; Raz, Yotam; Nakamura, Shuhei; Heestand, Bree; Liu, Wei; Späth, Martin; Suchiman, H Eka D; Müller, Roman-Ulrich; Slagboom, P Eline; Partridge, Linda; Antebi, Adam

2016-08-30

Animal lifespan is regulated by conserved metabolic signalling pathways and specific transcription factors, but whether these pathways affect common downstream mechanisms remains largely elusive. Here we show that NCL-1/TRIM2/Brat tumour suppressor extends lifespan and limits nucleolar size in the major C. elegans longevity pathways, as part of a convergent mechanism focused on the nucleolus. Long-lived animals representing distinct longevity pathways exhibit small nucleoli, and decreased expression of rRNA, ribosomal proteins, and the nucleolar protein fibrillarin, dependent on NCL-1. Knockdown of fibrillarin also reduces nucleolar size and extends lifespan. Among wildtype C. elegans, individual nucleolar size varies, but is highly predictive for longevity. Long-lived dietary restricted fruit flies and insulin-like-peptide mutants exhibit small nucleoli and fibrillarin expression, as do long-lived dietary restricted and IRS1 knockout mice. Furthermore, human muscle biopsies from individuals who underwent modest dietary restriction coupled with exercise also display small nucleoli. We suggest that small nucleoli are a cellular hallmark of longevity and metabolic health conserved across taxa.

A family longevity selection score: ranking sibships by their longevity, size, and availability for study.

PubMed

Sebastiani, Paola; Hadley, Evan C; Province, Michael; Christensen, Kaare; Rossi, Winifred; Perls, Thomas T; Ash, Arlene S

2009-12-15

Family studies of exceptional longevity can potentially identify genetic and other factors contributing to long life and healthy aging. Although such studies seek families that are exceptionally long lived, they also need living members who can provide DNA and phenotype information. On the basis of these considerations, the authors developed a metric to rank families for selection into a family study of longevity. Their measure, the family longevity selection score (FLoSS), is the sum of 2 components: 1) an estimated family longevity score built from birth-, gender-, and nation-specific cohort survival probabilities and 2) a bonus for older living siblings. The authors examined properties of FLoSS-based family rankings by using data from 3 ongoing studies: the New England Centenarian Study, the Framingham Heart Study, and screenees for the Long Life Family Study. FLoSS-based selection yields families with exceptional longevity, satisfactory sibship sizes and numbers of living siblings, and high ages. Parameters in the FLoSS formula can be tailored for studies of specific populations or age ranges or with different conditions. The first component of the FLoSS also provides a conceptually sound survival measure to characterize exceptional longevity in individuals or families in various types of studies and correlates well with later-observed longevity.

A Remarkable Age-Related Increase in SIRT1 Protein Expression against Oxidative Stress in Elderly: SIRT1 Gene Variants and Longevity in Human

PubMed Central

Kilic, Ulkan; Gok, Ozlem; Erenberk, Ufuk; Dundaroz, Mehmet Rusen; Torun, Emel; Kucukardali, Yasar; Elibol-Can, Birsen; Uysal, Omer; Dundar, Tolga

2015-01-01

Aging is defined as the accumulation of progressive organ dysfunction. Controlling the rate of aging by clarifying the complex pathways has a significant clinical importance. Nowadays, sirtuins have become famous molecules for slowing aging and decreasing age-related disorders. In the present study, we analyzed the SIRT1 gene polymorphisms (rs7895833 A>G, rs7069102 C>G and rs2273773 C>T) and its relation with levels of SIRT1, eNOS, PON-1, cholesterol, TAS, TOS, and OSI to demonstrate the association between genetic variation in SIRT1 and phenotype at different ages in humans. We observed a significant increase in the SIRT1 level in older people and found a significant positive correlation between SIRT1 level and age in the overall studied population. The oldest people carrying AG genotypes for rs7895833 have the highest SIRT1 level suggesting an association between rs7895833 SNP and lifespan longevity. Older people have lower PON-1 levels than those of adults and children which may explain the high levels of SIRT1 protein as a compensatory mechanism for oxidative stress in the elderly. The eNOS protein level was significantly decreased in older people as compared to adults. There was no significant difference in the eNOS level between older people and children. The current study is the first to demonstrate age-related changes in SIRT1 levels in humans and it is important for a much better molecular understanding of the role of the longevity gene SIRT1 and its protein product in aging. It is also the first study presenting the association between SIRT1 expression in older people and rs7895833 in SIRT1 gene. PMID:25785999

Evolution, mutations, and human longevity: European royal and noble families.

PubMed

Gavrilova, N S; Gavrilov, L A; Evdokushkina, G N; Semyonova, V G; Gavrilova, A L; Evdokushkina, N N; Kushnareva, Y E; Kroutko, V N; Andreyev AYu

1998-08-01

The evolutionary theory of aging predicts that the equilibrium gene frequency for deleterious mutations should increase with age at onset of mutation action because of weaker (postponed) selection against later-acting mutations. According to this mutation accumulation hypothesis, one would expect the genetic variability for survival (additive genetic variance) to increase with age. The ratio of additive genetic variance to the observed phenotypic variance (the heritability of longevity) can be estimated most reliably as the doubled slope of the regression line for offspring life span on paternal age at death. Thus, if longevity is indeed determined by late-acting deleterious mutations, one would expect this slope to become steeper at higher paternal ages. To test this prediction of evolutionary theory of aging, we computerized and analyzed the most reliable and accurate genealogical data on longevity in European royal and noble families. Offspring longevity for each sex (8409 records for males and 3741 records for females) was considered as a dependent variable in the multiple regression model and as a function of three independent predictors: paternal age at death (for estimation of heritability of life span), paternal age at reproduction (control for parental age effects), and cohort life expectancy (control for cohort and secular trends and fluctuations). We found that the regression slope for offspring longevity as a function of paternal longevity increases with paternal longevity, as predicted by the evolutionary theory of aging and by the mutation accumulation hypothesis in particular.

Of Malthus and Methuselah: does longevity treatment aggravate global catastrophic risks?

NASA Astrophysics Data System (ADS)

Jebari, Karim

2014-12-01

Global catastrophic risk is a term that refers to the risk of the occurrence of an event that kills at least millions of people across several continents. While it has been argued by a number of scholars that one major potential risk comes from technology, the obscure nature of future technologies makes it difficult to utilize traditional probabilistic risk for the meaningful study of these risks. This article describes an alternative approach and applies it to a research program that has attracted a considerable amount of resources recently: namely longevity research. The aim of this research is to delay or reverse the ageing process. This article argues that this research program is much more risky or less beneficial than its proponents argue. In particular, they tend to underestimate the concerns associated with the potentially drastic population growth that longevity treatment could cause. The ethical benefit often ascribed to longevity treatment is that such treatment would add more subjective life-years that are worth living. However, in light of contemporary environmental problems, such an increase of the human population might be reckless. Drastically reducing fertility to reduce risks associated with environmental stress would make the benefits of such technology much less compelling.

The Companion Dog as a Model for the Longevity Dividend

PubMed Central

Creevy, Kate E.; Austad, Steven N.; Hoffman, Jessica M.; O’Neill, Dan G.; Promislow, Daniel E.L.

2016-01-01

The companion dog is the most phenotypically diverse species on the planet. This enormous variability between breeds extends not only to morphology and behavior but also to longevity and the disorders that affect dogs. There are remarkable overlaps and similarities between the human and canine species. Dogs closely share our human environment, including its many risk factors, and the veterinary infrastructure to manage health in dogs is second only to the medical infrastructure for humans. Distinct breed-based health profiles, along with their well-developed health record system and high overlap with the human environment, make the companion dog an exceptional model to improve understanding of the physiological, social, and economic impacts of the longevity dividend (LD). In this review, we describe what is already known about age-specific patterns of morbidity and mortality in companion dogs, and then explore whether this existing evidence supports the LD. We also discuss some potential limitations to using dogs as models of aging, including the fact that many dogs are euthanized before they have lived out their natural life span. Overall, we conclude that the companion dog offers high potential as a model system that will enable deeper research into the LD than is otherwise possible. PMID:26729759

Understanding the natural and social factors behind regional longevity in Guangxi, China—Is centenarian ratio a good enough indicator for assessing the longevity level?

NASA Astrophysics Data System (ADS)

Deng, Q.; Wei, Y.; Zhao, Y.

2017-12-01

Despite a number of longevity indicators having been used in previous longevity studies, few studies have critically evaluated whether these indicators are suitable. In addition, an increasing number of studies have attempted to determine the influence of socio-economic and natural factors on regional longevity, but only certain factors were considered. The present study bridges this gap by determining the relationship between the seven longevity indicators and selecting 24 natural and socio-economic indicators in the 91 selected counties and districts in Guangxi, China. The seven longevity indicators here refer to Centenarian ratio, Longevity index, Longevity level, Aging tendency, 80+ ratio, 90+ ratio and 95+ ratio. Natural indicators in this study mainly refer to climatic ones. Socio-economic indicators can be categorized into those related to economic, education, local infrastructure, and health care facilities. These data were mainly drawn from the Meteorological Data Sharing Service System and Guangxi's sixth population census. Stepwise regression analysis has been used as the primary research method to determine the relationship between the longevity indicators and the natural, social, and economic indicators. The results show that the climate factors regarding atmospheric pressure, humidity, and rainfall are the most significant contributors to the longevity of the 60- to 90-year-old elderly in Guangxi, while the difference of mean annual temperature could have negative impacts. Also, the natural and socioeconomic factors that impact the extremely old population (those over 95 years old) in Guangxi are still not clear. This study reveals that the longevity index and longevity level are useful supplementary indexes to the centenarian ratio for assessing the regional longevity as they could help reflect the regional longevity regarding the proportion of young-old and old-old population and not just limit to those over 100 years old. The elderly (those from 60-90 years old) are more likely to be influenced by climate factors. It is, therefore, important to understand the risk of climate change for the elderly, which could provide insights for constructing a healthy aging society in the future.

Signaling pathway cloud regulation for in silico screening and ranking of the potential geroprotective drugs

PubMed Central

Zhavoronkov, Alex; Buzdin, Anton A.; Garazha, Andrey V.; Borisov, Nikolay M.; Moskalev, Alexey A.

2014-01-01

The major challenges of aging research include absence of the comprehensive set of aging biomarkers, the time it takes to evaluate the effects of various interventions on longevity in humans and the difficulty extrapolating the results from model organisms to humans. To address these challenges we propose the in silico method for screening and ranking the possible geroprotectors followed by the high-throughput in vivo and in vitro validation. The proposed method evaluates the changes in the collection of activated or suppressed signaling pathways involved in aging and longevity, termed signaling pathway cloud, constructed using the gene expression data and epigenetic profiles of young and old patients' tissues. The possible interventions are selected and rated according to their ability to regulate age-related changes and minimize differences in the signaling pathway cloud. While many algorithmic solutions to simulating the induction of the old into young metabolic profiles in silico are possible, this flexible and scalable approach may potentially be used to predict the efficacy of the many drugs that may extend human longevity before conducting pre-clinical work and expensive clinical trials. PMID:24624136

Endogenous longevity, biological deterioration and economic growth.

PubMed

Sanso, Marcos; Aísa, Rosa M

2006-05-01

The identification of the types of bidirectional interactions that take place between longevity and economic growth in the long-run is carried out by means of the integration of human capital accumulation, innovation in medical technology, a health goods sector, and individual decisions on health and longevity in a dynamic general equilibrium set-up. In this context, in which individual agents decide not only on their "quality" of life but also on its "quantity", the mere process of biological deterioration, that is to say, the continuous loss of health goods effectiveness in maintaining a given level of health as individuals age, provides the reason for an additional, and new, engine of growth.

Antecedents of cell aging research.

PubMed

Hayflick, L

1989-01-01

Our observation that normal human and animal cells have a limited capacity to divide and function in vitro overturned a dogma held since the turn of the century. The dogma held that cultured normal cells are immortal and gerontologists interpreted this to mean that aging, therefore, could not be the result of intracellular events. We concluded that longevity and aging do result from intracellular events, and, in the subsequent 30 years, the validity of our finding has been widely confirmed. Other major findings have been made: (a) The number of population doublings and functional events that a cultured normal cell can undergo is inversely proportional to donor age and, probably, directly proportional to species longevity; (b) the limit on cell division and function also occurs in vivo when normal cells are transplanted seriatim; (c) as cell doublings or functional events reach their limit, changes occur in hundreds of variables from the molecular to the whole cell. Most importantly, many of these changes are identical to those seen in intact humans and animals as they age; (d) WI-38, the first widely distributed normal human cell strain has retained its memory of population doubling level during 27 years of cryogenic storage. This is the longest time that any normal human cell has ever been preserved. Evidence that longevity is determined by genetic events is overwhelming but evidence that age changes are the result of gene expression is not. Normal age changes must be distinguished from disease. Because few feral animals ever become old, natural selection could not have favored the development of a genetically programmed aging process. In the 2 or 3 million years of human existence, too few old humans existed to have provided a selective advantage favoring the development of a genetic program that would determine age changes. The selective advantage of maintaining physiological vigor for as long as possible in order to insure maximum reproductive success may be the essential indirect determinant of longevity. Natural selection has provided sexually mature animals with extraordinary reserve capacities in virtually all organs. After sexual maturation, animals continue to function by utilizing the reserve capacity that evolved to insure that they would attain reproductive success. The magnitude of reserve capacity is the essential element in determining postdevelopmental longevity. Thus "Why do we age?" may be the wrong question. The right question may be "Why do we live as long as we do?"

How Genes Modulate Patterns of Aging-Related Changes on the Way to 100: Biodemographic Models and Methods in Genetic Analyses of Longitudinal Data

PubMed Central

Yashin, Anatoliy I.; Arbeev, Konstantin G.; Wu, Deqing; Arbeeva, Liubov; Kulminski, Alexander; Kulminskaya, Irina; Akushevich, Igor; Ukraintseva, Svetlana V.

2016-01-01

Background and Objective To clarify mechanisms of genetic regulation of human aging and longevity traits, a number of genome-wide association studies (GWAS) of these traits have been performed. However, the results of these analyses did not meet expectations of the researchers. Most detected genetic associations have not reached a genome-wide level of statistical significance, and suffered from the lack of replication in the studies of independent populations. The reasons for slow progress in this research area include low efficiency of statistical methods used in data analyses, genetic heterogeneity of aging and longevity related traits, possibility of pleiotropic (e.g., age dependent) effects of genetic variants on such traits, underestimation of the effects of (i) mortality selection in genetically heterogeneous cohorts, (ii) external factors and differences in genetic backgrounds of individuals in the populations under study, the weakness of conceptual biological framework that does not fully account for above mentioned factors. One more limitation of conducted studies is that they did not fully realize the potential of longitudinal data that allow for evaluating how genetic influences on life span are mediated by physiological variables and other biomarkers during the life course. The objective of this paper is to address these issues. Data and Methods We performed GWAS of human life span using different subsets of data from the original Framingham Heart Study cohort corresponding to different quality control (QC) procedures and used one subset of selected genetic variants for further analyses. We used simulation study to show that approach to combining data improves the quality of GWAS. We used FHS longitudinal data to compare average age trajectories of physiological variables in carriers and non-carriers of selected genetic variants. We used stochastic process model of human mortality and aging to investigate genetic influence on hidden biomarkers of aging and on dynamic interaction between aging and longevity. We investigated properties of genes related to selected variants and their roles in signaling and metabolic pathways. Results We showed that the use of different QC procedures results in different sets of genetic variants associated with life span. We selected 24 genetic variants negatively associated with life span. We showed that the joint analyses of genetic data at the time of bio-specimen collection and follow up data substantially improved significance of associations of selected 24 SNPs with life span. We also showed that aging related changes in physiological variables and in hidden biomarkers of aging differ for the groups of carriers and non-carriers of selected variants. Conclusions . The results of these analyses demonstrated benefits of using biodemographic models and methods in genetic association studies of these traits. Our findings showed that the absence of a large number of genetic variants with deleterious effects may make substantial contribution to exceptional longevity. These effects are dynamically mediated by a number of physiological variables and hidden biomarkers of aging. The results of these research demonstrated benefits of using integrative statistical models of mortality risks in genetic studies of human aging and longevity. PMID:27773987

Longevity and aging. Role of free radicals and xanthine oxidase. A review.

PubMed

Labat-Robert, J; Robert, L

2014-04-01

Longevity and aging are differently regulated. Longevity has an important part of genetic determinants, aging is essentially post-genetic. Among the genes involved in longevity determination, sirtuins, activated also by calorie restriction and some others as the TOR pathway, attracted special interest after the insulin–IGF pathway first shown to regulate longevity in model organisms. For most of these genes, postponement of life-threatening diseases is the basis of their action which never exceeds about 35% of all determinants, in humans. Among the post-genetic mechanisms responsible for age-related decline of function, free radicals attracted early interest as well as the Maillard reaction, generating also free radicals. Most attempts to remediate to free radical damage failed however, although different scavenger mechanisms and protective substances are present in the organism. Synthetic protectors were also tested without success. The only example of a successful treatment of a free radical mediated pathology is the case of xanthine oxidase, involved in cardiovascular pathology, essentially during the ischemia-reperfusion process. Its inhibition by allopurinol is currently used to fight this deadly syndrome.

Selection for sow longevity.

PubMed

Serenius, T; Stalder, K J

2006-04-01

Sow longevity plays an important role in economically efficient piglet production because sow longevity is related to the number of piglets produced during its productive lifetime; however, selection for sow longevity is not commonly practiced in any pig breeding program. There is relatively little scientific literature concerning the genetic parameters (genetic variation and genetic correlations) or methods available for breeding value estimation for effective selection for sow longevity. This paper summarizes the current knowledge about the genetics of sow longevity and discusses the available breeding value estimation methods for sow longevity traits. The studies in the literature clearly indicate that sow longevity is a complex trait, and even the definition of sow longevity is variable depending on the researcher and research objective. In general, the measures and analyses of sow longevity can be divided into 1) continuous traits (e.g., productive lifetime) analyzed with proportional hazard models; and 2) more simple binary traits such as stayability until some predetermined fixed parity. Most studies have concluded that sufficient genetic variation exists for effective selection on sow longevity, and heritability estimates have ranged between 0.02 and 0.25. Moreover, sow longevity has shown to be genetically associated with prolificacy and leg conformation traits. Variable results from previous research have led to a lack of consensus among swine breeders concerning the valid methodology of estimating breeding values for longevity traits. One can not deny the superiority of survival analysis in the modeling approach of longevity data; however, multiple-trait analyses are not possible using currently available survival analysis software. Less sophisticated approaches have the advantage of evaluating multiple traits simultaneously, and thus, can use the genetic associations between sow longevity and other traits. Additional research is needed to identify the most efficient selection methods for sow longevity. Future research needs to concentrate on multiple trait analysis of sow longevity traits. Moreover, because longevity is a fitness trait, the nonadditive genetic effects (e.g., dominance) may play important role in the inheritance of sow longevity. Currently, not a single estimate for dominance variance of sow longevity could be identified from the scientific literature.

Evolutionary conserved longevity genes and human cognitive abilities in elderly cohorts

PubMed Central

Lopez, Lorna M; Harris, Sarah E; Luciano, Michelle; Liewald, Dave; Davies, Gail; Gow, Alan J; Tenesa, Albert; Payton, Antony; Ke, Xiayi; Whalley, Lawrence J; Fox, Helen; Haggerty, Paul; Ollier, William; Pickles, Andrew; Porteous, David J; Horan, Michael A; Pendleton, Neil; Starr, John M; Deary, Ian J

2012-01-01

Genetic influences have an important role in the ageing process. The genetic factors that influence success in bodily ageing may also contribute to the successful ageing of cognitive abilities. A comparative genomics approach found longevity genes conserved between yeast Saccharomyces cerevisiae and nematode Caenorhabditis elegans. We hypothesised that these longevity genes influence variance in cognitive ability and age-related cognitive decline in humans. Here, we investigated six of these genes that have human orthologs and show expression in the brain. We tested AFG3L2 (MIM: 604581, AFG3 ATPase family gene 3-like 2 (yeast)), FRAP1 (MIM: 601231, a FK506 binding protein 12-rapamycin associated protein), MAT1A, MAT2A (MIM: 610550 and 601468, methionine adenosyltransferases I alpha and II alpha, respectively), SYNJ1 and SYNJ2 (MIM: 604297 and 609410, synaptojanin-1 and synaptojanin-2, respectively) in approximately 1000 healthy older Scots: the Lothian Birth Cohort 1936 (LBC1936). They were tested on general cognitive ability at age 11 years. At a mean age of 70 years, they re-sat the same general cognitive ability test and underwent an additional battery of diverse cognitive tests. In all, 70 tag and functional SNPs in the six longevity genes were genotyped and tested for association with cognition and cognitive ageing in LBC1936. Suggestive associations were detected between SNPs in SYNJ2, MAT1A, AFG3L2 and SYNJ1 and a general memory factor and general cognitive ability at age 11 and 70 years. Replication studies for cognitive ability associations were performed in 2506 samples from the Cognitive Ageing Genetics in England and Scotland consortium. A meta-analysis replicated the SYNJ2 association with cognitive abilities (lowest P=0.00077). SYNJ2 is a novel gene in which variation is potentially associated with cognitive abilities. PMID:22045296

Serum Heat Shock Protein 70 Level as a Biomarker of Exceptional Longevity

PubMed Central

Terry, Dellara F.; Wyszynski, Diego F.; Nolan, Vikki G.; Atzmon, Gil; Schoenhofen, Emily A.; Pennington, JaeMi Y.; Andersen, Stacy L.; Wilcox, Marsha A.; Farrer, Lindsay A.; Barzilai, Nir; Baldwin, Clinton T.; Asea, Alexzander

2006-01-01

Heat shock proteins are highly conserved proteins that, when produced intracellularly, protect stress exposed cells. In contrast, extracellular Hsp70 has been shown to have both protective and deleterious effects. In this study, we assessed heat shock protein 70 (Hsp70) for its potential role in human longevity. Because of the importance of HSP to disease processes, cellular protection, and inflammation, we hypothesized that: (1) Hsp70 levels in centenarians and centenarian offspring are different from controls and (2) alleles in genes associated with Hsp70 explain these differences. In this cross-sectional study, we assessed serum Hsp70 levels from participants enrolled in either the New England Centenarian Study (NECS) or the Longevity Genes Project (LGP): 87 centenarians (from LGP), 93 centenarian offspring (from NECS), and 126 controls (43 from NECS, 83 from LGP). We also examined genotypic and allelic frequencies of polymorphisms in HSP70-A1A and HSP70-A1B in 347 centenarians (266 from the NECS, 81 from the LGP), 260 NECS centenarian offspring, and 238 controls (NECS: 53 spousal controls and 106 septuagenarian offspring controls; LGP: 79 spousal controls). The adjusted mean serum Hsp70 levels (ng/mL) for the NECS centenarian offspring, LGP centenarians, LGP spousal controls, and NECS controls were 1.05, 1.13, 3.05, 6.93, respectively, suggesting that a low serum Hsp70 level is associated with longevity; however, no genetic associations were found with two SNPs within two hsp70 genes. PMID:17027907

Serum heat shock protein 70 level as a biomarker of exceptional longevity.

PubMed

Terry, Dellara F; Wyszynski, Diego F; Nolan, Vikki G; Atzmon, Gil; Schoenhofen, Emily A; Pennington, JaeMi Y; Andersen, Stacy L; Wilcox, Marsha A; Farrer, Lindsay A; Barzilai, Nir; Baldwin, Clinton T; Asea, Alexzander

2006-11-01

Heat shock proteins are highly conserved proteins that, when produced intracellularly, protect stress exposed cells. In contrast, extracellular heat shock protein 70 (Hsp70) has been shown to have both protective and deleterious effects. In this study, we assessed heat shock protein 70 for its potential role in human longevity. Because of the importance of HSP to disease processes, cellular protection, and inflammation, we hypothesized that: (1) Hsp70 levels in centenarians and centenarian offspring are different from controls and (2) alleles in genes associated with Hsp70 explain these differences. In this cross-sectional study, we assessed serum Hsp70 levels from participants enrolled in either the New England Centenarian Study (NECS) or the Longevity Genes Project (LGP): 87 centenarians (from LGP), 93 centenarian offspring (from NECS), and 126 controls (43 from NECS, 83 from LGP). We also examined genotypic and allelic frequencies of polymorphisms in HSP70-A1A and HSP70-A1B in 347 centenarians (266 from the NECS, 81 from the LGP), 260 NECS centenarian offspring, and 238 controls (NECS: 53 spousal controls and 106 septuagenarian offspring controls; LGP: 79 spousal controls). The adjusted mean serum Hsp70 levels (ng/mL) for the NECS centenarian offspring, LGP centenarians, LGP spousal controls, and NECS controls were 1.05, 1.13, 3.07, 6.93, respectively, suggesting that a low serum Hsp70 level is associated with longevity; however, no genetic associations were found with two SNPs within two hsp70 genes.

Plastic Responses Contribute to Explaining Altitudinal and Temporal Variation in Potential Flower Longevity in High Andean Rhodolirion montanum.

PubMed

Pacheco, Diego Andrés; Dudley, Leah S; Cabezas, Josefina; Cavieres, Lohengrin A; Arroyo, Mary T K

2016-01-01

The tendency for flower longevity to increase with altitude is believed by many alpine ecologists to play an important role in compensating for low pollination rates at high altitudes due to cold and variable weather conditions. However, current studies documenting an altitudinal increase in flower longevity in the alpine habitat derive principally from studies on open-pollinated flowers where lower pollinator visitation rates at higher altitudes will tend to lead to flower senescence later in the life-span of a flower in comparison with lower altitudes, and thus could confound the real altitudinal pattern in a species´ potential flower longevity. In a two-year study we tested the hypothesis that a plastic effect of temperature on flower longevity could contribute to an altitudinal increase in potential flower longevity measured in pollinator-excluded flowers in high Andean Rhodolirium montanum Phil. (Amaryllidaceae). Using supplemental warming we investigated whether temperature around flowers plastically affects potential flower longevity. We determined tightly temperature-controlled potential flower longevity and flower height for natural populations on three alpine sites spread over an altitudinal transect from 2350 and 3075 m a.s.l. An experimental increase of 3.1°C around flowers significantly decreased flower longevity indicating a plastic response of flowers to temperature. Flower height in natural populations decreased significantly with altitude. Although temperature negatively affects flower longevity under experimental conditions, we found no evidence that temperature around flowers explains site variation in flower longevity over the altitudinal gradient. In a wetter year, despite a 3.5°C temperature difference around flowers at the extremes of the altitudinal range, flower longevity showed no increase with altitude. However, in a drier year, flower longevity increased significantly with altitude. The emerging picture suggests an increase in flower longevity along the altitudinal gradient is less common for potential flower longevity than for open-pollination flower longevity. Independently of any selection that may occur on potential longevity, plastic responses of flowers to environmental conditions are likely to contribute to altitudinal variation in flower longevity, especially in dry alpine areas. Such plastic responses could push flowers of alpine species towards shorter life-lengths under climate change, with uncertain consequences for successful pollination and plant fitness in a warming world.

Plastic Responses Contribute to Explaining Altitudinal and Temporal Variation in Potential Flower Longevity in High Andean Rhodolirion montanum

PubMed Central

Cavieres, Lohengrin A.

2016-01-01

The tendency for flower longevity to increase with altitude is believed by many alpine ecologists to play an important role in compensating for low pollination rates at high altitudes due to cold and variable weather conditions. However, current studies documenting an altitudinal increase in flower longevity in the alpine habitat derive principally from studies on open-pollinated flowers where lower pollinator visitation rates at higher altitudes will tend to lead to flower senescence later in the life-span of a flower in comparison with lower altitudes, and thus could confound the real altitudinal pattern in a species´ potential flower longevity. In a two-year study we tested the hypothesis that a plastic effect of temperature on flower longevity could contribute to an altitudinal increase in potential flower longevity measured in pollinator-excluded flowers in high Andean Rhodolirium montanum Phil. (Amaryllidaceae). Using supplemental warming we investigated whether temperature around flowers plastically affects potential flower longevity. We determined tightly temperature-controlled potential flower longevity and flower height for natural populations on three alpine sites spread over an altitudinal transect from 2350 and 3075 m a.s.l. An experimental increase of 3.1°C around flowers significantly decreased flower longevity indicating a plastic response of flowers to temperature. Flower height in natural populations decreased significantly with altitude. Although temperature negatively affects flower longevity under experimental conditions, we found no evidence that temperature around flowers explains site variation in flower longevity over the altitudinal gradient. In a wetter year, despite a 3.5°C temperature difference around flowers at the extremes of the altitudinal range, flower longevity showed no increase with altitude. However, in a drier year, flower longevity increased significantly with altitude. The emerging picture suggests an increase in flower longevity along the altitudinal gradient is less common for potential flower longevity than for open-pollination flower longevity. Independently of any selection that may occur on potential longevity, plastic responses of flowers to environmental conditions are likely to contribute to altitudinal variation in flower longevity, especially in dry alpine areas. Such plastic responses could push flowers of alpine species towards shorter life-lengths under climate change, with uncertain consequences for successful pollination and plant fitness in a warming world. PMID:27861586

Randomized cross-over trial of short-term water-only fasting: metabolic and cardiovascular consequences.

PubMed

Horne, B D; Muhlestein, J B; Lappé, D L; May, H T; Carlquist, J F; Galenko, O; Brunisholz, K D; Anderson, J L

2013-11-01

Routine, periodic fasting is associated with a lower prevalence of coronary artery disease (CAD). Animal studies show that fasting may increase longevity and alter biological parameters related to longevity. We evaluated whether fasting initiates acute changes in biomarker expression in humans that may impact short- and long-term health. Apparently-healthy volunteers (N = 30) without a recent history of fasting were enrolled in a randomized cross-over trial. A one-day water-only fast was the intervention and changes in biomarkers were the study endpoints. Bonferroni correction required p ≤ 0.00167 for significance (p < 0.05 was a trend that was only suggestively significant). The one-day fasting intervention acutely increased human growth hormone (p = 1.1 × 10⁻⁴), hemoglobin (p = 4.8 × 10⁻⁷), red blood cell count (p = 2.5 × 10⁻⁶), hematocrit (p = 3.0 × 10⁻⁶), total cholesterol (p = 5.8 × 10⁻⁵), and high-density lipoprotein cholesterol (p = 0.0015), and decreased triglycerides (p = 1.3 × 10⁻⁴), bicarbonate (p = 3.9 × 10⁻⁴), and weight (p = 1.0 × 10⁻⁷), compared to a day of usual eating. For those randomized to fast the first day (n = 16), most factors including human growth hormone and cholesterol returned to baseline after the full 48 h, with the exception of weight (p = 2.5 × 10⁻⁴) and (suggestively significant) triglycerides (p = 0.028). Fasting induced acute changes in biomarkers of metabolic, cardiovascular, and general health. The long-term consequences of these short-term changes are unknown but repeated episodes of periodic short-term fasting should be evaluated as a preventive treatment with the potential to reduce metabolic disease risk. Clinical trial registration (ClinicalTrials.gov): NCT01059760 (Expression of Longevity Genes in Response to Extended Fasting [The Fasting and Expression of Longevity Genes during Food abstinence {FEELGOOD} Trial]). Copyright © 2012 Elsevier B.V. All rights reserved.

Mitochondrial-Nuclear Epistasis: Implications for Human Aging and Longevity

PubMed Central

Tranah, Gregory

2010-01-01

There is substantial evidence that mitochondria are involved in the aging process. Mitochondrial function requires the coordinated expression of hundreds of nuclear genes and a few dozen mitochondrial genes, many of which have been associated with either extended or shortened life span. Impaired mitochondrial function resulting from mtDNA and nuclear DNA variation is likely to contribute to an imbalance in cellular energy homeostasis, increased vulnerability to oxidative stress, and an increased rate of cellular senescence and aging. The complex genetic architecture of mitochondria suggests that there may be an equally complex set of gene interactions (epistases) involving genetic variation in the nuclear and mitochondrial genomes. Results from Drosophila suggest that the effects of mtDNA haplotypes on longevity vary among different nuclear allelic backgrounds, which could account for the inconsistent associations that have been observed between mitochondrial DNA (mtDNA) haplogroups and survival in humans. A diversity of pathways may influence the way mitochondria and nuclear – mitochondrial interactions modulate longevity, including: oxidative phosphorylation; mitochondrial uncoupling; antioxidant defenses; mitochondrial fission and fusion; and sirtuin regulation of mitochondrial genes. We hypothesize that aging and longevity, as complex traits having a significant genetic component, are likely to be controlled by nuclear gene variants interacting with both inherited and somatic mtDNA variability. PMID:20601194

Meta-analysis of genetic variants associated with human exceptional longevity

PubMed Central

Sebastiani, Paola; Bae1, Harold; Sun, Fangui X.; Andersen, Stacy L.; Daw, E. Warwick; Malovini, Alberto; Kojima, Toshio; Hirose, Nobuyoshi; Schupf, Nicole; Puca, Annibale; Perls, Thomas T

2013-01-01

Despite evidence from family studies that there is a strong genetic influence upon exceptional longevity, relatively few genetic variants have been associated with this trait. One reason could be that many genes individually have such weak effects that they cannot meet standard thresholds of genome wide significance, but as a group in specific combinations of genetic variations, they can have a strong influence. Previously we reported that such genetic signatures of 281 genetic markers associated with about 130 genes can do a relatively good job of differentiating centenarians from non-centenarians particularly if the centenarians are 106 years and older. This would support our hypothesis that the genetic influence upon exceptional longevity increases with older and older (and rarer) ages. We investigated this list of markers using similar genetic data from 5 studies of centenarians from the USA, Europe and Japan. The results from the meta-analysis show that many of these variants are associated with survival to these extreme ages in other studies. Since many centenarians compress morbidity and disability towards the end of their lives, these results could point to biological pathways and therefore new therapeutics to increase years of healthy lives in the general population. PMID:24244950

Prevention of Neuromusculoskeletal Frailty in Slow-Aging Ames Dwarf Mice: Longitudinal Investigation of Interaction of Longevity Genes and Caloric Restriction

PubMed Central

Arum, Oge; Rasche, Zachary Andrew; Rickman, Dustin John; Bartke, Andrzej

2013-01-01

Ames dwarf (Prop1 df/df) mice are remarkably long-lived and exhibit many characteristics of delayed aging and extended healthspan. Caloric restriction (CR) has similar effects on healthspan and lifespan, and causes an extension of longevity in Ames dwarf mice. Our study objective was to determine whether Ames dwarfism or CR influence neuromusculoskeletal function in middle-aged (82 ± 12 weeks old) or old (128 ± 14 w.o.) mice. At the examined ages, strength was improved by dwarfism, CR, and dwarfism plus CR in male mice; balance/ motor coordination was improved by CR in old animals and in middle-aged females; and agility/ motor coordination was improved by a combination of dwarfism and CR in both genders of middle-aged mice and in old females. Therefore, extension of longevity by congenital hypopituitarism is associated with improved maintenance of the examined measures of strength, agility, and motor coordination, key elements of frailty during human aging, into advanced age. This study serves as a particularly important example of knowledge related to addressing aging-associated diseases and disorders that results from studies in long-lived mammals. PMID:24155868

Prevention of neuromusculoskeletal frailty in slow-aging ames dwarf mice: longitudinal investigation of interaction of longevity genes and caloric restriction.

PubMed

Arum, Oge; Rasche, Zachary Andrew; Rickman, Dustin John; Bartke, Andrzej

2013-01-01

Ames dwarf (Prop1 (df/df) ) mice are remarkably long-lived and exhibit many characteristics of delayed aging and extended healthspan. Caloric restriction (CR) has similar effects on healthspan and lifespan, and causes an extension of longevity in Ames dwarf mice. Our study objective was to determine whether Ames dwarfism or CR influence neuromusculoskeletal function in middle-aged (82 ± 12 weeks old) or old (128 ± 14 w.o.) mice. At the examined ages, strength was improved by dwarfism, CR, and dwarfism plus CR in male mice; balance/ motor coordination was improved by CR in old animals and in middle-aged females; and agility/ motor coordination was improved by a combination of dwarfism and CR in both genders of middle-aged mice and in old females. Therefore, extension of longevity by congenital hypopituitarism is associated with improved maintenance of the examined measures of strength, agility, and motor coordination, key elements of frailty during human aging, into advanced age. This study serves as a particularly important example of knowledge related to addressing aging-associated diseases and disorders that results from studies in long-lived mammals.

Evolutionary Pressure on Mitochondrial Cytochrome b Is Consistent with a Role of CytbI7T Affecting Longevity during Caloric Restriction

PubMed Central

Beckstead, Wesley A.; Ebbert, Mark T. W.; Rowe, Mark J.; McClellan, David A.

2009-01-01

Background Metabolism of energy nutrients by the mitochondrial electron transport chain (ETC) is implicated in the aging process. Polymorphisms in core ETC proteins may have an effect on longevity. Here we investigate the cytochrome b (cytb) polymorphism at amino acid 7 (cytbI7T) that distinguishes human mitochondrial haplogroup H from haplogroup U. Principal Findings We compared longevity of individuals in these two haplogroups during historical extremes of caloric intake. Haplogroup H exhibits significantly increased longevity during historical caloric restriction compared to haplogroup U (p = 0.02) while during caloric abundance they are not different. The historical effects of natural selection on the cytb protein were estimated with the software TreeSAAP using a phylogenetic reconstruction for 107 mammal taxa from all major mammalian lineages using 13 complete protein-coding mitochondrial gene sequences. With this framework, we compared the biochemical shifts produced by cytbI7T with historical evolutionary pressure on and near this polymorphic site throughout mammalian evolution to characterize the role cytbI7T had on the ETC during times of restricted caloric intake. Significance Our results suggest the relationship between caloric restriction and increased longevity in human mitochondrial haplogroup H is determined by cytbI7T which likely enhances the ability of water to replenish the Qi binding site and decreases the time ubisemiquinone is at the Qo site, resulting in a decrease in the average production rate of radical oxygen species (ROS). PMID:19503808

Short telomeres in hatchling snakes: erythrocyte telomere dynamics and longevity in tropical pythons.

PubMed

Ujvari, Beata; Madsen, Thomas

2009-10-16

Telomere length (TL) has been found to be associated with life span in birds and humans. However, other studies have demonstrated that TL does not affect survival among old humans. Furthermore, replicative senescence has been shown to be induced by changes in the protected status of the telomeres rather than the loss of TL. In the present study we explore whether age- and sex-specific telomere dynamics affect life span in a long-lived snake, the water python (Liasis fuscus). Erythrocyte TL was measured using the Telo TAGGG TL Assay Kit (Roche). In contrast to other vertebrates, TL of hatchling pythons was significantly shorter than that of older snakes. However, during their first year of life hatchling TL increased substantially. While TL of older snakes decreased with age, we did not observe any correlation between TL and age in cross-sectional sampling. In older snakes, female TL was longer than that of males. When using recapture as a proxy for survival, our results do not support that longer telomeres resulted in an increased water python survival/longevity. In fish high telomerase activity has been observed in somatic cells exhibiting high proliferation rates. Hatchling pythons show similar high somatic cell proliferation rates. Thus, the increase in TL of this group may have been caused by increased telomerase activity. In older humans female TL is longer than that of males. This has been suggested to be caused by high estrogen levels that stimulate increased telomerase activity. Thus, high estrogen levels may also have caused the longer telomeres in female pythons. The lack of correlation between TL and age among old snakes and the fact that longer telomeres did not appear to affect python survival do not support that erythrocyte telomere dynamics has a major impact on water python longevity.

Heritability of and mortality prediction with a longevity phenotype: the healthy aging index.

PubMed

Sanders, Jason L; Minster, Ryan L; Barmada, M Michael; Matteini, Amy M; Boudreau, Robert M; Christensen, Kaare; Mayeux, Richard; Borecki, Ingrid B; Zhang, Qunyuan; Perls, Thomas; Newman, Anne B

2014-04-01

Longevity-associated genes may modulate risk for age-related diseases and survival. The Healthy Aging Index (HAI) may be a subphenotype of longevity, which can be constructed in many studies for genetic analysis. We investigated the HAI's association with survival in the Cardiovascular Health Study and heritability in the Long Life Family Study. The HAI includes systolic blood pressure, pulmonary vital capacity, creatinine, fasting glucose, and Modified Mini-Mental Status Examination score, each scored 0, 1, or 2 using approximate tertiles and summed from 0 (healthy) to 10 (unhealthy). In Cardiovascular Health Study, the association with mortality and accuracy predicting death were determined with Cox proportional hazards analysis and c-statistics, respectively. In Long Life Family Study, heritability was determined with a variance component-based family analysis using a polygenic model. Cardiovascular Health Study participants with unhealthier index scores (7-10) had 2.62-fold (95% confidence interval: 2.22, 3.10) greater mortality than participants with healthier scores (0-2). The HAI alone predicted death moderately well (c-statistic = 0.643, 95% confidence interval: 0.626, 0.661, p < .0001) and slightly worse than age alone (c-statistic = 0.700, 95% confidence interval: 0.684, 0.717, p < .0001; p < .0001 for comparison of c-statistics). Prediction increased significantly with adjustment for demographics, health behaviors, and clinical comorbidities (c-statistic = 0.780, 95% confidence interval: 0.765, 0.794, p < .0001). In Long Life Family Study, the heritability of the HAI was 0.295 (p < .0001) overall, 0.387 (p < .0001) in probands, and 0.238 (p = .0004) in offspring. The HAI should be investigated further as a candidate phenotype for uncovering longevity-associated genes in humans.

Heritability of and Mortality Prediction With a Longevity Phenotype: The Healthy Aging Index

PubMed Central

2014-01-01

Background. Longevity-associated genes may modulate risk for age-related diseases and survival. The Healthy Aging Index (HAI) may be a subphenotype of longevity, which can be constructed in many studies for genetic analysis. We investigated the HAI’s association with survival in the Cardiovascular Health Study and heritability in the Long Life Family Study. Methods. The HAI includes systolic blood pressure, pulmonary vital capacity, creatinine, fasting glucose, and Modified Mini-Mental Status Examination score, each scored 0, 1, or 2 using approximate tertiles and summed from 0 (healthy) to 10 (unhealthy). In Cardiovascular Health Study, the association with mortality and accuracy predicting death were determined with Cox proportional hazards analysis and c-statistics, respectively. In Long Life Family Study, heritability was determined with a variance component–based family analysis using a polygenic model. Results. Cardiovascular Health Study participants with unhealthier index scores (7–10) had 2.62-fold (95% confidence interval: 2.22, 3.10) greater mortality than participants with healthier scores (0–2). The HAI alone predicted death moderately well (c-statistic = 0.643, 95% confidence interval: 0.626, 0.661, p < .0001) and slightly worse than age alone (c-statistic = 0.700, 95% confidence interval: 0.684, 0.717, p < .0001; p < .0001 for comparison of c-statistics). Prediction increased significantly with adjustment for demographics, health behaviors, and clinical comorbidities (c-statistic = 0.780, 95% confidence interval: 0.765, 0.794, p < .0001). In Long Life Family Study, the heritability of the HAI was 0.295 (p < .0001) overall, 0.387 (p < .0001) in probands, and 0.238 (p = .0004) in offspring. Conclusion. The HAI should be investigated further as a candidate phenotype for uncovering longevity-associated genes in humans. PMID:23913930

Mood, stress and longevity: convergence on ANK3.

PubMed

Rangaraju, S; Levey, D F; Nho, K; Jain, N; Andrews, K D; Le-Niculescu, H; Salomon, D R; Saykin, A J; Petrascheck, M; Niculescu, A B

2016-08-01

Antidepressants have been shown to improve longevity in C. elegans. It is plausible that orthologs of genes involved in mood regulation and stress response are involved in such an effect. We sought to understand the underlying biology. First, we analyzed the transcriptome from worms treated with the antidepressant mianserin, previously identified in a large-scale unbiased drug screen as promoting increased lifespan in worms. We identified the most robust treatment-related changes in gene expression, and identified the corresponding human orthologs. Our analysis uncovered a series of genes and biological pathways that may be at the interface between antidepressant effects and longevity, notably pathways involved in drug metabolism/degradation (nicotine and melatonin). Second, we examined which of these genes overlap with genes which may be involved in depressive symptoms in an aging non-psychiatric human population (n=3577), discovered using a genome-wide association study (GWAS) approach in a design with extremes of distribution of phenotype. Third, we used a convergent functional genomics (CFG) approach to prioritize these genes for relevance to mood disorders and stress. The top gene identified was ANK3. To validate our findings, we conducted genetic and gene-expression studies, in C. elegans and in humans. We studied C. elegans inactivating mutants for ANK3/unc-44, and show that they survive longer than wild-type, particularly in older worms, independently of mianserin treatment. We also show that some ANK3/unc-44 expression is necessary for the effects of mianserin on prolonging lifespan and survival in the face of oxidative stress, particularly in younger worms. Wild-type ANK3/unc-44 increases in expression with age in C. elegans, and is maintained at lower youthful levels by mianserin treatment. These lower levels may be optimal in terms of longevity, offering a favorable balance between sufficient oxidative stress resistance in younger worms and survival effects in older worms. Thus, ANK3/unc-44 may represent an example of antagonistic pleiotropy, in which low-expression level in young animals are beneficial, but the age-associated increase becomes detrimental. Inactivating mutations in ANK3/unc-44 reverse this effect and cause detrimental effects in young animals (sensitivity to oxidative stress) and beneficial effect in old animals (increased survival). In humans, we studied if the most significant single nucleotide polymorphism (SNP) for depressive symptoms in ANK3 from our GWAS has a relationship to lifespan, and show a trend towards longer lifespan in individuals with the risk allele for depressive symptoms in men (odds ratio (OR) 1.41, P=0.031) but not in women (OR 1.08, P=0.33). We also examined whether ANK3, by itself or in a panel with other top CFG-prioritized genes, acts as a blood gene-expression biomarker for biological age, in two independent cohorts, one of live psychiatric patients (n=737), and one of suicide completers from the coroner's office (n=45). We show significantly lower levels of ANK3 expression in chronologically younger individuals than in middle age individuals, with a diminution of that effect in suicide completers, who presumably have been exposed to more severe and acute negative mood and stress. Of note, ANK3 was previously reported to be overexpressed in fibroblasts from patients with Hutchinson-Gilford progeria syndrome, a form of accelerated aging. Taken together, these studies uncover ANK3 and other genes in our dataset as biological links between mood, stress and longevity/aging, that may be biomarkers as well as targets for preventive or therapeutic interventions. Drug repurposing bioinformatics analyses identified the relatively innocuous omega-3 fatty acid DHA (docosahexaenoic acid), piracetam, quercetin, vitamin D and resveratrol as potential longevity promoting compounds, along with a series of existing drugs, such as estrogen-like compounds, antidiabetics and sirolimus/rapamycin. Intriguingly, some of our top candidate genes for mood and stress-modulated longevity were changed in expression in opposite direction in previous studies in the Alzheimer disease. Additionally, a whole series of others were changed in expression in opposite direction in our previous studies on suicide, suggesting the possibility of a "life switch" actively controlled by mood and stress.

Values Reflected in the Human Development Index

ERIC Educational Resources Information Center

Lind, Niels

2004-01-01

The Human Development Index (HDI) implicitly defines "human development" and ranks countries accordingly. To elucidate the HDI's meaning of "human development," the paper examines the sensitivity of the HDI to changes in its components, namely social indicators of education, longevity and standard of living. The HDI is next compared with two…

Comparative Pathology of Aging Great Apes: Bonobos, Chimpanzees, Gorillas, and Orangutans.

PubMed

Lowenstine, L J; McManamon, R; Terio, K A

2016-03-01

The great apes (chimpanzees, bonobos, gorillas, and orangutans) are our closest relatives. Despite the many similarities, there are significant differences in aging among apes, including the human ape. Common to all are dental attrition, periodontitis, tooth loss, osteopenia, and arthritis, although gout is uniquely human and spondyloarthropathy is more prevalent in apes than humans. Humans are more prone to frailty, sarcopenia, osteoporosis, longevity past reproductive senescence, loss of brain volume, and Alzheimer dementia. Cerebral vascular disease occurs in both humans and apes. Cardiovascular disease mortality increases in aging humans and apes, but coronary atherosclerosis is the most significant type in humans. In captive apes, idiopathic myocardial fibrosis and cardiomyopathy predominate, with arteriosclerosis of intramural coronary arteries. Similar cardiac lesions are occasionally seen in wild apes. Vascular changes in heart and kidneys and aortic dissections in gorillas and bonobos suggest that hypertension may be involved in pathogenesis. Chronic kidney disease is common in elderly humans and some aging apes and is linked with cardiovascular disease in orangutans. Neoplasms common to aging humans and apes include uterine leiomyomas in chimpanzees, but other tumors of elderly humans, such as breast, prostate, lung, and colorectal cancers, are uncommon in apes. Among the apes, chimpanzees have been best studied in laboratory settings, and more comparative research is needed into the pathology of geriatric zoo-housed and wild apes. Increasing longevity of humans and apes makes understanding aging processes and diseases imperative for optimizing quality of life in all the ape species. © The Author(s) 2015.

Somatotropic Signaling: Trade-Offs Between Growth, Reproductive Development, and Longevity

PubMed Central

Sun, Liou Y.; Longo, Valter

2013-01-01

Growth hormone (GH) is a key determinant of postnatal growth and plays an important role in the control of metabolism and body composition. Surprisingly, deficiency in GH signaling delays aging and remarkably extends longevity in laboratory mice. In GH-deficient and GH-resistant animals, the “healthspan” is also extended with delays in cognitive decline and in the onset of age-related disease. The role of hormones homologous to insulin-like growth factor (IGF, an important mediator of GH actions) in the control of aging and lifespan is evolutionarily conserved from worms to mammals with some homologies extending to unicellular yeast. The combination of reduced GH, IGF-I, and insulin signaling likely contributes to extended longevity in GH or GH receptor-deficient organisms. Diminutive body size and reduced fecundity of GH-deficient and GH-resistant mice can be viewed as trade-offs for extended longevity. Mechanisms responsible for delayed aging of GH-related mutants include enhanced stress resistance and xenobiotic metabolism, reduced inflammation, improved insulin signaling, and various metabolic adjustments. Pathological excess of GH reduces life expectancy in men as well as in mice, and GH resistance or deficiency provides protection from major age-related diseases, including diabetes and cancer, in both species. However, there is yet no evidence of increased longevity in GH-resistant or GH-deficient humans, possibly due to non-age-related deaths. Results obtained in GH-related mutant mice provide striking examples of mutations of a single gene delaying aging, reducing age-related disease, and extending lifespan in a mammal and providing novel experimental systems for the study of mechanisms of aging. PMID:23589828

Association between increased serum thyrotropin concentration and the oldest old: what do we know?

PubMed Central

Duarte, Glaucia Cruzes; Cendoroglo, Maysa Seabra; Araújo, Lara Miguel Quirino; Almada, Clineu de Mello

2015-01-01

To assess studies that evaluate the relation between serum thyrotropin concentration, very old subjects, and their events. We searched the PubMed, SciELO, and LILACS databases for articles published between 2004 and 2012. Our search was restricted to studies involving humans aged 65 years or older, and written in English, Spanish, or Portuguese. Studies that evaluated the association between elevated serum thyrotropin concentration among elderly subjects with subclinical hypothyroidism were chosen since at least in part they included a subpopulation of individuals aged 80 years and above. Thirteen studies were selected. No significant increase in risk of cardiovascular events, coronary heart disease, or total mortality was observed. Elevated thyrotropin concentration was associated with longevity. More randomized controlled trials are required to better define the potential benefits of elevated thyrotropin concentration in this oldest old population, hormone replacement, and longevity. PMID:25807244

Human longevity and variation in GH/IGF-1/insulin signaling, DNA damage signaling and repair and pro/antioxidant pathway genes: cross sectional and longitudinal studies.

PubMed

Soerensen, Mette; Dato, Serena; Tan, Qihua; Thinggaard, Mikael; Kleindorp, Rabea; Beekman, Marian; Jacobsen, Rune; Suchiman, H Eka D; de Craen, Anton J M; Westendorp, Rudi G J; Schreiber, Stefan; Stevnsner, Tinna; Bohr, Vilhelm A; Slagboom, P Eline; Nebel, Almut; Vaupel, James W; Christensen, Kaare; McGue, Matt; Christiansen, Lene

2012-05-01

Here we explore association with human longevity of common genetic variation in three major candidate pathways: GH/IGF-1/insulin signaling, DNA damage signaling and repair and pro/antioxidants by investigating 1273 tagging SNPs in 148 genes composing these pathways. In a case-control study of 1089 oldest-old (age 92-93) and 736 middle-aged Danes we found 1 pro/antioxidant SNP (rs1002149 (GSR)), 5 GH/IGF-1/INS SNPs (rs1207362 (KL), rs2267723 (GHRHR), rs3842755 (INS), rs572169 (GHSR), rs9456497 (IGF2R)) and 5 DNA repair SNPs (rs11571461 (RAD52), rs13251813 (WRN), rs1805329 (RAD23B), rs2953983 (POLB), rs3211994 (NTLH1)) to be associated with longevity after correction for multiple testing. In a longitudinal study with 11 years of follow-up on survival in the oldest-old Danes we found 2 pro/antioxidant SNPs (rs10047589 (TNXRD1), rs207444 (XDH)), 1 GH/IGF-1/INS SNP (rs26802 (GHRL)) and 3 DNA repair SNPs (rs13320360 (MLH1), rs2509049 (H2AFX) and rs705649 (XRCC5)) to be associated with mortality in late life after correction for multiple testing. When examining the 11 SNPs from the case-control study in the longitudinal data, rs3842755 (INS), rs13251813 (WRN) and rs3211994 (NTHL1) demonstrated the same directions of effect (p<0.05), while rs9456497 (IGF2R) and rs1157146 (RAD52) showed non-significant tendencies, indicative of effects also in late life survival. In addition, rs207444 (XDH) presented the same direction of effect when inspecting the 6 SNPs from the longitudinal study in the case-control data, hence, suggesting an effect also in survival from middle age to old age. No formal replications were observed when investigating the 11 SNPs from the case-control study in 1613 oldest-old (age 95-110) and 1104 middle-aged Germans, although rs11571461 (RAD52) did show a supportive non-significant tendency (OR=1.162, 95% CI=0.927-1.457). The same was true for rs10047589 (TNXRD1) (HR=0.758, 95%CI=0.543-1.058) when examining the 6 SNPs from the longitudinal study in a Dutch longitudinal cohort of oldest-old (age 85+, N=563). In conclusion, the present candidate gene based association study, the largest to date applying a pathway approach, not only points to potential new longevity loci, but also underlines the difficulties of replicating association findings in independent study populations and thus the difficulties in identifying universal longevity polymorphisms. Copyright © 2012 Elsevier Inc. All rights reserved.

Body-composition changes in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE)-2 study: A 2-y randomized controlled trial of calorie restriction in nonobese humans

USDA-ARS?s Scientific Manuscript database

Calorie restriction (CR) retards aging and increases longevity in many animal models. However, it is unclear whether CR can be implemented in humans without adverse effects on body composition. We evaluated the effect of a 2-year CR regimen on body composition including the influence of sex and body...

The Biology of Aging: Citizen Scientists and Their Pets as a Bridge Between Research on Model Organisms and Human Subjects.

PubMed

Kaeberlein, M

2016-03-01

A fundamental goal of research into the basic mechanisms of aging is to develop translational strategies that improve human health by delaying the onset and progression of age-related pathology. Several interventions have been discovered that increase life span in invertebrate organisms, some of which have similar effects in mice. These include dietary restriction and inhibition of the mechanistic target of rapamycin by treatment with rapamycin. Key challenges moving forward will be to assess the extent to which these and other interventions improve healthy longevity and increase life span in mice and to develop practical strategies for extending this work to the clinic. Companion animals may provide an optimal intermediate between laboratory models and humans. By improving healthy longevity in companion animals, important insights will be gained regarding human aging while improving the quality of life for people and their pets. © The Author(s) 2015.

The emergence of longevous populations

PubMed Central

Colchero, Fernando; Rau, Roland; Barthold, Julia A.; Conde, Dalia A.; Lenart, Adam; Nemeth, Laszlo; Scheuerlein, Alexander; Schoeley, Jonas; Torres, Catalina; Zarulli, Virginia; Altmann, Jeanne; Brockman, Diane K.; Bronikowski, Anne M.; Fedigan, Linda M.; Pusey, Anne E.; Stoinski, Tara S.; Strier, Karen B.; Baudisch, Annette; Alberts, Susan C.; Vaupel, James W.

2016-01-01

The human lifespan has traversed a long evolutionary and historical path, from short-lived primate ancestors to contemporary Japan, Sweden, and other longevity frontrunners. Analyzing this trajectory is crucial for understanding biological and sociocultural processes that determine the span of life. Here we reveal a fundamental regularity. Two straight lines describe the joint rise of life expectancy and lifespan equality: one for primates and the second one over the full range of human experience from average lifespans as low as 2 y during mortality crises to more than 87 y for Japanese women today. Across the primate order and across human populations, the lives of females tend to be longer and less variable than the lives of males, suggesting deep evolutionary roots to the male disadvantage. Our findings cast fresh light on primate evolution and human history, opening directions for research on inequality, sociality, and aging. PMID:27872299

Living long and ageing well: is epigenomics the missing link between nature and nurture?

PubMed

Rea, Irene Maeve; Dellet, Margaret; Mills, Ken I

2016-02-01

Human longevity is a complex trait and increasingly we understand that both genes and lifestyle interact in the longevity phenotype. Non-genetic factors, including diet, physical activity, health habits, and psychosocial factors contribute approximately 50% of the variability in human lifespan with another 25% explained by genetic differences. Family clusters of nonagenarian and centenarian siblings, who show both exceptional age-span and health-span, are likely to have inherited facilitatory gene groups, but also have nine decades of life experiences and behaviours which have interacted with their genetic profiles. Identification of their shared genes is just one small step in the link from genes to their physical and psychological profiles. Behavioural genomics is beginning to demonstrate links to biological mechanisms through regulation of gene expression, which directs the proteome and influences the personal phenotype. Epigenetics has been considered the missing link between nature and nurture. Although there is much that remains to be discovered, this article will discuss some of genetic and environmental factors which appear important in good quality longevity and link known epigenetic mechanisms to themes identified by nonagenarians themselves related to their longevity. Here we suggest that exceptional 90-year old siblings have adopted a range of behaviours and life-styles which have contributed to their ageing-well-phenotype and which link with important public health messages.

A LINE-1 Component to Human Aging: Do LINE elements exact a longevity cost for evolutionary advantage?

PubMed Central

Laurent, Georges St.; Hammell, Neil; McCaffrey, Timothy A.

2010-01-01

Advancing age remains the largest risk factor for devastating diseases, such as heart disease, stroke, and cancer. The mechanisms by which advancing age predisposes to disease are now beginning to unfold, due in part, to genetic and environmental manipulations of longevity in lower organisms. Converging lines of evidence suggest that DNA damage may be a final common pathway linking several proposed mechanisms of aging. The present review forwards a theory for an additional aging pathway that involves modes of inherent genetic instability. Long interspersed nuclear elements (LINEs) are endogenous non-LTR retrotransposons that compose about 20% of the human genome. The LINE-1 (L1) gene products, ORF1p and ORF2p, possess mRNA binding, endonuclease, and reverse transcriptase activity that enable retrotransposition. While principally active only during embryogenesis, L1 transcripts are detected in adult somatic cells under certain conditions. The present hypothesis proposes that L1s act as an ‘endogenous clock’, slowly eroding genomic integrity by competing with the organism’s double-strand break repair mechanism. Thus, while L1s are an accepted mechanism of genetic variation fueling evolution, it is proposed that longevity is negatively impacted by somatic L1 activity. The theory predicts testable hypotheses about the relationship between L1 activity, DNA repair, healthy aging, and longevity. PMID:20346965

On the Mechanism of Human Red Blood Cell Longevity: Roles of Calcium, the Sodium Pump, PIEZO1, and Gardos Channels.

PubMed

Lew, Virgilio L; Tiffert, Teresa

2017-01-01

In a healthy adult, the transport of O 2 and CO 2 between lungs and tissues is performed by about 2 · 10 13 red blood cells, of which around 1.7 · 10 11 are renewed every day, a turnover resulting from an average circulatory lifespan of about 120 days. Cellular lifespan is the result of an evolutionary balance between the energy costs of maintaining cells in a fit functional state versus cell renewal. In this Review we examine how the set of passive and active membrane transporters of the mature red blood cells interact to maximize their circulatory longevity thus minimizing costs on expensive cell turnover. Red blood cell deformability is critical for optimal rheology and gas exchange functionality during capillary flow, best fulfilled when the volume of each human red blood cell is kept at a fraction of about 0.55-0.60 of the maximal spherical volume allowed by its membrane area, the optimal-volume-ratio range. The extent to which red blood cell volumes can be preserved within or near these narrow optimal-volume-ratio margins determines the potential for circulatory longevity. We show that the low cation permeability of red blood cells allows volume stability to be achieved with extraordinary cost-efficiency, favouring cell longevity over cell turnover. We suggest a mechanism by which the interplay of a declining sodium pump and two passive membrane transporters, the mechanosensitive PIEZO1 channel, a candidate mediator of P sickle in sickle cells, and the Ca 2+ -sensitive, K + -selective Gardos channel, can implement red blood cell volume stability around the optimal-volume-ratio range, as required for extended circulatory longevity.

On the Mechanism of Human Red Blood Cell Longevity: Roles of Calcium, the Sodium Pump, PIEZO1, and Gardos Channels

PubMed Central

Lew, Virgilio L.; Tiffert, Teresa

2017-01-01

In a healthy adult, the transport of O2 and CO2 between lungs and tissues is performed by about 2 · 1013 red blood cells, of which around 1.7 · 1011 are renewed every day, a turnover resulting from an average circulatory lifespan of about 120 days. Cellular lifespan is the result of an evolutionary balance between the energy costs of maintaining cells in a fit functional state versus cell renewal. In this Review we examine how the set of passive and active membrane transporters of the mature red blood cells interact to maximize their circulatory longevity thus minimizing costs on expensive cell turnover. Red blood cell deformability is critical for optimal rheology and gas exchange functionality during capillary flow, best fulfilled when the volume of each human red blood cell is kept at a fraction of about 0.55–0.60 of the maximal spherical volume allowed by its membrane area, the optimal-volume-ratio range. The extent to which red blood cell volumes can be preserved within or near these narrow optimal-volume-ratio margins determines the potential for circulatory longevity. We show that the low cation permeability of red blood cells allows volume stability to be achieved with extraordinary cost-efficiency, favouring cell longevity over cell turnover. We suggest a mechanism by which the interplay of a declining sodium pump and two passive membrane transporters, the mechanosensitive PIEZO1 channel, a candidate mediator of Psickle in sickle cells, and the Ca2+-sensitive, K+-selective Gardos channel, can implement red blood cell volume stability around the optimal-volume-ratio range, as required for extended circulatory longevity. PMID:29311949

Comparative Endocrinology of Aging and Longevity Regulation

PubMed Central

Allard, John B.; Duan, Cunming

2011-01-01

Hormones regulate growth, development, metabolism, and other complex processes in multicellular animals. For many years it has been suggested that hormones may also influence the rate of the aging process. Aging is a multifactorial process that causes biological systems to break down and cease to function in adult organisms as time passes, eventually leading to death. The exact underlying causes of the aging process remain a topic for debate, and clues that may shed light on these causes are eagerly sought after. In the last two decades, gene mutations that result in delayed aging and extended longevity have been discovered, and many of the affected genes have been components of endocrine signaling pathways. In this review we summarize the current knowledge on the roles of endocrine signaling in the regulation of aging and longevity in various animals. We begin by discussing the notion that conserved systems, including endocrine signaling pathways, “regulate” the aging process. Findings from the major model organisms: worms, flies, and rodents, are then outlined. Unique lessons from studies of non-traditional models: bees, salmon, and naked mole rats, are also discussed. Finally, we summarize the endocrinology of aging in humans, including changes in hormone levels with age, and the involvement of hormones in aging-related diseases. The most well studied and widely conserved endocrine pathway that affects aging is the insulin/insulin-like growth factor system. Mutations in genes of this pathway increase the lifespan of worms, flies, and mice. Population genetic evidence also suggests this pathway’s involvement in human aging. Other hormones including steroids have been linked to aging only in a subset of the models studied. Because of the value of comparative studies, it is suggested that the aging field could benefit from adoption of additional model organisms. PMID:22654825

Autophagy mediates pharmacological lifespan extension by spermidine and resveratrol.

PubMed

Morselli, Eugenia; Galluzzi, Lorenzo; Kepp, Oliver; Criollo, Alfredo; Maiuri, Maria Chiara; Tavernarakis, Nektarios; Madeo, Frank; Kroemer, Guido

2009-12-23

Although autophagy has widely been conceived as a self-destructive mechanism that causes cell death, accumulating evidence suggests that autophagy usually mediates cytoprotection, thereby avoiding the apoptotic or necrotic demise of stressed cells. Recent evidence produced by our groups demonstrates that autophagy is also involved in pharmacological manipulations that increase longevity. Exogenous supply of the polyamine spermidine can prolong the lifespan of (while inducing autophagy in) yeast, nematodes and flies. Similarly, resveratrol can trigger autophagy in cells from different organisms, extend lifespan in nematodes, and ameliorate the fitness of human cells undergoing metabolic stress. These beneficial effects are lost when essential autophagy modulators are genetically or pharmacologically inactivated, indicating that autophagy is required for the cytoprotective and/or anti-aging effects of spermidine and resveratrol. Genetic and functional studies indicate that spermidine inhibits histone acetylases, while resveratrol activates the histone deacetylase Sirtuin 1 to confer cytoprotection/longevity. Although it remains elusive whether the same histones (or perhaps other nuclear or cytoplasmic proteins) act as the downstream targets of spermidine and resveratrol, these results point to an essential role of protein hypoacetylation in autophagy control and in the regulation of longevity.

Longevity and Stress Resistant Property of 6-Gingerol from Zingiber officinale Roscoe in Caenorhabditis elegans.

PubMed

Lee, Eun Byeol; Kim, Jun Hyeong; An, Chang Wan; Kim, Yeong Jee; Noh, Yun Jeong; Kim, Su Jin; Kim, Ju-Eun; Shrestha, Abinash Chandra; Ham, Ha-Neul; Leem, Jae-Yoon; Jo, Hyung-Kwon; Kim, Dae-Sung; Moon, Kwang Hyun; Lee, Jeong Ho; Jeong, Kyung Ok; Kim, Dae Keun

2018-03-14

In order to discover lifespan-extending compounds made from natural resources, activity-guided fractionation of Zingiber officinale Roscoe (Zingiberaceae) ethanol extract was performed using the Caenorhabditis elegans ( C. elegans ) model system. The compound 6-gingerol was isolated from the most active ethyl acetate soluble fraction, and showed potent longevity-promoting activity. It also elevated the survival rate of worms against stressful environment including thermal, osmotic, and oxidative conditions. Additionally, 6-gingerol elevated the antioxidant enzyme activities of C. elegans , and showed a dose-depend reduction of intracellular reactive oxygen species (ROS) accumulation in worms. Further studies demonstrated that the increased stress tolerance of 6-gingerol-mediated worms could result from the promotion of stress resistance proteins such as heat shock protein (HSP-16.2) and superoxide dismutase (SOD-3). The lipofuscin levels in 6-gingerol treated intestinal worms were decreased in comparison to the control group. No significant 6-gingerol-related changes, including growth, food intake, reproduction, and movement were noted. These results suggest that 6-gingerol exerted longevity-promoting activities independently of these factors and could extend the human lifespan.

Nutrients and ageing: what can we learn about ageing interactions from animal biology?

PubMed

Stenvinkel, Peter; Kooman, Jeroen P; Shiels, Paul G

2016-01-01

Many prevalent clinical conditions, such as chronic kidney disease, diabetes mellitus, chronic obstructive pulmonary, and cardiovascular disease associate with features of premature ageing, such as muscle wasting, hypogonadism, osteoporosis, and arteriosclerosis. Studies on various animal models have shown that caloric restriction prolongs lifespan. Studies of animals with unusual long or short life for their body size may also contribute to better understanding of ageing processes. The aim of the present article is to review what we can learn about nutritional modulations and ageing interactions from animal biology. Caloric restriction is a powerful intervention that increases longevity in animals ranging from short-lived species, such as worms and flies, to primates. As long-term studies on caloric restriction are not feasible to conduct in humans, much interest has focused on the impact of caloric restriction mimetics, such as resveratrol, on ageing processes. Recent data from studies on the long-lived naked mole rat have provided important novel information on metabolic alterations and antioxidative defense mechanisms that characterize longevity. Better understanding of the biology of exceptionally long-lived animals will contribute to better understanding of ageing processes and novel interventions to extend lifespan also in humans.

Differential DNA methylation and lymphocyte proportions in a Costa Rican high longevity region.

PubMed

McEwen, Lisa M; Morin, Alexander M; Edgar, Rachel D; MacIsaac, Julia L; Jones, Meaghan J; Dow, William H; Rosero-Bixby, Luis; Kobor, Michael S; Rehkopf, David H

2017-01-01

The Nicoya Peninsula in Costa Rica has one of the highest old-age life expectancies in the world, but the underlying biological mechanisms of this longevity are not well understood. As DNA methylation is hypothesized to be a component of biological aging, we focused on this malleable epigenetic mark to determine its association with current residence in Nicoya versus elsewhere in Costa Rica. Examining a population's unique DNA methylation pattern allows us to differentiate hallmarks of longevity from individual stochastic variation. These differences may be characteristic of a combination of social, biological, and environmental contexts. In a cross-sectional subsample of the Costa Rican Longevity and Healthy Aging Study, we compared whole blood DNA methylation profiles of residents from Nicoya ( n  = 48) and non-Nicoya (other Costa Rican regions, n  = 47) using the Infinium HumanMethylation450 microarray. We observed a number of differences that may be markers of delayed aging, such as bioinformatically derived differential CD8+ T cell proportions. Additionally, both site- and region-specific analyses revealed DNA methylation patterns unique to Nicoyans. We also observed lower overall variability in DNA methylation in the Nicoyan population, another hallmark of younger biological age. Nicoyans represent an interesting group of individuals who may possess unique immune cell proportions as well as distinct differences in their epigenome, at the level of DNA methylation.

The Significance of Education for Mortality Compression in the United States*

PubMed Central

Brown, Dustin C.; Hayward, Mark D.; Montez, Jennifer Karas; Humme, Robert A.; Chiu, Chi-Tsun; Hidajat, Mira M.

2012-01-01

Recent studies of old-age mortality trends assess whether longevity improvements over time are linked to increasing compression of mortality at advanced ages. The historical backdrop of these studies is the long-term improvements in a population's socioeconomic resources that fueled longevity gains. We extend this line of inquiry by examining whether socioeconomic differences in longevity within a population are accompanied by old-age mortality compression. Specifically, we document educational differences in longevity and mortality compression for older men and women in the United States. Drawing on the fundamental cause of disease framework, we hypothesize that both longevity and compression increase with higher levels of education and that women with the highest levels of education will exhibit the greatest degree of longevity and compression. Results based on the Health and Retirement Study and the National Health Interview Survey Linked Mortality File confirm a strong educational gradient in both longevity and mortality compression. We also find that mortality is more compressed within educational groups among women than men. The results suggest that educational attainment in the United States maximizes life chances by delaying the biological aging process. PMID:22556045

Reproductive cessation and post-reproductive lifespan in Asian elephants and pre-industrial humans

PubMed Central

2014-01-01

Introduction Short post-reproductive lifespan is widespread across species, but prolonged post-reproductive life-stages of potential adaptive significance have been reported only in few mammals with extreme longevity. Long post-reproductive lifespan contradicts classical evolutionary predictions of simultaneous senescence in survival and reproduction, and raises the question of whether extreme longevity in mammals promotes such a life-history. Among terrestrial mammals, elephants share the features with great apes and humans, of having long lifespan and offspring with long dependency. However, little data exists on the frequency of post-reproductive lifespan in elephants. Here we use extensive demographic records on semi-captive Asian elephants (n = 1040) and genealogical data on pre-industrial women (n = 5336) to provide the first comparisons of age-specific reproduction, survival and post-reproductive lifespan in both of these long-lived species. Results We found that fertility decreased after age 50 in elephants, but the pattern differed from a total loss of fertility in menopausal women with many elephants continuing to reproduce at least until the age of 65 years. The probability of entering a non-reproductive state increased steadily in elephants from the earliest age of reproduction until age 65, with the longer living elephants continuing to reproduce until older ages, in contrast to humans whose termination probability increased rapidly after age 35 and reached 1 at 56 years, but did not depend on longevity. Post-reproductive lifespan reached 11–17 years in elephants and 26–27 years in humans living until old age (depending on method), but whereas half of human adult lifespan (of those reproductive females surviving to the age of 5% fecundity) was spent as post-reproductive, only one eighth was in elephants. Consequently, although some elephants have long post-reproductive lifespans, relatively few individuals reach such a phase and the decline in fertility generally parallels declines in survivorship in contrast to humans with a decoupling of senescence in somatic and reproductive functions. Conclusions Our results show that the reproductive and survival patterns of Asian elephants differ from other long-lived animals exhibiting menopause, such as humans, and extreme longevity alone does not promote the evolution of menopause or post-reproductive lifespan, adding weight to the unusual kin-selected benefits suggested to favour such traits in humans and killer whales. PMID:25183990

Association Analysis of FOXO3 Longevity Variants With Blood Pressure and Essential Hypertension

PubMed Central

Chen, Randi; Donlon, Timothy A.; Evans, Daniel S.; Tranah, Gregory J.; Parimi, Neeta; Ehret, Georg B.; Newton-Cheh, Christopher; Seto, Todd; Willcox, D. Craig; Masaki, Kamal H.; Kamide, Kei; Ryuno, Hirochika; Oguro, Ryosuke; Nakama, Chikako; Kabayama, Mai; Yamamoto, Koichi; Sugimoto, Ken; Ikebe, Kazunori; Masui, Yukie; Arai, Yasumichi; Ishizaki, Tatsuro; Gondo, Yasuyuki; Rakugi, Hiromi; Willcox, Bradley J.

2016-01-01

BACKGROUND The minor alleles of 3 FOXO3 single nucleotide polymorphisms (SNPs)—rs2802292, rs2253310, and rs2802288—are associated with human longevity. The aim of the present study was to test these SNPs for association with blood pressure (BP) and essential hypertension (EHT). METHODS In a primary study involving Americans of Japanese ancestry drawn from the Family Blood Pressure Program II we genotyped 411 female and 432 male subjects aged 40–79 years and tested for statistical association by contingency table analysis and generalized linear models that included logistic regression adjusting for sibling correlation in the data set. Replication of rs2802292 with EHT was attempted in Japanese SONIC study subjects and of each SNP in a meta-analysis of genome-wide association studies of BP in individuals of European ancestry. RESULTS In Americans of Japanese ancestry, women homozygous for the longevity-associated (minor) allele of each FOXO3 SNP had 6mm Hg lower systolic BP and 3mm Hg lower diastolic BP compared with major allele homozygotes (Bonferroni corrected P < 0.05 and >0.05, respectively). Frequencies of minor allele homozygotes were 3.3–3.9% in women with EHT compared with 9.5–9.6% in normotensive women (P = 0.03–0.04; haplotype analysis P = 0.0002). No association with BP or EHT was evident in males. An association with EHT was seen for the minor allele of rs2802292 in the Japanese SONIC cohort (P = 0.03), while in European subjects the minor allele of each SNP was associated with higher systolic and diastolic BP. CONCLUSION Longevity-associated FOXO3 variants may be associated with lower BP and EHT in Japanese women. PMID:26476085

Association Analysis of FOXO3 Longevity Variants With Blood Pressure and Essential Hypertension.

PubMed

Morris, Brian J; Chen, Randi; Donlon, Timothy A; Evans, Daniel S; Tranah, Gregory J; Parimi, Neeta; Ehret, Georg B; Newton-Cheh, Christopher; Seto, Todd; Willcox, D Craig; Masaki, Kamal H; Kamide, Kei; Ryuno, Hirochika; Oguro, Ryosuke; Nakama, Chikako; Kabayama, Mai; Yamamoto, Koichi; Sugimoto, Ken; Ikebe, Kazunori; Masui, Yukie; Arai, Yasumichi; Ishizaki, Tatsuro; Gondo, Yasuyuki; Rakugi, Hiromi; Willcox, Bradley J

2016-11-01

The minor alleles of 3 FOXO3 single nucleotide polymorphisms (SNPs)- rs2802292 , rs2253310 , and rs2802288 -are associated with human longevity. The aim of the present study was to test these SNPs for association with blood pressure (BP) and essential hypertension (EHT). In a primary study involving Americans of Japanese ancestry drawn from the Family Blood Pressure Program II we genotyped 411 female and 432 male subjects aged 40-79 years and tested for statistical association by contingency table analysis and generalized linear models that included logistic regression adjusting for sibling correlation in the data set. Replication of rs2802292 with EHT was attempted in Japanese SONIC study subjects and of each SNP in a meta-analysis of genome-wide association studies of BP in individuals of European ancestry. In Americans of Japanese ancestry, women homozygous for the longevity-associated (minor) allele of each FOXO3 SNP had 6mm Hg lower systolic BP and 3mm Hg lower diastolic BP compared with major allele homozygotes (Bonferroni corrected P < 0.05 and >0.05, respectively). Frequencies of minor allele homozygotes were 3.3-3.9% in women with EHT compared with 9.5-9.6% in normotensive women ( P = 0.03-0.04; haplotype analysis P = 0.0002). No association with BP or EHT was evident in males. An association with EHT was seen for the minor allele of rs2802292 in the Japanese SONIC cohort ( P = 0.03), while in European subjects the minor allele of each SNP was associated with higher systolic and diastolic BP. Longevity-associated FOXO3 variants may be associated with lower BP and EHT in Japanese women.

High-Density Genomewide Linkage Analysis of Exceptional Human Longevity Identifies Multiple Novel Loci

PubMed Central

Boyden, Steven E.; Kunkel, Louis M.

2010-01-01

Background Human lifespan is approximately 25% heritable, and genetic factors may be particularly important for achieving exceptional longevity. Accordingly, siblings of centenarians have a dramatically higher probability of reaching extreme old age than the general population. Methodology/Principal Findings To map the loci conferring a survival advantage, we performed the second genomewide linkage scan on human longevity and the first using a high-density marker panel of single nucleotide polymorphisms. By systematically testing a range of minimum age cutoffs in 279 families with multiple long-lived siblings, we identified a locus on chromosome 3p24-22 with a genomewide significant allele-sharing LOD score of 4.02 (empirical P = 0.037) and a locus on chromosome 9q31-34 with a highly suggestive LOD score of 3.89 (empirical P = 0.054). The empirical P value for the combined result was 0.002. A third novel locus with a LOD score of 4.05 on chromosome 12q24 was detected in a subset of the data, and we also obtained modest evidence for a previously reported interval on chromosome 4q22-25. Conclusions/Significance Our linkage data should facilitate the discovery of both common and rare variants that determine genetic variability in lifespan. PMID:20824210

Stress biology and aging mechanisms: toward understanding the deep connection between adaptation to stress and longevity.

PubMed

Epel, Elissa S; Lithgow, Gordon J

2014-06-01

The rate of biological aging is modulated in part by genes interacting with stressor exposures. Basic research has shown that exposure to short-term stress can strengthen cellular responses to stress ("hormetic stress"). Hormetic stress promotes longevity in part through enhanced activity of molecular chaperones and other defense mechanisms. In contrast, prolonged exposure to stress can overwhelm compensatory responses ("toxic stress") and shorten lifespan. One key question is whether the stressors that are well understood in basic models of aging can help us understand psychological stressors and human health. The psychological stress response promotes regulatory changes important in aging (e.g., increases in stress hormones, inflammation, oxidative stress, insulin). The negative effects of severe stress are well documented in humans. Potential positive effects of acute stress (stress resistance) are less studied, especially at the cellular level. Can stress resistance slow the rate of aging in humans, as it does in model organisms? If so, how can we promote stress resistance in humans? We urge a new research agenda embracing the continuum from cellular stress to psychological stress, using basic and human research in tandem. This will require interdisciplinary novel approaches that hold much promise for understanding and intervening in human chronic disease. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Do r/K reproductive strategies apply to human differences?

PubMed

Rushton, J P

1988-01-01

This article discusses the r/K theory of Social Biology and how it relates to humans. The symbols r and K originate in the mathematics of population biology and refer to 2 ends of a continuum in which a compensatory exchange occurs between gamete production (the r-strategy) and longevity (the K-strategy). Both across and within species, r and K strategists differ in a suite of correlated characteristics. Humans are the most K of all. K's supposedly have a longer gestation period, a higher birthweight, a more delayed sexual maturation, a lower sex drive, and a longer life. Studies providing evidence for the expected covariation among K attributes are presented. Additional evidence for r/K theory comes from the comparison of human population known to differ in gamete production. The pattern of racial differences observed to occur in sexual behavior has also been found to exist on numerous other indices of K. For instance, there are racial differences in brain size, intelligence, and maturation rate, among others. The findings suggest that, on the average, Mongoloids are more K than Caucasoids, who in turn, are more K than Negroids. Recently conducted studies have extended the data in favor of r/K theory, and further research is currently underway, including whether r/K attributes underlie individual and social class differences in health and longevity.

Lifespan effects of simple and complex nutraceutical combinations fed isocalorically to mice.

PubMed

Spindler, Stephen R; Mote, Patricia L; Flegal, James M

2014-04-01

Present data suggest that the consumption of individual dietary supplements does not enhance the health or longevity of healthy rodents or humans. It might be argued that more complex combinations of such agents might extend lifespan or health-span by more closely mimicking the complexity of micronutrients in fruits and vegetables, which appear to extend health-span and longevity. To test this hypothesis we treated long-lived, male, F1 mice with published and commercial combinations of dietary supplements and natural product extracts, and determined their effects on lifespan and health-span. Nutraceutical, vitamin or mineral combinations reported to extend the lifespan or health-span of healthy or enfeebled rodents were tested, as were combinations of botanicals and nutraceuticals implicated in enhanced longevity by a longitudinal study of human aging. A cross-section of commercial nutraceutical combinations sold as potential health enhancers also were tested, including Bone Restore®, Juvenon®, Life Extension Mix®, Ortho Core®, Ortho Mind®, Super K w k2®, and Ultra K2®. A more complex mixture of vitamins, minerals, botanical extracts and other nutraceuticals was compounded and tested. No significant increase in murine lifespan was found for any supplement mixture. Our diverse supplement mixture significantly decreased lifespan. Thus, our results do not support the hypothesis that simple or complex combinations of nutraceuticals, including antioxidants, are effective in delaying the onset or progress of the major causes of death in mice. The results are consistent with epidemiological studies suggesting that dietary supplements are not beneficial and even may be harmful for otherwise healthy individuals.

Genetic Signatures of Exceptional Longevity in Humans

PubMed Central

Sebastiani, Paola; Solovieff, Nadia; DeWan, Andrew T.; Walsh, Kyle M.; Puca, Annibale; Hartley, Stephen W.; Melista, Efthymia; Andersen, Stacy; Dworkis, Daniel A.; Wilk, Jemma B.; Myers, Richard H.; Steinberg, Martin H.; Montano, Monty; Baldwin, Clinton T.; Hoh, Josephine; Perls, Thomas T.

2012-01-01

Like most complex phenotypes, exceptional longevity is thought to reflect a combined influence of environmental (e.g., lifestyle choices, where we live) and genetic factors. To explore the genetic contribution, we undertook a genome-wide association study of exceptional longevity in 801 centenarians (median age at death 104 years) and 914 genetically matched healthy controls. Using these data, we built a genetic model that includes 281 single nucleotide polymorphisms (SNPs) and discriminated between cases and controls of the discovery set with 89% sensitivity and specificity, and with 58% specificity and 60% sensitivity in an independent cohort of 341 controls and 253 genetically matched nonagenarians and centenarians (median age 100 years). Consistent with the hypothesis that the genetic contribution is largest with the oldest ages, the sensitivity of the model increased in the independent cohort with older and older ages (71% to classify subjects with an age at death>102 and 85% to classify subjects with an age at death>105). For further validation, we applied the model to an additional, unmatched 60 centenarians (median age 107 years) resulting in 78% sensitivity, and 2863 unmatched controls with 61% specificity. The 281 SNPs include the SNP rs2075650 in TOMM40/APOE that reached irrefutable genome wide significance (posterior probability of association = 1) and replicated in the independent cohort. Removal of this SNP from the model reduced the accuracy by only 1%. Further in-silico analysis suggests that 90% of centenarians can be grouped into clusters characterized by different “genetic signatures” of varying predictive values for exceptional longevity. The correlation between 3 signatures and 3 different life spans was replicated in the combined replication sets. The different signatures may help dissect this complex phenotype into sub-phenotypes of exceptional longevity. PMID:22279548

Being cool: how body temperature influences ageing and longevity.

PubMed

Keil, Gerald; Cummings, Elizabeth; de Magalhães, João Pedro

2015-08-01

Temperature is a basic and essential property of any physical system, including living systems. Even modest variations in temperature can have profound effects on organisms, and it has long been thought that as metabolism increases at higher temperatures so should rates of ageing. Here, we review the literature on how temperature affects longevity, ageing and life history traits. From poikilotherms to homeotherms, there is a clear trend for lower temperature being associated with longer lifespans both in wild populations and in laboratory conditions. Many life-extending manipulations in rodents, such as caloric restriction, also decrease core body temperature. Nonetheless, an inverse relationship between temperature and lifespan can be obscured or reversed, especially when the range of body temperatures is small as in homeotherms. An example is observed in humans: women appear to have a slightly higher body temperature and yet live longer than men. The mechanisms involved in the relationship between temperature and longevity also appear to be less direct than once thought with neuroendocrine processes possibly mediating complex physiological responses to temperature changes. Lastly, we discuss species differences in longevity in mammals and how this relates to body temperature and argue that the low temperature of the long-lived naked mole-rat possibly contributes to its exceptional longevity.

Aging and longevity in the simplest animals and the quest for immortality

PubMed Central

Petralia, Ronald S.; Mattson, Mark P.; Yao, Pamela J.

2014-01-01

Here we review the examples of great longevity and potential immortality in the earliest animal types and contrast and compare these to humans and other higher animals. We start by discussing aging in single-celled organisms such as yeast and ciliates, and the idea of the immortal cell clone. Then we describe how these cell clones could become organized into colonies of different cell types that lead to multicellular animal life. We survey aging and longevity in all of the basal metazoan groups including ctenophores (comb jellies), sponges, placozoans, cnidarians (hydras, jellyfish, corals and sea anemones) and myxozoans. Then we move to the simplest bilaterian animals (with a head, three body cell layers, and bilateral symmetry), the two phyla of flatworms. A key determinant of longevity and immortality in most of these simple animals is the large numbers of pluripotent stem cells that underlie the remarkable abilities of these animals to regenerate and rejuvenate themselves. Finally, we discuss briefly the evolution of the higher bilaterians and how longevity was reduced and immortality lost due to attainment of greater body complexity and cell cycle strategies that protect these complex organisms from developing tumors. We also briefly consider how the evolution of multiple aging-related mechanisms/pathwayshinders our ability to understand and modify the aging process in higher organisms. PMID:24910306

An Analysis of the Relationship Between Metabolism, Developmental Schedules, and Longevity Using Phylogenetic Independent Contrasts

PubMed Central

de Magalhães, João Pedro; Costa, Joana; Church, George M.

2008-01-01

Comparative studies of aging are often difficult to interpret because of the different factors that tend to correlate with longevity. We used the AnAge database to study these factors, particularly metabolism and developmental schedules, previously associated with longevity in vertebrate species. Our results show that, after correcting for body mass and phylogeny, basal metabolic rate does not correlate with longevity in eutherians or birds, although it negatively correlates with marsupial longevity and time to maturity. We confirm the idea that age at maturity is typically proportional to adult life span, and show that mammals that live longer for their body size, such as bats and primates, also tend to have a longer developmental time for their body size. Lastly, postnatal growth rates were negatively correlated with adult life span in mammals but not in birds. Our work provides a detailed view of factors related to species longevity with implications for how comparative studies of aging are interpreted. PMID:17339640

Biology of Healthy Aging and Longevity.

PubMed

Carmona, Juan José; Michan, Shaday

2016-01-01

As human life expectancy is prolonged, age-related diseases are thriving. Aging is a complex multifactorial process of molecular and cellular decline that affects tissue function over time, rendering organisms frail and susceptible to disease and death. Over the last decades, a growing body of scientific literature across different biological models, ranging from yeast, worms, flies, and mice to primates, humans and other long-lived animals, has contributed greatly towards identifying conserved biological mechanisms that ward off structural and functional deterioration within living systems. Collectively, these data offer powerful insights into healthy aging and longevity. For example, molecular integrity of the genome, telomere length, epigenetic landscape stability, and protein homeostasis are all features linked to "youthful" states. These molecular hallmarks underlie cellular functions associated with aging like mitochondrial fitness, nutrient sensing, efficient intercellular communication, stem cell renewal, and regenerative capacity in tissues. At present, calorie restriction remains the most robust strategy for extending health and lifespan in most biological models tested. Thus, pathways that mediate the beneficial effects of calorie restriction by integrating metabolic signals to aging processes have received major attention, such as insulin/insulin growth factor-1, sirtuins, mammalian target of rapamycin, and 5' adenosine monophosphate-activated protein kinase. Consequently, small-molecule targets of these pathways have emerged in the impetuous search for calorie restriction mimetics, of which resveratrol, metformin, and rapamycin are the most extensively studied. A comprehensive understanding of the molecular and cellular mechanisms that underlie age-related deterioration and repair, and how these pathways interconnect, remains a major challenge for uncovering interventions to slow human aging while extending molecular and physiological youthfulness, vitality, and health. This review summarizes key molecular mechanisms underlying the biology of healthy aging and longevity.

MOVEMENT AND LONGEVITY OF VIRUSES IN THE SUBSURFACE

EPA Science Inventory

Since human pathogens, in particular human enteric viruses, are not completely adsorbed or inactivated by conventional waste treatment facilities, sound management practices must be devised which rely on knowledge of the fate of these pollutant in the environment in order to prot...

Growing old, yet staying young: The role of telomeres in bats' exceptional longevity.

PubMed

Foley, Nicole M; Hughes, Graham M; Huang, Zixia; Clarke, Michael; Jebb, David; Whelan, Conor V; Petit, Eric J; Touzalin, Frédéric; Farcy, Olivier; Jones, Gareth; Ransome, Roger D; Kacprzyk, Joanna; O'Connell, Mary J; Kerth, Gerald; Rebelo, Hugo; Rodrigues, Luísa; Puechmaille, Sébastien J; Teeling, Emma C

2018-02-01

Understanding aging is a grand challenge in biology. Exceptionally long-lived animals have mechanisms that underpin extreme longevity. Telomeres are protective nucleotide repeats on chromosome tips that shorten with cell division, potentially limiting life span. Bats are the longest-lived mammals for their size, but it is unknown whether their telomeres shorten. Using >60 years of cumulative mark-recapture field data, we show that telomeres shorten with age in Rhinolophus ferrumequinum and Miniopterus schreibersii , but not in the bat genus with greatest longevity, Myotis . As in humans, telomerase is not expressed in Myotis myotis blood or fibroblasts. Selection tests on telomere maintenance genes show that ATM and SETX , which repair and prevent DNA damage, potentially mediate telomere dynamics in Myotis bats. Twenty-one telomere maintenance genes are differentially expressed in Myotis , of which 14 are enriched for DNA repair, and 5 for alternative telomere-lengthening mechanisms. We demonstrate how telomeres, telomerase, and DNA repair genes have contributed to the evolution of exceptional longevity in Myotis bats, advancing our understanding of healthy aging.

Season of Birth and Exceptional Longevity: Comparative Study of American Centenarians, Their Siblings, and Spouses

PubMed Central

Gavrilov, Leonid A.; Gavrilova, Natalia S.

2011-01-01

This study explores the effects of month of birth (a proxy for early-life environmental influences) on the chances of survival to age 100. Months of birth for 1,574 validated centenarians born in the United States in 1880–1895 were compared to the same information obtained for centenarians' 10,885 shorter-lived siblings and 1,083 spouses. Comparison was conducted using a within-family analysis by the method of conditional logistic regression, which allows researchers to control for unobserved shared childhood or adulthood environment and common genetic background. It was found that months of birth have significant long-lasting effect on survival to age 100: siblings born in September–November have higher odds to become centenarians compared to siblings born in March. A similar month-of-birth pattern was found for centenarian spouses. These results support the idea of early-life programming of human aging and longevity. PMID:22187646

Induction of autophagy by spermidine promotes longevity.

PubMed

Eisenberg, Tobias; Knauer, Heide; Schauer, Alexandra; Büttner, Sabrina; Ruckenstuhl, Christoph; Carmona-Gutierrez, Didac; Ring, Julia; Schroeder, Sabrina; Magnes, Christoph; Antonacci, Lucia; Fussi, Heike; Deszcz, Luiza; Hartl, Regina; Schraml, Elisabeth; Criollo, Alfredo; Megalou, Evgenia; Weiskopf, Daniela; Laun, Peter; Heeren, Gino; Breitenbach, Michael; Grubeck-Loebenstein, Beatrix; Herker, Eva; Fahrenkrog, Birthe; Fröhlich, Kai-Uwe; Sinner, Frank; Tavernarakis, Nektarios; Minois, Nadege; Kroemer, Guido; Madeo, Frank

2009-11-01

Ageing results from complex genetically and epigenetically programmed processes that are elicited in part by noxious or stressful events that cause programmed cell death. Here, we report that administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extended the lifespan of yeast, flies and worms, and human immune cells. In addition, spermidine administration potently inhibited oxidative stress in ageing mice. In ageing yeast, spermidine treatment triggered epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), suppressing oxidative stress and necrosis. Conversely, depletion of endogenous polyamines led to hyperacetylation, generation of reactive oxygen species, early necrotic death and decreased lifespan. The altered acetylation status of the chromatin led to significant upregulation of various autophagy-related transcripts, triggering autophagy in yeast, flies, worms and human cells. Finally, we found that enhanced autophagy is crucial for polyamine-induced suppression of necrosis and enhanced longevity.

LONGEVITY IN NORTH KOREA AND SOUTH KOREA: PREVALENCE OF CENTENARIANS IN ONE THE POOREST AND ONE OF THE RICHEST NATIONS.

PubMed

Schwekendiek, Daniel

2018-03-01

Over recent decades, economic living conditions have dramatically improved in South Korea, which now represents one of the most developed nations. At the same time, its twin in the North remains one of the poorest countries on earth. Thus, the Korean peninsula represents a unique historical experiment that allows for study of the effects of environment on human development under a variety of ceteris paribus cultural, genetic and climatic conditions. Previous studies comparing the biosocial performances of the two Koreas have focused on indicators such as weight, height, mid-upper arm circumference and age at menarche. The purpose of the present study was to investigate longevity based on the number of centenarians living in the two Koreas by drawing on censuses implemented around 1925 and 2010. The study found that North Korea had some 0.7 centenarians per one million persons in 1925, and this rate moderately improved to 2.7 around 2010. Conversely, rates skyrocketed in South Korea from 2.7 in 1925 to 38.2 around 2010. This suggests that the rate of centenarians in North Korea around 2010 corresponds to that of South Korea in 1925, suggesting a chronological lag in delayed human development of some 85 years. The prevalence of centenarians is fourteen times higher in contemporary South Korea compared with the North - broadly confirming previous biosocial studies on the two Koreas and two Germanies reporting improved human development in market-oriented systems compared with socialist ones.

Genomic prediction and genome-wide association analysis of female longevity in a composite beef cattle breed

USDA-ARS?s Scientific Manuscript database

Longevity is a highly important trait to the efficiency of beef cattle production. The objective of this study was to evaluate the genomic prediction of longevity and identify genomic regions associated with this trait. The data used in this study consisted of 547 Composite Gene Combination (CGC) c...

Metabolic acceleration and the evolution of human brain size and life history.

PubMed

Pontzer, Herman; Brown, Mary H; Raichlen, David A; Dunsworth, Holly; Hare, Brian; Walker, Kara; Luke, Amy; Dugas, Lara R; Durazo-Arvizu, Ramon; Schoeller, Dale; Plange-Rhule, Jacob; Bovet, Pascal; Forrester, Terrence E; Lambert, Estelle V; Thompson, Melissa Emery; Shumaker, Robert W; Ross, Stephen R

2016-05-19

Humans are distinguished from the other living apes in having larger brains and an unusual life history that combines high reproductive output with slow childhood growth and exceptional longevity. This suite of derived traits suggests major changes in energy expenditure and allocation in the human lineage, but direct measures of human and ape metabolism are needed to compare evolved energy strategies among hominoids. Here we used doubly labelled water measurements of total energy expenditure (TEE; kcal day(-1)) in humans, chimpanzees, bonobos, gorillas and orangutans to test the hypothesis that the human lineage has experienced an acceleration in metabolic rate, providing energy for larger brains and faster reproduction without sacrificing maintenance and longevity. In multivariate regressions including body size and physical activity, human TEE exceeded that of chimpanzees and bonobos, gorillas and orangutans by approximately 400, 635 and 820 kcal day(-1), respectively, readily accommodating the cost of humans' greater brain size and reproductive output. Much of the increase in TEE is attributable to humans' greater basal metabolic rate (kcal day(-1)), indicating increased organ metabolic activity. Humans also had the greatest body fat percentage. An increased metabolic rate, along with changes in energy allocation, was crucial in the evolution of human brain size and life history.

Autophagy mediates pharmacological lifespan extension by spermidine and resveratrol

PubMed Central

Morselli, Eugenia; Galluzzi, Lorenzo; Kepp, Oliver; Criollo, Alfredo; Maiuri, Maria Chiara; Tavernarakis, Nektarios; Madeo, Frank; Kroemer, Guido

2009-01-01

Although autophagy has widely been conceived as a self-destructive mechanism that causes cell death, accumulating evidence suggests that autophagy usually mediates cytoprotection, thereby avoiding the apoptotic or necrotic demise of stressed cells. Recent evidence produced by our groups demonstrates that autophagy is also involved in pharmacological manipulations that increase longevity. Exogenous supply of the polyamine spermidine can prolong the lifespan of (while inducing autophagy in) yeast, nematodes and flies. Similarly, resveratrol can trigger autophagy in cells from different organisms, extend lifespan in nematodes, and ameliorate the fitness of human cells undergoing metabolic stress. These beneficial effects are lost when essential autophagy modulators are genetically or pharmacologically inactivated, indicating that autophagy is required for the cytoprotective and/or anti-aging effects of spermidine and resveratrol. Genetic and functional studies indicate that spermidine inhibits histone acetylases, while resveratrol activates the histone deacetylase Sirtuin 1 to confer cytoprotection/longevity. Although it remains elusive whether the same histones (or perhaps other nuclear or cytoplasmic proteins) act as the downstream targets of spermidine and resveratrol, these results point to an essential role of protein hypoacetylation in autophagy control and in the regulation of longevity. PMID:20157579

Heart rate reduction and longevity in mice.

PubMed

Gent, Sabine; Kleinbongard, Petra; Dammann, Philip; Neuhäuser, Markus; Heusch, Gerd

2015-03-01

Heart rate correlates inversely with life span across all species, including humans. In patients with cardiovascular disease, higher heart rate is associated with increased mortality, and such patients benefit from pharmacological heart rate reduction. However, cause-and-effect relationships between heart rate and longevity, notably in healthy individuals, are not established. We therefore prospectively studied the effects of a life-long pharmacological heart rate reduction on longevity in mice. We hypothesized, that the total number of cardiac cycles is constant, and that a 15% heart rate reduction might translate into a 15% increase in life span. C57BL6/J mice received either placebo or ivabradine at a dose of 50 mg/kg/day in drinking water from 12 weeks to death. Heart rate and body weight were monitored. Autopsy was performed on all non-autolytic cadavers, and parenchymal organs were evaluated macroscopically. Ivabradine reduced heart rate by 14% (median, interquartile range 12-15%) throughout life, and median life span was increased by 6.2% (p = 0.01). Body weight and macroscopic findings were not different between placebo and ivabradine. Life span was not increased to the same extent as heart rate was reduced, but nevertheless significantly prolonged by 6.2%.

Floral longevity and autonomous selfing are altered by pollination and water availability in Collinsia heterophylla.

PubMed

Jorgensen, Rachael; Arathi, H S

2013-09-01

A plant investing in reproduction partitions resources between flowering and seed production. Under resource limitation, altered allocations may result in floral trait variations, leading to compromised fecundity. Floral longevity and timing of selfing are often the traits most likely to be affected. The duration of corolla retention determines whether fecundity results from outcrossing or by delayed selfing-mediated reproductive assurance. In this study, the role of pollination schedules and soil water availability on floral longevity and seed production is tested in Collinsia heterophylla (Plantaginaceae). Using three different watering regimes and pollination schedules, effects on floral longevity and seed production were studied in this protandrous, flowering annual. The results reveal that soil water status and pollination together influence floral longevity with low soil water and hand-pollinations early in the floral lifespan reducing longevity. However, early pollinations under excess water did not extend longevity, implying that resource surplus does not lengthen the outcrossing period. The results also indicate that pollen receipt, a reliable cue for fecundity, accelerates flower drop. Early corolla abscission under drought stress could potentially exacerbate sexual conflict in this protandrous, hermaphroditic species by ensuring self-pollen paternity and enabling male control of floral longevity. While pollination schedules did not affect fecundity, water stress reduced per-capita seed numbers. Unmanipulated flowers underwent delayed autonomous selfing, producing very few seeds, suggesting that inbreeding depression may limit benefits of selfing. In plants where herkogamy and dichogamy facilitate outcrossing, floral longevity determines reproductive success and mating system. Reduction in longevity under drought suggests a strong environmental effect that could potentially alter the preferred breeding mode in this mixed-mated species. Extrapolating the findings to unpredictable global drought cycles, it is suggested that in addition to reducing yield, water stress may influence the evolutionary trajectory of plant mating system.

Is Floral Longevity Influenced by Reproductive Costs and Pollination Success in Cohniella ascendens (Orchidaceae)?

PubMed Central

Abdala-Roberts, Luis; Parra-Tabla, Víctor; Navarro, Jorge

2007-01-01

Background and Aims Although studies have shown that pollen addition and/or removal decreases floral longevity, less attention has been paid to the relationship between reproductive costs and floral longevity. In addition, the influence of reproductive costs on floral longevity responses to pollen addition and/or removal has not yet been evaluated. Here, the orchid Cohniella ascendens is used to answer the following questions. (a) Does experimental removal of flower buds in C. ascendens increase flower longevity? (b) Does pollen addition and/or removal decrease floral longevity, and does this response depend on plant reproductive resource status? Methods To study the effect of reproductive costs on floral longevity 21 plants were selected from which we removed 50 % of the developing flower buds on a marked inflorescence. Another 21 plants were not manipulated (controls). One month later, one of four flowers on each marked inflorescence received one of the following pollen manipulation treatments: control, pollinia removal, pollination without pollinia removal or pollination with pollinia removal. The response variable measured was the number of days each flower remained open (i.e. longevity). Key Results The results showed significant flower bud removal and pollen manipulation effects on floral longevity; the interaction between these two factors was not significant. Flowers on inflorescences with previously removed flower buds remained open significantly longer than flowers on control inflorescences. On the other hand, pollinated flowers closed much faster than control and removed-pollinia flowers, the latter not closing significantly faster than control flowers, although this result was marginal. Conclusions The results emphasize the strong relationship between floral longevity and pollination in orchids, as well as the influence of reproductive costs on the former. PMID:17881335

Gender-specific association of ADA genetic polymorphism with human longevity.

PubMed

Napolioni, Valerio; Lucarini, Nazzareno

2010-08-01

Aim of this study was to investigate whether the polymorphic ADA (Adenosine Deaminase, EC 3.5.4.4) gene, which determines the cellular level of adenosine and plays a crucial role in the regulation of the immune system and in the control of metabolic rates, is involved in longevity. 884 unrelated healthy individuals (age range 10-106 years, 400 males and 484 females) from central Italy were studied. ADA genotyping was performed by RFLP-PCR. Frequency distributions were compared using the chi-square test and a three-way contingency table analysis by a log linear model was applied to test independence between the variables. We found that ADA influences human life-span in a sex and age specific way. An increased frequency of ADA*2 carriers was found in males aged 80-85, and a decreased frequency in males over 85 (chi(2) = 13.93; df = 3; P = 0.003); significant differences among the age groups was not found in females. A strong interaction among age groups, ADA genotype and sex (G = 15.086; df = 3; P = 0.0017) was found. Males aged 80-85 could be protected from ischemic stroke by higher levels of adenosine (determined by the ADA*2 allele). The decrease of ADA*2 carriers in males over 85 may depend essentially on immunological factors; reduced levels of adenosine protect from asthma and other pulmonary diseases and lead to a reduced activation of inflammatory cells and pro-inflammatory cytokines production. Moreover, the low level of adenosine may potentiate the activity of NK and other cellular effectors against tumor cells. The negligible effect of ADA genetic polymorphism in females suggest a marginal influence of genetic factors in determining longevity in this sex, confirming previous reports.

Plasmodium infection decreases fecundity and increases survival of mosquitoes.

PubMed

Vézilier, J; Nicot, A; Gandon, S; Rivero, A

2012-10-07

Long-lived mosquitoes maximize the chances of Plasmodium transmission. Yet, in spite of decades of research, the effect of Plasmodium parasites on mosquito longevity remains highly controversial. On the one hand, many studies report shorter lifespans in infected mosquitoes. On the other hand, parallel (but separate) studies show that Plasmodium reduces fecundity and imply that this is an adaptive strategy of the parasite aimed at redirecting resources towards longevity. No study till date has, however, investigated fecundity and longevity in the same individuals to see whether this prediction holds. In this study, we follow for both fecundity and longevity in Plasmodium-infected and uninfected mosquitoes using a novel, albeit natural, experimental system. We also explore whether the genetic variations that arise through the evolution of insecticide resistance modulate the effect of Plasmodium on these two life-history traits. We show that (i) a reduction in fecundity in Plasmodium-infected mosquitoes is accompanied by an increase in longevity; (ii) this increase in longevity arises through a trade-off between reproduction and survival; and (iii) in insecticide-resistant mosquitoes, the slope of this trade-off is steeper when the mosquito is infected by Plasmodium (cost of insecticide resistance).

Beyond Calories: An Integrated Approach to Promote Health, Longevity, and Well-Being.

PubMed

Bertozzi, Beatrice; Tosti, Valeria; Fontana, Luigi

2017-01-01

In 1948, the World Health Organization defined health as 'a state of complete physical, mental, and social well-being, and not merely the absence of disease or infirmity'. Detractors claim that this definition of health is utopian and unrealistic. However, accumulating evidence from experimental studies suggests that aging is not inevitably linked with the development of chronic diseases, and the age-associated accumulation of molecular damage can be prevented or greatly delayed by dietary and genetic manipulations that downregulate key cellular nutrient-sensing pathways. Nonetheless, to obtain a state of complete physical, mental, and social well-being, we as human beings need to go beyond nutrition or pharmacological treatments and implement a combination of interventions that enhance not only our metabolic health but also our psychological, emotional, intellectual and spiritual development, our social relationships and cultural well-being. This perspective highlights a range of scientific research-based interventions that can potentially be used to promote human health and longevity. We will also briefly address the importance of environmental health in achieving this goal. © 2016 S. Karger AG, Basel.

Lithium Promotes Longevity through GSK3/NRF2-Dependent Hormesis

PubMed Central

Castillo-Quan, Jorge Iván; Li, Li; Kinghorn, Kerri J.; Ivanov, Dobril K.; Tain, Luke S.; Slack, Cathy; Kerr, Fiona; Nespital, Tobias; Thornton, Janet; Hardy, John; Bjedov, Ivana; Partridge, Linda

2016-01-01

Summary The quest to extend healthspan via pharmacological means is becoming increasingly urgent, both from a health and economic perspective. Here we show that lithium, a drug approved for human use, promotes longevity and healthspan. We demonstrate that lithium extends lifespan in female and male Drosophila, when administered throughout adulthood or only later in life. The life-extending mechanism involves the inhibition of glycogen synthase kinase-3 (GSK-3) and activation of the transcription factor nuclear factor erythroid 2-related factor (NRF-2). Combining genetic loss of the NRF-2 repressor Kelch-like ECH-associated protein 1 (Keap1) with lithium treatment revealed that high levels of NRF-2 activation conferred stress resistance, while low levels additionally promoted longevity. The discovery of GSK-3 as a therapeutic target for aging will likely lead to more effective treatments that can modulate mammalian aging and further improve health in later life. PMID:27068460

Klotho: a humeral mediator in CSF and plasma that influences longevity and susceptibility to multiple complex disorders, including depression.

PubMed

Pavlatou, M G; Remaley, A T; Gold, P W

2016-08-30

Klotho is a hormone secreted into human cerebrospinal fluid (CSF), plasma and urine that promotes longevity and influences the onset of several premature senescent phenotypes in mice and humans, including atherosclerosis, cardiovascular disease, stroke and osteoporosis. Preliminary studies also suggest that Klotho possesses tumor suppressor properties. Klotho's roles in these phenomena were first suggested by studies demonstrating that a defect in the Klotho gene in mice results in a significant decrease in lifespan. The Klotho-deficient mouse dies prematurely at 8-9 weeks of age. At 4-5 weeks of age, a syndrome resembling human ageing emerges consisting of atherosclerosis, osteoporosis, cognitive disturbances and alterations of hippocampal architecture. Several deficits in Klotho-deficient mice are likely to contribute to these phenomena. These include an inability to defend against oxidative stress in the central nervous system and periphery, decreased capacity to generate nitric oxide to sustain normal endothelial reactivity, defective Klotho-related mediation of glycosylation and ion channel regulation, increased insulin/insulin-like growth factor signaling and a disturbed calcium and phosphate homeostasis accompanied by altered vitamin D levels and ectopic calcification. Identifying the mechanisms by which Klotho influences multiple important pathways is an emerging field in human biology that will contribute significantly to understanding basic physiologic processes and targets for the treatment of complex diseases. Because many of the phenomena seen in Klotho-deficient mice occur in depressive illness, major depression and bipolar disorder represent illnesses potentially associated with Klotho dysregulation. Klotho's presence in CSF, blood and urine should facilitate its study in clinical populations.

Restoration longevity in an Australian Defence Force population.

PubMed

Dawson, A S; Smales, R J

1992-06-01

Replacement of restorations comprises a considerable portion of the work of most dentists. Consequently, factors that affect restoration longevity can influence the pattern of dental practice in a given community. Based on the results of research into treatment provision in the General Dental Service in Scotland, it was considered possible that factors such as the frequency with which patients were examined, and the frequency with which they changed dentists, might influence restoration longevity in other populations. Therefore, the present study was initiated to investigate the effects of these two factors in a population of 100 long-term members of the Royal Australian Air Force. No statistically significant relationship could be found between examination frequency, or frequent changes in dental practitioner, and restoration longevity. It is proposed that the large differences found in restoration longevity between this study and the Scottish study upon which it was based, may be due in part to the differing modes of remuneration of the dentists in the two studies.

MicroRNA Predictors of Longevity in Caenorhabditis elegans

PubMed Central

Pincus, Zachary; Smith-Vikos, Thalyana; Slack, Frank J.

2011-01-01

Neither genetic nor environmental factors fully account for variability in individual longevity: genetically identical invertebrates in homogenous environments often experience no less variability in lifespan than outbred human populations. Such variability is often assumed to result from stochasticity in damage accumulation over time; however, the identification of early-life gene expression states that predict future longevity would suggest that lifespan is least in part epigenetically determined. Such “biomarkers of aging,” genetic or otherwise, nevertheless remain rare. In this work, we sought early-life differences in organismal robustness in unperturbed individuals and examined the utility of microRNAs, known regulators of lifespan, development, and robustness, as aging biomarkers. We quantitatively examined Caenorhabditis elegans reared individually in a novel apparatus and observed throughout their lives. Early-to-mid–adulthood measures of homeostatic ability jointly predict 62% of longevity variability. Though correlated, markers of growth/muscle maintenance and of metabolic by-products (“age pigments”) report independently on lifespan, suggesting that graceful aging is not a single process. We further identified three microRNAs in which early-adulthood expression patterns individually predict up to 47% of lifespan differences. Though expression of each increases throughout this time, mir-71 and mir-246 correlate with lifespan, while mir-239 anti-correlates. Two of these three microRNA “biomarkers of aging” act upstream in insulin/IGF-1–like signaling (IIS) and other known longevity pathways, thus we infer that these microRNAs not only report on but also likely determine longevity. Thus, fluctuations in early-life IIS, due to variation in these microRNAs and from other causes, may determine individual lifespan. PMID:21980307

A Method to Find Longevity-Selected Positions in the Mammalian Proteome

PubMed Central

Semeiks, Jeremy; Grishin, Nick V.

2012-01-01

Evolutionary theory suggests that the force of natural selection decreases with age. To explore the extent to which this prediction directly affects protein structure and function, we used multiple regression to find longevity-selected positions, defined as the columns of a sequence alignment conserved in long-lived but not short-lived mammal species. We analyzed 7,590 orthologous protein families in 33 mammalian species, accounting for body mass, phylogeny, and species-specific mutation rate. Overall, we found that the number of longevity-selected positions in the mammalian proteome is much higher than would be expected by chance. Further, these positions are enriched in domains of several proteins that interact with one another in inflammation and other aging-related processes, as well as in organismal development. We present as an example the kinase domain of anti-Müllerian hormone type-2 receptor (AMHR2). AMHR2 inhibits ovarian follicle recruitment and growth, and a homology model of the kinase domain shows that its longevity-selected positions cluster near a SNP associated with delayed human menopause. Distinct from its canonical role in development, this region of AMHR2 may function to regulate the protein’s activity in a lifespan-specific manner. PMID:22701678

Blood miRNomes and transcriptomes reveal novel longevity mechanisms in the long-lived bat, Myotis myotis.

PubMed

Huang, Zixia; Jebb, David; Teeling, Emma C

2016-11-10

Chiroptera, the bats, are the only order of mammals capable of true self-powered flight. Bats exhibit a number of other exceptional traits such as echolocation, viral tolerance and, perhaps most puzzlingly, extreme longevity given their body size. Little is known about the molecular mechanisms driving their extended longevity particularly at the levels of gene expression and post-transcriptional regulation. To elucidate the molecular mechanisms that may underlie their unusual longevity, we have deep sequenced 246.5 million small RNA reads from whole blood of the long-lived greater mouse-eared bats, Myotis myotis, and conducted a series of genome-wide comparative analyses between bat and non-bat mammals (human, pig and cow) in both blood miRNomes and transcriptomes, for the first time. We identified 539 miRNA gene candidates from bats, of which 468 unique mature miRNA were obtained. More than half of these miRNA (65.1 %) were regarded as bat-specific, regulating genes involved in the immune, ageing and tumorigenesis pathways. We have also developed a stringent pipeline for genome-wide miRNome comparisons across species, and identified 37 orthologous miRNA groups shared with bat, human, pig and cow, 6 of which were differentially expressed. For bats, 3 out of 4 up-regulated miRNA (miR-101-3p, miR-16-5p, miR-143-3p) likely function as tumor suppressors against various kinds of cancers, while one down-regulated miRNA (miR-221-5p) acts as a tumorigenesis promoter in human breast and pancreatic cancers. Additionally, a genome-wide comparison of mRNA transcriptomes across species also revealed specific gene expression patterns in bats. 127 up-regulated genes were enriched mainly in mitotic cell cycle and DNA repair mechanisms, while 364 down-regulated genes were involved primarily in mitochondrial activity. Our comprehensive and integrative analyses revealed bat-specific and differentially expressed miRNA and mRNA that function in key longevity pathways, producing a distinct bat gene expression pattern. For the first time, we show that bats may possess unique regulatory mechanisms for resisting tumorigenesis, repairing cellular damage and preventing oxidative stresses, all of which likely contribute to the extraordinary lifespan of Myotis myotis.

Book Longevity. Reports of the Committee on Production Guidelines for Book Longevity.

ERIC Educational Resources Information Center

Bailey, Herbert S., Jr.; And Others

In 1979, a Committee on Production Guidelines for Book Longevity was formed to study some aspects of the book preservation problem. Composed of representatives from libraries, publishing, and the paper industry, the committee set two primary objectives: to increase knowledge about the durability of books and other materials, and to encourage…

Personality and Longevity: Knowns, Unknowns, and Implications for Public Health and Personalized Medicine

PubMed Central

Chapman, Benjamin P.; Roberts, Brent; Duberstein, Paul

2011-01-01

We review evidence for links between personality traits and longevity. We provide an overview of personality for health scientists, using the primary organizing framework used in the study of personality and longevity. We then review data on various aspects of personality linked to longevity. In general, there is good evidence that higher level of conscientiousness and lower levels of hostility and Type D or “distressed” personality are associated with greater longevity. Limited evidence suggests that extraversion, openness, perceived control, and low levels of emotional suppression may be associated with longer lifespan. Findings regarding neuroticism are mixed, supporting the notion that many component(s) of neuroticism detract from life expectancy, but some components at some levels may be healthy or protective. Overall, evidence suggests various personality traits are significant predictors of longevity and points to several promising directions for further study. We conclude by discussing the implications of these links for epidemiologic research and personalized medicine and lay out a translational research agenda for integrating the psychology of individual differences into public health and medicine. PMID:21766032

Personality profile of the children of long-lived parents.

PubMed

Antoniou, Evangelia E; Dutta, Ambarish; Langa, Kenneth M; Melzer, David; Llewellyn, David

2013-09-01

Past research has shown that parental longevity is related to offspring physical health and longevity. Preliminary studies suggest that parental longevity may be linked to the offspring's personality traits. A comprehensive 5-factor personality model has been related to physical health, but the association with parental longevity has not yet been investigated. We used a 5-factor personality model to investigate the relationship between parental longevity and offspring personality. Data from the longitudinal Health and Retirement Study (HRS) was used in the analyses. Using the Midlife Development Inventory and the Life Orientation test, the relationship between parental attained age and offspring personality was assessed using regression models for both men and women. Male offspring of long-lived fathers and mothers were more likely to be open to new experiences (p < .01) and be more extroverted (p = .03) compared with male offspring of short-lived fathers or mothers. Maternal or paternal attained age had no effect on the female offspring personality traits. Personality is an important phenotype to consider when investigating genetic and environmental determinants of longevity. Further research is needed to investigate the potential of gender-specific mechanisms.

Dietary Interventions to Extend Life Span and Health Span Based on Calorie Restriction

PubMed Central

Minor, Robin K.; Allard, Joanne S.; Younts, Caitlin M.; Ward, Theresa M.

2010-01-01

The societal impact of obesity, diabetes, and other metabolic disorders continues to rise despite increasing evidence of their negative long-term consequences on health span, longevity, and aging. Unfortunately, dietary management and exercise frequently fail as remedies, underscoring the need for the development of alternative interventions to successfully treat metabolic disorders and enhance life span and health span. Using calorie restriction (CR)—which is well known to improve both health and longevity in controlled studies—as their benchmark, gerontologists are coming closer to identifying dietary and pharmacological therapies that may be applicable to aging humans. This review covers some of the more promising interventions targeted to affect pathways implicated in the aging process as well as variations on classical CR that may be better suited to human adaptation. PMID:20371545

Genetics of healthy aging and longevity.

PubMed

Brooks-Wilson, Angela R

2013-12-01

Longevity and healthy aging are among the most complex phenotypes studied to date. The heritability of age at death in adulthood is approximately 25 %. Studies of exceptionally long-lived individuals show that heritability is greatest at the oldest ages. Linkage studies of exceptionally long-lived families now support a longevity locus on chromosome 3; other putative longevity loci differ between studies. Candidate gene studies have identified variants at APOE and FOXO3A associated with longevity; other genes show inconsistent results. Genome-wide association scans (GWAS) of centenarians vs. younger controls reveal only APOE as achieving genome-wide significance (GWS); however, analyses of combinations of SNPs or genes represented among associations that do not reach GWS have identified pathways and signatures that converge upon genes and biological processes related to aging. The impact of these SNPs, which may exert joint effects, may be obscured by gene-environment interactions or inter-ethnic differences. GWAS and whole genome sequencing data both show that the risk alleles defined by GWAS of common complex diseases are, perhaps surprisingly, found in long-lived individuals, who may tolerate them by means of protective genetic factors. Such protective factors may 'buffer' the effects of specific risk alleles. Rare alleles are also likely to contribute to healthy aging and longevity. Epigenetics is quickly emerging as a critical aspect of aging and longevity. Centenarians delay age-related methylation changes, and they can pass this methylation preservation ability on to their offspring. Non-genetic factors, particularly lifestyle, clearly affect the development of age-related diseases and affect health and lifespan in the general population. To fully understand the desirable phenotypes of healthy aging and longevity, it will be necessary to examine whole genome data from large numbers of healthy long-lived individuals to look simultaneously at both common and rare alleles, with impeccable control for population stratification and consideration of non-genetic factors such as environment.

Meat and Nicotinamide: A Causal Role in Human Evolution, History, and Demographics

PubMed Central

Williams, Adrian C; Hill, Lisa J

2017-01-01

Hunting for meat was a critical step in all animal and human evolution. A key brain-trophic element in meat is vitamin B3 / nicotinamide. The supply of meat and nicotinamide steadily increased from the Cambrian origin of animal predators ratcheting ever larger brains. This culminated in the 3-million-year evolution of Homo sapiens and our overall demographic success. We view human evolution, recent history, and agricultural and demographic transitions in the light of meat and nicotinamide intake. A biochemical and immunological switch is highlighted that affects fertility in the ‘de novo’ tryptophan-to-kynurenine-nicotinamide ‘immune tolerance’ pathway. Longevity relates to nicotinamide adenine dinucleotide consumer pathways. High meat intake correlates with moderate fertility, high intelligence, good health, and longevity with consequent population stability, whereas low meat/high cereal intake (short of starvation) correlates with high fertility, disease, and population booms and busts. Too high a meat intake and fertility falls below replacement levels. Reducing variances in meat consumption might help stabilise population growth and improve human capital. PMID:28579800

The Epidemiology of Longevity and Exceptional Survival

PubMed Central

Newman, Anne B.; Murabito, Joanne M.

2013-01-01

The field of the “epidemiology of longevity” has been expanding rapidly in recent years. Several long-term cohort studies have followed older adults long enough to identify the most long-lived and to define many factors that lead to a long life span. Very long-lived people such as centenarians have been examined using case-control study designs. Both cohort and case-control studies have been the subject of genome-wide association studies that have identified genetic variants associated with longevity. With growing recognition of the importance of rare variations, family studies of longevity will be useful. Most recently, exome and whole-genome sequencing, gene expression, and epigenetic studies have been undertaken to better define functional variation and regulation of the genome. In this review, we consider how these studies are leading to a deeper understanding of the underlying biologic pathways to longevity. PMID:23372024

Learning of nature: The curious case of the naked mole rat.

PubMed

Lagunas-Rangel, Francisco Alejandro; Chávez-Valencia, Venice

2017-06-01

Naked mole rats (NMRs) are the longest-living rodents known, living up to approximately 30 years and showing sustained good health. Nowadays, NMRs are considered excellent models for aging and, additionally, for cancer research, due to the evidence of a remarkable cancer resistance demonstrated through thousands of necropsies performed with very few cases that describe this pathology, which is believed to be a disease that unavoidably accompanies aging. Since some years ago, several studies have tried to explain the possible mechanisms underlying longevity and cancer resistance in NMRs through different perspectives and directions, creating new knowledge that subsequently could be used for cancer prevention and delaying aging in humans. Thus, the purpose of this review is to summarize the recent knowledge on naked mole rats with a particular emphasis on the molecular mechanisms associated with their longevity and cancer resistance. Copyright © 2017 Elsevier B.V. All rights reserved.

Popular perceptions of emerging influences on mortality and longevity in Bangladesh and West Bengal.

PubMed

Amin, Sajeda; Basu, Alaka Malwade

2004-01-01

Relatively little is known about how environmental and pathological threats to human survival and longevity are perceived by the public. In this study in rural Bangladesh and West Bengal, India, which used individual interviews and focus-group discussions to investigate the changing costs of and motivations for reproduction, respondents were questioned about their perceptions of changes in mortality. The findings show that, while child mortality levels are perceived to have fallen dramatically in recent times, the health and survival prospects of the middle aged and the elderly are seen to have been better in the past. The perceived decline in adult health is attributed to environmental deterioration and lifestyle changes accompanying modernization. This paper explores people's reasons for this unexpected worldview. References to pesticides and chemical fertilizers as causes of death abound in their explanations and are seen to be associated with unhealthy agricultural practices and impiety.

Controlling factors of soil selenium distribution in a watershed in Se-enriched and longevity region of South China.

PubMed

Shao, Ya; Cai, Chongfa; Zhang, Haitao; Fu, Wei; Zhong, Xuemei; Tang, Shen

2018-05-10

Selenium (Se) is an essential nutritional element for human beings. Many studies have been conducted on concentration and distribution patterns of soil Se in low Se, Se-enriched, and selenosis areas; however, soil Se has not been systematically studied in a watershed, especially in Se-enriched longevity region and karst area in South China. This study is carried out to explore the controlling factors of Se-enriched soils in Baishou river tributary watershed, where soils are Se-enriched, and local people have the phenomenon of longevity. The area-weighted average rock Se concentration in the watershed is 0.054 mg/kg, and there are no significant differences in rock Se concentration between different strata and between different lithological rocks. The area-weighted average concentration of Se in soils (0-20 cm) is 0.80 mg/kg, and the soil Se concentration is of high level in the watershed. Soil Se concentration decreases from upstream to downstream in the watershed, and significantly correlated with elevation. Climate is the main factor causing high content of soil Se in the watershed which lacks black rock series. The difference of clastic and carbonate parent materials in soil forming process and the physical and chemical properties (pH, OM, etc.) are the main reasons for the spatial variation of Se distribution in the watershed. The research will be beneficial to the development and utilization of Se-enriched soil in Se-enriched area.

Longer leukocyte telomere length in Costa Rica's Nicoyan Peninsula: A population-based study

PubMed Central

Rehkopf, David H; Dow, William H; Rosero-Bixby, Luis; Lin, Jue; Epel, Elissa S; Blackburn, Elizabeth H

2013-01-01

Studies in humans suggest that leukocyte telomere length may act as a marker of biological aging. We investigated whether individuals in the Nicoya region of Costa Rica, known for exceptional longevity, had longer telomere length than those in other parts of the country. After controlling for age, age squared, rurality, rainy season and gender, mean leukocyte telomere length in Nicoya was substantially longer (81 base pairs, p<0.05) than in other areas of Costa Rica, providing evidence of a biological pathway to which this notable longevity may be related. This relationship remains unchanged (79 base pairs, p<0.05) after statistically controlling for nineteen potential biological, dietary and social and demographic mediators. Thus the difference in mean leukocyte telomere length that characterizes this unique region does not appear to be explainable by traditional behavioral and biological risk factors. More detailed examination of mean leukocyte telomere length by age shows that the regional telomere length difference declines at older ages. PMID:23988653

Gender, aging and longevity in humans: an update of an intriguing/neglected scenario paving the way to a gender-specific medicine

PubMed Central

Ostan, Rita; Monti, Daniela; Gueresi, Paola; Bussolotto, Mauro; Franceschi, Claudio

2016-01-01

Data showing a remarkable gender difference in life expectancy and mortality, including survival to extreme age, are reviewed starting from clinical and demographic data and stressing the importance of a comprehensive historical perspective and a gene–environment/lifestyle interaction. Gender difference regarding prevalence and incidence of the most important age-related diseases, such as cardiovascular and neurodegenerative diseases, cancer, Type 2 diabetes, disability, autoimmunity and infections, are reviewed and updated with particular attention to the role of the immune system and immunosenescence. On the whole, gender differences appear to be pervasive and still poorly considered and investigated despite their biomedical relevance. The basic biological mechanisms responsible for gender differences in aging and longevity are quite complex and still poorly understood. The present review focuses on centenarians and their offspring as a model of healthy aging and summarizes available knowledge on three basic biological phenomena, i.e. age-related X chromosome inactivation skewing, gut microbiome changes and maternally inherited mitochondrial DNA genetic variants. In conclusion, an appropriate gender-specific medicine approach is urgently needed and should be systematically pursued in studies on healthy aging, longevity and age-related diseases, in a globalized world characterized by great gender differences which have a high impact on health and diseases. PMID:27555614

Sex differences in oxidative stress resistance in relation to longevity in Drosophila melanogaster.

PubMed

Niveditha, S; Deepashree, S; Ramesh, S R; Shivanandappa, T

2017-10-01

Gender differences in lifespan and aging are known across species. Sex differences in longevity within a species can be useful to understand sex-specific aging. Drosophila melanogaster is a good model to study the problem of sex differences in longevity since females are longer lived than males. There is evidence that stress resistance influences longevity. The objective of this study was to investigate if there is a relationship between sex differences in longevity and oxidative stress resistance in D. melanogaster. We observed a progressive age-dependent decrease in the activity of SOD and catalase, major antioxidant enzymes involved in defense mechanisms against oxidative stress in parallel to the increased ROS levels over time. Longer-lived females showed lower ROS levels and higher antioxidant enzymes than males as a function of age. Using ethanol as a stressor, we have shown differential susceptibility of the sexes to ethanol wherein females exhibited higher resistance to ethanol-induced mortality and locomotor behavior compared to males. Our results show strong correlation between sex differences in oxidative stress resistance, antioxidant defenses and longevity. The study suggests that higher antioxidant defenses in females may confer resistance to oxidative stress, which could be a factor that influences sex-specific aging in D. melanogaster.

Genome-wide association study for longevity with whole-genome sequencing in 3 cattle breeds.

PubMed

Zhang, Qianqian; Guldbrandtsen, Bernt; Thomasen, Jørn Rind; Lund, Mogens Sandø; Sahana, Goutam

2016-09-01

Longevity is an important economic trait in dairy production. Improvements in longevity could increase the average number of lactations per cow, thereby affecting the profitability of the dairy cattle industry. Improved longevity for cows reduces the replacement cost of stock and enables animals to achieve the highest production period. Moreover, longevity is an indirect indicator of animal welfare. Using whole-genome sequencing variants in 3 dairy cattle breeds, we carried out an association study and identified 7 genomic regions in Holstein and 5 regions in Red Dairy Cattle that were associated with longevity. Meta-analyses of 3 breeds revealed 2 significant genomic regions, located on chromosomes 6 (META-CHR6-88MB) and 18 (META-CHR18-58MB). META-CHR6-88MB overlaps with 2 known genes: neuropeptide G-protein coupled receptor (NPFFR2; 89,052,210-89,059,348 bp) and vitamin D-binding protein precursor (GC; 88,695,940-88,739,180 bp). The NPFFR2 gene was previously identified as a candidate gene for mastitis resistance. META-CHR18-58MB overlaps with zinc finger protein 717 (ZNF717; 58,130,465-58,141,877 bp) and zinc finger protein 613 (ZNF613; 58,115,782-58,117,110 bp), which have been associated with calving difficulties. Information on longevity-associated genomic regions could be used to find causal genes/variants influencing longevity and exploited to improve the reliability of genomic prediction. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The Normalized Failure Index: a method for summarizing the results of studies on restoration longevity?

PubMed

Burke, F J T; Singh, V; Wilson, N H F

2013-01-01

Satisfactory restoration longevity is central to operative dentistry and is the subject of a wide variety of publications. However, combining the results of a number of studies to provide an overview, for example, for a meta-analysis may be problematic because of the heterogeneity of the data, and a high proportion of studies may therefore not be included. It is the purpose of this study to present a means whereby the data from cohort studies may be combined to present a representation of restoration longevity, termed the "Normalized Failure Index."

The Nestor Effect: Extending Evolutionary Developmental Psychology to a Lifespan Perspective

ERIC Educational Resources Information Center

Greve, Werner; Bjorklund, David F.

2009-01-01

We extend an evolutionary perspective of development to the lifespan, proposing that human longevity may be related to the experience, knowledge, and wisdom provided by older members of human groups. In addition to the assistance in childcare provided by grandmothers to their daughters, the experience of wise elders could have served to benefit…

Genomewide mechanisms of chronological longevity by dietary restriction in budding yeast.

PubMed

Campos, Sergio E; Avelar-Rivas, J Abraham; Garay, Erika; Juárez-Reyes, Alejandro; DeLuna, Alexander

2018-06-01

Dietary restriction is arguably the most promising nonpharmacological intervention to extend human life and health span. Yet, only few genetic regulators mediating the cellular response to dietary restriction are known, and the question remains which other regulatory factors are involved. Here, we measured at the genomewide level the chronological lifespan of Saccharomyces cerevisiae gene deletion strains under two nitrogen source regimens, glutamine (nonrestricted) and γ-aminobutyric acid (restricted). We identified 473 mutants with diminished or enhanced extension of lifespan. Functional analysis of such dietary restriction genes revealed novel processes underlying longevity by the nitrogen source quality, which also allowed us to generate a prioritized catalogue of transcription factors orchestrating the dietary restriction response. Importantly, deletions of transcription factors Msn2, Msn4, Snf6, Tec1, and Ste12 resulted in diminished lifespan extension and defects in cell cycle arrest upon nutrient starvation, suggesting that regulation of the cell cycle is a major mechanism of chronological longevity. We further show that STE12 overexpression is enough to extend lifespan, linking the pheromone/invasive growth pathway with cell survivorship. Our global picture of the genetic players of longevity by dietary restriction highlights intricate regulatory cross-talks in aging cells. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Endurance exercise and selective breeding for longevity extend Drosophila healthspan by overlapping mechanisms.

PubMed

Sujkowski, Alyson; Bazzell, Brian; Carpenter, Kylie; Arking, Robert; Wessells, Robert J

2015-08-01

Endurance exercise has emerged as a powerful intervention that promotes healthy aging by maintaining the functional capacity of critical organ systems. In addition, long-term exercise reduces the incidence of age-related diseases in humans and in model organisms. Despite these evident benefits, the genetic pathways required for exercise interventions to achieve these effects are still relatively poorly understood. Here, we compare gene expression changes during endurance training in Drosophila melanogaster to gene expression changes during selective breeding for longevity. Microarrays indicate that 65% of gene expression changes found in flies selectively bred for longevity are also found in flies subjected to three weeks of exercise training. We find that both selective breeding and endurance training increase endurance, cardiac performance, running speed, flying height, and levels of autophagy in adipose tissue. Both interventions generally upregulate stress defense, folate metabolism, and lipase activity, while downregulating carbohydrate metabolism and odorant receptor expression. Several members of the methuselah-like (mthl) gene family are downregulated by both interventions. Knockdown of mthl-3 was sufficient to provide extension of negative geotaxis behavior, endurance and cardiac stress resistance. These results provide support for endurance exercise as a broadly acting anti-aging intervention and confirm that exercise training acts in part by targeting longevity assurance pathways.

Significant Discrepancy Between Estimated and Actual Longevity in St. Jude Medical Implantable Cardioverter-Defibrillators.

PubMed

Doppalapudi, Harish; Barrios, James; Cuellar, Jose; Gannon, Melanie; Yamada, Takumi; Kumar, Vineet; Maddox, William R; Plumb, Vance J; Brown, Todd M; McElderry, H Tom

2017-05-01

Real-time estimated longevity has been reported in pacemakers for several years, and was recently introduced in implantable cardioverter-defibrillators (ICDs). We sought to evaluate the accuracy of this longevity estimate in St. Jude Medical (SJM) ICDs, especially as the device battery approaches depletion. Among patients with SJM ICDs who underwent generator replacements due to reaching elective replacement indicator (ERI) at our institution, we identified those with devices that provided longevity estimates and reviewed their device interrogations in the 18 months prior to ERI. Significant discrepancy was defined as a difference of more than 12 months between estimated and actual longevity at any point during this period. Forty-six patients with Current/Promote devices formed the study group (40 cardiac resynchronization therapy [CRT] and 6 single/dual chamber). Of these, 34 (74%) had significant discrepancy between estimated and actual longevity (28 CRT and all single/dual). Longevity was significantly overestimated by the device algorithm (mean maximum discrepancy of 18.8 months), more in single/dual than CRT devices (30.5 vs. 17.1 months). Marked discrepancy was seen at voltages ≥2.57 volts, with maximum discrepancy at 2.57 volts (23 months). The overall longevity was higher in the discrepant group of CRT devices than in the nondiscrepant group (67 vs. 61 months, log-rank P = 0.03). There was significant overestimation of longevity in nearly three-fourths of Current/Promote SJM ICDs in the last 18 months prior to ERI. Longevity estimates of SJM ICDs may not be reliable for making clinical decisions on frequency of follow-up, as the battery approaches depletion. © 2017 Wiley Periodicals, Inc.

Longevity and aging: role of genes and of the extracellular matrix.

PubMed

Robert, L; Labat-Robert, J

2015-02-01

Longevity is different for every animal species as well as their genome, suggesting a correlation between genes and life-span. Estimates put the genetic effect from 5 to 35% approximately, suggesting that even genetic effects are dependent on environmental conditions. This contention is largely confirmed by the study of identical twins raised apart. They do not die at the same age and also for different reasons. Aging is not "genetically programmed", it is outside evolutionary constraint. Evolution favors early and efficient reproduction, but does not care for longevity. A number of mechanisms were shown to be involved in the age-dependent decline of vital functions, among them the Maillard reaction (non-enzymatic glycosylation) and the age-dependent upregulation of proteolytic activity. Aging of ECM is a complex process, comprising progressive modification of its macromolecular components and of cell-matrix interactions. An important process is the uncoupling with age of the elastin-receptor from its "young" transmission pathway loosing all physiological effects, but enhancing free radical and elastase release. These processes contribute to age-related ECM degradation, production of matrikins (ECM degradation products with biological activity) aggravating functional loss with age. Both genetic and post-genetic mechanisms are susceptible to be influenced by medical, pharmacological and dietary interventions. Among the genetic mechanisms, those attributed to Sirtuins (7 orthologs identified in the human genome) are especially important. Among the environmental effects, nutrition, hygiene and weather conditions play a role. These data justify some predictions on the evolution of life expectancy taking in account also socio-economic factors. Biological constraints become evident by the comparison of centenarians and supercentenarians (less than 1% of the centenarians) putting an upper limit to the attainable human lifespan.

Sociodemographic and psychosocial factors in childhood as predictors of adult mortality.

PubMed Central

Schwartz, J E; Friedman, H S; Tucker, J S; Tomlinson-Keasey, C; Wingard, D L; Criqui, M H

1995-01-01

OBJECTIVES: Childhood sociodemographic, psychosocial, and environmental factors are often assumed to affect adult health and longevity. These relationships were prospectively tested by using the 7-decade Terman Life Cycle Study of Children With High Ability (n = 1285). METHODS: Parental socioeconomic status, childhood health, objective childhood stressors (e.g., death or divorce of parents), and childhood personality were considered as potential predictors in hazard regression analyses of longevity through 1991. RESULTS: Parental divorce during childhood predicted decreased longevity, with sex controlled. Other potential social predictors failed to show significant associations with longevity. Three dimensions of childhood personality--conscientiousness, lack of cheerfulness, and permanency of mood (males only)--predicted increased longevity. The effects of parental divorce and childhood personality were largely independent and did not account for any of the gender difference in mortality. CONCLUSIONS: A small number of childhood factors significantly predicted mortality across the life span in this sample. Further research should focus on how these psychosocial factors influence longevity. PMID:7661231

In Search of Rationality in Human Longevity and Immortality

PubMed Central

Bhar, Gopal C.

2016-01-01

The human body is machine-like, but self-moving, self-regulating, and self-adjusting, governed by willpower and intelligence. Aging of the body is basically a maintenance problem and so it could perhaps be postponed by thorough and frequent maintenance. Aging brings on a cascade of ills and health problems leading to deterioration of physical, mental, emotional, and social dimensions of life. This paper deals with solution of the problem philosophically in the light of Indian scriptures without entering into traditional bioethical issues. With a meaningful reason for existence, life can be extended. Examining the scientific perspectives on aging, some common manipulations for its extension are discussed. These are calorie restriction, vitamin and antioxidant treatment, exercise and hormonal interventions, etc. Finally, the question of longevity is explored through pursuance of eternal value-based activity and spirituality in the tradition of Indian heritage. PMID:28031631

A retrospective clinical study of cervical restorations: longevity and failure-prognostic variables.

PubMed

Namgung, C; Rho, Y J; Jin, B H; Lim, B S; Cho, B H

2013-01-01

The aim of this retrospective clinical study was to compare the longevity of cervical restorations between resin composite (RC) and glass ionomer (GI) and to investigate variables predictive of their outcome. The clinical performance of the two restorative materials in function was compared using the ratings of the modified United States Public Health Service (USPHS) criteria. A total of 479 cervical restorations were included in the study. Ninety-one already-replaced restorations were reviewed from dental records. The other 388 restorations still in function were evaluated according to the modified USPHS criteria by two investigators. Longevity and prognostic variables were analyzed with the Kaplan-Meier survival analysis and multivariate Cox proportional hazard model. The clinical performances of the two materials were evaluated according to the ratings of the USPHS criteria and compared using the Pearson chi-square test and Fisher exact test. The longevity was not significantly different between RC and GI (median survival time, 10.4 ± 0.7 and 11.5 ± 1.1 years, respectively). The main reasons for failure were loss of retention (82.2%) and secondary caries (17.8%). The longevity of cervical restoration was significantly influenced by tooth group and operator group (Wald test, p<0.05), while material, gender, presence or absence of systemic diseases, arch, and reason for treatment did not affect the longevity. Contrary to the longevity, the clinical performance of RC was superior to GI in the criteria of retention, marginal discoloration, and marginal adaptation, but similar in secondary caries, wear, and postoperative sensitivity.

Copulation, genital damage and early death in Callosobruchus maculatus

PubMed Central

Eady, Paul E; Hamilton, Leticia; Lyons, Ruth E

2006-01-01

Antagonistic sexual coevolution stems from the notion that male and female interests over reproduction are in conflict. Such conflicts appear to be particularly obvious when male genital armature inflicts damage to the female reproductive tract resulting in reduced female longevity. However, studies of mating frequency, genital damage and female longevity are difficult to interpret because females not only sustain more genital damage, but also receive more seminal fluid when they engage in multiple copulations. Here, we attempt to disentangle the effects of genital damage and seminal fluid transfer on female longevity in the beetle Callosobruchus maculatus (Coleoptera: Bruchidae). Males copulating for the sixth time in succession inflicted greater levels of genital damage, but transferred smaller ejaculates in comparison with virgin males. The number of copulations performed by males was negatively related to female fecundity and positively related to female longevity, suggesting a trade-off between fecundity and longevity. However, inclusion of fecundity as a covariate revealed sperm and/or seminal fluid transfer to have a negative impact on female longevity above that caused by the fecundity–longevity trade-off. The consequences of multiple copulations on female longevity were examined. Females that mated twice laid more eggs and died sooner than those that mated once. However, incorporation of fecundity as a covariate into our statistical model removed the effect of female mating frequency on female longevity, indicating that double-mated females suffer greater mortality owing to the trade-off between fecundity and longevity. Males of this species are known to transfer very large ejaculates (up to 8% of their body weight), which may represent a significant nutritional benefit to females. However, the receipt of large ejaculates appears to carry costs. Thus, the interpretation of multiple mating experiments on female longevity and associated functional explanations of polyandry in this species are likely to be complex. PMID:17035168

Copulation, genital damage and early death in Callosobruchus maculatus.

PubMed

Eady, Paul E; Hamilton, Leticia; Lyons, Ruth E

2007-01-22

Antagonistic sexual coevolution stems from the notion that male and female interests over reproduction are in conflict. Such conflicts appear to be particularly obvious when male genital armature inflicts damage to the female reproductive tract resulting in reduced female longevity. However, studies of mating frequency, genital damage and female longevity are difficult to interpret because females not only sustain more genital damage, but also receive more seminal fluid when they engage in multiple copulations. Here, we attempt to disentangle the effects of genital damage and seminal fluid transfer on female longevity in the beetle Callosobruchus maculatus (Coleoptera: Bruchidae). Males copulating for the sixth time in succession inflicted greater levels of genital damage, but transferred smaller ejaculates in comparison with virgin males. The number of copulations performed by males was negatively related to female fecundity and positively related to female longevity, suggesting a trade-off between fecundity and longevity. However, inclusion of fecundity as a covariate revealed sperm and/or seminal fluid transfer to have a negative impact on female longevity above that caused by the fecundity-longevity trade-off. The consequences of multiple copulations on female longevity were examined. Females that mated twice laid more eggs and died sooner than those that mated once. However, incorporation of fecundity as a covariate into our statistical model removed the effect of female mating frequency on female longevity, indicating that double-mated females suffer greater mortality owing to the trade-off between fecundity and longevity. Males of this species are known to transfer very large ejaculates (up to 8% of their body weight), which may represent a significant nutritional benefit to females. However, the receipt of large ejaculates appears to carry costs. Thus, the interpretation of multiple mating experiments on female longevity and associated functional explanations of polyandry in this species are likely to be complex.

What are the roles of calorie restriction and diet quality in promoting healthy longevity?

PubMed

Rizza, Wanda; Veronese, Nicola; Fontana, Luigi

2014-01-01

Epidemiological and experimental data indicate that diet plays a central role in the pathogenesis of many age-associated chronic diseases, and in the biology of aging itself. Data from several animal studies suggest that the degree and time of calorie restriction (CR) onset, the timing of food intake as well as diet composition, play major roles in promoting health and longevity, breaking the old dogma that only calorie intake is important in extending healthy lifespan. Data from human studies indicate that long-term CR with adequate intake of nutrients results in several metabolic adaptations that reduce the risk of developing type 2 diabetes, hypertension, cardiovascular disease and cancer. Moreover, CR opposes the expected age-associated alterations in myocardial stiffness, autonomic function, and gene expression in the human skeletal muscle. However, it is possible that some of the beneficial effects on metabolic health are not entirely due to CR, but to the high quality diets consumed by the CR practitioners, as suggested by data collected in individuals consuming strict vegan diets. More studies are needed to understand the interactions among single nutrient modifications (e.g. protein/aminoacid, fatty acids, vitamins, phytochemicals, and minerals), the degree of CR and the frequency of food consumption in modulating anti-aging metabolic and molecular pathways, and in the prevention of age-associated diseases. Copyright © 2013 Elsevier B.V. All rights reserved.

Human longevity is associated with regular sleep patterns, maintenance of slow wave sleep, and favorable lipid profile

PubMed Central

Mazzotti, Diego Robles; Guindalini, Camila; Moraes, Walter André dos Santos; Andersen, Monica Levy; Cendoroglo, Maysa Seabra; Ramos, Luiz Roberto; Tufik, Sergio

2014-01-01

Some individuals are able to successfully reach very old ages, reflecting higher adaptation against age-associated effects. Sleep is one of the processes deeply affected by aging; however few studies evaluating sleep in long-lived individuals (aged over 85) have been reported to date. The aim of this study was to characterize the sleep patterns and biochemical profile of oldest old individuals (N = 10, age 85–105 years old) and compare them to young adults (N = 15, age 20–30 years old) and older adults (N = 13, age 60–70 years old). All subjects underwent full-night polysomnography, 1-week of actigraphic recording and peripheral blood collection. Sleep electroencephalogram spectral analysis was also performed. The oldest old individuals showed lower sleep efficiency and REM sleep when compared to the older adults, while stage N3 percentage and delta power were similar across the groups. Oldest old individuals maintained strictly regular sleep-wake schedules and also presented higher HDL-cholesterol and lower triglyceride levels than older adults. The present study revealed novel data regarding specific sleep patterns and maintenance of slow wave sleep in the oldest old group. Taken together with the favorable lipid profile, these results contribute with evidence to the importance of sleep and lipid metabolism regulation in the maintenance of longevity in humans. PMID:25009494

Is Older Colder or Colder Older? The Association of Age With Body Temperature in 18,630 Individuals

PubMed Central

Buxbaum, Joel N.

2011-01-01

In animal studies, caloric restriction resulting in increased longevity is associated with a reduction in body temperature, which is strain specific and likely under genetic control. Small studies in humans have suggested that temperatures may be lower among elderly populations, usually attributed to loss of thermoregulation. We analyzed cross-sectional data from 18,630 white adults aged 20–98 years (mean 58.3 years) who underwent oral temperature measurement as part of a standardized health appraisal at a large U.S. health maintenance organization. Overall, women had higher mean temperatures (97.5 ± 1.2°F) than men (97.2 ± 1.1°F; p < .0001). Mean temperature decreased with age, with a difference of 0.3°F between oldest and youngest groups after controlling for sex, body mass index, and white blood cell count. The results are consistent with low body temperature as a biomarker for longevity. Prospective studies are needed to confirm whether this represents a survival advantage associated with lifetime low steady state temperature. PMID:21324956

Demographics, phenotypic health characteristics and genetic analysis of centenarians in China.

PubMed

Zeng, Yi; Feng, Qiushi; Gu, Danan; Vaupel, James W

2017-07-01

After a brief introduction to the background, significance and unique features of the centenarian population in China, we describe the Chinese Longitudinal Healthy Longevity Study (CLHLS), which is the world's largest study of centenarians, nonagenarians, octogenarians, and compatible young-old aged 65-79. Based on the CLHLS data and other relevant studies, we summarize demographic and socioeconomic characteristics as well as self-reported and objectively-tested health indicators of centenarians in China, with an emphasis on gender differences and rural/urban disparities. We then compare five-year-age-specific trajectories of physical and cognitive functions, self-reported health, and life satisfactions from ages 65-69 to 100+, concluding that good psychological resilience and optimism are keys to the exceptional longevity enjoyed by centenarians. We discuss recent findings of novel loci and pathways that are significantly associated with longevity based on the genome-wide association study (GWAS) of the CLHLS centenarian sample, which is 2.7 times as large as prior GWAS of longevity. We also highlight colleagues' and our own studies on longevity candidate genes and gene-environment interaction analyses. Finally, we discuss limitations inherent in our studies of centenarians in China and further research perspectives. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

77 FR 40368 - National Institute on Aging; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-09

... personal privacy. Name of Committee: National Institute on Aging Special Emphasis Panel Age, Gene..., Genes and Longevity in Humans. Date: July 27, 2012. Time: 12:30 p.m. to 4 p.m. Agenda: To review and...

Associations of triglyceride levels with longevity and frailty: A Mendelian randomization analysis

PubMed Central

Liu, Zuyun; Burgess, Stephen; Wang, Zhengdong; Deng, Wan; Chu, Xuefeng; Cai, Jian; Zhu, Yinsheng; Shi, Jianming; Xie, Xuejuan; Wang, Yong; Jin, Li; Wang, Xiaofeng

2017-01-01

Observational studies suggest associations of triglyceride levels with longevity and frailty. This study aimed to test whether the associations are causal. We used data from the Rugao Longevity and Ageing Study, a population-based cohort study performed in Rugao, China. A variant in the APOA5 gene region (rs662799) was used as the genetic instrument. Mendelian randomization (MR) analyses were performed to examine the associations of genetically predicted triglycerides with two ageing phenotypes – longevity ( ≥95 years) and frailty (modified Fried frailty phenotype and Rockwood frailty index). C allele of rs662799 was robustly associated with higher triglyceride levels in the comparison group (β = 0.301 mmol/L per allele, p < 0.001), with an F statistic of 95.3 and R2 = 0.040. However MR analysis did not provide strong evidence for an association between genetically predicted triglyceride levels and probability of longevity (OR: 0.61; 95% CI: 0.35, 1.07 per 1 mmol/L increase in triglycerides). In the ageing arm (70–84 years), genetically predicted triglyceride levels were not associated with the frailty index (β = 0.008; 95% CI: −0.013, 0.029) or the frailty phenotype (OR: 1.91; 95% CI: 0.84, 4.37). In conclusion, there is currently a lack of sufficient evidence to support causal associations of triglyceride levels with longevity and frailty in elderly populations. PMID:28134330

No Association between Variation in Longevity Candidate Genes and Aging-related Phenotypes in Oldest-old Danes.

PubMed

Soerensen, Mette; Nygaard, Marianne; Debrabant, Birgit; Mengel-From, Jonas; Dato, Serena; Thinggaard, Mikael; Christensen, Kaare; Christiansen, Lene

2016-06-01

In this study we explored the association between aging-related phenotypes previously reported to predict survival in old age and variation in 77 genes from the DNA repair pathway, 32 genes from the growth hormone 1/ insulin-like growth factor 1/insulin (GH/IGF-1/INS) signalling pathway and 16 additional genes repeatedly considered as candidates for human longevity: APOE, APOA4, APOC3, ACE, CETP, HFE, IL6, IL6R, MTHFR, TGFB1, SIRTs 1, 3, 6; and HSPAs 1A, 1L, 14. Altogether, 1,049 single nucleotide polymorphisms (SNPs) were genotyped in 1,088 oldest-old (age 92-93 years) Danes and analysed with phenotype data on physical functioning (hand grip strength), cognitive functioning (mini mental state examination and a cognitive composite score), activity of daily living and self-rated health. Five SNPs showed association to one of the phenotypes; however, none of these SNPs were associated with a change in the relevant phenotype over time (7 years of follow-up) and none of the SNPs could be confirmed in a replication sample of 1,281 oldest-old Danes (age 94-100). Hence, our study does not support association between common variation in the investigated longevity candidate genes and aging-related phenotypes consistently shown to predict survival. It is possible that larger sample sizes are needed to robustly reveal associations with small effect sizes. Copyright © 2016 Elsevier Inc. All rights reserved.

Does the degree of endocrine dyscrasia post-reproduction dictate post-reproductive lifespan? Lessons from semelparous and iteroparous species.

PubMed

Atwood, Craig S; Hayashi, Kentaro; Meethal, Sivan Vadakkadath; Gonzales, Tina; Bowen, Richard L

2017-02-01

Post-reproductive lifespan varies greatly among species; human post-reproductive lifespan comprises ~30-50% of their total longevity, while semelparous salmon and dasyurid marsupials post-reproductive lifespan comprises <4% of their total longevity. To examine if the magnitude of hypothalamic-pituitary-gonadal (HPG) axis dyscrasia at the time of reproductive senescence determines post-reproductive lifespan, we examined the difference between pre- and post-reproductive (1) circulating sex hormones and (2) the ratio of sex steroids to gonadotropins (e.g., 17β-estradiol/follicle-stimulating hormone (FSH)), an index of the dysregulation of the HPG axis and the level of dyotic (death) signaling post-reproduction. Animals with a shorter post-reproductive lifespan (<4% total longevity) had a more marked decline in circulating sex steroids and corresponding elevation in gonadotropins compared to animals with a longer post-reproductive lifespan (30-60% total longevity). In semelparous female salmon of short post-reproductive lifespan (1%), these divergent changes in circulating hormone concentration post-reproduction equated to a 711-fold decrease in the ratio of 17β-estradiol/FSH between the reproductive and post-reproductive periods. In contrast, the decrease in the ratio of 17β-estradiol/FSH in iteroparous female mammals with long post-reproductive lifespan was significantly less (1.7-34-fold) post-reproduction. Likewise, in male semelparous salmon, the decrease in the ratio of testosterone/FSH (82-fold) was considerably larger than for iteroparous species (1.3-11-fold). These results suggest that (1) organisms with greater reproductive endocrine dyscrasia more rapidly undergo senescence and die, and (2) the contribution post-reproduction by non-gonadal (and perhaps gonadal) tissues to circulating sex hormones dictates post-reproductive tissue health and longevity. In this way, reproduction and longevity are coupled, with the degree of non-gonadal tissue hormone production dictating the rate of somatic tissue demise post-reproduction and the differences in post-reproductive lifespans between species.

The longevity in the yeast Saccharomyces cerevisiae: A comparison of two approaches for assessment the lifespan.

PubMed

Molon, Mateusz; Zadrag-Tecza, Renata; Bilinski, Tomasz

2015-05-08

Longevity of the selected "longevity mutants" of yeast was studied using two methods. The standard method was based on counting the number of daughter cells produced. Modification of that method allowed for establishing the length of life expressed in units of time. It appeared that all the studied "deletion longevity mutants" showed a statistically meaningful increase in the number of daughters produced (replicative lifespan), whereas only one of the mutants, previously regarded as "short lived", showed a meaningful increase in the time of life. The analysis of the available data shows that the time of life of most yeast strains is similar irrespective of their genetic background and mutations, which suggests a quasi-programmed nature of yeast death. Copyright © 2015 Elsevier Inc. All rights reserved.

Innate immunity mediated longevity and longevity induced by germ cell removal converge on the C-type lectin domain protein IRG-7

PubMed Central

Yunger, Elad; Safra, Modi; Levi-Ferber, Mor; Haviv-Chesner, Anat

2017-01-01

In C. elegans, removal of the germline triggers molecular events in the neighboring intestine, which sends an anti-aging signal to the rest of the animal. In this study, we identified an innate immunity related gene, named irg-7, as a novel mediator of longevity in germlineless animals. We consider irg-7 to be an integral downstream component of the germline longevity pathway because its expression increases upon germ cell removal and its depletion interferes with the activation of the longevity-promoting transcription factors DAF-16 and DAF-12 in germlineless animals. Furthermore, irg-7 activation by itself sensitizes the animals' innate immune response and extends the lifespan of animals exposed to live bacteria. This lifespan-extending pathogen resistance relies on the somatic gonad as well as on many genes previously associated with the reproductive longevity pathway. This suggests that these genes are also relevant in animals with an intact gonad, and can affect their resistance to pathogens. Altogether, this study demonstrates the tight association between germline homeostasis and the immune response of animals, and raises the possibility that the reproductive system can act as a signaling center to divert resources towards defending against putative pathogen attacks. PMID:28196094

Transgenerational programming of longevity and reproduction by post-eclosion dietary manipulation in Drosophila

PubMed Central

Xia, Brian; de Belle, Steven

2016-01-01

Accumulating evidence suggests that early-life diet may program one's health status by causing permanent alternations in specific organs, tissues, or metabolic or homeostatic pathways, and such programming effects may propagate across generations through heritable epigenetic modifications. However, it remains uninvestigated whether postnatal dietary changes may program longevity across generations. To address this question of important biological and public health implications, newly-born flies (F0) were collected and subjected to various post-eclosion dietary manipulations (PDMs) with different protein-carbohydrate (i.e., LP, IP or HP for low-, intermediate- or high-protein) contents or a control diet (CD). Longevity and fecundity analyses were performed with these treated F0 flies and their F1, F2 and F3 offspring, while maintained on CD at all times. The LP and HP PDMs shortened longevity, while the IP PDM extended longevity significantly up to the F3 generation. Furthermore, the LP reduced while the IP PDM increased lifetime fecundity across the F0-F2 generations. Our observations establish the first animal model for studying transgenerational inheritance of nutritional programming of longevity, making it possible to investigate the underlying epigenetic mechanisms and identify gene targets for drug discovery in future studies. PMID:27025190

Uneven futures of human lifespans: reckonings from Gompertz mortality rates, climate change, and air pollution.

PubMed

Finch, Caleb E; Beltrán-Sánchez, Hiram; Crimmins, Eileen M

2014-01-01

The past 200 years have enabled remarkable increases in human lifespans through improvements in the living environment that have nearly eliminated infections as a cause of death through improved hygiene, public health, medicine, and nutrition. We argue that the limit to lifespan may be approaching. Since 1997, no one has exceeded Jeanne Calment's record of 122.5 years, despite an exponential increase of centenarians. Moreover, the background mortality may be approaching a lower limit. We calculate from Gompertz coefficients that further increases in longevity to approach a life expectancy of 100 years in 21st century cohorts would require 50% slower mortality rate accelerations, which would be a fundamental change in the rate of human aging. Looking into the 21st century, we see further challenges to health and longevity from the continued burning of fossil fuels that contribute to air pollution as well as global warming. Besides increased heat waves to which elderly are vulnerable, global warming is anticipated to increase ozone levels and facilitate the spread of pathogens. We anticipate continuing socioeconomic disparities in life expectancy.

Mondo complexes regulate TFEB via TOR inhibition to promote longevity in response to gonadal signals

PubMed Central

Nakamura, Shuhei; Karalay, Özlem; Jäger, Philipp S.; Horikawa, Makoto; Klein, Corinna; Nakamura, Kayo; Latza, Christian; Templer, Sven E.; Dieterich, Christoph; Antebi, Adam

2016-01-01

Germline removal provokes longevity in several species and shifts resources towards survival and repair. Several Caenorhabditis elegans transcription factors regulate longevity arising from germline removal; yet, how they work together is unknown. Here we identify a Myc-like HLH transcription factor network comprised of Mondo/Max-like complex (MML-1/MXL-2) to be required for longevity induced by germline removal, as well as by reduced TOR, insulin/IGF signalling and mitochondrial function. Germline removal increases MML-1 nuclear accumulation and activity. Surprisingly, MML-1 regulates nuclear localization and activity of HLH-30/TFEB, a convergent regulator of autophagy, lysosome biogenesis and longevity, by downregulating TOR signalling via LARS-1/leucyl-transfer RNA synthase. HLH-30 also upregulates MML-1 upon germline removal. Mammalian MondoA/B and TFEB show similar mutual regulation. MML-1/MXL-2 and HLH-30 transcriptomes show both shared and preferential outputs including MDL-1/MAD-like HLH factor required for longevity. These studies reveal how an extensive interdependent HLH transcription factor network distributes responsibility and mutually enforces states geared towards reproduction or survival. PMID:27001890

Positive emotion word use and longevity in famous deceased psychologists.

PubMed

Pressman, Sarah D; Cohen, Sheldon

2012-05-01

This study examined whether specific types of positive and negative emotional words used in the autobiographies of well-known deceased psychologists were associated with longevity. For each of the 88 psychologists, the percent of emotional words used in writing was calculated and categorized by valence (positive or negative) and arousal (activated [e.g., lively, anxious] or not activated [e.g., calm, drowsy]) based on existing emotion scales and models of emotion categorization. After controlling for sex, year of publication, health (based on disclosed illness in autobiography), native language, and year of birth, the use of more activated positive emotional words (e.g., lively, vigorous, attentive, humorous) was associated with increased longevity. Negative terms (e.g., angry, afraid, drowsy, sluggish) and unactivated positive terms (e.g., peaceful, calm) were not related to longevity. The association of activated positive emotions with longevity was also independent of words indicative of social integration, optimism, and the other affect/activation categories. Results indicate that in writing, not every type of emotion correlates with longevity and that there may be value to considering different categories beyond emotional valence in health relevant outcomes.

Inequalities of Income and Inequalities of Longevity: A Cross-Country Study

PubMed Central

Plümper, Thomas

2016-01-01

Objectives. We examined the effects of market income inequality (income inequality before taxes and transfers) and income redistribution via taxes and transfers on inequality in longevity. Methods. We used life tables to compute Gini coefficients of longevity inequality for all individuals and for individuals who survived to at least 10 years of age. We regressed longevity inequality on market income inequality and income redistribution, and we controlled for potential confounders, in a cross-sectional time-series sample of up to 28 predominantly Western developed countries and up to 37 years (1974–2011). Results. Income inequality before taxes and transfers was positively associated with inequality in the number of years lived; income redistribution (the difference between market income inequality and income inequality after taxes and transfers were accounted for) was negatively associated with longevity inequality. Conclusions. To the extent that our estimated effects derived from observational data are causal, governments can reduce longevity inequality not only via public health policies, but also via their influence on market income inequality and the redistribution of incomes from the relatively rich to the relatively poor. PMID:26562120

Topics on distance correlation, feature screening and lifetime expectancy with application to Beaver Dam eye study data

NASA Astrophysics Data System (ADS)

Kong, Jing

This thesis includes 4 pieces of work. In Chapter 1, we present the work with a method for examining mortality as it is seen to run in families, and lifestyle factors that are also seen to run in families, in a subpopulation of the Beaver Dam Eye Study that has died by 2011. We find significant distance correlations between death ages, lifestyle factors, and family relationships. Considering only sib pairs compared to unrelated persons, distance correlation between siblings and mortality is, not surprisingly, stronger than that between more distantly related family members and mortality. Chapter 2 introduces a feature screening procedure with the use of distance correlation and covariance. We demonstrate a property for distance covariance, which is incorporated in a novel feature screening procedure based on distance correlation as a stopping criterion. The approach is further implemented to two real examples, namely the famous small round blue cell tumors data and the Cancer Genome Atlas ovarian cancer data Chapter 3 pays attention to the right censored human longevity data and the estimation of lifetime expectancy. We propose a general framework of backward multiple imputation for estimating the conditional lifetime expectancy function and the variance of the estimator in the right censoring setting and prove the properties of the estimator. In addition, we apply the method to the Beaver Dam eye study data to study human longevity, where the expected human lifetime are modeled with smoothing spline ANOVA based on the covariates including baseline age, gender, lifestyle factors and disease variables. Chapter 4 compares two imputation methods for right censored data, namely the famous Buckley-James estimator and the backward imputation method proposed in Chapter 3 and shows that backward imputation method is less biased and more robust with heterogeneity.

Predictors of the Longevity Difference: A 25-Year Follow-Up.

ERIC Educational Resources Information Center

Palmore, Erdman B.

1982-01-01

Studied predictors of longevity among 252 panelists in a 25-year longitudinal study of aging. The strongest independent predictors for men were health self-rating, work satisfaction, and performance intelligence; for women they were health satisfaction, and physical function rating. (Author)

The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy.

PubMed

McCarty, Mark F; Barroso-Aranda, Jorge; Contreras, Francisco

2009-02-01

Recent studies confirm that dietary methionine restriction increases both mean and maximal lifespan in rats and mice, achieving "aging retardant" effects very similar to those of caloric restriction, including a suppression of mitochondrial superoxide generation. Although voluntary caloric restriction is never likely to gain much popularity as a pro-longevity strategy for humans, it may be more feasible to achieve moderate methionine restriction, in light of the fact that vegan diets tend to be relatively low in this amino acid. Plant proteins - especially those derived from legumes or nuts - tend to be lower in methionine than animal proteins. Furthermore, the total protein content of vegan diets, as a function of calorie content, tends to be lower than that of omnivore diets, and plant protein has somewhat lower bioavailability than animal protein. Whole-food vegan diets that moderate bean and soy intake, while including ample amounts of fruit and wine or beer, can be quite low in methionine, while supplying abundant nutrition for health (assuming concurrent B12 supplementation). Furthermore, low-fat vegan diets, coupled with exercise training, can be expected to promote longevity by decreasing systemic levels of insulin and free IGF-I; the latter effect would be amplified by methionine restriction - though it is not clear whether IGF-I down-regulation is the sole basis for the impact of low-methionine diets on longevity in rodents.

Gender, aging and longevity in humans: an update of an intriguing/neglected scenario paving the way to a gender-specific medicine.

PubMed

Ostan, Rita; Monti, Daniela; Gueresi, Paola; Bussolotto, Mauro; Franceschi, Claudio; Baggio, Giovannella

2016-10-01

Data showing a remarkable gender difference in life expectancy and mortality, including survival to extreme age, are reviewed starting from clinical and demographic data and stressing the importance of a comprehensive historical perspective and a gene-environment/lifestyle interaction. Gender difference regarding prevalence and incidence of the most important age-related diseases, such as cardiovascular and neurodegenerative diseases, cancer, Type 2 diabetes, disability, autoimmunity and infections, are reviewed and updated with particular attention to the role of the immune system and immunosenescence. On the whole, gender differences appear to be pervasive and still poorly considered and investigated despite their biomedical relevance. The basic biological mechanisms responsible for gender differences in aging and longevity are quite complex and still poorly understood. The present review focuses on centenarians and their offspring as a model of healthy aging and summarizes available knowledge on three basic biological phenomena, i.e. age-related X chromosome inactivation skewing, gut microbiome changes and maternally inherited mitochondrial DNA genetic variants. In conclusion, an appropriate gender-specific medicine approach is urgently needed and should be systematically pursued in studies on healthy aging, longevity and age-related diseases, in a globalized world characterized by great gender differences which have a high impact on health and diseases. © 2016 The Author(s).

Transcription factors CEP-1/p53 and CEH-23 collaborate with AAK-2/AMPK to modulate longevity in Caenorhabditis elegans.

PubMed

Chang, Hsin-Wen; Pisano, Steve; Chaturbedi, Amaresh; Chen, Jennifer; Gordon, Sarah; Baruah, Aiswarya; Lee, Siu Sylvia

2017-08-01

A decline in mitochondrial electron transport chain (ETC) function has long been implicated in aging and various diseases. Recently, moderate mitochondrial ETC dysfunction has been found to prolong lifespan in diverse organisms, suggesting a conserved and complex role of mitochondria in longevity determination. Several nuclear transcription factors have been demonstrated to mediate the lifespan extension effect associated with partial impairment of the ETC, suggesting that compensatory transcriptional response to be crucial. In this study, we showed that the transcription factors CEP-1/p53 and CEH-23 act through a similar mechanism to modulate longevity in response to defective ETC in Caenorhabditis elegans. Genomewide gene expression profiling comparison revealed a new link between these two transcription factors and AAK-2/AMP kinase (AMPK) signaling. Further functional analyses suggested that CEP-1/p53 and CEH-23 act downstream of AAK-2/AMPK signaling and CRTC-1 transcriptional coactivator to promote stress resistance and lifespan. As AAK-2, CEP-1, and CEH-23 are all highly conserved, our findings likely provide important insights for understanding the organismal adaptive response to mitochondrial dysfunction in diverse organisms and will be relevant to aging and pathologies with a mitochondrial etiology in human. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Exceptional Longevity: An Introduction to the Iowa Centenarian Study

ERIC Educational Resources Information Center

Martin, Peter; Deshpande-Kamat, Neha; Margrett, Jennifer A.; Franke, Warren; Garasky, Steven

2012-01-01

The primary objective of the Iowa Centenarian Study is to further our understanding of determinants of exceptional longevity above and beyond health outcomes, particularly in rural environments. This introductory article provides a general overview of the study, its methodology and basic descriptive results. One hundred and fifty-two centenarians…

Molecular characterization of the acquisition of longevity during seed maturation in soybean

PubMed Central

Lalanne, David; Rossi, Rubiana Falopa; Pelletier, Sandra; da Silva, Edvaldo Aparecido Amaral

2017-01-01

Seed longevity, defined as the ability to remain alive during storage, is an important agronomic factor. Poor longevity negatively impacts seedling establishment and consequently crop yield. This is particularly problematic for soybean as seeds have a short lifespan. While the economic importance of soybean has fueled a large number of transcriptome studies during embryogenesis and seed filling, the mechanisms regulating seed longevity during late maturation remain poorly understood. Here, a detailed physiological and molecular characterization of late seed maturation was performed in soybean to obtain a comprehensive overview of the regulatory genes that are potentially involved in longevity. Longevity appeared at physiological maturity at the end of seed filling before maturation drying and progressively doubled until the seeds reached the dry state. The increase in longevity was associated with the expression of genes encoding protective chaperones such as heat shock proteins and the repression of nuclear and chloroplast genes involved in a range of chloroplast activities, including photosynthesis. An increase in the raffinose family oligosaccharides (RFO)/sucrose ratio together with changes in RFO metabolism genes was also associated with longevity. A gene co-expression network analysis revealed 27 transcription factors whose expression profiles were highly correlated with longevity. Eight of them were previously identified in the longevity network of Medicago truncatula, including homologues of ERF110, HSF6AB, NFXL1 and members of the DREB2 family. The network also contained several transcription factors associated with auxin and developmental cell fate during flowering, organ growth and differentiation. A transcriptional transition occurred concomitant with seed chlorophyll loss and detachment from the mother plant, suggesting the activation of a post-abscission program. This transition was enriched with AP2/EREBP and WRKY transcription factors and genes associated with growth, germination and post-transcriptional processes, suggesting that this program prepares the seed for the dry quiescent state and germination. PMID:28700604

Analysis of implantable defibrillator longevity under clinical circumstances: implications for device selection.

PubMed

Knops, Paul; Theuns, Dominic A M J; Res, Jan C J; Jordaens, Luc

2009-10-01

Information about implantable cardioverter-defibrillator (ICD) longevity is mostly calculated from measurements under ideal laboratory conditions. However, little information about longevity under clinical circumstances is available. This survey gives an overview on ICD service times and generator replacements in a cohort of consecutive ICD patients. Indications for replacement were classified as a normal end-of-service (EOS), premature EOS, system malfunction, infection and device advisory, or recall actions. From the premature and normal EOS group, longevity from single-chamber (SC), dual-chamber (DC), and cardiac resynchronization therapy defibrillator (CRT-D), rate-responsive (RR) settings, high output (HO) stimulation, and indication for ICD therapy was compared. Differences between brands were compared as well. In a total of 854 patients, 203 ICD replacements (165 patients) were recorded. Premature and normal EOS replacements consisted of 32 SC, 98 DC and 24 CRT-D systems. Longevity was significantly longer in SC systems compared to DC and CRT-D systems (54 +/- 19 vs. 40 +/- 17 and 42 +/- 15 months; P = 0.008). Longevity between non-RR (n = 143) and RR (n = 11) settings was not significantly different (43 +/- 18 vs. 45 +/- 13 months) as it also was not for HO versus non-HO stimulation (43 +/- 19 vs. 46 +/- 17 months). Longevity of ICDs was not significantly different between primary and secondary prevention (42 +/- 19 vs. 44 +/- 18 months). The average longevity on account of a device-based EOS message was 43 +/- 18 months. Average longevity for Biotronik (BIO, n = 72) was 33 +/- 10 months, for ELA Medical (ELA, n = 12) 44 +/- 17 months, for Guidant (GDT, n = 36) 49 +/- 12 months, for Medtronic (MDT, n = 29) 62 +/- 22 months, and for St. Jude Medical (SJM, n = 5) 31 +/- 9 months (P < 0.001). SC ICD generators had a longer service time compared to DC and CRT-D systems. No influence of indication for ICD therapy and HO stimulation on generator longevity was observed in this study. MDT ICDs had the longest service time.

Comparison of biochemical data, blood pressure and physical activity between longevity and non-longevity districts in Japan.

PubMed

Mori, Ichiro; Ishizuka, Tatsuo; Morita, Hiroyuki; Matsumoto, Masami; Uno, Yoshihiro; Kajita, Kazuo; Ikeda, Takahide; Fujioka, Kei; Matsubara, Kenji

2008-10-01

There is controversy about longevity-associated factors, including environmental and genetic factors. Clinical and epidemiological studies suggest that multiple risk factors decrease life-span, but there has not been a definitive report regarding the association of risk factors with longevity. The ultimate aim of the present study was to prevent the overwhelming increase in life-style-related diseases by evaluating this association in 2 districts in Japan. Plasma glucose levels, hemoglobin (Hb) A1c, lipids, dehydroepiandrosterone-sulfate, adiponectin and physical activity were examined in 133 subjects (M/F 47/86, 67+/-1 years) in Kokufu, a longevity district (mean life span: 80.4 years according to 2000 Japanese census) and 69 subjects (M/F 29/40, 62+/-1 years) in Miyama, a non-longevity district (mean life span 77.4 years, 2000 census). There were significant differences in systolic and diastolic blood pressures (BPs, p < 0.001), exercise capacity (p < 0.0001) and plasma adiponectin levels (p < 0.04) between the districts. Plasma adiponectin level was significantly correlated with high-density lipoprotein-cholesterol (HDL-C) (r = 0.333, p < 0.0001), triglyceride (TG) (r = -0.161, p < 0.04), HbA1c (r = -0.163, p < 0.03) and HOMA-R (r = -0.163, p < 0.03). Life-style-related factors such as BP, exercise capacity and plasma adiponectin levels might play an important role in longevity, and those of HDL-C and TG, as well as glucose tolerance, might be associated with adiponectin levels.

Lifestyle and nutrition related to male longevity in Sardinia: an ecological study.

PubMed

Pes, G M; Tolu, F; Poulain, M; Errigo, A; Masala, S; Pietrobelli, A; Battistini, N C; Maioli, M

2013-03-01

A demographic analysis in the Mediterranean island of Sardinia revealed marked differences in extreme longevity across the 377 municipalities and particularly identified a mountain inner area where the proportion of oldest subjects among male population has one of the highest validated value worldwide. The cause(s) of this unequal distribution of male longevity may be attributed to a concurrence of environmental, lifestyle and genetic factors. In this study we focussed on some lifestyle and nutrition variables recorded in the island's population in early decades of 20th century, when agricultural and pastoral economy was still prevalent, and try to verify through ecological spatial models if they may account for the variability in male longevity. By computing the Extreme Longevity Index (the proportion of newborns in a given municipality who reach age 100) the island's territory was divided in two areas with relatively higher and lower level of population longevity. Most nutritional variables do not show any significant difference between these two areas whereas a significant difference was found with respect to pastoralism (P = 0.0001), physical activity estimated by the average slope of the territory in each municipality (P = 0.0001), and average daily distance required by the active population to reach the usual workplace (P = 0.0001). Overall, these findings suggest that factors affecting the average energy expenditure of male population such as occupational activity and geographic characteristics of the area where the population mainly resides, are important in explaining the spatial variation of Sardinian extreme longevity. Copyright © 2011 Elsevier B.V. All rights reserved.

Effects of hierarchical features on longevity of submerged superhydrophobic surfaces with parallel grooves

NASA Astrophysics Data System (ADS)

Hemeda, A. A.; Gad-el-Hak, M.; Tafreshi, H. Vahedi

2014-08-01

While the air-water interface over superhydrophobic surfaces decorated with hierarchical micro- or nanosized geometrical features have shown improved stability under elevated pressures, their underwater longevity—-the time that it takes for the surface to transition to the Wenzel state—-has not been studied. The current work is devised to study the effects of such hierarchical features on the longevity of superhydrophobic surfaces. For the sake of simplicity, our study is limited to superhydrophobic surfaces composed of parallel grooves with side fins. The effects of fins on the critical pressure—-the pressure at which the surface starts transitioning to the Wenzel state—-and longevity are predicted using a mathematical approach based on the balance of forces across the air-water interface. Our results quantitatively demonstrate that the addition of hierarchical fins significantly improves the mechanical stability of the air-water interface, due to the high advancing contact angles that can be achieved when an interface comes in contact with the fins sharp corners. For longevity on the contrary, the hierarchical fins were only effective at hydrostatic pressures below the critical pressure of the original smooth-walled groove. Our results indicate that increasing the length of the fins decreases the critical pressure of a submerged superhydrophobic groove but increases its longevity. Increasing the thickness of the fins can improve both the critical pressure and longevity of a submerged groove. The mathematical framework presented in this paper can be used to custom-design superhydrophobic surfaces for different applications.

Vertebral Bomb Radiocarbon Suggests Extreme Longevity in White Sharks

PubMed Central

Hamady, Li Ling; Natanson, Lisa J.; Skomal, Gregory B.; Thorrold, Simon R.

2014-01-01

Conservation and management efforts for white sharks (Carcharodon carcharias) remain hampered by a lack of basic demographic information including age and growth rates. Sharks are typically aged by counting growth bands sequentially deposited in their vertebrae, but the assumption of annual deposition of these band pairs requires testing. We compared radiocarbon (Δ14C) values in vertebrae from four female and four male white sharks from the northwestern Atlantic Ocean (NWA) with reference chronologies documenting the marine uptake of 14C produced by atmospheric testing of thermonuclear devices to generate the first radiocarbon age estimates for adult white sharks. Age estimates were up to 40 years old for the largest female (fork length [FL]: 526 cm) and 73 years old for the largest male (FL: 493 cm). Our results dramatically extend the maximum age and longevity of white sharks compared to earlier studies, hint at possible sexual dimorphism in growth rates, and raise concerns that white shark populations are considerably more sensitive to human-induced mortality than previously thought. PMID:24416189

Vertebral bomb radiocarbon suggests extreme longevity in white sharks.

PubMed

Hamady, Li Ling; Natanson, Lisa J; Skomal, Gregory B; Thorrold, Simon R

2014-01-01

Conservation and management efforts for white sharks (Carcharodon carcharias) remain hampered by a lack of basic demographic information including age and growth rates. Sharks are typically aged by counting growth bands sequentially deposited in their vertebrae, but the assumption of annual deposition of these band pairs requires testing. We compared radiocarbon (Δ(14)C) values in vertebrae from four female and four male white sharks from the northwestern Atlantic Ocean (NWA) with reference chronologies documenting the marine uptake of (14)C produced by atmospheric testing of thermonuclear devices to generate the first radiocarbon age estimates for adult white sharks. Age estimates were up to 40 years old for the largest female (fork length [FL]: 526 cm) and 73 years old for the largest male (FL: 493 cm). Our results dramatically extend the maximum age and longevity of white sharks compared to earlier studies, hint at possible sexual dimorphism in growth rates, and raise concerns that white shark populations are considerably more sensitive to human-induced mortality than previously thought.

"Real life" longevity of implantable cardioverter-defibrillator devices.

PubMed

Manolis, Antonis S; Maounis, Themistoklis; Koulouris, Spyridon; Vassilikos, Vassilios

2017-09-01

Manufacturers of implantable cardioverter-defibrillators (ICDs) promise a 5- to 9-year projected longevity; however, real-life data indicate otherwise. The aim of the present study was to assess ICD longevity among 685 consecutive patients over the last 20 years. Real-life longevity of ICDs may differ from that stated by the manufacturers. The study included 601 men and 84 women (mean age, 63.1 ± 13.3 years). The underlying disease was coronary (n = 396) or valvular (n = 15) disease, cardiomyopathy (n = 220), or electrical disease (n = 54). The mean ejection fraction was 35%. Devices were implanted for secondary (n = 562) or primary (n = 123) prevention. Single- (n = 292) or dual-chamber (n = 269) or cardiac resynchronization therapy (CRT) devices (n = 124) were implanted in the abdomen (n = 17) or chest (n = 668). Over 20 years, ICD pulse generator replacements were performed in 238 patients (209 men; age 63.7 ± 13.9 years; ejection fraction, 37.7% ± 14.0%) who had an ICD for secondary (n = 210) or primary (n = 28) prevention. The mean ICD longevity was 58.3 ± 18.7 months. In 20 (8.4%) patients, devices exhibited premature battery depletion within 36 months. Most (94%) patients had none, minor, or modest use of ICD therapy. Longevity was longest for single-chamber devices and shortest for CRT devices. Latest-generation devices replaced over the second decade lasted longer compared with devices replaced during the first decade. When analyzed by manufacturer, Medtronic devices appeared to have longer longevity by 13 to 18 months. ICDs continue to have limited longevity of 4.9 ± 1.6 years, and 8% demonstrate premature battery depletion by 3 years. CRT devices have the shortest longevity (mean, 3.8 years) by 13 to 17 months, compared with other ICD devices. These findings have important implications, particularly in view of the high expense involved with this type of electrical therapy. © 2017 Wiley Periodicals, Inc.

The effect of caloric restriction and glycemic load on measures of oxidative stress and antioxidants in humans: results from the calerie trial of human caloric restriction

USDA-ARS?s Scientific Manuscript database

Reducing oxidative stress and increasing antioxidant defense is suggested as one mechanism by which caloric restriction (CR) increases longevity in animals. A total of 46 moderately overweight volunteers (BMI: 25-30 kg/m2), ages 20-42 yr were randomized to either high glycemic (HG) or low glycemic ...

Health and life style-related determinants of survival rate in the male residents of the city of Łódź.

PubMed

Smigielski, Janusz; Bielecki, Wojciech; Drygas, Wojciech

2013-06-01

The article presents a selected part of an analysis of health- and lifestyle-related determinants of the longevity of male residents of the city of Łódź. The WHO strategy for the European region assumes that the term' lifestyle' refers to the way of life based on the association between conditions of life understood in a broad sense and individual patterns of behaviour determined by socio-cultural factors and individual features. On this basis, the aim of this study is to identify the multiple statistical relationships on the mortality of men living in Łódź, particularly the influence of the following variables on the probability of survival: age, subjective health assessment, nutritional habits, alcohol consumption and tobacco smoking. The study sample (1004 respondents) was selected, and the study was carried out, based on the standards of the CINDI WHO Programme. The investigations included socio-demographic data, health status, lifestyle and anthropometric measurements. From the results of the first-study performed in Poland of the longevity of men with identified risk factors of cardiovascular diseases, it has been found that: 1) Tobacco smoking has a negative influence on male longevity; 2) Alcohol consumed in moderate amounts favours male longevity; 3) The level of physical activity observed among the studied men was too low to affect longevity; 4) A diet rich in fish and consumption of yellow cheese are positive predictors of longevity, while additional use of table salt at meals and consumption of sweets (cakes) are negative ones. Risky lifestyles and a reluctance to abandon them are responsible for a shorter lifespan among men in Poland. Reducing this difference between women and men is a real challenge for public health professionals and preventive medicine specialists.

A prospective study of associations among helping, health, and longevity.

PubMed

Hilbrand, Sonja; Coall, David A; Meyer, Andrea H; Gerstorf, Denis; Hertwig, Ralph

2017-08-01

How does helping behavior contribute to the health and the longevity of older helpers? From an evolutionary perspective, the ultimate cause may be rooted in ancestral parenting and grandparenting. These activities may have generalized to a neural and hormonal caregiving system that also enabled prosocial behavior beyond the family. From a psychological perspective, helping others may be associated with healthy aging, which, in turn, contributes to longevity as a proximate cause. Yet little is known about the extent to which mediating factors such as the health benefits of helping behaviors translate into enhanced longevity, particularly in regard to grandparenting. To fill this gap, we conducted mediation analyses (structural equation models) to examine whether grandparenting and supporting others in the social network contributed directly or indirectly (through better health 5-6 years later) to the longevity of older helpers. We drew on longitudinal data from the Berlin Aging Study (N = 516), in which older adults in Berlin, Germany, were interviewed at baseline (1990-1993, mean age at entry = 85 years) and continuously followed up until 2009. Results suggest that the associations of both grandparenting and supporting others with enhanced longevity are mediated by better prospective health (indirect effect). The effect of helping was not fully mediated, however-helping was also directly associated with increased longevity independently of the health indicators measured. The results were robust against effects of the helper's preexisting health status and sociodemographic characteristics of participants, their children, and grandchildren. We conclude that better prospective health contributes to the link between helping and longevity, but does not fully account for it. Other potential contributing mechanisms remain to be identified. As populations age across the globe, identifying mechanisms that foster health in old age can help to highlight potential targets for public health interventions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ages at menarche and menopause and reproductive lifespan as predictors of exceptional longevity in women: the Women's Health Initiative.

PubMed

Shadyab, Aladdin H; Macera, Caroline A; Shaffer, Richard A; Jain, Sonia; Gallo, Linda C; Gass, Margery L S; Waring, Molly E; Stefanick, Marcia L; LaCroix, Andrea Z

2017-01-01

The aim of the present study was to investigate associations between reproductive factors and survival to age 90 years. This was a prospective study of postmenopausal women from the Women's Health Initiative recruited from 1993 to 1998 and followed until the last outcomes evaluation on August 29, 2014. Participants included 16,251 women born on or before August 29, 1924 for whom survival to age 90 during follow-up was ascertained. Women were classified as having survived to age 90 (exceptional longevity) or died before age 90. Multivariable logistic regression models were used to evaluate associations of ages at menarche and menopause (natural or surgical) and reproductive lifespan with longevity, adjusting for demographic, lifestyle, and reproductive characteristics. Participants were on average aged 74.7 years (range, 69-81 y) at baseline. Of 16,251 women, 8,892 (55%) survived to age 90. Women aged at least 12 years at menarche had modestly increased odds of longevity (odds ratio [OR], 1.09; 95% CI, 1.00-1.19). There was a significant trend toward increased longevity for later age at menopause (natural or surgical; Ptrend = 0.01), with ORs (95% CIs) of 1.19 (1.04-1.36) and 1.18 (1.02-1.36) for 50 to 54 and at least 55 compared with less than 40 years, respectively. Later age at natural menopause as a separate exposure was also significantly associated with increased longevity (Ptrend = 0.02). Longer reproductive lifespan was significantly associated with increased longevity (Ptrend = 0.008). The odds of longevity were 13% (OR 1.13; 95% CI, 1.03-1.25) higher in women with more than 40 compared with less than 33 reproductive years. Reproductive characteristics were associated with late-age survival in older women.

Estimation of the effects of multipoint pacing on battery longevity in routine clinical practice.

PubMed

Akerström, Finn; Narváez, Irene; Puchol, Alberto; Pachón, Marta; Martín-Sierra, Cristina; Rodríguez-Mañero, Moisés; Rodríguez-Padial, Luis; Arias, Miguel A

2017-09-23

Multipoint pacing (MPP) permits simultaneous multisite pacing of the left ventricle (LV); initial studies suggest haemodynamic and clinical benefits over conventional (single LV site) cardiac resynchronization therapy (CRT). The aim of this study was to estimate the impact of MPP activation on battery longevity in routine clinical practice. Patient (n = 46) and device data were collected from two centres at least 3 months after MPP-CRT device implantation. Multipoint pacing programming was based on the maximal possible anatomical LV1/LV2 separation according to three predefined LV pacing capture threshold (PCT) cut-offs (≤1.5 V; ≤4.0 V; and ≤6.5 V). Estimated battery longevity was calculated using the programmed lower rate limit, lead impedances, outputs, and pacing percentages. Relative to the longevity for conventional CRT using the lowest PCT (8.9 ± 1.2 years), MPP activation significantly shortened battery longevity for all three PCT cut-offs (≤1.5 V, -5.6%; ≤4.0 V, -16.9%; ≤6.5 V, -21.3%; P's <0.001). When compared with conventional CRT based on longest right ventricle-LV delay (8.3 ± 1.3 years), battery longevity was significantly shortened for the MPP ≤ 4.0 V and ≤6.5 V cut-offs (-10.8 and -15.7%, respectively; P's <0.001). Maximal LV1/LV2 spacing was possible in 23.9% (≤1.5 V), 56.5% (≤4.0 V), and 69.6% (≤6.5 V) of patients. Multipoint pacing activation significantly reduces battery longevity compared with that for conventional CRT configuration. When reasonable MPP LV vector PCTs (≤4.0 V) are achieved, the decrease in battery longevity is relatively small which may prompt the clinician to activate MPP. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

The lysosomal membrane protein SCAV-3 maintains lysosome integrity and adult longevity

PubMed Central

Li, Yuan; Chen, Baohui; Zou, Wei; Wang, Xin; Wu, Yanwei; Zhao, Dongfeng; Sun, Yanan; Liu, Yubing

2016-01-01

Lysosomes degrade macromolecules and recycle metabolites as well as being involved in diverse processes that regulate cellular homeostasis. The lysosome is limited by a single phospholipid bilayer that forms a barrier to separate the potent luminal hydrolases from other cellular constituents, thus protecting the latter from unwanted degradation. The mechanisms that maintain lysosomal membrane integrity remain unknown. Here, we identified SCAV-3, the Caenorhabditis elegans homologue of human LIMP-2, as a key regulator of lysosome integrity, motility, and dynamics. Loss of scav-3 caused rupture of lysosome membranes and significantly shortened lifespan. Both of these phenotypes were suppressed by reinforced expression of LMP-1 or LMP-2, the C. elegans LAMPs, indicating that longevity requires maintenance of lysosome integrity. Remarkably, reduction in insulin/insulin-like growth factor 1 (IGF-1) signaling suppressed lysosomal damage and extended the lifespan in scav-3(lf) animals in a DAF-16–dependent manner. Our data reveal that SCAV-3 is essential for preserving lysosomal membrane stability and that modulation of lysosome integrity by the insulin/IGF-1 signaling pathway affects longevity. PMID:27810910

Physical activity and telomere biology: exploring the link with aging-related disease prevention.

PubMed

Ludlow, Andrew T; Roth, Stephen M

2011-02-21

Physical activity is associated with reduced risk of several age-related diseases as well as with increased longevity in both rodents and humans. Though these associations are well established, evidence of the molecular and cellular factors associated with reduced disease risk and increased longevity resulting from physical activity is sparse. A long-standing hypothesis of aging is the telomere hypothesis: as a cell divides, telomeres shorten resulting eventually in replicative senescence and an aged phenotype. Several reports have recently associated telomeres and telomere-related proteins to diseases associated with physical inactivity and aging including cardiovascular disease, insulin resistance, and hypertension. Interestingly several reports have also shown that longer telomeres are associated with higher physical activity levels, indicating a potential mechanistic link between physical activity, reduced age-related disease risk, and longevity. The primary purpose of this review is to discuss the potential importance of physical activity in telomere biology in the context of inactivity- and age-related diseases. A secondary purpose is to explore potential mechanisms and important avenues for future research in the field of telomeres and diseases associated with physical inactivity and aging.

Novel treatment strategies for chronic kidney disease: insights from the animal kingdom.

PubMed

Stenvinkel, Peter; Painer, Johanna; Kuro-O, Makoto; Lanaspa, Miguel; Arnold, Walter; Ruf, Thomas; Shiels, Paul G; Johnson, Richard J

2018-04-01

Many of the >2 million animal species that inhabit Earth have developed survival mechanisms that aid in the prevention of obesity, kidney disease, starvation, dehydration and vascular ageing; however, some animals remain susceptible to these complications. Domestic and captive wild felids, for example, show susceptibility to chronic kidney disease (CKD), potentially linked to the high protein intake of these animals. By contrast, naked mole rats are a model of longevity and are protected from extreme environmental conditions through mechanisms that provide resistance to oxidative stress. Biomimetic studies suggest that the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) offers protection in extreme environmental conditions and promotes longevity in the animal kingdom. Similarly, during months of fasting, immobilization and anuria, hibernating bears are protected from muscle wasting, azotaemia, thrombotic complications, organ damage and osteoporosis - features that are often associated with CKD. Improved understanding of the susceptibility and protective mechanisms of these animals and others could provide insights into novel strategies to prevent and treat several human diseases, such as CKD and ageing-associated complications. An integrated collaboration between nephrologists and experts from other fields, such as veterinarians, zoologists, biologists, anthropologists and ecologists, could introduce a novel approach for improving human health and help nephrologists to find novel treatment strategies for CKD.

Impact of nutrition on the ageing process.

PubMed

Mathers, John C

2015-01-01

Human life expectancy has been increasing steadily for almost two centuries and is now approximately double what it was at the beginning of the Victorian era. This remarkable demographic change has been accompanied by a shift in disease prevalence so that age is now the major determinant of most common diseases. The challenge is to enhance healthy ageing and to reduce the financial and social burdens associated with chronic ill health in later life. Studies in model organisms have demonstrated that the ageing phenotype arises because of the accumulation of macromolecular damage within the cell and that the ageing process is plastic. Nutritional interventions that reduce such damage, or which enhance the organism's capacity to repair damage, lead to greater longevity and to reduced risk of age-related diseases. Dietary (energy) restriction increases lifespan in several model organisms, but it is uncertain whether it is effective in primates, including humans. However, excess energy storage leading to increased adiposity is a risk factor for premature mortality and for age-related diseases so that obesity prevention is likely to be a major public health route to healthy ageing. In addition, adherence to healthy eating patterns, such as the Mediterranean dietary pattern, is associated with longevity and reduced risk of age-related diseases.

The association between adult mortality risk and family history of longevity: the moderating effects of socioeconomic status.

PubMed

Temby, Owen F; Smith, Ken R

2014-11-01

Studies consistently show that increasing levels of socioeconomic status (SES) and having a familial history of longevity reduce the risk of mortality. But do these two variables interact, such that individuals with lower levels of SES, for example, may experience an attenuated longevity penalty by virtue of having long-lived relatives? This article examines this interaction by analysing survival past age 40 based on data from the Utah Population Database on an extinct cohort of men born from the years 1840 to 1909. Cox proportional hazards regression and logistic regression are used to test for the main and interaction mortality effects of SES and familial excess longevity (FEL), a summary measure of an individual's history of longevity among his or her relatives. This research finds that the mortality hazard rate for men in the top 15th percentile of occupational status decreases more as FEL increases than it does among men in the bottom 15th percentile. In addition, the mortality hazard rate among farmers decreases more as FEL increases than it does for non-farmers. With a strong family history of longevity as a proxy for a genetic predisposition, this research suggests that a gene-environment interaction occurs whereby the benefits of familial excess longevity are more available to those who have occupations with more autonomy and greater economic resources and/or opportunities for physical activity.

Aging in the natural world: comparative data reveal similar mortality patterns across primates.

PubMed

Bronikowski, Anne M; Altmann, Jeanne; Brockman, Diane K; Cords, Marina; Fedigan, Linda M; Pusey, Anne; Stoinski, Tara; Morris, William F; Strier, Karen B; Alberts, Susan C

2011-03-11

Human senescence patterns-late onset of mortality increase, slow mortality acceleration, and exceptional longevity-are often described as unique in the animal world. Using an individual-based data set from longitudinal studies of wild populations of seven primate species, we show that contrary to assumptions of human uniqueness, human senescence falls within the primate continuum of aging; the tendency for males to have shorter life spans and higher age-specific mortality than females throughout much of adulthood is a common feature in many, but not all, primates; and the aging profiles of primate species do not reflect phylogenetic position. These findings suggest that mortality patterns in primates are shaped by local selective forces rather than phylogenetic history.

Cell culture-based profiling across mammals reveals DNA repair and metabolism as determinants of species longevity.

PubMed

Ma, Siming; Upneja, Akhil; Galecki, Andrzej; Tsai, Yi-Miau; Burant, Charles F; Raskind, Sasha; Zhang, Quanwei; Zhang, Zhengdong D; Seluanov, Andrei; Gorbunova, Vera; Clish, Clary B; Miller, Richard A; Gladyshev, Vadim N

2016-11-22

Mammalian lifespan differs by >100 fold, but the mechanisms associated with such longevity differences are not understood. Here, we conducted a study on primary skin fibroblasts isolated from 16 species of mammals and maintained under identical cell culture conditions. We developed a pipeline for obtaining species-specific ortholog sequences, profiled gene expression by RNA-seq and small molecules by metabolite profiling, and identified genes and metabolites correlating with species longevity. Cells from longer lived species up-regulated genes involved in DNA repair and glucose metabolism, down-regulated proteolysis and protein transport, and showed high levels of amino acids but low levels of lysophosphatidylcholine and lysophosphatidylethanolamine. The amino acid patterns were recapitulated by further analyses of primate and bird fibroblasts. The study suggests that fibroblast profiling captures differences in longevity across mammals at the level of global gene expression and metabolite levels and reveals pathways that define these differences.

p53/CEP-1 Increases or Decreases Lifespan, Depending on Level of Mitochondrial Bioenergetic Stress

PubMed Central

Ventura, Natascia; Rea, Shane L.; Schiavi, Alfonso; Torgovnick, Alessandro; Testi, Roberto; Johnson, Thomas E.

2009-01-01

SUMMARY Mitochondrial pathologies underlie a number of life-shortening diseases in humans. In the nematode Caenorhabditis elegans, severely reduced expression of mitochondrial proteins involved in electron transport chain-mediated energy production also leads to pathological phenotypes, including arrested development and/or shorter life; in sharp contrast, mild suppression of these same proteins extends lifespan. Here we show that the C. elegans p53 ortholog cep-1 mediates these opposite effects. We find that cep-1 is required to extend longevity in response to mild suppression of several bioenergetically relevant mitochondrial proteins, including frataxin - the protein defective in patients with Friedreich’s Ataxia. Importantly we show that cep-1 also mediates both the developmental arrest and life shortening induced by severe mitochondrial stress. Our findings support an evolutionarily conserved function for p53 in modulating organismal responses to mitochondrial dysfunction and suggest that metabolic checkpoint responses may play a role in longevity control and in human mitochondrial-associated diseases. PMID:19416129

Do cacti form soil seed banks? An evaluation using species from the Southern Central Andes.

PubMed

Lindow-López, Lucía; Galíndez, Guadalupe; Sühring, Silvia; Pastrana-Ignes, Valeria; Gorostiague, Pablo; Gutiérrez, Angela; Ortega-Baes, Pablo

2018-06-22

There is controversy over whether cactus species form soil seed banks. Although it is commonly assumed that cacti do not form seed banks, very few studies have evaluated them. In this work, we analyzed whether cactus species form soil seed banks, studying seed distribution, seed density and seed longevity in the Southern Central Andes. Soil samples were collected in two microhabitats (under nurse plants and in bare areas) at 12 selected sites. We determined seed presence-absence, density and distribution for 32 native cactus species. Seed longevity for six of these species was determined through a burial experiment. We recorded viable seeds for 62.5% of the 32 evaluated species, finding variation in seed density between microenvironments and among populations. In some species, the greatest seed density was found under potential nurse plants. Seed germination and seed viability decreased with burial time, with seed longevity always being less than 24 months after burial. Our results show strong evidence that cactus species do form seed banks. Seed density can vary between microenvironments and among populations, suggesting that cactus-nurse plant associations can also be explained by differential seed dispersal and not only by differential establishment. We found that Echinopsis and Gymnocalycium species form short-term seed banks. Our results will help to better understand the population dynamics of cactus species, a focal species group for conservation actions because many of them are threatened by human activities. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Longevity and aging. Mechanisms and perspectives.

PubMed

Labat-Robert, J; Robert, L

2015-12-01

Longevity can mostly be determined with relative accuracy from birth and death registers when available. Aging is a multifactorial process, much more difficult to quantitate. Every measurable physiological function declines with specific speeds over a wide range. The mechanisms involved are also different, genetic factors are of importance for longevity determinations. The best-known genes involved are the Sirtuins, active at the genetic and epigenetic level. Aging is multifactorial, not "coded" in the genome. There are, however, a number of well-studied physical and biological parameters involved in aging, which can be determined and quantitated. We shall try to identify parameters affecting longevity as well as aging and suggest some reasonable predictions for the future. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

The evolution of capture myopathy in hooved mammals: a model for human stress cardiomyopathy?

PubMed

Blumstein, Daniel T; Buckner, Janet; Shah, Sajan; Patel, Shane; Alfaro, Michael E; Natterson-Horowitz, Barbara

2015-07-21

Capture myopathy (CM) syndromes in wildlife may be a model for human stress cardiomyopathy, including Takotsubo cardiomyopathy. Emotional stress or grief may trigger heart attack-like symptoms, and occasionally, sudden death in some humans. Similarly, wildlife exposed to predatory stresses, chase, or capture occasionally results in sudden death. To better understand the nature of vulnerability to stress-induced sudden death, we studied cases of CM in hooved mammals-ungulates-and hypothesized that CM would be associated with a syndrome of longevity-related traits. We reconstructed the evolution of CM in ungulates then determined how a set of life history traits explained variation in the likelihood that CM was reported. CM is broadly reported, but not in all genera, and phylogenetic analyses suggest that it is an evolutionarily labile trait. We found that the following traits were significantly associated with reports of CM: greater brain mass, faster maximum running speed, greater minimum group size and greater maximum longevity. CM may be an unavoidable consequence of adaptations to reduce predation risk that include increased running speed, sociality and having larger brains. Moreover, longer-lived species seem to be more likely to be susceptible to CM. Exploring variable susceptibility to CM highlights the evolutionary origins of the disorder, potential basic mechanisms that underlie vulnerability to the phenomenon, and the potential for reduction of risk through modification of life history trajectory. © The Author(s) 2015. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

Neuropathology of supercentenarians - four autopsy case studies.

PubMed

Takao, Masaki; Hirose, Nobuyoshi; Arai, Yasumichi; Mihara, Ban; Mimura, Masaru

2016-09-02

Supercentenarians (aged 110 years old or more) are extremely rare in the world population (the number of living supercentenarians is estimated as 47 in the world), and details about their neuropathological information are limited. Based on previous studies, centenarians (aged 100-109 years old) exhibit several types of neuropathological changes, such as Alzheimer's disease and Lewy body disease pathology, primary age-related tauopathy, TDP-43 pathology, and hippocampal sclerosis. In the present study, we provide results from neuropathological analyses of four supercentenarian autopsy cases using conventional and immunohistochemical analysis for neurodegenerative disorders. In particular, we focused on the pathology of Alzheimer's disease and Lewy body disease, as well as the status of hippocampal sclerosis, TDP-43 pathology, aging-related tau astrogliopathy, and cerebrovascular diseases. Three cases were characterized as an "intermediate" level of Alzheimer's disease changes (NIA-AA guideline) and one was characterized as primary age-related tauopathy. TDP-43 deposits were present in the hippocampus in two cases. Neither Lewy body pathology nor hippocampal sclerosis was observed. Aging-related tau astrogliopathy was consistently observed, particularly in the basal forebrain. Small vessel diseases were also present, but they were relatively mild for cerebral amyloid-beta angiopathy and arteriolosclerosis. Although our study involved a small number of cases, the results provide a better understanding about human longevity. Neuropathological alterations associated with aging were mild to moderate in the supercentenarian brain, suggesting that these individuals might have some neuroprotective factors against aging. Future prospective studies and extensive molecular analyses are needed to determine the mechanisms of human longevity.

Longevity of highway pavements in Illinois : 2000 update

DOT National Transportation Integrated Search

2002-12-01

Results of the latest round of pavement longevity studies in Illinois provide updated performance data through 2000 for HMAC, JRCP, : and CRCP new construction as well as AC overlays (first, second, and third overlays) of these original pavements. Th...

Effects of nutritional components on aging

PubMed Central

Lee, Dongyeop; Hwang, Wooseon; Artan, Murat; Jeong, Dae-Eun; Lee, Seung-Jae

2015-01-01

Nutrients including carbohydrates, proteins, lipids, vitamins, and minerals regulate various physiological processes and are essential for the survival of organisms. Reduced overall caloric intake delays aging in various organisms. However, the role of each nutritional component in the regulation of lifespan is not well established. In this review, we describe recent studies focused on the regulatory role of each type of nutrient in aging. Moreover, we will discuss how the amount or composition of each nutritional component may influence longevity or health in humans. PMID:25339542

Parental longevity and offspring's home blood pressure: the Ohasama study.

PubMed

Watanabe, Yumiko; Metoki, Hirohito; Ohkubo, Takayoshi; Hirose, Takuo; Kikuya, Masahiro; Asayama, Kei; Inoue, Ryusuke; Hara, Azusa; Obara, Taku; Hoshi, Haruhisa; Totsune, Kazuhito; Imai, Yutaka

2010-02-01

Longevity is clustered in particular families. Some studies using conventional blood pressure (BP) reported an association between parental longevity and offspring's BP. No study has used self-measurement of BP at home (home BP). We examined the association between parental longevity and home BP values of adult Japanese offspring. Home and conventional BPs were measured in 1961 residents aged 40 years and over in the general population of Ohasama, Japan. Information about the ages of offspring's parents (age at death or current age) was obtained from a standardized questionnaire. The mean +/- SD values of systolic/diastolic home BP in offspring whose mothers died at less than 69 years of age, at 69-84 years of age, and in offspring whose mothers were alive at age 84 years were 127.4 +/- 13.2/76.2 +/- 9.1, 124.8 +/- 15.0/74.4 +/- 10.0, and 123.4 +/- 15.2/74.4 +/- 10.3 mmHg (P = 0.0002/0.009), respectively. Corresponding values in offspring whose fathers died at less than 66 years of age, at 66-80 years of age, and in offspring whose fathers were alive at age 80 years were 125.7 +/- 15.2/75.6 +/- 10.6, 124.7 +/- 14.1/75.0 +/- 9.2 and 122.4 +/- 14.6/73.6 +/- 9.5 mmHg (P = 0.001/0.003), respectively. Multivariate analysis demonstrated associations that were only weakly observed for conventional BP values (conventional BP: P = 0.3/0.4 for maternal and P = 0.3/0.3 for paternal longevity; home BP: P = 0.05/0.2 for maternal and P = 0.0004/0.007 for paternal longevity). Parental premature death was significantly associated with higher home BP levels in adult offspring, suggesting that parental longevity might be a useful additional marker for screening adult offspring at higher risk of hypertension.

Longevity and its regulation: centenarians and beyond.

PubMed

Robert, L; Fulop, T

2014-01-01

Regulation of longevity depends on genetic and environmental factors. According to Svanborg, a Swedish geriatrician, over the last decades human life expectancy increased as well as the age at onset of fatal diseases. Nevertheless, autopsies of centenarians revealed the presence of several severe pathologies which could have killed them much earlier. Therefore, the emphasis is on regulation of resistance dependent on the expression of genes such as Sirtuins, mTOR pathway and others controlling body resistance. Only a small fraction (<1%) of centenarians live to become supercentenarians (110 years), indicating a limit of performance and resistance of the body. This limit can be interpreted as 'tinkering' of nature instead of producing masterpieces as suggested by F. Jacob. These facts and theories are described in this chapter.

Beneficial influences of systemic cooperation and sociological behavior on longevity.

PubMed

Mountz, John D; Zant, Gary Van; Allison, David B; Zhang, Huang-Ge; Hsu, Hui-Chen

2002-04-30

During his long research career in the field of aging, Dr Bernard Strehler developed a series of theories concerning the identity of genes that can promote longevity and their role in natural selection. As a tribute to Dr Strehler, we have taken this opportunity to summarize a selection of these theories and to illustrate how these insights have influenced our search for longevity genes within the immune system. The identification of longevity genes has proven difficult. We believe that, at least in part, this reflects the emphasis on the concept of survival of the 'physically' fittest. We have used the immune system as a model to demonstrate that, over and above the self-evident advantage of those genes that contribute the attributes commonly associated with survival of the 'physically' fittest, those genes that lead to a predisposition to cooperate also confer a competitive survival advantage. As the acquisition of cooperativity in a society is linked to support mechanisms provided by older individuals, the search for longevity genes should not be limited to those genes that are associated with extended expression of a youthful phenotype. Rather these studies should be expanded to include identification of those genes that regulate physiologic parameters that affect individual longevity, even if they do not correspond with the traditional view of reproductive competitiveness. At the societal level, longevity genes may encode attributes that regulate sociologic or psychological parameters that may contribute to a tendency to non-aggressive or cooperative behavior that leads to achievement of common goals necessary for the survival of the species. This view of the selection for longevity impacts the analysis of longevity genes and aging at the organismal level. Dr Strehler viewed organismal aging as an integrated functional state, in which he conceived the outcome as reflecting the net balance of functional decrementers and evolved compensatory features. We propose that, in more evolved species, the longevity genes will be those genes, or sets of genes, that counterbalance of age-related functional decrementers with the age-related manifestation of evolved compensatory features. Thus, as illustrated here through analysis of the immune system, the longevity genes may well be those genes that promote overall systemic cooperation and compensation within the immune system and associated systems, rather than the genes that prevent age-related alterations in only one or a limited number of pathways.

Intelligence and Semen Quality Are Positively Correlated

ERIC Educational Resources Information Center

Arden, Rosalind; Gottfredson, Linda S.; Miller, Geoffrey; Pierce, Arand

2009-01-01

Human cognitive abilities inter-correlate to form a positive matrix, from which a large first factor, called "Spearman's g" or general intelligence, can be extracted. General intelligence itself is correlated with many important health outcomes including cardio-vascular function and longevity. However, the important evolutionary question of…

Personality predictors of longevity: Activity, Emotional Stability, and Conscientiousness

PubMed Central

Terracciano, Antonio; Löckenhoff, Corinna E.; Zonderman, Alan B.; Ferrucci, Luigi; Costa, Paul T.

2008-01-01

Objective To examine the association between personality traits and longevity. Methods Using the Guilford-Zimmerman Temperament Survey, personality traits were assessed in 2359 participants (38% women; age: 17 to 98 years, M = 50) from the Baltimore Longitudinal Study of Aging (BLSA), starting in 1958. Over the duration of the study, 943 (40%) participants died, on average 18 years after their personality assessment. The association of each trait with longevity was examined by Cox regression controlling for demographic variables. Results In preliminary analyses among the deceased, those who scored one SD above the mean on General Activity (a facet of Extraversion), Emotional Stability (low Neuroticism), or Conscientiousness lived on average two to three years longer than those scoring one SD below the mean. Survival analyses on the full sample confirmed the association of General Activity, Emotional Stability, and Conscientiousness with lower risk of death, such that every one SD increase was related to about 13%, 15%, and 27% risk reduction, respectively. The association of personality traits with longevity was largely independent from the influence of smoking and obesity. Personality predictors of longevity did not differ by sex, except for Ascendance (a facet of Extraversion). Emotional Stability was a significant predictor when the analyses were limited to deaths due to cardiovascular disease, with comparable effect sizes for General Activity and Conscientiousness. Conclusions In a large sample of generally healthy individuals followed for almost five decades, longevity was associated with being conscientious, emotionally stable, and active. PMID:18596250

Personality predictors of longevity: activity, emotional stability, and conscientiousness.

PubMed

Terracciano, Antonio; Löckenhoff, Corinna E; Zonderman, Alan B; Ferrucci, Luigi; Costa, Paul T

2008-07-01

To examine the association between personality traits and longevity. Using the Guilford-Zimmerman Temperament Survey, personality traits were assessed in 2359 participants (38% women; age = 17 to 98 years, mean = 50 years) from the Baltimore Longitudinal Study of Aging, starting in 1958. Over the duration of the study, 943 (40%) participants died, on average 18 years after their personality assessment. The association of each trait with longevity was examined by Cox regression controlling for demographic variables. In preliminary analyses among the deceased, those who scored 1 standard deviation (SD) above the mean on General Activity (a facet of Extraversion), Emotional Stability (low Neuroticism), or Conscientiousness lived on average 2 to 3 years longer than those scoring 1 SD below the mean. Survival analyses on the full sample confirmed the association of General Activity, Emotional Stability, and Conscientiousness with lower risk of death, such that every 1-SD increase was related to about 13%, 15%, and 27% risk reduction, respectively. The association of personality traits with longevity was largely independent from the influence of smoking and obesity. Personality predictors of longevity did not differ by sex, except for Ascendance (a facet of Extraversion). Emotional Stability was a significant predictor when the analyses were limited to deaths due to cardiovascular disease, with comparable effect sizes for General Activity and Conscientiousness. In a large sample of generally healthy individuals followed for almost five decades, longevity was associated with being conscientious, emotionally stable, and active.

Sublethal effects of imidacloprid on the fecundity, longevity, and enzyme activity of Sitobion avenae (Fabricius) and Rhopalosiphum padi (Linnaeus).

PubMed

Lu, Y-H; Zheng, X-S; Gao, X-W

2016-08-01

The aphid species Sitobion avenae and Rhopalosiphum padi are the most important pests in wheat growing regions of many countries. In this study, we investigated the sublethal effects of imidacloprid on fecundity, longevity, and enzyme activity in both aphid species by comparing 3-h exposure for one or three generations. Our results indicated that 3-h exposure to sublethal doses of imidacloprid for one generation had no discernible effect on the survival, fecundity, longevity, or enzyme activity levels of aphids. However, when pulse exposures to imidacloprid were sustained over three generations, both fecundity and longevity were significantly decreased in both S. avenae and R. padi. Interestingly, the fecundity of R. padi had almost recovered by the F5 generation, but its longevity was still deleteriously affected. These results indicated that R. padi laid eggs in shorter time lags and has a more fast resilience. The change in reproduction behavior may be a phenomenon of R. padi to compensate its early death. If this is stable for the next generation, it means that the next generation is more competitive than unexposed populations, which could be the reason underlying population outbreaks that occur after longer-term exposure to an insecticide. This laboratory-based study highlights the sublethal effects of imidacloprid on the longevity and fecundity of descendants and provides an empirical basis from which to consider management decisions for chemical control in the field.

Ages at Menarche and Menopause and Reproductive Lifespan As Predictors of Exceptional Longevity in Women: The Women's Health Initiative

PubMed Central

Shadyab, Aladdin H.; Macera, Caroline A.; Shaffer, Richard A.; Jain, Sonia; Gallo, Linda C.; Gass, Margery L.S.; Waring, Molly E.; Stefanick, Marcia L.; LaCroix, Andrea Z.

2016-01-01

Objective To investigate associations between reproductive factors and survival to age 90 years. Methods This was a prospective study of postmenopausal women from the Women's Health Initiative recruited from 1993-1998 and followed until the last outcomes evaluation on August 29, 2014. Participants included 16,251 women born on or before August 29, 1924 for whom survival to age 90 during follow-up was ascertained. Women were classified as having survived to age 90 (exceptional longevity) or died before age 90. Multivariable logistic regression models were used to evaluate associations of ages at menarche and menopause (natural or surgical) and reproductive lifespan with longevity, adjusting for demographic, lifestyle, and reproductive characteristics. Results Participants were on average aged 74.7 years (range, 69-81 years) at baseline. Of 16,251 women, 8,892 (55%) survived to age 90. Women aged ≥12 years at menarche had modestly increased odds of longevity (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.00-1.19). There was a significant trend toward increased longevity for later age at menopause (natural or surgical; Ptrend =0.01), with ORs (95% CIs) of 1.19 (1.04-1.36) and 1.18 (1.02-1.36) for 50-54 and ≥55 compared with <40 years, respectively. Later age at natural menopause as a separate exposure was also significantly associated with increased longevity (Ptrend =0.02). Longer reproductive lifespan was significantly associated with increased longevity (Ptrend=0.008). The odds of longevity were 13% (OR, 1.13; 95% CI, 1.03-1.25) higher in women with >40 compared with <33 reproductive years. Conclusions Reproductive characteristics were associated with late-age survival in older women. PMID:27465713

Coevolution of cultural intelligence, extended life history, sociality, and brain size in primates

PubMed Central

Street, Sally E.; Navarrete, Ana F.; Laland, Kevin N.

2017-01-01

Explanations for primate brain expansion and the evolution of human cognition and culture remain contentious despite extensive research. While multiple comparative analyses have investigated variation in brain size across primate species, very few have addressed why primates vary in how much they use social learning. Here, we evaluate the hypothesis that the enhanced reliance on socially transmitted behavior observed in some primates has coevolved with enlarged brains, complex sociality, and extended lifespans. Using recently developed phylogenetic comparative methods we show that, across primate species, a measure of social learning proclivity increases with absolute and relative brain volume, longevity (specifically reproductive lifespan), and social group size, correcting for research effort. We also confirm relationships of absolute and relative brain volume with longevity (both juvenile period and reproductive lifespan) and social group size, although longevity is generally the stronger predictor. Relationships between social learning, brain volume, and longevity remain when controlling for maternal investment and are therefore not simply explained as a by-product of the generally slower life history expected for larger brained species. Our findings suggest that both brain expansion and high reliance on culturally transmitted behavior coevolved with sociality and extended lifespan in primates. This coevolution is consistent with the hypothesis that the evolution of large brains, sociality, and long lifespans has promoted reliance on culture, with reliance on culture in turn driving further increases in brain volume, cognitive abilities, and lifespans in some primate lineages. PMID:28739950

Evolution of increased adult longevity in Drosophila melanogaster populations selected for adaptation to larval crowding.

PubMed

Shenoi, V N; Ali, S Z; Prasad, N G

2016-02-01

In holometabolous animals such as Drosophila melanogaster, larval crowding can affect a wide range of larval and adult traits. Adults emerging from high larval density cultures have smaller body size and increased mean life span compared to flies emerging from low larval density cultures. Therefore, adaptation to larval crowding could potentially affect adult longevity as a correlated response. We addressed this issue by studying a set of large, outbred populations of D. melanogaster, experimentally evolved for adaptation to larval crowding for 83 generations. We assayed longevity of adult flies from both selected (MCUs) and control populations (MBs) after growing them at different larval densities. We found that MCUs have evolved increased mean longevity compared to MBs at all larval densities. The interaction between selection regime and larval density was not significant, indicating that the density dependence of mean longevity had not evolved in the MCU populations. The increase in longevity in MCUs can be partially attributed to their lower rates of ageing. It is also noteworthy that reaction norm of dry body weight, a trait probably under direct selection in our populations, has indeed evolved in MCU populations. To the best of our knowledge, this is the first report of the evolution of adult longevity as a correlated response of adaptation to larval crowding. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

Impact of automatic adjustment of stimulation outputs on pacemaker longevity in a new dual-chamber pacing system.

PubMed

Brockes, Christiane; Rahn-Schönbeck, Mariette; Duru, Firat; Candinas, Reto; Turina, Marko

2003-02-01

Automatic capture verification using the Autocapture (AC) feature enabled by paced evoked response detection and delivery of high energy back-up pulses intends to increase patient safety. Furthermore, adjustment of stimulation outputs can save energy and potentially improve pacemaker (PM) longevity. The purpose of this study was to evaluate the theoretical longevity of a new dual chamber PM with the integrated AC feature (Affinity DR, St. Jude Medical) in comparison to the longevity of a previous model from the same manufacturer without AC (Trilogy DR). Affinity PMs were implanted in 16 patients and connected to a compatible lead with low polarization properties. AC was activated when the evoked response was significantly higher than the polarization voltage. Theoretical PM longevity was calculated with and without AC during follow-up. The measured and calculated values were compared to measurements in 19 patients, who consecutively received Trilogy-PMs during the same time period. In only one patient the evoked response was not adequate, and as a result, AC was not programmed. The calculated longevity of the Affinity-PMs 79 +/- 28 days after implantation was significantly higher in comparison to the Trilogy-PMs (Affinity-PMs: 8.9 +/- 1.2 years without and 9.5 +/- 1.1 years with AC; Trilogy-PMs: 6.5 +/- 0.8 years) (p < 0.005). The AC feature is an optional algorithm that can be activated in most patients and it significantly prolongs predicted battery longevity due to automatic adjustment of stimulation outputs.

The Evolution of Human Longevity: Toward a Biocultural Theory.

ERIC Educational Resources Information Center

Mayer, Peter J.

Homo sapiens is the only extant species for which there exists a significant post-reproductive period in the normal lifespan. Explanations for the evolution of this species-specific trait are possible through "non-deterministic" theories of aging positing "wear and tear" or the failure of nature to eliminate imperfection, or…

Aging children of long-lived parents experience slower cognitive decline.

PubMed

Dutta, Ambarish; Henley, William; Robine, Jean-Marie; Llewellyn, David; Langa, Kenneth M; Wallace, Robert B; Melzer, David

2014-10-01

Parental longevity confers lower risks for some age-related diseases in offspring. We tested the association between parental longevity and late-life cognitive decline or dementia. Data were from the Health and Retirement Study (HRS), a US national sample. Biennial cognitive assessment (Telephone Interview of Cognitive Status-Modified [TICS-m]) occurred for ages 64 years or older in 1996 through 2008 (maximum, 79 years), including physician-diagnosed memory disorder. Offspring were categorized into parental longevity groups based on gender-specific distributional cut points. Model covariates included race, respondents' education, and income status during childhood and adulthood. Offspring groups did not differ on TICS-m scores at baseline. During follow-up, offspring of two long-lived parents experienced 40% slower rates of TICS-m decline than those with no long-lived parents (95% confidence interval, 12-72; P=.003; n=4731). Increased parental longevity was also associated with lower risk of physician-diagnosed memory disorder. Estimates did not change after controlling for environmental variables. Parental longevity is associated inversely with cognitive decline and self-reported diagnosed memory disorders in aging offspring. Parental longevity may be a valuable trait for identifying early biomarkers for resistance to cognitive decline in aging. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

The Genetics of Extreme Longevity: Lessons from the New England Centenarian Study

PubMed Central

Sebastiani, Paola; Perls, Thomas T.

2012-01-01

The New England Centenarian Study (NECS) was founded in 1994 as a longitudinal study of centenarians to determine if centenarians could be a model of healthy human aging. Over time, the NECS along with other centenarian studies have demonstrated that the majority of centenarians markedly delay high mortality risk-associated diseases toward the ends of their lives, but many centenarians have a history of enduring more chronic age-related diseases for many years, women more so than men. However, the majority of centenarians seem to deal with these chronic diseases more effectively, not experiencing disability until well into their nineties. Unlike most centenarians who are less than 101 years old, people who live to the most extreme ages, e.g., 107+ years, are generally living proof of the compression of morbidity hypothesis. That is, they compress morbidity and disability to the very ends of their lives. Various studies have also demonstrated a strong familial component to extreme longevity and now evidence particularly from the NECS is revealing an increasingly important genetic component to survival to older and older ages beyond 100 years. It appears to us that this genetic component consists of many genetic modifiers each with modest effects, but as a group they can have a strong influence. PMID:23226160

The genetics of exceptional longevity: Insights from centenarians.

PubMed

Santos-Lozano, Alejandro; Santamarina, Ana; Pareja-Galeano, Helios; Sanchis-Gomar, Fabian; Fiuza-Luces, Carmen; Cristi-Montero, Carlos; Bernal-Pino, Aranzazu; Lucia, Alejandro; Garatachea, Nuria

2016-08-01

As the world population ages, so the prevalence increases of individuals aged 100 years or more, known as centenarians. Reaching this age has been described as exceptional longevity (EL) and is attributed to both genetic and environmental factors. Many genetic variations known to affect life expectancy exist in centenarians. This review of studies conducted on centenarians and supercentenarians (older than 110 years) updates knowledge of the impacts on longevity of the twenty most widely investigated single nucleotide polymorphisms (SNPs). Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A Longitudinal Study of the Associations among Adolescent Conflict Resolution Styles, Depressive Symptoms, and Romantic Relationship Longevity

ERIC Educational Resources Information Center

Ha, Thao; Overbeek, Geertjan; Cillessen, Antonius H. N.; Engels, Rutger C. M. E.

2012-01-01

This study investigated whether adolescents' conflict resolution styles mediated between depressive symptoms and relationship longevity. Data were used from a sample of 80 couples aged 13-19 years old (Mage = 15.48, SD = 1.16). At Time 1 adolescents reported their depressive symptoms and conflict resolution styles. Additionally, time until…

Potential long-term consequences of fad diets on health, cancer, and longevity: lessons learned from model organism studies.

PubMed

Ruden, Douglas M; Rasouli, Parsa; Lu, Xiangyi

2007-06-01

While much of the third world starves, many in the first world are undergoing an obesity epidemic, and the related epidemics of type II diabetes, heart disease, and other diseases associated with obesity. The amount of economic wealth being directly related to a decline in health by obesity is ironic because rich countries contribute billions of dollars to improve the health of their citizens. Nevertheless, nutritional experiments in model organisms such as yeast, C. elegans, Drosophila, and mice confirm that "caloric restriction" (CR), which is defined generally as a 30-40% decrease in caloric intake, a famine-like condition for humans seen only in the poorest of countries, promotes good health and increases longevity in model organisms. Because caloric restriction, and dieting in general, requires a great deal of will power to deal with the feelings of deprivation, many fad diets, such as the Atkins, South Beach, and Protein Power, have been developed which allow people to lose weight purportedly without the severe feelings of deprivation. However, the long-term effects of such fad diets are not known and few experiments have been performed in the laboratory to investigate possible side affects and adverse consequences. In this paper, we review studies with fad-like dietary conditions in humans and model organisms, and we propose a "Dietary Ames Test" to rapidly screen fad diets, dietary supplements, and drugs for potential long-term health consequences in model organisms.

Investigating longevity of corrosion inhibitors and performance of deicer products under storage or after pavement application.

DOT National Transportation Integrated Search

2011-06-01

This study evaluated the longevity of corrosion inhibitors and the performance of inhibited deicer products under storage or after pavement application. No significant degradation of corrosion inhibitor or loss of chlorides was seen during the months...

Cost of reproduction in Callosobruchus maculatus: effects of mating on male longevity and the effect of male mating status on female longevity.

PubMed

Paukku, Satu; Kotiaho, Janne S

2005-11-01

One of the most studied life-history trade-offs is that resulting from the cost of reproduction: a trade-off arises when reproduction diverts limited resources from other life-history traits. We examine the cost of reproduction in male, and the effect of male mating status on female Callosobruchus maculatus seed beetles. Cost of reproduction for male C. maculatus was manifested as reduced longevity. There was also a positive relationship between male body size and male longevity. Females mated to males that had already copulated twice did not live as long as females mated to males that had copulated once or not at all. The third copulation of males also lasted longer than the two previous ones. We conclude that even though the cost of reproduction for males has been studied much less than that in females, there is growing evidence that male reproductive effort is more complex than has traditionally been thought.

Long-term pathogenic response to Plasmodium relictum infection in Culex pipiens mosquito.

PubMed

Pigeault, Romain; Villa, Manon

2018-01-01

The transmission of Plasmodium within a vertebrate host population is strongly associated with the life history traits of its vector. Therefore the effect of malaria infection on mosquito fecundity and longevity has traditionally received a lot of attention. Several species of malaria parasites reduce mosquito fecundity, nevertheless almost all of the studies have focused only on the first gonotrophic cycle. Yet, during their lifetime, female mosquitoes go through several gonotrophic cycles, which raises the question of whether they are able to compensate the fecundity costs induced by the parasite. The impact of Plasmodium infection on female longevity is not so clear and has produced conflicting results. Here we measured the impact of Plasmodium relictum on its vector's longevity and fecundity during three consecutive gonotrophic cycles. In accordance with previous studies, we observed a negative impact of Plasmodium infection on mosquito (Culex pipiens) fecundity in the first gonotrophic cycle. Interestingly, despite having taken two subsequent uninfected blood meals, the negative impact of malaria parasite persisted. Nevertheless no impact of infection on mosquito longevity was observed. Our results are not in line with the hypothesis that the reduction of fecundity observed in infected mosquitoes is an adaptive strategy of Plasmodium to increase the longevity of its vector. We discuss the different underlying mechanisms that may explain our results.

3β-Hydroxy-urs-12-en-28-oic Acid Modulates Dietary Restriction Mediated Longevity and Ameliorates Toxic Protein Aggregation in C. elegans.

PubMed

Negi, Hema; Saikia, Shilpi Khare; Pandey, Rakesh

2017-11-09

Species from lower invertebrates to a spectrum of mammals show antiaging health benefits of phytochemical(s). Here, we explored the pro-longevity effects of a natural triterpenoid, ursolic acid (3β-hydroxy-urs-12-en-28-oic acid; UA) in Caenorhabditis elegans with maximal life span being evident at 25 µM UA. Similar to eat-2 mutants, UA uptake by worm results in reduced fat storage and attenuation of reactive oxygen species (ROS), independent of superoxide dismutase(s) activation. The genetic requirements for UA-mediated longevity are quite similar to dietary restriction (DR) achieved through SKN-1/NRF-2 exhibiting upregulation of downstream target genes gcs-1 and daf-9. Longevity mechanism was independent of PHA-4/FOXA and attributed to partial dependence on sir-2.1. Altogether, our study suggests differential use of UA-elicited signaling cascades in nutrient sensing for longevity. Both the redox state and the proteostasis of an organism play critical role in aging and disease resistance. Interestingly, we observed a reduction of toxic protein aggregation in transgenic polyglutamine (polyQ) C. elegans model and UA-mediated JNK-1 (c-Jun-NH2-terminal kinase) activation in wild-type animals. Thus, our study demonstrates a small extent of prevention against proteotoxic stress by UA coupled with positive aspects of DR-mediated longevity. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Polyamines: Bio-Molecules with Diverse Functions in Plant and Human Health and Disease

PubMed Central

Handa, Avtar K.; Fatima, Tahira; Mattoo, Autar K.

2018-01-01

Biogenic amines—polyamines (PAs), particularly putrescine, spermidine and spermine are ubiquitous in all living cells. Their indispensable roles in many biochemical and physiological processes are becoming commonly known, including promoters of plant life and differential roles in human health and disease. PAs positively impact cellular functions in plants—exemplified by increasing longevity, reviving physiological memory, enhancing carbon and nitrogen resource allocation/signaling, as well as in plant development and responses to extreme environments. Thus, one or more PAs are commonly found in genomic and metabolomics studies using plants, particulary during different abiotic stresses. In humans, a general decline in PA levels with aging occurs parallel with some human health disorders. Also, high PA dose is detrimental to patients suffering from cancer, aging, innate immunity and cognitive impairment during Alzheimer and Parkinson diseases. A dichotomy exists in that while PAs may increase longevity and reduce some age-associated cardiovascular diseases, in disease conditions involving higher cellular proliferation, their intake has negative consequences. Thus, it is essential that PA levels be rigorously quantified in edible plant sources as well as in dietary meats. Such a database can be a guide for medical experts in order to recommend which foods/meats a patient may consume and which ones to avoid. Accordingly, designing both high and low polyamine diets for human consumption are in vogue, particularly in medical conditions where PA intake may be detrimental, for instance, cancer patients. In this review, literature data has been collated for the levels of the three main PAs, putrescine, spermidine and spermine, in different edible sources—vegetables, fruits, cereals, nuts, meat, sea food, cheese, milk, and eggs. Based on our analysis of vast literature, the effects of PAs in human/animal health fall into two broad, Yang and Yin, categories: beneficial for the physiological processes in healthy cells and detrimental under pathological conditions. PMID:29468148

Polyamines: Bio-Molecules with diverse functions in plant and human health and disease

NASA Astrophysics Data System (ADS)

Handa, Avtar K.; Fatima, Tahira; Mattoo, Autar K.

2018-02-01

Biogenic amines – polyamines (PAs), particularly putrescine, spermidine and spermine (and thermospermine) are ubiquitous in all living cells. Their indispensable roles in many biochemical and physiological processes are becoming commonly known, including promoters of plant life and differential roles in human health and disease. PAs positively impact cellular functions in plants – exemplified by increasing longevity, reviving physiological memory, enhancing carbon and nitrogen resource allocation/signaling, as well as in plant development and responses to extreme environments. Thus, one or more PAs are commonly found in genomic and metabolomics studies using plants, particulary during different abiotic stresses. In humans, a general decline in PA levels with aging occurs parallel with some human health disorders. Also, high PA dose is detrimental to patients suffering from cancer, aging, innate immunity and cognitive impairment during Alzheimer and Parkinson diseases. A dichotomy exists in that while PAs may increase longevity and reduce some age-associated cardiovascular diseases, in disease conditions involving higher cellular proliferation, their intake has negative consequences. Thus, it is essential that PA levels be rigorously quantified in edible plant sources as well as in dietary meats. Such a database can be a guide for medical experts in order to recommend which foods/meats a patient may consume and which ones to avoid. Accordingly, designing both high and low polyamine diets for human consumption are in vogue, particularly in medical conditions where PA intake may be detrimental, for instance, cancer patients. In this review, literature data has been collated for the levels of the three main PAs, putrescine, spermidine and spermine, in different edible sources - vegetables, fruits, cereals, nuts, meat, sea food, cheese, milk and eggs. Based on our analysis of vast literature, the effects of PAs in human/animal health fall into two broad, Yang and Yin, categories: beneficial for the physiological processes in healthy cells and detrimental under pathological conditions.

Battery longevity of implantable cardioverter-defibrillators and cardiac resynchronization therapy defibrillators: technical, clinical and economic aspects. An expert review paper from EHRA.

PubMed

Boriani, Giuseppe; Merino, Josè; Wright, David J; Gadler, Fredrik; Schaer, Beat; Landolina, Maurizio

2018-05-10

In recent years an extension of devices longevity has been obtained for implantable cardioverter-defibrillators (ICDs), including ICDs for cardiac resynchronization therapy (CRT-D) through improved battery chemistry and device technology and this implies important clinical benefits (reduced need for device replacements and associated complications, particularly infections), as well as economic benefits, in line with patient preferences and needs. From a clinical point of view, the availability of this improvement in technology allows to better tune the choice of the device to be implanted, taking into account that the reasons supporting the value of an extended device longevity as a clinical priority may differ according to the clinical setting (purely electrical diseases or left ventricular dysfunction/heart failure, respectively). From an economic point of view, extension of device longevity may have an important impact in reducing long-term costs of device therapy, with substantial daily savings in favour of devices with extended longevity, up to 30%, depending on clinical scenarios. In studies based on projections, an extension of device longevity allowed to calculate that the cost per day of ICDs may be substantially reduced, and this allows to overcome the frequent perception of ICD and CRT-D devices as treatments with unaffordable costs and to overturn the misconception that up-front costs are the only metric with which to value device treatments. In view of its clinical and economic value, device longevity should be a determining factor in device choice by physicians and healthcare commissioners and should be appropriately considered and valued in comparative tenders.

Constraints on the Longevity of the 2010 Eyjaföll Eruption Cloud From Analog Experiments and Modeling

NASA Astrophysics Data System (ADS)

Carazzo, G.; Jellinek, M.

2010-12-01

The prolonged disruption of global air travel as a result of the 2010 Eyjafjöll eruption in Iceland underscores the value of discerning the dynamics of volcanic ash-clouds in the atmosphere. Understanding the longevity of these clouds is a particularly long standing problem that bears not only on volcanic hazards to humans but also on the nature and time scale of volcanic forcings on climate change. Since early work on the subject, the common practice to tackle the problem of cloud longevity has been to account for the dynamics of sedimentation by individual particle settling. We use 1D modeling and analog experiments of a turbulent particle-laden umbrella cloud to show that this classical view can be misleading and that the residence times of these ash-clouds in the atmosphere depends strongly on the collective behavior of the solid fraction. Diffusive convection driven by the differential diffusion of constituents altering the cloud density (ash, temperature, sulfur dioxide) may enhance particle scavenging and extend the cloud longevity over time scales orders of magnitude longer than currently expected (i.e., years rather than days for powerful eruptions). Records of this behavior can be found in real-time measurements of stratospheric post-volcanic aerosols following the 1974 Fuego, the 1982 El Chichon, the 1991 Hudson and Pinatubo events, and more recently, from the 14 April 2010 Eyjafjöll eruption. The importance of diffusive convection in volcanic ash-clouds depends strongly on particle size distribution and concentration. For the 2010 Eyjafjöll eruption, we predict that particles larger than 10 microns should settle individually as commonly assumed, but particles smaller than 1 micron should diffuse slowly in layers extending the cloud longevity to several weeks rather than days. These predictions are found to be in good agreement with a number of satellite and ground-based lidar data on ash size and mass estimates performed at different locations across Europe.

Gene-gene interaction between CETP and APOE polymorphisms confers higher risk for hypertriglyceridemia in oldest-old Chinese women.

PubMed

Sun, Liang; Hu, Caiyou; Zheng, Chenguang; Huang, Zezhi; Lv, Zeping; Huang, Jin; Liang, Siying; Shi, Xiaohong; Zhu, Xiaoquan; Yuan, Huiping; Yang, Ze

2014-07-01

The knowledge of dyslipidemia and its genetic contributors in oldest-old subjects is limited; in addition, the majority of oldest-old subjects are females. Evidence has accumulated that multiple genetic factors play important roles in determining susceptibility to dyslipidemia and extended life span. Cholesterol ester transfer protein (CETP) and apolipoprotein E (APOE) are two plausible candidate genes for human longevity owing to their functionally related modulation of circulating lipid homeostasis; however, few studies have considered their interplay. In this study, we analyzed the distribution of CETP*V (rs5882) and APOE*4 (rs429358 and rs7412) in 372 oldest-old Chinese women (aged 80-109) and 340 controls (aged 20-58). In addition to replicating the association of longevity, our main goal was to evaluate the contribution of CETP*V, APOE*4 and CETP*APOE interaction to the risk of dyslipidemia. Only APOE*4 conferred a risk against longevity and was associated with high-cholesterol (hTC) and mixed dyslipidemia for oldest-old females. Moreover, CETP*V was found to be associated with hypertriglyceridemia (hTG) independently from APOE*4, age, BMI, alcohol drinking, TC, TG, HDL-c, and LDL-c. The stratification test, multivariable-adjusted logistic regression, and nonparametric MDR analysis all suggested a significant CETP*APOE interaction associated with hTG. The unadjusted odds for hTG were more than 4-fold in subjects with CETP*V and APOE*4 than those without either (OR=4.36, P<0.001). These results provide evidence of strong independent associations between hTG and CETP*V in oldest-old Chinese females, and APOE*4, as an independently non-significant variant, might interact with CETP*V resulting in an increased risk for hTG. Copyright © 2014 Elsevier Inc. All rights reserved.

A Multiple Regression Analysis of Factors Concerning Superintendent Longevity and Continuity Relative to Student Achievement

ERIC Educational Resources Information Center

Plotts, Timothy

2011-01-01

The purpose of this quantitative study was to examine the relationship between the length of superintendent tenure, longevity, and continuity relative to student achievement as evidenced by the 2008-2009 3rd Grade New Jersey Assessment of Skills and Knowledge (NJASK) in language arts. Achievement in the study was defined as those students who…

Self-Rated Activity Levels and Longevity: Evidence from a 20 Year Longitudinal Study

ERIC Educational Resources Information Center

Mullee, Mark A.; Coleman, Peter G.; Briggs, Roger S. J.; Stevenson, James E.; Turnbull, Joanne C.

2008-01-01

The study reports on factors predicting the longevity of 328 people over the age of 65 drawn from an English city and followed over 20 years. Both the reported activities score and the individual's comparative evaluation of their own level of activity independently reduced the risk of death, even when health and cognitive status were taken into…

Tumour necrosis factor-α regulates human eosinophil apoptosis via ligation of TNF-receptor 1 and balance between NF-κB and AP-1.

PubMed

Kankaanranta, Hannu; Ilmarinen, Pinja; Zhang, Xianzhi; Adcock, Ian M; Lahti, Aleksi; Barnes, Peter J; Giembycz, Mark A; Lindsay, Mark A; Moilanen, Eeva

2014-01-01

Eosinophils play a central role in asthma. The present study was performed to investigate the effect of tumour necrosis factor-α (TNF-α) on longevity of isolated human eosinophils. In contrast to Fas, TNF-α inhibited eosinophil apoptosis as evidenced by a combination of flow cytometry, DNA fragmentation assay and morphological analyses. The effect of TNF-α on eosinophil apoptosis was reversed by a TNF-α neutralising antibody. The anti-apoptotic effect of TNF-α was not due to autocrine release of known survival-prolonging cytokines interleukins 3 and 5 or granulocyte-macrophage-colony-stimulating factor as their neutralisation did not affect the effect of TNF-α. The anti-apoptotic signal was mediated mainly by the TNF-receptor 1. TNF-α induced phosphorylation and degradation of IκB and an increase in NF-κB DNA-binding activity. The survival-prolonging effect of TNF-α was reversed by inhibitors of NF-κB pyrrolidinedithiocarbamate and gliotoxin and by an inhibitor of IκB kinase, BMS-345541. TNF-α induced also an increase in AP-1 DNA-binding activity and the antiapoptotic effect of TNF-α was potentiated by inhibitors of AP-1, SR 11302 and tanshinone IIA and by an inhibitor of c-jun-N-terminal kinase, SP600125, which is an upstream kinase activating AP-1. Our results thus suggest that TNF-α delays human eosinophil apoptosis via TNF-receptor 1 and the resulting changes in longevity depend on yin-yang balance between activation of NF-κB and AP-1.

Female Superintendents' Longevity: Their Experiences

ERIC Educational Resources Information Center

Sampson, Pauline M.

2018-01-01

This paper describes a qualitative research study of the experiences of Texas female superintendents with longevity. Specifically, five superintendents with tenure of at least six years in one school district were interviewed to hear their voices. Findings show that a strong working relationship with their boards, a solid connection with their…

Mating and social contact change egg production and longevity in adult females of the mirid Lygus hesperus

USDA-ARS?s Scientific Manuscript database

There is frequently a tradeoff between fecundity and longevity, but the relationship is inconsistent across species and influenced by various exogenous and endogenous factors. Previous studies of Lygus hesperus Knight (Hemiptera: Miridae) established that female egg production is promoted by insemin...

Influence of internal current and pacing current on pacemaker longevity.

PubMed

Schuchert, A; Kuck, K H

1994-01-01

The effects of lower pulse amplitude on battery current and pacemaker longevity were studied comparing the new, small-sized VVI pacemaker, Minix 8341, with the former model, Pasys 8329. Battery current was telemetrically measured at 0.8, 1.6, 2.5, and 5.0 V pulse amplitude and 0.05, 0.25, 0.5, and 1.0 msec pulse duration. Internal current was assumed to be equal to the battery current at 0.8 V and 0.05 msec. Pacing current was calculated subtracting internal current from battery current. The Minix pacemaker had a significantly lower battery current because of a lower internal current (Minix: 4.1 +/- 0.1 microA; Pasys: 16.1 +/- 0.1 microA); pacing current of both units was similar. At 0.5 msec pulse duration, the programming from 5.0-2.5 V pulse amplitude resulted in a greater relative reduction of battery current in the newer pacemaker (51% vs 25%). Projected longevity of each pacemaker was 7.9 years at 5.0 V and 0.5 msec. The programming from 5.0-2.5 V extended the projected longevity by 2.3 years (Pasys) and by 7.1 years (Minix). The longevity was negligibly longer after programming to 1.6 V. extension of pacemaker longevity can be achieved with the programming to 2.5 V or less if the connected pacemakers need a low internal current for their circuitry.

Work-Family Context and the Longevity Disadvantage of US Women

PubMed Central

Montez, Jennifer Karas; Martikainen, Pekka; Remes, Hanna; Avendano, Mauricio

2015-01-01

Female life expectancy is currently shorter in the United States than in most high-income countries. This study examines work-family context as a potential explanation. While work-family context changed similarly across high-income countries during the past half century, the United States has not implemented institutional supports, such as universally available childcare and family leave, to help Americans contend with these changes. We compare the United States to Finland—a country with similar trends in work-family life but generous institutional supports—and test two hypotheses to explain US women's longevity disadvantage: (1) US women may be less likely than Finnish women to combine employment with childrearing; and (2) US women's longevity may benefit less than Finnish women's longevity from combining employment with childrearing. We used data from women aged 30–60 years during 1988–2006 in the US National Health Interview Survey Linked Mortality File and harmonized it with data from Finnish national registers. We found stronger support for hypothesis 1, especially among low-educated women. Contrary to hypothesis 2, combining employment and childrearing was not less beneficial for US women's longevity. In a simulation exercise, more than 75 percent of US women's longevity disadvantage was eliminated by raising their employment levels to Finnish levels and reducing mortality rates of non-married/non-employed US women to Finnish rates. PMID:27773947

Risk Management of Digital Information: A File Format Investigation.

ERIC Educational Resources Information Center

Lawrence, Gregory W.; Kehoe, William R.; Rieger, Oya Y.; Walters, William H.; Kenney, Anne R.

Given the right hardware and software, digital information is easy to create, copy, and disseminate; however it is very hard to preserve. At present, it is impossible to guarantee the longevity and legibility of digital information for even one human generation. Migration can be defined as the periodic transfer of digital materials from one…

takeout-dependent longevity is associated with altered Juvenile Hormone signaling

PubMed Central

Chamseddin, Khalil H.; Khan, Sabina Q.; Nguyen, Mai L.H.; Antosh, Michael; Morris, Siti Nur Sarah; Kolli, Santharam; Neretti, Nicola; Helfand, Stephen L.; Bauer, Johannes H.

2012-01-01

In order to understand the molecular mechanisms of longevity regulation, we recently performed a screen designed to enrich for genes common to several longevity interventions. Using this approach, we identified the Drosophila melanogaster gene takeout. takeout is upregulated in a variety of long-lived flies, and extends life span when overexpressed. Here, we investigate the mechanisms of takeout-dependent longevity. takeout overexpression specifically in the fat body is sufficient to increase fly longevity and is additive to the longevity effects of dietary restriction. takeout long-lived flies do not show phenotypes often associated with increased longevity, such as enhanced stress resistance or major metabolic abnormalities. However, males exhibit greatly diminished courtship behavior, leading to a reduction in fertility. Interestingly, takeout contains a binding domain for Juvenile Hormone, a fly hormone that plays a role in the regulation of developmental transitions. Importantly, the longevity and courtship phenotypes of takeout overexpressing flies are reversed by treatment with the Juvenile Hormone analog methoprene. These data suggest that takeout is a key player in the tradeoff-switch between fertility and longevity. takeout may control fertility via modulation of courtship behavior. This regulation may occur through Juvenile Hormone binding to takeout and a subsequent reduction in Juvenile Hormone signaling activity. PMID:22940452

The journey of resveratrol from yeast to human

PubMed Central

Timmers, Silvie; Auwerx, Johan; Schrauwen, Patrick

2012-01-01

The natural polyphenolic compound resveratrol was first discovered in the 1940s. In the recent years, this compound received renewed interest as several findings implicated resveratrol as a potent SIRT1 activator capable of mimicking the effects of calorie restriction, and regulating longevity in lower organisms. Given the worldwide increase in age-related metabolic diseases the beneficial effects of resveratrol on metabolism and healthy aging in humans are currently a topic of intense investigation. PMID:22436213

Insights into human CD8(+) T-cell memory using the yellow fever and smallpox vaccines.

PubMed

Ahmed, Rafi; Akondy, Rama S

2011-03-01

Live virus vaccines provide a unique opportunity to study human CD8(+) T-cell memory in the context of a controlled, primary acute viral infection. Yellow fever virus-17D and Dryvax are two such live-virus vaccines that are highly efficacious, used worldwide and provide long-term immunity against yellow fever and smallpox respectively. In this review, we describe the properties of virus-specific memory CD8(+) T cells generated in smallpox and yellow fever vaccinees. We address fundamental questions regarding magnitude, functional quality and longevity of the CD8(+) T-cell response, which are otherwise challenging to address in humans. These findings provide insights into the attributes of the human immune system as well as provide a benchmark for the optimal quality of a CD8(+) T-cell response that can be used to evaluate novel candidate vaccines.

Occupational Therapists' Views of Nussbaum's Life Capability: An Exploratory Study.

PubMed

Mousavi, Tahmineh; Dharamsi, Shafik; Forwell, Susan; Dean, Elizabeth

2015-10-01

Life Capability is the first and most fundamental of Nussbaum's 10 Central Human Functional Capabilities (CHFCs). This capability refers to a person having a quality life of normal duration. The purpose of this study was to explore the views' of occupational therapists about Life Capability, specifically, their perspectives of this capability and its perceived relevance to practice. Semi-structured interviews with 14 occupational therapists in British Columbia, Canada, were conducted and thematically analyzed. Within this Canadian context, three themes emerged regarding occupational therapists' views about Life Capability: basic human right, quality of life, and longevity. Occupational therapists appear to view Life Capability as being consistent with the values of the occupational therapy profession. Nussbaum's other CHFCs warrant study to explore the degree to which the Capabilities Approach could complement existing occupational therapy theories, science, and practice. © The Author(s) 2015.

Oxygen availability strongly affects chronological lifespan and thermotolerance in batch cultures of Saccharomyces cerevisiae

PubMed Central

Bisschops, Markus M.; Vos, Tim; Martínez-Moreno, Rubén; Cortés, Pilar T.; Pronk, Jack T.; Daran-Lapujade, Pascale

2015-01-01

Stationary-phase (SP) batch cultures of Saccharomyces cerevisiae, in which growth has been arrested by carbon-source depletion, are widely applied to study chronological lifespan, quiescence and SP-associated robustness. Based on this type of experiments, typically performed under aerobic conditions, several roles of oxygen in aging have been proposed. However, SP in anaerobic yeast cultures has not been investigated in detail. Here, we use the unique capability of S. cerevisiae to grow in the complete absence of oxygen to directly compare SP in aerobic and anaerobic bioreactor cultures. This comparison revealed strong positive effects of oxygen availability on adenylate energy charge, longevity and thermotolerance during SP. A low thermotolerance of anaerobic batch cultures was already evident during the exponential growth phase and, in contrast to the situation in aerobic cultures, was not substantially increased during transition into SP. A combination of physiological and transcriptome analysis showed that the slow post-diauxic growth phase on ethanol, which precedes SP in aerobic, but not in anaerobic cultures, endowed cells with the time and resources needed for inducing longevity and thermotolerance. When combined with literature data on acquisition of longevity and thermotolerance in retentostat cultures, the present study indicates that the fast transition from glucose excess to SP in anaerobic cultures precludes acquisition of longevity and thermotolerance. Moreover, this study demonstrates the importance of a preceding, calorie-restricted conditioning phase in the acquisition of longevity and stress tolerance in SP yeast cultures, irrespective of oxygen availability. PMID:28357268

New clinical findings on the longevity gene in disease, health, & longevity: Sirtuin 1 often decreases with advanced age & serious diseases in most parts of the human body, while relatively high & constant Sirtuin 1 regardless of age was first found in the hippocampus of supercentenarians.

PubMed

Omura, Yoshiaki; Lu, Dominic P; Jones, Marilyn; O'Young, Brian; Duvvi, Harsha; Paluch, Kamila; Shimotsuura, Yasuhiro; Ohki, Motomu

2011-01-01

The expression of the longevity gene, Sirtuin 1, was non-invasively measured using Electro-Magnetic Field (EMF) resonance phenomenon between a known amount of polyclonal antibody of the C-terminal of Sirtuin 1 & Sirtuin 1 molecule inside of the body. Our measurement of over 100 human adult males and females, ranging between 20-122 years old, indicated that the majority of subjects had Sirtuin 1 levels of 5-10 pg BDORT units in most parts of the body. When Sirtuin 1 was less than 1 pg, the majority of the people had various degrees of tumors or other serious diseases. When Sirtuin 1 levels were less than 0.25 pg BDORT units, a high incidence of AIDS was also detected. Very few people had Sirtuin 1 levels of over 25 pg BDORT units in most parts of the body. We selected 7 internationally recognized supercentenarians who lived between 110-122 years old. To our surprise, most of their body Sirtuin 1 levels were between 2.5-10 pg BDORT units. However, by evaluating different parts of the brain, we found that both sides of the Hippocampus had a much higher amount of Sirtuin 1, between 25-100 pg BDORT units. With most subjects, Sirtuin 1 was found to be higher in the Hippocampus than in the rest of the body and remains relatively constant regardless of age. We found that Aspartame, plastic eye contact lenses, and asbestos in dental apparatuses, which reduce normal cell telomeres, also significantly reduce Sirtuin 1. In addition, we found that increasing normal cell telomere by electrical or mechanical stimulation of True ST-36 increases the expression of the Sirtuin 1 gene in people in which expression is low. This measurement of Sirtuin 1 in the Hippocampus has become a reliable indicator for detecting potential longevity of an individual.

Insulin Sensitivity as a Key Mediator of Growth Hormone Actions on Longevity

PubMed Central

Panici, Jacob A.; Bonkowski, Michael S.; Hughes, Larry F.; Bartke, Andrzej

2009-01-01

Reduced insulin sensitivity and glucose intolerance have been long suspected of having important involvement in aging. Here we report that in studies of calorie restriction (CR) effects in mutant (Prop1df and growth hormone receptor knockout [GHRKO]) and normal mice, insulin sensitivity was strongly associated with longevity. Of particular interest was enhancement of the already increased insulin sensitivity in CR df/df mice in which longevity was also further extended and the lack of changes in insulin sensitivity in calorically restricted GHRKO mice in which there was no further increase in average life span. We suggest that enhanced insulin sensitivity, in conjunction with reduced insulin levels, may represent an important (although almost certainly not exclusive) mechanism of increased longevity in hypopituitary, growth hormone (GH)-resistant, and calorie-restricted animals. We also report that the effects of GH treatment on insulin sensitivity may be limited to the period of GH administration. PMID:19304940

[Influence of electromagnetic radiation on toxicity of Vipera lebetina obtusa venom].

PubMed

Abiev, G A; Babaev, E I; Topchieva, Sh A; Chumburidze, T B; Nemsitsveridze, N G

2009-11-01

The aim of the article was to study the effect of electromagnetic radiation on toxicity of Vipera lebetina obtusa venom. It was found that mice intoxicated with snake venom, with moderate to high exposure to electromagnetic radiation and mice intoxicated with venom, which had not been exposed to the radiation showed the same symptoms of intoxication and death. At the same time, the longevity of mice intoxicated with venom exposed to electromagnetic radiation was higher. The longevity of mice in control group was 25+/-5 min. The longevity of mice intoxicated with exposed to electromagnetic radiation snake venom was from 29 to 60 min. The research showed that the longevity of mice intoxicated with snake venom rose with the level of electromagnetic radiation intensity the snake was exposed to. Accordingly, snake venom, with exposure to high intensity electromagnetic radiation is less toxic.

Investigating Connections between Metabolism, Longevity, and Behavior in Caenorhabditis elegans.

PubMed

Lemieux, George A; Ashrafi, Kaveh

2016-08-01

An overview of Caenorhabditis elegans as an experimental organism for studying energy balance is presented. Some of the unresolved questions that complicate the interpretation of lipid measurements from C. elegans are highlighted. We review studies that show that both lipid synthesis and lipid breakdown pathways are activated and needed for the longevity of hermaphrodites that lack their germlines. These findings illustrate the heterogeneity of triglyceride-rich lipid particles in C. elegans and reveal specific lipid signals that promote longevity. Finally, we provide a brief overview of feeding behavioral responses of C. elegans to varying nutritional conditions and highlight an unanticipated metabolic pathway that allows the incorporation of experience in feeding behavior. Copyright © 2016 Elsevier Ltd. All rights reserved.

Should visceral fat be reduced to increase longevity?

PubMed

Finelli, Carmine; Sommella, Luigi; Gioia, Saverio; La Sala, Nicolina; Tarantino, Giovanni

2013-09-01

Several epidemiologic studies have implicated visceral fat as a major risk factor for insulin resistance, type 2 diabetes mellitus, cardiovascular disease, stroke, metabolic syndrome and death. Utilizing novel models of visceral obesity, numerous studies have demonstrated that the relationship between visceral fat and longevity is causal while the accrual of subcutaneous fat does not appear to play an important role in the etiology of disease risk. Specific recommended intake levels vary based on a number of factors, including current weight, activity levels, and weight loss goals. It is discussed the need of reducing the visceral fat as a potential treatment strategy to prevent or delay age-related diseases and to increase longevity. Copyright © 2013 Elsevier B.V. All rights reserved.

Big brains, meat, tuberculosis and the nicotinamide switches: co-evolutionary relationships with modern repercussions on longevity and disease?

PubMed

Williams, Adrian C; Dunbar, Robin I M

2014-07-01

Meat eating has been an important trigger for human evolution however the responsible component in meat has not been clearly identified. Here we propose that the limiting factors for expanding brains and increasing longevity were the micronutrient nicotinamide (vitamin B3) and the metabolically related essential amino-acid, tryptophan. Meat offers significant sourcing challenges and lack causes a deficiency of nicotinamide and tryptophan and consequently the energy carrier nicotinamide adenine dinucleotide (NAD) that gets consumed in regulatory circuits important for survival, resulting in premature ageing, poor cognition and brain atrophy. If a trophic supply of dietary nicotinamide/tryptophan is so essential for building brains, constraining their size and connectivity, we hypothesise that back-up mechanisms to ensure the supply evolved. One strategy may be increasing the reliance on gut symbionts to break down celluloses that produces NADH and only nicotinamide indirectly, and may cause diarrhoea. We suggest that a direct supplier was the chronic mycobacterial infection tuberculosis (TB) that is a surprise candidate but it co-evolved early, does not inevitably cause disease (90-95% of those infected are healthy), and secretes (and is inhibited by) nicotinamide. We hypothesise that TB evolved first as a symbiont that enabled humans to cope with short-lived shortages of meat and only later behaved as a pathogen when the supply deteriorated chronically, for those in poverty. (TB immunology and epidemiology is riddled with paradoxes for a conventional pathogen). We test this in pilot data showing that sharp declines in TB (and diarrhoea) - `environmental enteropathy' strongly correlate with increasing meat consumption and therefore nicotinamide exposure, unlike later onset cancers and Parkinson's disease that increased in incidence, perhaps - as we propose a hypothetical hypervitaminosis B3 (to include obesity and the metabolic syndrome) - as the trade-off for increased brain power and longevity, a recently evolved human characteristic. Copyright © 2014 Elsevier Ltd. All rights reserved.

Stress exposure in early post-natal life reduces telomere length: an experimental demonstration in a long-lived seabird

PubMed Central

Herborn, Katherine A.; Heidinger, Britt J.; Boner, Winnie; Noguera, Jose C.; Adam, Aileen; Daunt, Francis; Monaghan, Pat

2014-01-01

Exposure to stressors early in life is associated with faster ageing and reduced longevity. One important mechanism that could underlie these late life effects is increased telomere loss. Telomere length in early post-natal life is an important predictor of subsequent lifespan, but the factors underpinning its variability are poorly understood. Recent human studies have linked stress exposure to increased telomere loss. These studies have of necessity been non-experimental and are consequently subjected to several confounding factors; also, being based on leucocyte populations, where cell composition is variable and some telomere restoration can occur, the extent to which these effects extend beyond the immune system has been questioned. In this study, we experimentally manipulated stress exposure early in post-natal life in nestling European shags (Phalacrocorax aristotelis) in the wild and examined the effect on telomere length in erythrocytes. Our results show that greater stress exposure during early post-natal life increases telomere loss at this life-history stage, and that such an effect is not confined to immune cells. The delayed effects of increased telomere attrition in early life could therefore give rise to a ‘time bomb’ that reduces longevity in the absence of any obvious phenotypic consequences early in life. PMID:24648221

Mitochondrial DNA haplogroup D4a is a marker for extreme longevity in Japan.

PubMed

Bilal, Erhan; Rabadan, Raul; Alexe, Gabriela; Fuku, Noriyuki; Ueno, Hitomi; Nishigaki, Yutaka; Fujita, Yasunori; Ito, Masafumi; Arai, Yasumichi; Hirose, Nobuyoshi; Ruckenstein, Andrei; Bhanot, Gyan; Tanaka, Masashi

2008-06-11

We report results from the analysis of complete mitochondrial DNA (mtDNA) sequences from 112 Japanese semi-supercentenarians (aged above 105 years) combined with previously published data from 96 patients in each of three non-disease phenotypes: centenarians (99-105 years of age), healthy non-obese males, obese young males and four disease phenotypes, diabetics with and without angiopathy, and Alzheimer's and Parkinson's disease patients. We analyze the correlation between mitochondrial polymorphisms and the longevity phenotype using two different methods. We first use an exhaustive algorithm to identify all maximal patterns of polymorphisms shared by at least five individuals and define a significance score for enrichment of the patterns in each phenotype relative to healthy normals. Our study confirms the correlations observed in a previous study showing enrichment of a hierarchy of haplogroups in the D clade for longevity. For the extreme longevity phenotype we see a single statistically significant signal: a progressive enrichment of certain "beneficial" patterns in centenarians and semi-supercentenarians in the D4a haplogroup. We then use Principal Component Spectral Analysis of the SNP-SNP Covariance Matrix to compare the measured eigenvalues to a Null distribution of eigenvalues on Gaussian datasets to determine whether the correlations in the data (due to longevity) arises from some property of the mutations themselves or whether they are due to population structure. The conclusion is that the correlations are entirely due to population structure (phylogenetic tree). We find no signal for a functional mtDNA SNP correlated with longevity. The fact that the correlations are from the population structure suggests that hitch-hiking on autosomal events is a possible explanation for the observed correlations.

Mitochondrial DNA Haplogroup D4a Is a Marker for Extreme Longevity in Japan

PubMed Central

Bilal, Erhan; Rabadan, Raul; Alexe, Gabriela; Fuku, Noriyuki; Ueno, Hitomi; Nishigaki, Yutaka; Fujita, Yasunori; Ito, Masafumi; Arai, Yasumichi; Hirose, Nobuyoshi; Ruckenstein, Andrei; Bhanot, Gyan; Tanaka, Masashi

2008-01-01

We report results from the analysis of complete mitochondrial DNA (mtDNA) sequences from 112 Japanese semi-supercentenarians (aged above 105 years) combined with previously published data from 96 patients in each of three non-disease phenotypes: centenarians (99–105 years of age), healthy non-obese males, obese young males and four disease phenotypes, diabetics with and without angiopathy, and Alzheimer's and Parkinson's disease patients. We analyze the correlation between mitochondrial polymorphisms and the longevity phenotype using two different methods. We first use an exhaustive algorithm to identify all maximal patterns of polymorphisms shared by at least five individuals and define a significance score for enrichment of the patterns in each phenotype relative to healthy normals. Our study confirms the correlations observed in a previous study showing enrichment of a hierarchy of haplogroups in the D clade for longevity. For the extreme longevity phenotype we see a single statistically significant signal: a progressive enrichment of certain “beneficial” patterns in centenarians and semi-supercentenarians in the D4a haplogroup. We then use Principal Component Spectral Analysis of the SNP-SNP Covariance Matrix to compare the measured eigenvalues to a Null distribution of eigenvalues on Gaussian datasets to determine whether the correlations in the data (due to longevity) arises from some property of the mutations themselves or whether they are due to population structure. The conclusion is that the correlations are entirely due to population structure (phylogenetic tree). We find no signal for a functional mtDNA SNP correlated with longevity. The fact that the correlations are from the population structure suggests that hitch-hiking on autosomal events is a possible explanation for the observed correlations. PMID:18545700

Lifestyle factors of people with exceptional longevity.

PubMed

Rajpathak, Swapnil N; Liu, Yingheng; Ben-David, Orit; Reddy, Saritha; Atzmon, Gil; Crandall, Jill; Barzilai, Nir

2011-08-01

To assess lifestyle factors including physical activity, smoking, alcohol consumption, and dietary habits in men and women with exceptional longevity. Retrospective cohort study. A cohort of community-dwelling Ashkenazi Jewish individuals with exceptional longevity defined as survival and living independently at age 95 and older. Four hundred seventy-seven individuals (mean 97.3 ± 2.8, range 95-109; 74.6% women) and a subset of participants of the National Health and Nutrition Examination Survey (NHANES) I (n = 3,164) representing the same birth cohort as a comparison group. A trained interviewer administrated study questionnaires to collect information on lifestyle factors and collected data on anthropometry. People with exceptional longevity had similar mean body mass index (men, 25.4 ± 2.8 kg/m² vs 25.6 ± 4.0 kg/m² , P=.63; women, 25.0 ± 3.5 kg/m² vs 24.9 ± 5.4 kg/m² ; P = .90) and a similar proportion of daily alcohol consumption (men, 23.9 vs 22.4, P = .77; women, 12.1 vs 11.3, P = .80), of regular physical activity (men: 43.1 vs 57.2; P = .07; women: 47.0 vs 44.1, P = .76), and of a low-calorie diet (men: 20.8 vs 21.1, P=.32; women: 27.3 vs 27.1, P=.14) as the NHANES I population. People with exceptional longevity are not distinct in terms of lifestyle factors from the general population, suggesting that people with exceptional longevity may interact with environmental factors differently than others. This requires further investigation. © 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.

Therapeutic landscapes and longevity: Wellness tourism in Bama.

PubMed

Huang, Liyuan; Xu, Honggang

2018-01-01

Due to the rising demand for healthcare products and concern over environmental pollution, wellness tourism has been booming in China in recent years. The therapeutic landscape theory provides a multi-scale interpretation of wellness tourism to explore how wellness tourists achieve health in healing places. By presenting the results of 83 interviews conducted in Bama, China, this study reveals that the "longevity village" Bama, endorsed by centenarians, provides a retreat that combines natural beauty and a harmonious neighbourhood for wellness tourists. This article argues that although three themes-natural environment, social interaction and symbolic landscape-work together in the healing process of tourists, the symbolic landscape, which is significantly shaped by the longevity culture, plays a dominant role. Longevity in Chinese culture symbolizes the alignment of a strong body, graceful mind, and pleasant habitat. Furthermore, tourism reinforces the importance of symbols and imagination (of a place), the perception of longevity demonstrates the symbolic landscape and thus increases tourists' attachment to the place, and the unusual environment leads to a different therapeutic landscape from that of daily life. Finally, since to date there has been very few works on therapeutic landscapes in China, it is expected that this study will fill the knowledge gap and broaden the scope of application as well as conceptualization of the therapeutic landscape. Copyright © 2017 Elsevier Ltd. All rights reserved.

A regulatory network-based approach dissects late maturation processes related to the acquisition of desiccation tolerance and longevity of Medicago truncatula seeds.

PubMed

Verdier, Jerome; Lalanne, David; Pelletier, Sandra; Torres-Jerez, Ivone; Righetti, Karima; Bandyopadhyay, Kaustav; Leprince, Olivier; Chatelain, Emilie; Vu, Benoit Ly; Gouzy, Jerome; Gamas, Pascal; Udvardi, Michael K; Buitink, Julia

2013-10-01

In seeds, desiccation tolerance (DT) and the ability to survive the dry state for prolonged periods of time (longevity) are two essential traits for seed quality that are consecutively acquired during maturation. Using transcriptomic and metabolomic profiling together with a conditional-dependent network of global transcription interactions, we dissected the maturation events from the end of seed filling to final maturation drying during the last 3 weeks of seed development in Medicago truncatula. The network revealed distinct coexpression modules related to the acquisition of DT, longevity, and pod abscission. The acquisition of DT and dormancy module was associated with abiotic stress response genes, including late embryogenesis abundant (LEA) genes. The longevity module was enriched in genes involved in RNA processing and translation. Concomitantly, LEA polypeptides accumulated, displaying an 18-d delayed accumulation compared with transcripts. During maturation, gulose and stachyose levels increased and correlated with longevity. A seed-specific network identified known and putative transcriptional regulators of DT, including ABSCISIC ACID-INSENSITIVE3 (MtABI3), MtABI4, MtABI5, and APETALA2/ ETHYLENE RESPONSE ELEMENT BINDING PROTEIN (AtAP2/EREBP) transcription factor as major hubs. These transcriptional activators were highly connected to LEA genes. Longevity genes were highly connected to two MtAP2/EREBP and two basic leucine zipper transcription factors. A heat shock factor was found at the transition of DT and longevity modules, connecting to both gene sets. Gain- and loss-of-function approaches of MtABI3 confirmed 80% of its predicted targets, thereby experimentally validating the network. This study captures the coordinated regulation of seed maturation and identifies distinct regulatory networks underlying the preparation for the dry and quiescent states.

Effect of Smaller Left Ventricular Capture Threshold Safety Margins to Improve Device Longevity in Recipients of Cardiac Resynchronization-Defibrillation Therapy.

PubMed

Steinhaus, Daniel A; Waks, Jonathan W; Collins, Robert; Kleckner, Karen; Kramer, Daniel B; Zimetbaum, Peter J

2015-07-01

Device longevity in cardiac resynchronization therapy (CRT) is affected by the pacing capture threshold (PCT) and programmed pacing amplitude of the left ventricular (LV) pacing lead. The aims of this study were to evaluate the stability of LV pacing thresholds in a nationwide sample of CRT defibrillator recipients and to determine potential longevity improvements associated with a decrease in the LV safety margin while maintaining effective delivery of CRT. CRT defibrillator patients in the Medtronic CareLink database were eligible for inclusion. LV PCT stability was evaluated using ≥2 measurements over a 14-day period. Separately, a random sample of 7,250 patients with programmed right atrial and right ventricular amplitudes ≤2.5 V, LV thresholds ≤ 2.5 V, and LV pacing ≥90% were evaluated to estimate theoretical battery longevity improvement using LV safety margins of 0.5 and 1.5 V. Threshold stability analysis in 43,256 patients demonstrated LV PCT stability of <0.5 V in 77% of patients and <1 V in 95%. Device longevity analysis showed that the use of a 0.5-V safety margin increased average battery longevity by 0.62 years (95% confidence interval 0.61 to 0.63) compared with a safety margin of 1.5 V. Patients with LV PCTs >1 V had the greatest increases in battery life (mean increase 0.86 years, 95% confidence interval 0.85 to 0.87). In conclusion, nearly all CRT defibrillator patients had LV PCT stability <1.0 V. Decreasing the LV safety margin from 1.5 to 0.5 V provided consistent delivery of CRT for most patients and significantly improved battery longevity. Copyright © 2015 Elsevier Inc. All rights reserved.

A Regulatory Network-Based Approach Dissects Late Maturation Processes Related to the Acquisition of Desiccation Tolerance and Longevity of Medicago truncatula Seeds1[C][W][OPEN

PubMed Central

Verdier, Jerome; Lalanne, David; Pelletier, Sandra; Torres-Jerez, Ivone; Righetti, Karima; Bandyopadhyay, Kaustav; Leprince, Olivier; Chatelain, Emilie; Vu, Benoit Ly; Gouzy, Jerome; Gamas, Pascal; Udvardi, Michael K.; Buitink, Julia

2013-01-01

In seeds, desiccation tolerance (DT) and the ability to survive the dry state for prolonged periods of time (longevity) are two essential traits for seed quality that are consecutively acquired during maturation. Using transcriptomic and metabolomic profiling together with a conditional-dependent network of global transcription interactions, we dissected the maturation events from the end of seed filling to final maturation drying during the last 3 weeks of seed development in Medicago truncatula. The network revealed distinct coexpression modules related to the acquisition of DT, longevity, and pod abscission. The acquisition of DT and dormancy module was associated with abiotic stress response genes, including late embryogenesis abundant (LEA) genes. The longevity module was enriched in genes involved in RNA processing and translation. Concomitantly, LEA polypeptides accumulated, displaying an 18-d delayed accumulation compared with transcripts. During maturation, gulose and stachyose levels increased and correlated with longevity. A seed-specific network identified known and putative transcriptional regulators of DT, including ABSCISIC ACID-INSENSITIVE3 (MtABI3), MtABI4, MtABI5, and APETALA2/ ETHYLENE RESPONSE ELEMENT BINDING PROTEIN (AtAP2/EREBP) transcription factor as major hubs. These transcriptional activators were highly connected to LEA genes. Longevity genes were highly connected to two MtAP2/EREBP and two basic leucine zipper transcription factors. A heat shock factor was found at the transition of DT and longevity modules, connecting to both gene sets. Gain- and loss-of-function approaches of MtABI3 confirmed 80% of its predicted targets, thereby experimentally validating the network. This study captures the coordinated regulation of seed maturation and identifies distinct regulatory networks underlying the preparation for the dry and quiescent states. PMID:23929721

Survival of influenza virus on hands and fomites in community and laboratory settings.

PubMed

Mukherjee, Dhritiman V; Cohen, Bevin; Bovino, Mary Ellen; Desai, Shailesh; Whittier, Susan; Larson, Elaine L

2012-09-01

Transmission dynamics modeling provides a practical method for virtual evaluation of the impact of public health interventions in response to prospective influenza pandemics and also may help determine the relative contribution of different modes of transmission to overall infection rates. Accurate estimates of longevity for all forms of viral particles are needed for such models to be useful. We conducted a time course study to determine the viability and longevity of H1N1 virus on naturally contaminated hands and household surfaces of 20 individuals with laboratory-confirmed infection. Participants coughed or sneezed into their hands, which were sampled immediately and again after 5, 10, and 30 minutes. Samples also were obtained from household surfaces handled by the participants immediately after coughing/sneezing. Clinically obtained H1N1 isolates were used to assess the viability and longevity of the virus on various artificially inoculated common household surfaces and human hands in a controlled laboratory setting. Viral detection was achieved by culture and real-time reverse-transcriptase polymerase chain reaction. The results suggest that H1N1 does not survive long on naturally contaminated skin and fomites, and that secretions deposited on hands by coughing or sneezing have a concentration of <2.15 × 10 to 2.94 × 10 TCID(50)/mL. These data can be used to estimate the relative contribution of direct and indirect contact transmission on overall infection rates. Copyright © 2012 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Genetic Biomarkers for ALS Disease in Transgenic SOD1G93A Mice

PubMed Central

Calvo, Ana C.; Manzano, Raquel; Atencia-Cibreiro, Gabriela; Oliván, Sara; Muñoz, María J.; Zaragoza, Pilar; Cordero-Vázquez, Pilar; Esteban-Pérez, Jesús; García-Redondo, Alberto; Osta, Rosario

2012-01-01

The pathophysiological mechanisms of both familial and sporadic Amyotrophic Lateral Sclerosis (ALS) are unknown, although growing evidence suggests that skeletal muscle tissue is a primary target of ALS toxicity. Skeletal muscle biopsies were performed on transgenic SOD1G93A mice, a mouse model of ALS, to determine genetic biomarkers of disease longevity. Mice were anesthetized with isoflurane, and three biopsy samples were obtained per animal at the three main stages of the disease. Transcriptional expression levels of seventeen genes, Ankrd1, Calm1, Col19a1, Fbxo32, Gsr, Impa1, Mef2c, Mt2, Myf5, Myod1, Myog, Nnt, Nogo A, Pax7, Rrad, Sln and Snx10, were tested in each muscle biopsy sample. Total RNA was extracted using TRIzol Reagent according to the manufacturer's protocol, and variations in gene expression were assayed by real-time PCR for all of the samples. The Pearson correlation coefficient was used to determine the linear correlation between transcriptional expression levels throughout disease progression and longevity. Consistent with the results obtained from total skeletal muscle of transgenic SOD1G93A mice and 74-day-old denervated mice, five genes (Mef2c, Gsr, Col19a1, Calm1 and Snx10) could be considered potential genetic biomarkers of longevity in transgenic SOD1G93A mice. These results are important because they may lead to the exploration of previously unexamined tissues in the search for new disease biomarkers and even to the application of these findings in human studies. PMID:22412900

Jurors' Responses to "Longevity and the Secondary Theatre Arts Teacher: A Case Study."

ERIC Educational Resources Information Center

Klein, Jeanne

1999-01-01

Responds to an article in the same issue of this journal which examines factors influencing longevity in the career of a particular high school theatre arts teacher. Notes responses of some jurors regarding methodological concerns and theoretical grounding, but appreciates the writer's personal affinity with her subject and welcomes the…

Association of exceptional parental longevity and physical function in aging.

PubMed

Ayers, Emmeline; Barzilai, Nir; Crandall, Jill P; Milman, Sofiya; Verghese, Joe

2014-01-01

Offspring of parents with exceptional longevity (OPEL), who are more likely to carry longevity-associated genotypes, may age more successfully than offspring of parents with usual survival (OPUS). Maintenance of physical function is a key attribute of successful aging. While many genetic and non-genetic factors interact to determine physical phenotype in aging, examination of the contribution of exceptional parental longevity to physical function in aging is limited. The LonGenity study recruited a relatively genetically homogenous cohort of Ashkenazi Jewish (AJ) adults age 65 and older, who were defined as either OPEL (having at least one parent who lived to age 95 or older) or OPUS (neither parent survived to age 95). Subjective and objective measures of physical function were compared between the two groups, accounting for potential confounders. Of the 893 LonGenity subjects, 365 were OPEL and 528 were OPUS. OPEL had better objective and subjective measures of physical function than OPUS, especially on unipedal stance (p = 0.009) and gait speed (p = 0.002). Results support the protective role of exceptional parental longevity in preventing decline in physical function, possibly via genetic mechanisms that should be further explored.

Reprogramming somatic cell differentiation and the Hayflick Limit: contrasting two modern molecular bioengineering aims and their impact on the future of mankind.

PubMed

Sills, E S; Takeuchi, T; Rosenwaks, Z; Palermo, G D

2001-08-01

The molecular biology of human cloning and aging research depend on the closely related laboratory techniques supported by a thorough understanding of cell-signaling processes. Unfortunately, the link between these two research fields has received only marginal attention in the lay press. Cloning is possible when somatic cell differentiation is successfully reprogrammed, and clinical control of cellular senescence depends on a proper reconfiguration of the predetermined number of divisions permitted during the cell life-cycle (the so-called "Hayflick Limit"). In this paper, we discuss these two concepts and compare the impact likely to be associated with bioengineering studies that facilitate both human cloning and longevity therapy.

Development of reference transcriptomes for the major insect pests of cowpea: a toolbox for insect pest management approaches in West Africa

USDA-ARS?s Scientific Manuscript database

Cowpea crops are widely cultivated and a major nutritional source of protein for indigenous human populations in West Africa. Annual yields and longevity of grain storage is greatly reduced by feeding damage caused by a complex of insect pests that include Anoplocnemis curvipes, Aphis craccivora, Cl...

The mighty oak faces challenges in the Pacific West

Treesearch

Gail Wells

2010-01-01

In popular imagination, the oak tree stands for strength, endurance, and longevity. But in the coastal lowlands and central valleys of British Columbia, Washington, Oregon, and California, oaks face a battery of natural and human-induced threats. Sudden oak death, caused by a virulent pathogen identified in 2000, has killed millions of tanoaks, California black oaks,...

Regional Distribution of Longevity Population and Elements in Drinking Water in Jiangjin District, Chongqing City, China.

PubMed

Liu, Yonglin; Yuan, Yuyang; Luo, Kunli

2017-10-25

In order to determine the spatial variation of longevity population and elements contained in the drinking water of longevity region in Jiangjin and investigate the relationship between the elements in drinking water and longevity, population censuses on township level and 98 drinking water samples from Jiangjin District, Chongqing City in West China were collected and analyzed. Population statistics on township level showed that the number of centenarians per 100,000 inhabitants (OC), centenarity index (CI), and number of centenarians per 10,000 over 65-year-old subjects (UC) present obvious geographic distribution properties, generally Central region > Northern region > Southern region (Kruskal-Wallis test, p < 0.05). Moderate hard water (150 mg/L < total hardness (TH) = 156.17 mg/L < 300 mg/L) was mainly found in drinking water from longevity township (OC > 7.5) in Jiangjin District, whereas soft water (75 mg/L < TH = 111.23 mg/L < 150 mg/L) was mostly in non-longevity township (OC < 7.5). The mean concentration of strontium (Sr) (0.73 mg/L) in drinking water from the longevity township was apparently higher than that of non-longevity township (0.44 mg/L) (Mann-Whitney U test, p = 0.019 < 0.05). The concentrations of Ba, Li, Mn, Ni, and Se in drinking water from longevity township were also higher than those of non-longevity township (Mann-Whitney U test, p < 0.05). The research indicates that exercising strict control over the concentrations of TH, Sr, Ba, Li, Mn, Ni, and Se in drinking water might be good for the health and prolong people's life.

Sugar and Multivitamin Diet Effects on The Longevity and Mating Capacity of Laboratory-Reared Male Anopheline Mosquitoes.

PubMed

Phasomkusolsil, Siriporn; Pantuwatana, Kanchana; Tawong, Jaruwan; Khongtak, Weeraphan; Kertmanee, Yossasin; Monkanna, Nantaporn; Khaosanorh, Sakon; Wanja, Elizabeth W; Davidson, Silas A

2017-09-01

Successful mating by male mosquitoes is dependent on several factors, with sugar feeding being particularly important. The effect of ingested vitamins on adult male mosquitoes is poorly understood. This laboratory study used 3 anopheline species, Anopheles campestris, An. dirus, and An. sawadwongporni, to study the effect of sugar and vitamins on male longevity, copulation, and fecundity. Males were fed 1 of 5 diets containing different combinations of sugar and vitamins: 10% glucose, 10% sucrose, 10% multivitamin syrup, 10% multivitamin syrup + 10% glucose, and 10% multivitamin syrup + 10% sucrose. The longevity of males was measured for a period of 15 days. Forced mating was used to simulate copulation, and fecundity was measured by counting the number of eggs oviposited and the hatch rate of larvae. The longevity of An. campestris and An. dirus was greatest when fed a diet of 10% multivitamin syrup + 10% glucose, and the longevity of An. sawadwongporni was greatest when fed a diet of 10% multivitamin syrup + 10% sucrose. The 1st mating routinely produced the most viable eggs when males were mated with several females. The diet of 10% multivitamin syrup + 10% sucrose produced numerically greater egg production and larval emergence for all 3 species, although this was not always statistically significant due to variability and small sample size. These results indicate that the addition of multivitamin syrup to sucrose may produce healthier and more fit male anophelines. This has potential implications for increasing insectary operations and improving the fitness of laboratory-reared male mosquitoes that will be released for mosquito and disease-pathogen control studies.

Snag longevity in managed northern hardwoods

Treesearch

Mariko Yamasaki; William B. Leak

2006-01-01

Little information on standing snag and coarse woody debris longevity exists for New England forest types. Forest managers thus lack the information on changes over time of the habitat components influenced by the decay process. We examined the fate of 568 snags that occurred on a long-term hardwood growth study on the Bartlett Experimental Forest, NH. Approximately...

Evaluating the virulence and longevity of non-woven fiber bands impregnated with Metarhizium anisopliae against the Asian longhorned beetle, Anoplophora glabripennis (Coleoptera: Cerambycidae)

Treesearch

Ryan P. Shanley; Melody Keena; Micheal M. Wheeler; Jarrod Leland; Ann E. Hajek

2009-01-01

Fiber bands impregnated with entomopathogenic fungi (=fungal bands) provide an effective method for controlling the invasive Asian longhorned beetle, Anoplophora glabripennis (Motschulsky) (Coleoptera: Cerambycidae). In this study we investigated the effective longevity of fungal bands for use against A. glabripennis, using...

Ponderosa pine forest restoration treatment longevity: Implications of regeneration on fire hazard

Treesearch

Wade T. Tinkham; Chad M. Hoffman; Seth A. Ex; Michael A. Battaglia; Jarred D. Saralecos

2016-01-01

Restoration of pine forests has become a priority for managers who are beginning to embrace ideas of highly heterogeneous forest structures that potentially encourages high levels of regeneration. This study utilizes stem-mapped stands to assess how simulated regeneration timing and magnitude influence longevity of reduced fire behavior by linking growth and...

Psychosocial Dimensions of Exceptional Longevity: A Qualitative Exploration of Centenarians' Experiences, Personality, and Life Strategies

ERIC Educational Resources Information Center

Darviri, Christina; Demakakos, Panayotes; Tigani, Xanthi; Charizani, Fotini; Tsiou, Chrysoula; Tsagkari, Christina; Chliaoutakis, Joannes; Monos, Dimitrios

2009-01-01

This qualitative study provides a comprehensive account of the social and life experiences and strategies and personality attributes that characterize exceptional longevity (living to 100 or over). It is based on nine semi-structured interviews of relatively healthy and functional Greek centenarians of both sexes. The analytic approach was…

Fuel treatment longevity in a Sierra Nevada mixed conifer forest

Treesearch

Scott. L. Stephens; Brandon M. Collins; Gary. Roller

2012-01-01

Understanding the longevity of fuel treatments in terms of their ability to maintain fire behavior and effects within a desired range is an important question. The objective of this study was to determine how fuels, forest structure, and predicted fire behavior changed 7-years after initial treatments. Three different treatments: mechanical only, mechanical plus fire,...

Lower circulating insulin-like growth factor-I is associated with better cognition in females with exceptional longevity without compromise to muscle mass and function.

PubMed

Perice, Leland; Barzilai, Nir; Verghese, Joe; Weiss, Erica F; Holtzer, Roee; Cohen, Pinchas; Milman, Sofiya

2016-10-14

Mutations that reduce somatotropic signaling result in improved lifespan and health-span in model organisms and humans. However, whether reduced circulating insulin-like growth factor-I (IGF-I) level is detrimental to cognitive and muscle function in older adults remains understudied. A cross-sectional analysis was performed in Ashkenazi Jews with exceptional longevity (age ≥95 years). Cognition was assessed using the Mini-Mental State Examination and muscle function with the chair rise test, grip-strength, and gait speed. Muscle mass was estimated using the skeletal muscle index. Serum IGF-I was measured with liquid chromatography mass spectrometry. In gender stratified age-adjusted logistic regression analysis, females with IGF-I levels in the first tertile had lower odds of being cognitively impaired compared to females with IGF-I levels within the upper two tertiles, OR (95% CI) 0.39 (0.19-0.82). The result remained significant after adjustment for multiple parameters. No significant association was identified in males between IGF-I and cognition. No relationship was found between IGF-I tertiles and muscle function and muscle mass in females or males. Lower circulating IGF-I is associated with better cognitive function in females with exceptional longevity, with no detriment to skeletal muscle mass and function.

Increases in the longevity of desiccation-phase developing rice seeds: response to high-temperature drying depends on harvest moisture content

PubMed Central

Whitehouse, K. J.; Hay, F. R.; Ellis, R. H.

2015-01-01

Background and Aims Previous studies have suggested that the drying conditions routinely used by genebanks may not be optimal for subsequent seed longevity. The aim of this study was to compare the effect of hot-air drying and low-temperature drying on subsequent seed longevity for 20 diverse rice accessions and to consider how factors related to seed production history might influence the results. Methods Seeds of rice, Oryza sativa, were produced according to normal regeneration procedures at IRRI. They were harvested at different times [harvest date and days after anthesis (DAA), once for each accession] and dried either in a drying room (DR; 15 % relative humidity, 15 °C) or in a flat-bed heated-air batch dryer (BD; 45 °C, 8 h d–1) for up to six daily cycles followed by drying in the DR. Relative longevity was assessed by storage at 10·9 % moisture content and 45 °C. Key Results Initial drying in the BD resulted in significantly greater longevity compared with the DR for 14 accessions (seed lots): the period of time for viability to fall to 50 % for seeds dried in the BD as a percentage of that for seeds dried throughout in the DR varied between 1.3 and 372·2 % for these accessions. The seed lots that responded the most were those that were harvested earlier in the season and at higher moisture content. Drying in the BD did not reduce subsequent longevity compared with DR drying for any of the remaining accessions. Conclusions Seeds harvested at a moisture content where, according to the moisture desorption isotherm, they could still be metabolically active (>16·2 %) may be in the first stage of the post-mass maturity, desiccation phase of seed development and thus able to increase longevity in response to hot-air drying. The genebank standards regarding seed drying for rice and, perhaps, for other tropical species should therefore be reconsidered. PMID:26133688

Increases in the longevity of desiccation-phase developing rice seeds: response to high-temperature drying depends on harvest moisture content.

PubMed

Whitehouse, K J; Hay, F R; Ellis, R H

2015-08-01

Previous studies have suggested that the drying conditions routinely used by genebanks may not be optimal for subsequent seed longevity. The aim of this study was to compare the effect of hot-air drying and low-temperature drying on subsequent seed longevity for 20 diverse rice accessions and to consider how factors related to seed production history might influence the results. Seeds of rice, Oryza sativa, were produced according to normal regeneration procedures at IRRI. They were harvested at different times [harvest date and days after anthesis (DAA), once for each accession] and dried either in a drying room (DR; 15 % relative humidity, 15 °C) or in a flat-bed heated-air batch dryer (BD; 45 °C, 8 h d(-1)) for up to six daily cycles followed by drying in the DR. Relative longevity was assessed by storage at 10·9 % moisture content and 45 °C. Initial drying in the BD resulted in significantly greater longevity compared with the DR for 14 accessions (seed lots): the period of time for viability to fall to 50 % for seeds dried in the BD as a percentage of that for seeds dried throughout in the DR varied between 1.3 and 372·2 % for these accessions. The seed lots that responded the most were those that were harvested earlier in the season and at higher moisture content. Drying in the BD did not reduce subsequent longevity compared with DR drying for any of the remaining accessions. Seeds harvested at a moisture content where, according to the moisture desorption isotherm, they could still be metabolically active (>16·2 %) may be in the first stage of the post-mass maturity, desiccation phase of seed development and thus able to increase longevity in response to hot-air drying. The genebank standards regarding seed drying for rice and, perhaps, for other tropical species should therefore be reconsidered. © The Author 2015. Published by Oxford University Press on behalf of the Annals of Botany Company.

Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits.

PubMed

Teumer, Alexander; Qi, Qibin; Nethander, Maria; Aschard, Hugues; Bandinelli, Stefania; Beekman, Marian; Berndt, Sonja I; Bidlingmaier, Martin; Broer, Linda; Cappola, Anne; Ceda, Gian Paolo; Chanock, Stephen; Chen, Ming-Huei; Chen, Tai C; Chen, Yii-Der Ida; Chung, Jonathan; Del Greco Miglianico, Fabiola; Eriksson, Joel; Ferrucci, Luigi; Friedrich, Nele; Gnewuch, Carsten; Goodarzi, Mark O; Grarup, Niels; Guo, Tingwei; Hammer, Elke; Hayes, Richard B; Hicks, Andrew A; Hofman, Albert; Houwing-Duistermaat, Jeanine J; Hu, Frank; Hunter, David J; Husemoen, Lise L; Isaacs, Aaron; Jacobs, Kevin B; Janssen, Joop A M J L; Jansson, John-Olov; Jehmlich, Nico; Johnson, Simon; Juul, Anders; Karlsson, Magnus; Kilpelainen, Tuomas O; Kovacs, Peter; Kraft, Peter; Li, Chao; Linneberg, Allan; Liu, Yongmei; Loos, Ruth J F; Lorentzon, Mattias; Lu, Yingchang; Maggio, Marcello; Magi, Reedik; Meigs, James; Mellström, Dan; Nauck, Matthias; Newman, Anne B; Pollak, Michael N; Pramstaller, Peter P; Prokopenko, Inga; Psaty, Bruce M; Reincke, Martin; Rimm, Eric B; Rotter, Jerome I; Saint Pierre, Aude; Schurmann, Claudia; Seshadri, Sudha; Sjögren, Klara; Slagboom, P Eline; Strickler, Howard D; Stumvoll, Michael; Suh, Yousin; Sun, Qi; Zhang, Cuilin; Svensson, Johan; Tanaka, Toshiko; Tare, Archana; Tönjes, Anke; Uh, Hae-Won; van Duijn, Cornelia M; van Heemst, Diana; Vandenput, Liesbeth; Vasan, Ramachandran S; Völker, Uwe; Willems, Sara M; Ohlsson, Claes; Wallaschofski, Henri; Kaplan, Robert C

2016-10-01

The growth hormone/insulin-like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF-related proteins including IGF-I and IGF-binding protein-3 (IGFBP-3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Through genomewide association study of up to 30 884 adults of European ancestry from 21 studies, we confirmed and extended the list of previously identified loci associated with circulating IGF-I and IGFBP-3 concentrations (IGF1, IGFBP3, GCKR, TNS3, GHSR, FOXO3, ASXL2, NUBP2/IGFALS, SORCS2, and CELSR2). Significant sex interactions, which were characterized by different genotype-phenotype associations between men and women, were found only for associations of IGFBP-3 concentrations with SNPs at the loci IGFBP3 and SORCS2. Analyses of SNPs, gene expression, and protein levels suggested that interplay between IGFBP3 and genes within the NUBP2 locus (IGFALS and HAGH) may affect circulating IGF-I and IGFBP-3 concentrations. The IGF-I-decreasing allele of SNP rs934073, which is an eQTL of ASXL2, was associated with lower adiposity and higher likelihood of survival beyond 90 years. The known longevity-associated variant rs2153960 (FOXO3) was observed to be a genomewide significant SNP for IGF-I concentrations. Bioinformatics analysis suggested enrichment of putative regulatory elements among these IGF-I- and IGFBP-3-associated loci, particularly of rs646776 at CELSR2. In conclusion, this study identified several loci associated with circulating IGF-I and IGFBP-3 concentrations and provides clues to the potential role of the IGF axis in mediating effects of known (FOXO3) and novel (ASXL2) longevity-associated loci. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Honey bee (Apis mellifera) workers live longer in small than in large colonies

PubMed Central

Rueppell, Olav; Kaftanouglu, Osman; Page, Robert E.

2009-01-01

Social insect colonies are highly integrated units that can be regarded in some respects as superorganisms, with colony size and individuals analogous to body size and cells in unitary organisms. In both, unitary organisms and superorganisms, the relation between body/colony size and lifespan of the constituent units (cells/individuals) is important for understanding systemic aging but remains to be explored. Therefore, this study compared the life-history and longevity of individual honey bee workers between a large and a small colony social environment. We found that individuals in large colonies were consistently shorter lived than individuals in small colonies. This experimental effect occurred in both principal life history phases of honey bee workers, the in-hive and the foraging stage, independently of the age of the workers at their transition between the two. Nevertheless, this age of first foraging was a key determinant of worker longevity, in accordance with previous studies. The large colonies raised more brood, built more comb, and foraged at higher rates. Our results do not comply with the idea that social group size has a positive effect on individual longevity. Instead, our findings suggest that large and small colonies follow different demographic growth trajectories, trading off longevity of individuals for overall colony growth. Similarly, multi-cellular organisms might sacrifice maintenance and repair of their individual constituent cells for enhanced metabolic activity and organismal growth, leading to the widely-observed negative correlation between longevity and body size within species. PMID:19389467

Life History Traits of an Extended Longevity Phenotype of Drosophila melanogaster.

PubMed

Deepashree, S; Shivanandappa, T; Ramesh, S R

2017-01-01

Aging or senescence is a complex biological phenomenon. Artificially selected Drosophila for extended longevity is one of the experimental models used to understand the mechanisms involved in aging and to test various theories. To examine the life history traits and biochemical defenses in relation to aging in an extended longevity phenotype of Drosophila melanogaster. Life history traits viz., survivability, fecundity, development time, dry weight, wing size, lipid content, starvation, desiccation and cold resistances, locomotory ability, antioxidant enzyme activities and reactive oxygen species level between control and selected lines of D. melanogaster were investigated. In our model of Drosophila, extended longevity is associated with no trade-off in fecundity and shows variable resistance to environmental stress such as starvation, cold and desiccation. Enhanced biochemical defense involving the antioxidant enzymes was positively correlated with longevity. Extended longevity phenotypes of Drosophila represent genomic plasticity associated with variable life history traits attributed to the genetic background of the progenitor population and the environment of selection. Oxidative stress resistance seems to be a significant factor in longevity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Longevity extension of worker honey bees (Apis mellifera) by royal jelly: optimal dose and active ingredient

PubMed Central

Han, Mingfeng

2017-01-01

In the Western honey bee, Apis mellifera, queens and workers have different longevity although they share the same genome. Queens consume royal jelly (RJ) as the main food throughout their life, including as adults, but workers only eat worker jelly when they are larvae less than 3 days old. In order to explore the effect of RJ and the components affecting longevity of worker honey bees, we first determined the optimal dose for prolonging longevity of workers as 4% RJ in 50% sucrose solution, and developed a method of obtaining long lived workers. We then compared the effects of longevity extension by RJ 4% with bee-collected pollen from rapeseed (Brassica napus). Lastly, we determined that a water soluble RJ protein obtained by precipitation with 60% ammonium sulfate (RJP60) contained the main component for longevity extension after comparing the effects of RJ crude protein extract (RJCP), RJP30 (obtained by precipitation with 30% ammonium sulfate), and RJ ethanol extract (RJEE). Understanding what regulates worker longevity has potential to help increase colony productivity and improve crop pollination efficiency. PMID:28367370

Longevity extension of worker honey bees (Apis mellifera) by royal jelly: optimal dose and active ingredient.

PubMed

Yang, Wenchao; Tian, Yuanyuan; Han, Mingfeng; Miao, Xiaoqing

2017-01-01

In the Western honey bee, Apis mellifera , queens and workers have different longevity although they share the same genome. Queens consume royal jelly (RJ) as the main food throughout their life, including as adults, but workers only eat worker jelly when they are larvae less than 3 days old. In order to explore the effect of RJ and the components affecting longevity of worker honey bees, we first determined the optimal dose for prolonging longevity of workers as 4% RJ in 50% sucrose solution, and developed a method of obtaining long lived workers. We then compared the effects of longevity extension by RJ 4% with bee-collected pollen from rapeseed ( Brassica napus ). Lastly, we determined that a water soluble RJ protein obtained by precipitation with 60% ammonium sulfate (RJP 60 ) contained the main component for longevity extension after comparing the effects of RJ crude protein extract (RJCP), RJP 30 (obtained by precipitation with 30% ammonium sulfate), and RJ ethanol extract (RJEE). Understanding what regulates worker longevity has potential to help increase colony productivity and improve crop pollination efficiency.

A comparative cellular and molecular biology of longevity database.

PubMed

Stuart, Jeffrey A; Liang, Ping; Luo, Xuemei; Page, Melissa M; Gallagher, Emily J; Christoff, Casey A; Robb, Ellen L

2013-10-01

Discovering key cellular and molecular traits that promote longevity is a major goal of aging and longevity research. One experimental strategy is to determine which traits have been selected during the evolution of longevity in naturally long-lived animal species. This comparative approach has been applied to lifespan research for nearly four decades, yielding hundreds of datasets describing aspects of cell and molecular biology hypothesized to relate to animal longevity. Here, we introduce a Comparative Cellular and Molecular Biology of Longevity Database, available at ( http://genomics.brocku.ca/ccmbl/ ), as a compendium of comparative cell and molecular data presented in the context of longevity. This open access database will facilitate the meta-analysis of amalgamated datasets using standardized maximum lifespan (MLSP) data (from AnAge). The first edition contains over 800 data records describing experimental measurements of cellular stress resistance, reactive oxygen species metabolism, membrane composition, protein homeostasis, and genome homeostasis as they relate to vertebrate species MLSP. The purpose of this review is to introduce the database and briefly demonstrate its use in the meta-analysis of combined datasets.

National Pork Producers Council Maternal Line National Genetic Evaluation Program: a comparison of sow longevity and trait associations with sow longevity.

PubMed

Serenius, T; Stalder, K J; Baas, T J; Mabry, J W; Goodwin, R N; Johnson, R K; Robison, O W; Tokach, M; Miller, R K

2006-09-01

Data from the National Pork Producers Council Maternal Line National Genetic Evaluation Program were used to compare longevity of sows from 6 commercial genetic lines and to estimate the phenotypic associations of sow longevity with gilt backfat thickness, ADG, age at first farrowing, litter size at first farrowing, litter weight at first farrowing, average feed intake during lactation, and average backfat loss during lactation. The lines evaluated were American Diamond Genetics, Danbred North America, Dekalb-Monsanto DK44, Dekalb-Monsanto GPK347, Newsham Hybrids, and National Swine Registry. The data set contained information from 3,251 gilts, of which 17% had censored longevity records (sows lived longer than 6 parities). The line comparison was carried out by analyzing all lines simultaneously. Because the survival distribution functions differed among genetic lines, later analyses were carried out separately for each genetic line. All analyses were based on the non-parametric proportional hazard (Cox model). Dekalb-Monsanto GPK347 sows had a lower risk of being culled than sows from the other lines. Moreover, the shape of the survival distribution function of the Delkab-Monsanto GPK347 line was different from the other 5 lines. The Dekalb-Monsanto 347 line had lower culling rates because they had lower gilt reproductive failure before the first parity than gilts from the other lines. Within line, sows with lower feed intake and greater backfat loss during lactation had a shorter productive lifetime. Thus, producers should implement management practices having positive effects on sow lactation feed intake. Additionally, the swine genetics industry is challenged to simultaneously improve efficiency of gain of their terminal market pigs and to obtain high feed intake during lactation of their maternal lines for future improvement of sow longevity. Recording sow feed intake and backfat loss during lactation in nucleus and multiplication breeding herds should be considered. Between-line differences in this study indicate that it is possible to select for sow longevity, but more research is needed to determine the most efficient selection methods to improve sow longevity.

Effect of tooth brush abrasion and thermo-mechanical loading on direct and indirect veneer restorations.

PubMed

Rosentritt, Martin; Sawaljanow, Alexander; Behr, Michael; Kolbeck, Carola; Preis, Verena

2015-01-01

This study investigated toothbrush abrasion and in vitro aging on ceramic (indirect technique) and composite veneers (direct technique). Identical composite and individual human incisors were restored with industrially preformed composite veneers, indirectly produced ceramic veneers, and direct composite restorations. Surface roughness was determined before and after tooth brushing. A 5-year period of oral service was simulated by thermal cycling and mechanical loading (TCML). After TCML, all specimens were examined with microscopy and scanning electron microscopy. Specimens without failures during TCML were loaded until failure. analysis of variance; Bonferroni's post hoc analysis, Kaplan-Meier-Log Rank test (α = 0.05). Tooth brushing yielded a non-significant increase (p = 0.560) in roughness in all materials (industrial veneer, 0.12+/-0.07 μm, direct restoration, 0.18+/-0.14 μm, ceramic, 0.35+/-0.16 μm). No significant differences in roughness could be determined between the materials, neither before nor after testing (p < 0.001). After TCML of artificial teeth, direct and preformed composite veneers on composite teeth showed no failures or damages. Two ceramic veneers showed cracking in the labial area. After TCML of human teeth, transmission microscopy indicated a facial crack in a ceramic veneer and chipping in the cervical area of a preformed veneer. Two direct composite veneers lost retention. No significantly different survival rates were found between the three veneer groups. Fracture force on human teeth varied between 527.8+/-132.4 N (ceramic), 478.3+/-165.4 N (preformed composite), and 605.0+/-263.5 N (direct composite). All materials revealed comparable wear resistance. Indirect ceramic, direct restorative composite, and preformed composite veneers showed comparable failure rates and satisfying longevity. The results indicate similar longevity of the chosen materials for veneer restorations.

Assaying environmental nickel toxicity using model nematodes

USGS Publications Warehouse

Rudel, David; Douglas, Chandler; Huffnagle, Ian; Besser, John M.; Ingersoll, Christopher G.

2013-01-01

Although nickel exposure results in allergic reactions, respiratory conditions, and cancer in humans and rodents, the ramifications of excess nickel in the environment for animal and human health remain largely undescribed. Nickel and other cationic metals travel through waterways and bind to soils and sediments. To evaluate the potential toxic effects of nickel at environmental contaminant levels (8.9-7,600 µg Ni/g dry weight of sediment and 50-800 µg NiCl2/L of water), we conducted assays using two cosmopolitan nematodes, Caenorhabditis elegans and Pristionchus pacificus. We assayed the effects of both sediment-bound and aqueous nickel upon animal growth, developmental survival, lifespan, and fecundity. Uncontaminated sediments were collected from sites in the Midwestern United States and spiked with a range of nickel concentrations. We found that nickel-spiked sediment substantially impairs both survival from larval to adult stages and adult longevity in a concentration-dependent manner. Further, while aqueous nickel showed no adverse effects on either survivorship or longevity, we observed a significant decrease in fecundity, indicating that aqueous nickel could have a negative impact on nematode physiology. Intriguingly, C. elegansand P. pacificus exhibit similar, but not identical, responses to nickel exposure. Moreover, P. pacificus could be tested successfully in sediments inhospitable to C. elegans. Our results add to a growing body of literature documenting the impact of nickel on animal physiology, and suggest that environmental toxicological studies could gain an advantage by widening their repertoire of nematode species.

Assaying Environmental Nickel Toxicity Using Model Nematodes

PubMed Central

Rudel, David; Douglas, Chandler D.; Huffnagle, Ian M.; Besser, John M.; Ingersoll, Christopher G.

2013-01-01

Although nickel exposure results in allergic reactions, respiratory conditions, and cancer in humans and rodents, the ramifications of excess nickel in the environment for animal and human health remain largely undescribed. Nickel and other cationic metals travel through waterways and bind to soils and sediments. To evaluate the potential toxic effects of nickel at environmental contaminant levels (8.9-7,600 µg Ni/g dry weight of sediment and 50-800 µg NiCl2/L of water), we conducted assays using two cosmopolitan nematodes, Caenorhabditis elegans and Pristionchus pacificus. We assayed the effects of both sediment-bound and aqueous nickel upon animal growth, developmental survival, lifespan, and fecundity. Uncontaminated sediments were collected from sites in the Midwestern United States and spiked with a range of nickel concentrations. We found that nickel-spiked sediment substantially impairs both survival from larval to adult stages and adult longevity in a concentration-dependent manner. Further, while aqueous nickel showed no adverse effects on either survivorship or longevity, we observed a significant decrease in fecundity, indicating that aqueous nickel could have a negative impact on nematode physiology. Intriguingly, C. elegans and P. pacificus exhibit similar, but not identical, responses to nickel exposure. Moreover, P. pacificus could be tested successfully in sediments inhospitable to C. elegans. Our results add to a growing body of literature documenting the impact of nickel on animal physiology, and suggest that environmental toxicological studies could gain an advantage by widening their repertoire of nematode species. PMID:24116204

Molecular aspects of flower senescence and strategies to improve flower longevity

PubMed Central

Shibuya, Kenichi

2018-01-01

Flower longevity is one of the most important traits for ornamental plants. Ethylene plays a crucial role in flower senescence in some plant species. In several species that show ethylene-dependent flower senescence, genetic modification targeting genes for ethylene biosynthesis or signaling has improved flower longevity. Although little is known about regulatory mechanisms of petal senescence in flowers that show ethylene-independent senescence, a recent study of Japanese morning glory revealed that a NAC transcription factor, EPHEMERAL1 (EPH1), is a key regulator in ethylene-independent petal senescence. EPH1 is induced in an age-dependent manner irrespective of ethylene signal, and suppression of EPH1 expression dramatically delays petal senescence. In ethylene-dependent petal senescence, comprehensive transcriptome analyses revealed the involvement of transcription factors, a basic helix-loop-helix protein and a homeodomain-leucine zipper protein, in the transcriptional regulation of the ethylene biosynthesis enzymes. This review summarizes molecular aspects of flower senescence and discusses strategies to improve flower longevity by molecular breeding. PMID:29681752

Autophagy-mediated longevity is modulated by lipoprotein biogenesis

PubMed Central

Seah, Nicole E.; de Magalhaes Filho, C. Daniel; Petrashen, Anna P.; Henderson, Hope R.; Laguer, Jade; Gonzalez, Julissa; Dillin, Andrew; Hansen, Malene; Lapierre, Louis R.

2016-01-01

ABSTRACT Autophagy-dependent longevity models in C. elegans display altered lipid storage profiles, but the contribution of lipid distribution to life-span extension is not fully understood. Here we report that lipoprotein production, autophagy and lysosomal lipolysis are linked to modulate life span in a conserved fashion. We find that overexpression of the yolk lipoprotein VIT/vitellogenin reduces the life span of long-lived animals by impairing the induction of autophagy-related and lysosomal genes necessary for longevity. Accordingly, reducing vitellogenesis increases life span via induction of autophagy and lysosomal lipolysis. Life-span extension due to reduced vitellogenesis or enhanced lysosomal lipolysis requires nuclear hormone receptors (NHRs) NHR-49 and NHR-80, highlighting novel roles for these NHRs in lysosomal lipid signaling. In dietary-restricted worms and mice, expression of VIT and hepatic APOB (apolipoprotein B), respectively, are significantly reduced, suggesting a conserved longevity mechanism. Altogether, our study demonstrates that lipoprotein biogenesis is an important mechanism that modulates aging by impairing autophagy and lysosomal lipolysis. PMID:26671266

Calycophyllum spruceanum (Benth.), the Amazonian "Tree of Youth" Prolongs Longevity and Enhances Stress Resistance in Caenorhabditis elegans.

PubMed

Peixoto, Herbenya; Roxo, Mariana; Koolen, Hector; da Silva, Felipe; Silva, Emerson; Braun, Markus Santhosh; Wang, Xiaojuan; Wink, Michael

2018-02-27

The tree popularly known in Brazil as mulateiro or pau-mulato ( Calycophyllum spruceanum (Benth.) K. Schum.) is deeply embedded in the herbal medicine of the Amazon region. Different preparations of the bark are claimed to have anti-aging, antioxidant, antimicrobial, emollient, wound healing, hemostatic, contraceptive, stimulant, and anti-diabetic properties. The current study aims to provide the first step towards a science-based evidence of the beneficial effects of C. spruceanum in the promotion of longevity and in the modulation of age-related markers. For this investigation, we used the model system Caenorhabditis elegans to evaluate in vivo antioxidant and anti-aging activity of a water extract from C. spruceanum . To chemically characterize the extract, HPLC MS (High Performance Liquid Chromatography Mass Spectrometry)/MS analyses were performed. Five secondary metabolites were identified in the extract, namely gardenoside, 5-hydroxymorin, cyanidin, taxifolin, and 5-hydroxy-6-methoxycoumarin-7-glucoside. C. spruceanum extract was able to enhance stress resistance and to extend lifespan along with attenuation of aging-associated markers in C. elegans . The demonstrated bioactivities apparently depend on the DAF-16/FOXO pathway. The data might support the popular claims of mulateiro as the "tree of youth", however more studies are needed to clarify its putative benefits to human health.

Cooler biologically compatible core body temperatures may prolong longevity and combat neurodegenerative disorders.

PubMed

Salerian, Alen J; Saleri, Nansen G

2006-01-01

Scientific evidence suggests the critical role of temperature in regulating three mechanisms contributing to cellular damage: Oxidative stress, oxygen demand overload and inflammation. In this article, we propose that the Arrhenius rate law has a profound impact on aging and a variety of neurodegenerative disorders including Alzheimer's disease, and we review the supporting evidence. Published studies suggest empirical correlations between temperature and lifespan of various organisms, bolstering the hypothesis that variations in lifespan may stem from differences in the mitochondrial production rates of radicals - a process also influenced by temperature. Given the exponential temperature dependency of all biochemical factors, cooler body temperatures may promote longevity and combat neurodegenerative disorders. This promises to offer extraordinary yet unexplored weapons against two formidable enemies of the human body: aging and neurodegenerative disorders. Stated in the form of a thesis referred to as Salerian and Saleri Temperature Thesis (SSTT): "Cooler biologically compatible core body temperatures prolong lifespan and are of value to combat illness". Double blind studies of SSTT in therapeutic strategies against amyotrophic lateral sclerosis (ALS) or early-stage Alzheimer's disease may offer a reasonable first stage to validate SSTT. In view of the known rapid progressive neurodegeneration associated with ALS, minute variations in core body temperature may, in fact, demonstrate statistically significant differences in disease progression.

Dietary and microbiome factors determine longevity in Caenorhabditis elegans

PubMed Central

Sánchez-Blanco, Adolfo; Rodríguez-Matellán, Alberto; González-Paramás, Ana; González-Manzano, Susana; Kim, Stuart K.; Mollinedo, Faustino

2016-01-01

Diet composition affects organismal health. Nutrient uptake depends on the microbiome. Caenorhabditis elegans fed a Bacillus subtilis diet live longer than those fed the standard Escherichia coli diet. Here we report that this longevity difference is primarily caused by dietary coQ, an antioxidant synthesized by E. coli but not by B. subtilis. CoQ-supplemented E. coli fed worms have a lower oxidation state yet live shorter than coQ-less B. subtilis fed worms. We showed that mutations affecting longevity for E. coli fed worms do not always lead to similar effects when worms are fed B. subtilis. We propose that coQ supplementation by the E. coli diet alters the worm cellular REDOX homeostasis, thus decreasing longevity. Our results highlight the importance of microbiome factors in longevity, argue that antioxidant supplementation can be detrimental, and suggest that the C. elegans standard E. coli diet can alter the effect of signaling pathways on longevity. PMID:27510225

Homeodomain-Interacting Protein Kinase (HPK-1) regulates stress responses and ageing in C. elegans

PubMed Central

Berber, Slavica; Wood, Mallory; Llamosas, Estelle; Thaivalappil, Priya; Lee, Karen; Liao, Bing Mana; Chew, Yee Lian; Rhodes, Aaron; Yucel, Duygu; Crossley, Merlin; Nicholas, Hannah R

2016-01-01

Proteins of the Homeodomain-Interacting Protein Kinase (HIPK) family regulate an array of processes in mammalian systems, such as the DNA damage response, cellular proliferation and apoptosis. The nematode Caenorhabditis elegans has a single HIPK homologue called HPK-1. Previous studies have implicated HPK-1 in longevity control and suggested that this protein may be regulated in a stress-dependent manner. Here we set out to expand these observations by investigating the role of HPK-1 in longevity and in the response to heat and oxidative stress. We find that levels of HPK-1 are regulated by heat stress, and that HPK-1 contributes to survival following heat or oxidative stress. Additionally, we show that HPK-1 is required for normal longevity, with loss of HPK-1 function leading to a faster decline of physiological processes that reflect premature ageing. Through microarray analysis, we have found that HPK-1-regulated genes include those encoding proteins that serve important functions in stress responses such as Phase I and Phase II detoxification enzymes. Consistent with a role in longevity assurance, HPK-1 also regulates the expression of age-regulated genes. Lastly, we show that HPK-1 functions in the same pathway as DAF-16 to regulate longevity and reveal a new role for HPK-1 in development. PMID:26791749

Homeodomain-Interacting Protein Kinase (HPK-1) regulates stress responses and ageing in C. elegans.

PubMed

Berber, Slavica; Wood, Mallory; Llamosas, Estelle; Thaivalappil, Priya; Lee, Karen; Liao, Bing Mana; Chew, Yee Lian; Rhodes, Aaron; Yucel, Duygu; Crossley, Merlin; Nicholas, Hannah R

2016-01-21

Proteins of the Homeodomain-Interacting Protein Kinase (HIPK) family regulate an array of processes in mammalian systems, such as the DNA damage response, cellular proliferation and apoptosis. The nematode Caenorhabditis elegans has a single HIPK homologue called HPK-1. Previous studies have implicated HPK-1 in longevity control and suggested that this protein may be regulated in a stress-dependent manner. Here we set out to expand these observations by investigating the role of HPK-1 in longevity and in the response to heat and oxidative stress. We find that levels of HPK-1 are regulated by heat stress, and that HPK-1 contributes to survival following heat or oxidative stress. Additionally, we show that HPK-1 is required for normal longevity, with loss of HPK-1 function leading to a faster decline of physiological processes that reflect premature ageing. Through microarray analysis, we have found that HPK-1-regulated genes include those encoding proteins that serve important functions in stress responses such as Phase I and Phase II detoxification enzymes. Consistent with a role in longevity assurance, HPK-1 also regulates the expression of age-regulated genes. Lastly, we show that HPK-1 functions in the same pathway as DAF-16 to regulate longevity and reveal a new role for HPK-1 in development.

Symbolic significance of initials on longevity.

PubMed

Abel, Ernest L; Kruger, Michael L

2007-02-01

The longevities of deceased major league baseball players who died prior to 1950 (N=3835) and whose initials formed acronyms, words, or names with "positive" or "negative" affect, as rated a priori by two judges, were compared with those for a group of neutral controls matched for birth year and career length, using the Berkeley standardized mortality tables. Players (n=11) with positive initials, e.g., A.C.E., lived a mean of 13 years longer than players (n=30) with negative initials, e.g., D.E.D., or players with neutral initials (n=864). These results corroborated a previous study and suggest positive name symbols are associated with increased longevity in this sample.

Exercise, Aging and Longevity.

ERIC Educational Resources Information Center

Brown, Stanley P.; Cundiff, David E.

1988-01-01

The question of whether or not a lifelong program of exercise actually has a bearing on longevity is discussed. The effects of exercise on the aging process, and the longevity-exercise relationship are reviewed. The conflicting evidence on the subject is presented. (JL)

Fasting: Molecular Mechanisms and Clinical Applications

PubMed Central

Longo, Valter D.; Mattson, Mark P.

2014-01-01

Fasting has been practiced for millennia, but only recently studies have shed light on its role in adaptive cellular responses that reduce oxidative damage and inflammation, optimize energy metabolism and bolster cellular protection. In lower eukaryotes, chronic fasting extends longevity in part by reprogramming metabolic and stress resistance pathways. In rodents intermittent or periodic fasting protects against diabetes, cancers, heart disease and neurodegeneration, while in humans it helps reduce obesity, hypertension, asthma and rheumatoid arthritis. Thus, fasting has the potential to delay aging and help prevent and treat diseases while minimizing the side effects caused by chronic dietary interventions. PMID:24440038

[MEDICAL SOCIAL MODELING TECHNOLOGIES FOR ACTIVE AGING IN KAZAKHSTAN].

PubMed

Benberin, V V; Akhetov, A A; Tanbaeva, G Z

2015-01-01

The article discusses a new model for active ageing in Republic of Kazakhstan with participation the state, population and medical social services. Achieving active longevity will lead to positive trends in the development of human capital of the state, because it enables to use experience and knowledge of senior generation in enhancing the effectiveness of socio-economic transformation in health care. The study was carried out on the base of the Central clinical hospital of the President's affairs administration in Republic of Kazakhstan, with the participation of 147 admitted patients of elderly and senile age.

The circle of life: A cross-cultural comparison of children's attribution of life-cycle traits.

PubMed

Burdett, Emily R R; Barrett, Justin L

2016-06-01

Do children attribute mortality and other life-cycle traits to all minded beings? The present study examined whether culture influences young children's ability to conceptualize and differentiate human beings from supernatural beings (such as God) in terms of life-cycle traits. Three-to-5-year-old Israeli and British children were questioned whether their mother, a friend, and God would be subject to various life-cycle processes: Birth, death, ageing, existence/longevity, and parentage. Children did not anthropomorphize but differentiated among human and supernatural beings, attributing life-cycle traits to humans, but not to God. Although 3-year-olds differentiated significantly among agents, 5-year-olds attributed correct life-cycle traits more consistently than younger children. The results also indicated some cross-cultural variation in these attributions. Implications for biological conceptual development are discussed. © 2015 The British Psychological Society.

Health Status and Health Dynamics in an Empirical Model of Expected Longevity*

PubMed Central

Benítez-Silva, Hugo; Ni, Huan

2010-01-01

Expected longevity is an important factor influencing older individuals’ decisions such as consumption, savings, purchase of life insurance and annuities, claiming of Social Security benefits, and labor supply. It has also been shown to be a good predictor of actual longevity, which in turn is highly correlated with health status. A relatively new literature on health investments under uncertainty, which builds upon the seminal work by Grossman (1972), has directly linked longevity with characteristics, behaviors, and decisions by utility maximizing agents. Our empirical model can be understood within that theoretical framework as estimating a production function of longevity. Using longitudinal data from the Health and Retirement Study, we directly incorporate health dynamics in explaining the variation in expected longevities, and compare two alternative measures of health dynamics: the self-reported health change, and the computed health change based on self-reports of health status. In 38% of the reports in our sample, computed health changes are inconsistent with the direct report on health changes over time. And another 15% of the sample can suffer from information losses if computed changes are used to assess changes in actual health. These potentially serious problems raise doubts regarding the use and interpretation of the computed health changes and even the lagged measures of self-reported health as controls for health dynamics in a variety of empirical settings. Our empirical results, controlling for both subjective and objective measures of health status and unobserved heterogeneity in reporting, suggest that self-reported health changes are a preferred measure of health dynamics. PMID:18187217

A randomized trial of the effect of automated ventricular capture on device longevity and threshold measurement in pacemaker patients.

PubMed

Koplan, Bruce A; Gilligan, David M; Nguyen, Luc S; Lau, Theodore K; Thackeray, Lisa M; Berg, Kellie Chase

2008-11-01

An automatic capture (AC) algorithm adjusts ventricular pacing output to capture the ventricle while optimizing output to 0.5 V above threshold. AC maintains this output and confirms capture on a beat-to-beat basis in bipolar and unipolar pacing and sensing. To assess the AC algorithm and its impact on device longevity. Patients implanted with a pacemaker were randomized 1:1 to have the AC feature on or off for 12 months. Two threshold tests were conducted at each visit- automatic threshold and manual threshold. Average ventricular voltage output and projected device longevity were compared between AC on and off using nonparametric tests. Nine hundred ten patients were enrolled and underwent device implantation. Average ventricular voltage output was 1.6 V for the AC on arm (n = 444) and 3.1 V for the AC off arm (n = 446) (P < 0.001). Projected device longevity was 10.3 years for AC on and 8.9 years for AC off (P < 0.0001), or a 16% increase in longevity for AC on. The proportion of patients in whom there was a difference between automatic threshold and manual threshold of

Endocrine Function In Naturally Long-Living Small Mammals

PubMed Central

Buffenstein, Rochelle; Pinto, Mario

2015-01-01

The complex, highly integrative endocrine system regulates all aspects of somatic maintenance and reproduction and has been widely implicated as an important determinant of longevity in short-lived traditional model organisms of aging research. Genetic or experimental manipulation of hormone profiles in mice has been proven to definitively alter longevity. These hormonally induced lifespan extension mechanisms may not necessarily be relevant to humans and other long-lived organisms that naturally show successful slow aging. Long-lived species may have evolved novel anti-aging defenses germane to naturally retarding the aging process. Here we examine the available endocrine data associated with the vitamin D, insulin, grlucocorticoid and thyroid endocrine systems of naturally long-living small mammals. Generally, long-living rodents and bats maintain tightly regulated lower basal levels of these key pleiotropic hormones than shorter-lived rodents. Similarities with genetically manipulated suggest that evolutionarily wellconserved hormonal mechanisms are integrally involved in lifespan determination. PMID:18674586

How Research on Human Progeroid and Antigeroid Syndromes Can Contribute to the Longevity Dividend Initiative

PubMed Central

Hisama, Fuki M.; Oshima, Junko; Martin, George M.

2016-01-01

Although translational applications derived from research on basic mechanisms of aging are likely to enhance health spans and life spans for most of us (the longevity dividend), there will remain subsets of individuals with special vulnerabilities. Medical genetics is a discipline that describes such “private” patterns of aging and can reveal underlying mechanisms, many of which support genomic instability as a major mechanism of aging. We review examples of three classes of informative disorders: “segmental progeroid syndromes” (those that appear to accelerate multiple features of aging), “unimodal progeroid syndromes” (those that impact on a single disorder of aging), and “unimodal antigeroid syndromes,” variants that provide enhanced protection against specific disorders of aging; we urge our colleagues to expand our meager research efforts on the latter, including ancillary somatic cell genetic approaches. PMID:26931459

Whole-Genome Sequencing of the World’s Oldest People

PubMed Central

Gierman, Hinco J.; Fortney, Kristen; Roach, Jared C.; Coles, Natalie S.; Li, Hong; Glusman, Gustavo; Markov, Glenn J.; Smith, Justin D.; Hood, Leroy; Coles, L. Stephen; Kim, Stuart K.

2014-01-01

Supercentenarians (110 years or older) are the world’s oldest people. Seventy four are alive worldwide, with twenty two in the United States. We performed whole-genome sequencing on 17 supercentenarians to explore the genetic basis underlying extreme human longevity. We found no significant evidence of enrichment for a single rare protein-altering variant or for a gene harboring different rare protein altering variants in supercentenarian compared to control genomes. We followed up on the gene most enriched for rare protein-altering variants in our cohort of supercentenarians, TSHZ3, by sequencing it in a second cohort of 99 long-lived individuals but did not find a significant enrichment. The genome of one supercentenarian had a pathogenic mutation in DSC2, known to predispose to arrhythmogenic right ventricular cardiomyopathy, which is recommended to be reported to this individual as an incidental finding according to a recent position statement by the American College of Medical Genetics and Genomics. Even with this pathogenic mutation, the proband lived to over 110 years. The entire list of rare protein-altering variants and DNA sequence of all 17 supercentenarian genomes is available as a resource to assist the discovery of the genetic basis of extreme longevity in future studies. PMID:25390934

Whole-genome sequencing of the world's oldest people.

PubMed

Gierman, Hinco J; Fortney, Kristen; Roach, Jared C; Coles, Natalie S; Li, Hong; Glusman, Gustavo; Markov, Glenn J; Smith, Justin D; Hood, Leroy; Coles, L Stephen; Kim, Stuart K

2014-01-01

Supercentenarians (110 years or older) are the world's oldest people. Seventy four are alive worldwide, with twenty two in the United States. We performed whole-genome sequencing on 17 supercentenarians to explore the genetic basis underlying extreme human longevity. We found no significant evidence of enrichment for a single rare protein-altering variant or for a gene harboring different rare protein altering variants in supercentenarian compared to control genomes. We followed up on the gene most enriched for rare protein-altering variants in our cohort of supercentenarians, TSHZ3, by sequencing it in a second cohort of 99 long-lived individuals but did not find a significant enrichment. The genome of one supercentenarian had a pathogenic mutation in DSC2, known to predispose to arrhythmogenic right ventricular cardiomyopathy, which is recommended to be reported to this individual as an incidental finding according to a recent position statement by the American College of Medical Genetics and Genomics. Even with this pathogenic mutation, the proband lived to over 110 years. The entire list of rare protein-altering variants and DNA sequence of all 17 supercentenarian genomes is available as a resource to assist the discovery of the genetic basis of extreme longevity in future studies.

The rate of metabolism as a factor determining longevity of the Saccharomyces cerevisiae yeast.

PubMed

Molon, Mateusz; Szajwaj, Monika; Tchorzewski, Marek; Skoczowski, Andrzej; Niewiadomska, Ewa; Zadrag-Tecza, Renata

2016-02-01

Despite many controversies, the yeast Saccharomyces cerevisiae continues to be used as a model organism for the study of aging. Numerous theories and hypotheses have been created for several decades, yet basic mechanisms of aging have remained unclear. Therefore, the principal aim of this work is to propose a possible mechanism leading to increased longevity in yeast. In this paper, we suggest for the first time that there is a link between decreased metabolic activity, fertility and longevity expressed as time of life in yeast. Determination of reproductive potential and total lifespan with the use of fob1Δ and sfp1Δ mutants allows us to compare the "longevity" presented as the number of produced daughters with the longevity expressed as the time of life. The results of analyses presented in this paper suggest the need for a change in the definition of longevity of yeast by taking into consideration the time parameter. The mutants that have been described as "long-lived" in the literature, such as the fob1Δ mutant, have an increased reproductive potential but live no longer than their standard counterparts. On the other hand, the sfp1Δ mutant and the wild-type strain produce a similar number of daughter cells, but the former lives much longer. Our results demonstrate a correlation between the decreased efficiency of the translational apparatus and the longevity of the sfp1Δ mutant. We suggest that a possible factor regulating the lifespan is the rate of cell metabolism. To measure the basic metabolism of the yeast cells, we used the isothermal microcalorimetry method. In the case of sfp1Δ, the flow of energy, ATP concentration, polysome profile and translational fitness are significantly lower in comparison with the wild-type strain and the fob1Δ mutant.

Human Kunitz-type protease inhibitor engineered for enhanced matrix retention extends longevity of fibrin biomaterials.

PubMed

Briquez, Priscilla S; Lorentz, Kristen M; Larsson, Hans M; Frey, Peter; Hubbell, Jeffrey A

2017-08-01

Aprotinin is a broad-spectrum serine protease inhibitor used in the clinic as an anti-fibrinolytic agent in fibrin-based tissue sealants. However, upon re-exposure, some patients suffer from hypersensitivity immune reactions likely related to the bovine origin of aprotinin. Here, we aimed to develop a human-derived substitute to aprotinin. Based on sequence homology analyses, we identified the Kunitz-type protease inhibitor (KPI) domain of human amyloid-β A4 precursor protein as being a potential candidate. While KPI has a lower intrinsic anti-fibrinolytic activity than aprotinin, we reasoned that its efficacy is additionally limited by its fast release from fibrin material, just as aprotinin's is. Thus, we engineered KPI variants for controlled retention in fibrin biomaterials, using either covalent binding through incorporation of a substrate for the coagulation transglutaminase Factor XIIIa or through engineering of extracellular matrix protein super-affinity domains for sequestration into fibrin. We showed that both engineered KPI variants significantly slowed plasmin-mediated fibrinolysis in vitro, outperforming aprotinin. In vivo, our best engineered KPI variant (incorporating the transglutaminase substrate) extended fibrin matrix longevity by 50%, at a dose at which aprotinin did not show efficacy, thus qualifying it as a competitive substitute of aprotinin in fibrin sealants. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Effects of chronic kombucha ingestion on open-field behaviors, longevity, appetitive behaviors, and organs in c57-bl/6 mice: a pilot study.

PubMed

Hartmann, A M; Burleson, L E; Holmes, A K; Geist, C R

2000-09-01

Kombucha is a lightly fermented tea beverage popularly consumed as a self-prescribed folk-remedy for numerous ailments. Kombucha is claimed to enhance cognition, aid weight loss, and prolong life. This pilot study reports longevity, general health, and open-field exploratory behavioral outcomes from a 3-y longitudinal study of 64 C57-BL/6 mice (males and females), half of which chronically drank kombucha, and all of which experienced natural mortality. Compared by MANOVA to controls, mice that drank kombucha showed greater vertical exploration (P = 0.001) and a sex-interactive effect in novel object manipulation (P = 0.049). MANOVA of kombucha-drinking mice compared to controls detected differences in appetitive behaviors (food consumption, P < 0.001; beverage consumption, P = 0. 008), and gross body weight (P < 0.001). Appetitive behaviors changed with the addition of voluntary exercise on a running wheel, with differing patterns of change noted for males and females. Both male and female mice who drank kombucha lived longer than controls (P < 0.001), with the greatest variability among the male mice (sex interactive effect, P < 0.001). Comparable effects and mechanisms in humans remain uncertain, as do health safety issues, because serious health problems and fatalities have been reported and attributed to drinking kombucha.

Changing Napoleonic Leadership In The Department Of Homeland Security: The Identification Of Toxic Leadership Behaviors And How To Facilitate Change To Those Behaviors

DTIC Science & Technology

2016-02-06

of time. However, if a person is going to succeed as a leader, they must accept that leadership is a people business. Leadership involves human ...exercise 6 industry.7 As humans , we know that a healthy diet and exercise is something that we should do for longevity and quality of life.8 Yet...of empathy , beginning by early adulthood and present in a variety of contexts, as indicated by five (or more) of the following: (1) Has a grandiose

Longevity records for male and female flammulated owls

Treesearch

Richard T. Reynolds; Brian D. Linkhart

1990-01-01

A female Flammulated Owl (Otus flammeolus), banded as a breeding adult on 14 Jul. 1981 in central Colorado, was last captured on 9 Jul. 1987. On the same study area, a male Flammulated Owl was banded as a nestling on 15 Jul. 1981 and was last recaptured at a nest 2.5 km distant from its natal site on 6 Jul. 1989. These establish the longevity for...

Does comedy kill? A retrospective, longitudinal cohort, nested case-control study of humour and longevity in 53 British comedians.

PubMed

Stewart, Simon; Thompson, David R

2015-02-01

This work aims to test the hypothesis that the funniest comedians are most at risk of a premature death and reduced longevity compared to their relatively less funny counterparts. A retrospective longitudinal cohort study with a nested case-control analysis of longevity of 53 male British comedians born between 1900 and 1954 was conducted. All comedians were given a subjective score from 1 (relatively funny) to 10 (hilariously funny) by the study investigators. The survival profile of all comedians was then examined adjusting for decade of birth, whether they worked in a comedy team and their comedy score. A nested case-control analysis examined the longevity of those comedians working in teams according to their pre-specified status within the team (straight/less funny versus funny team member). On an adjusted basis, there was no correlation between the decade of birth (HR 0.94, 95% 0.65 to 1.38 per incremental decade; p=0.763) and comedy team status (HR 1.13, 95% 0.51 to 2.48 versus independent comedian; p=0.761) with longevity. However, an increasingly funny comedy score was associated with increased mortality (HR 1.24, 95% CI 1.06 to 1.44 per unit funny score; p=0.006). Of the 23 comedians adjudged to be very funny (score 8-10), 18 (78%) had died versus 12 (40%) of the rest; mean age at death 63.3±12.2 versus 72.3±14.7 (p=0.079). Within comedy teams, those identified as the funnier member(s) of the partnership were, on an adjusted basis, more than three times more likely to die prematurely when compared to their more serious comedy partners (HR 3.52, 95% CI 1.22, 10.1; p=0.020). These data suggest that elite comedians are at increased risk of premature death compared to their less funny counterparts. Mental health issues and personality characteristics that help shape their comedic talent and success may well explain their reduced longevity and raises serious issues for identifying and mitigating their risk of a premature death. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Intrinsic worker mortality depends on behavioral caste and the queens' presence in a social insect

NASA Astrophysics Data System (ADS)

Kohlmeier, Philip; Negroni, Matteo Antoine; Kever, Marion; Emmling, Stefanie; Stypa, Heike; Feldmeyer, Barbara; Foitzik, Susanne

2017-04-01

According to the classic life history theory, selection for longevity depends on age-dependant extrinsic mortality and fecundity. In social insects, the common life history trade-off between fecundity and longevity appears to be reversed, as the most fecund individual, the queen, often exceeds workers in lifespan several fold. But does fecundity directly affect intrinsic mortality also in social insect workers? And what is the effect of task on worker mortality? Here, we studied how social environment and behavioral caste affect intrinsic mortality of ant workers. We compared worker survival between queenless and queenright Temnothorax longispinosus nests and demonstrate that workers survive longer under the queens' absence. Temnothorax ant workers fight over reproduction when the queen is absent and dominant workers lay eggs. Worker fertility might therefore increase lifespan, possibly due to a positive physiological link between fecundity and longevity, or better care for fertile workers. In social insects, division of labor among workers is age-dependant with young workers caring for the brood and old ones going out to forage. We therefore expected nurses to survive longer than foragers, which is what we found. Surprisingly, inactive inside workers showed a lower survival than nurses but comparable to that of foragers. The reduced longevity of inactive workers could be due to them being older than the nurses, or due to a positive effect of activity on lifespan. Overall, our study points to behavioral caste-dependent intrinsic mortality rates and a positive association between fertility and longevity not only in queens but also in ant workers.

Cell-Nonautonomous Mechanisms Underlying Cellular and Organismal Aging.

PubMed

Medkour, Younes; Svistkova, Veronika; Titorenko, Vladimir I

2016-01-01

Cell-autonomous mechanisms underlying cellular and organismal aging in evolutionarily distant eukaryotes have been established; these mechanisms regulate longevity-defining processes within a single eukaryotic cell. Recent findings have provided valuable insight into cell-nonautonomous mechanisms modulating cellular and organismal aging in eukaryotes across phyla; these mechanisms involve a transmission of various longevity factors between different cells, tissues, and organisms. Herein, we review such cell-nonautonomous mechanisms of aging in eukaryotes. We discuss the following: (1) how low molecular weight transmissible longevity factors modulate aging and define longevity of cells in yeast populations cultured in liquid media or on solid surfaces, (2) how communications between proteostasis stress networks operating in neurons and nonneuronal somatic tissues define longevity of the nematode Caenorhabditis elegans by modulating the rates of aging in different tissues, and (3) how different bacterial species colonizing the gut lumen of C. elegans define nematode longevity by modulating the rate of organismal aging. Copyright © 2016. Published by Elsevier Inc.

The Homeobox Protein CEH-23 Mediates Prolonged Longevity in Response to Impaired Mitochondrial Electron Transport Chain in C. elegans

PubMed Central

Walter, Ludivine; Baruah, Aiswarya; Chang, Hsin-Wen; Pace, Heather Mae; Lee, Siu Sylvia

2011-01-01

Recent findings indicate that perturbations of the mitochondrial electron transport chain (METC) can cause extended longevity in evolutionarily diverse organisms. To uncover the molecular basis of how altered METC increases lifespan in C. elegans, we performed an RNAi screen and revealed that three predicted transcription factors are specifically required for the extended longevity of mitochondrial mutants. In particular, we demonstrated that the nuclear homeobox protein CEH-23 uniquely mediates the longevity but not the slow development, reduced brood size, or resistance to oxidative stress associated with mitochondrial mutations. Furthermore, we showed that ceh-23 expression levels are responsive to altered METC, and enforced overexpression of ceh-23 is sufficient to extend lifespan in wild-type background. Our data point to mitochondria-to-nucleus communications to be key for longevity determination and highlight CEH-23 as a novel longevity factor capable of responding to mitochondrial perturbations. These findings provide a new paradigm for how mitochondria impact aging and age-dependent diseases. PMID:21713031

Caloric restriction in primates and relevance to humans.

PubMed

Roth, G S; Ingram, D K; Lane, M A

2001-04-01

Dietary caloric restriction (CR) is the only intervention conclusively and reproducibly shown to slow aging and maintain health and vitality in mammals. Although this paradigm has been known for over 60 years, its precise biological mechanisms and applicability to humans remain unknown. We began addressing the latter question in 1987 with the first controlled study of CR in primates (rhesus and squirrel monkeys, which are evolutionarily much closer to humans than the rodents most frequently employed in CR studies). To date, our results strongly suggest that the same beneficial "antiaging" and/or "antidisease" effects observed in CR rodents also occur in primates. These include lower plasma insulin levels and greater sensitivity; lower body temperatures; reduced cholesterol, triglycerides, blood pressure, and arterial stiffness; elevated HDL; and slower age-related decline in circulating levels of DHEAS. Collectively, these biomarkers suggest that CR primates will be less likely to incur diabetes, cardiovascular problems, and other age-related diseases and may in fact be aging more slowly than fully fed counterparts. Despite these very encouraging results, it is unlikely that most humans would be willing to maintain a 30% reduced diet for the bulk of their adult life span, even if it meant more healthy years. For this reason, we have begun to explore CR mimetics, agents that might elicit the same beneficial effects as CR, without the necessity of dieting. Our initial studies have focused on 2-deoxyglucose (2DG), a sugar analogue with a limited metabolism that actually reduces glucose/energy flux without decreasing food intake in rats. In a six-month pilot study, 2DG lowered plasma insulin and body temperature in a manner analagous to that of CR. Thus, metabolic effects that mediate the CR mechanism can be attained pharmacologically. Doses were titrated to eliminate toxicity; a long-term longevity study is now under way. In addition, data from other laboratories suggest that at least some of the same physiological/metabolic end points that are associated with the beneficial effects of underfeeding may be obtained from other potential CR mimetic agents, some naturally occurring in food products. Much work remains to be done, but taken together, our successful results with CR in primates and 2DG administration to rats suggest that it may indeed be possible to obtain the health- and longevity-promoting effects of the former intervention without actually decreasing food intake.

Workforce Characteristics, Perceptions, Stress, and Satisfaction among Staff in Green House and Other Nursing Homes.

PubMed

Brown, Patrick B; Hudak, Sandra L; Horn, Susan D; Cohen, Lauren W; Reed, David Allen; Zimmerman, Sheryl

2016-02-01

To compare workforce characteristics and staff perceptions of safety, satisfaction, and stress between Green House (GH) and comparison nursing homes (CNHs). Primary data on staff perceptions of safety, stress, and satisfaction from 13 GHs and 8 comparison NHs in 11 states; secondary data from human resources records on workforce characteristics, turnover, and staffing from 01/01/2011-06/30/2012. Observational study. Workforce data were from human resources offices; staff perceptions were from surveys. Few significant differences were found between GH and CNHs. Exceptions were GH direct caregivers were older, provided twice the normalized hours per week budgeted per resident than CNAs in CNHs or Legacy NHs, and trended toward lower turnover. GH environment may promote staff longevity and does not negatively affect worker's stress, safety perceptions, or satisfaction. Larger studies are needed to confirm findings. © Health Research and Educational Trust.

Invited commentary: Physical activity, mortality, and genetics.

PubMed

Rankinen, Tuomo; Bouchard, Claude

2007-08-01

The importance of regular physical activity to human health has been recognized for a long time, and a physically active lifestyle is now defined as a major component of public health policies. The independent contribution of regular physical activity to lower morbidity and mortality rates is generally accepted, and the biologic mechanisms mediating these health effects are actively investigated. A few years ago, data from the Finnish Twin Registry suggested that genetic selection may account for some of the physical-activity-related benefits on mortality rates. However, results from the Swedish Twin Registry study reported by Carlsson et al. in the current issue of the Journal (Am J Epidemiol 2007;166:255-259) do not support the genetic selection hypothesis. In this commentary, the authors review the nature of the associations among physical activity level, fitness, and longevity, with special reference to the role of human genetic variation, and discuss potential reasons for different outcomes of these large twin studies.

Nothobranchius as a model for aging studies. A review

PubMed Central

Lucas-Sánchez, Alejandro; Almaida-Pagán, Pedro Francisco; Mendiola, Pilar; de Costa, Jorge

2014-01-01

In recent decades, the increase in human longevity has made it increasingly important to expand our knowledge on aging. To accomplish this, the use of animal models is essential, with the most common being mouse (phylogenetically similar to humans, and a model with a long life expectancy) and Caenorhabditis elegans (an invertebrate with a short life span, but quite removed from us in evolutionary terms). However, some sort of model is needed to bridge the differences between those mentioned above, achieving a balance between phylogenetic distance and life span. Fish of the genus Nothobranchius were suggested 10 years ago as a possible alternative for the study of the aging process. In the meantime, numerous studies have been conducted at different levels: behavioral (including the study of the rest-activity rhythm), populational, histochemical, biochemical and genetic, among others, with very positive results. This review compiles what we know about Nothobranchius to date, and examines its future prospects as a true alternative to the classic models for studies on aging. PMID:25110612

Behavioral Assessment of Spaceflight Effects on Neurocognitive Performance - Extent and Longevity

NASA Technical Reports Server (NTRS)

De Dios, Y.E.; Kofman, I.S.; Gadd, N.E.; Kreutzberg, G.A.; Peters, B.T.; Taylor, L.C.; Campbell, D.J.; Wood, S.J.; Bloomberg, J.J.; Seidler, R.D.;

Genome-Wide Association Study of Personality Traits in the Long Life Family Study

PubMed Central

Bae, Harold T.; Sebastiani, Paola; Sun, Jenny X.; Andersen, Stacy L.; Daw, E. Warwick; Terracciano, Antonio; Ferrucci, Luigi; Perls, Thomas T.

2013-01-01

Personality traits have been shown to be associated with longevity and healthy aging. In order to discover novel genetic modifiers associated with personality traits as related with longevity, we performed a genome-wide association study (GWAS) on personality factors assessed by NEO-five-factor inventory in individuals enrolled in the Long Life Family Study (LLFS), a study of 583 families (N up to 4595) with clustering for longevity in the United States and Denmark. Three SNPs, in almost perfect LD, associated with agreeableness reached genome-wide significance (p < 10−8) and replicated in an additional sample of 1279 LLFS subjects, although one (rs9650241) failed to replicate and the other two were not available in two independent replication cohorts, the Baltimore Longitudinal Study of Aging and the New England Centenarian Study. Based on 10,000,000 permutations, the empirical p-value of 2 × 10−7 was observed for the genome-wide significant SNPs. Seventeen SNPs that reached marginal statistical significance in the two previous GWASs (p-value <10−4 and 10−5), were also marginally significantly associated in this study (p-value <0.05), although none of the associations passed the Bonferroni correction. In addition, we tested age-by-SNP interactions and found some significant associations. Since scores of personality traits in LLFS subjects change in the oldest ages, and genetic factors outweigh environmental factors to achieve extreme ages, these age-by-SNP interactions could be a proxy for complex gene–gene interactions affecting personality traits and longevity. PMID:23658558

Conscientiousness, career success, and longevity: a lifespan analysis.

PubMed

Kern, Margaret L; Friedman, Howard S; Martin, Leslie R; Reynolds, Chandra A; Luong, Gloria

2009-04-01

Markers of executive functioning, such as prudent planning for the future and impulse control, are related to conscientiousness and may be central to both occupational success and health outcomes. The aim of the study was to examine relations among conscientiousness, career success, and mortality risk across a 65-year period. Using data derived from 693 male participants in the Terman Life Cycle Study, we examined associations among childhood personality, midlife objective career success, and lifelong mortality risk through 2006. Conscientiousness and career success each predicted lower mortality risk (N = 693, relative hazard (rh) = 0.82 [95% confidence interval = 0.74, 0.91] and rh = 0.80 [0.71, 0.91], respectively), with both shared and unique variance. Importantly, childhood personality moderated the success-longevity link; conscientiousness was most relevant for least successful individuals. Conscientiousness and career success predicted longevity, but not in a straightforward manner. Findings highlight the importance of lifespan processes.

Mechanisms by Which Different Functional States of Mitochondria Define Yeast Longevity

PubMed Central

Beach, Adam; Leonov, Anna; Arlia-Ciommo, Anthony; Svistkova, Veronika; Lutchman, Vicky; Titorenko, Vladimir I.

2015-01-01

Mitochondrial functionality is vital to organismal physiology. A body of evidence supports the notion that an age-related progressive decline in mitochondrial function is a hallmark of cellular and organismal aging in evolutionarily distant eukaryotes. Studies of the baker’s yeast Saccharomyces cerevisiae, a unicellular eukaryote, have led to discoveries of genes, signaling pathways and chemical compounds that modulate longevity-defining cellular processes in eukaryotic organisms across phyla. These studies have provided deep insights into mechanistic links that exist between different traits of mitochondrial functionality and cellular aging. The molecular mechanisms underlying the essential role of mitochondria as signaling organelles in yeast aging have begun to emerge. In this review, we discuss recent progress in understanding mechanisms by which different functional states of mitochondria define yeast longevity, outline the most important unanswered questions and suggest directions for future research. PMID:25768339

Effect of water content and temperature on seed longevity of seven Brassicaceae species after 5 years of storage.

PubMed

Mira, S; Estrelles, E; González-Benito, M E

2015-01-01

Maximising seed longevity is crucial for genetic resource preservation and longevity of orthodox seeds is determined by environmental conditions (water content and temperature). The effect of water content (down to 0.01 g·H₂O·g(-1) ) on seed viability was studied at different temperatures for a 5-year storage period in taxonomically related species. Seeds of seven Brassicaceae species (Brassica repanda, Eruca vesicaria, Malcolmia littorea, Moricandia arvensis, Rorippa nasturtium-aquaticum, Sinapis alba, Sisymbrium runcinatum) were stored at 48 environments comprising a combination of eight water contents, from 0.21 to 0.01 g·H₂O·g(-1) DW and six temperatures (45, 35, 20, 5, -25, -170 °C). Survival curves were modelled and P50 calculated for those conditions where germination was reduced over the 5-year assay period. Critical water content for storage of seeds of six species at 45 °C ranged from 0.02 to 0.03 g·H₂O·g(-1) . The effect of extreme desiccation at 45 °C showed variability among species: three species showed damaging effects of drying below the critical water content, while for three species it was neither detrimental nor beneficial to seed longevity. Lipid content could be related to longevity, depending on the storage conditions. A variable seed longevity response to water content among taxonomically related species was found. The relative position of some of the species as long- or short-lived at 45 °C varied depending on the humidity at which storage behaviour was evaluated. Therefore, predictions of survival under desiccated conditions based on results obtained at high humidity might be problematic for some species. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

Health status and health dynamics in an empirical model of expected longevity.

PubMed

Benítez-Silva, Hugo; Ni, Huan

2008-05-01

Expected longevity is an important factor influencing older individuals' decisions such as consumption, savings, purchase of life insurance and annuities, claiming of Social Security benefits, and labor supply. It has also been shown to be a good predictor of actual longevity, which in turn is highly correlated with health status. A relatively new literature on health investments under uncertainty, which builds upon the seminal work by Grossman [Grossman, M., 1972. On the concept of health capital and demand for health. Journal of Political Economy 80, 223-255] has directly linked longevity with characteristics, behaviors, and decisions by utility maximizing agents. Our empirical model can be understood within that theoretical framework as estimating a production function of longevity. Using longitudinal data from the Health and Retirement Study, we directly incorporate health dynamics in explaining the variation in expected longevities, and compare two alternative measures of health dynamics: the self-reported health change, and the computed health change based on self-reports of health status. In 38% of the reports in our sample, computed health changes are inconsistent with the direct report on health changes over time. And another 15% of the sample can suffer from information losses if computed changes are used to assess changes in actual health. These potentially serious problems raise doubts regarding the use and interpretation of the computed health changes and even the lagged measures of self-reported health as controls for health dynamics in a variety of empirical settings. Our empirical results, controlling for both subjective and objective measures of health status and unobserved heterogeneity in reporting, suggest that self-reported health changes are a preferred measure of health dynamics.

Longevity of implantable cardioverter defibrillators: a comparison among manufacturers and over time.

PubMed

von Gunten, Simon; Schaer, Beat A; Yap, Sing-Chien; Szili-Torok, Tamas; Kühne, Michael; Sticherling, Christian; Osswald, Stefan; Theuns, Dominic A M J

2016-05-01

Longevity of implantable cardioverter defibrillators (ICDs) is crucial for patients and healthcare systems as replacements impact on infection rates and cost-effectiveness. Aim was to determine longevity using very large databases of two teaching hospitals with a high number of replacements and a rather homogeneous distribution among manufacturers. The study population consists of all patients in whom an ICD was inserted in. All ICD manufacturers operating in Switzerland and the Netherlands and all implanted ICDs were included. Implantable cardioverter defibrillator replacements due to normal battery depletion were considered events, and other replacements were censored. Longevity was assessed depending on manufacturers, pacing mode, implant before/after 2006, and all parameters combined. We analysed data from 3436 patients in whom 4881 ICDs [44.2% VVI-ICDs, 27.4% DDD-ICDs, 26.3% cardiac resynchronization therapy (CRT)-ICDs, 2.0% subcutaneous ICDs] were implanted. The four major manufacturers had implant shares between 18.4 and 31.5%. Replacement due to battery depletion (27.4%) was performed for 1339 ICDs. Patient survival at 5 years was 80.1%. Longevity at 5 years improved in contemporary compared with elderly ICDs [63.9-80.6% across all ICDs, of 73.7-92.1% in VVIs, 58.2-76.1% in DDDs, and of 47.1-66.3% in CRT defibrillators, all P value < 0.05]. Remarkable differences were seen among manufacturers, and those with better performance in elderly ICDs were not those with better performance in contemporary ones. Implantable cardioverter defibrillator longevity increased in contemporary models independent of manufacturer and pacing mode. Still, significant differences exist among manufacturers. These results might impact on device selection. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

Is pollen removal or seed set favoured by flower longevity in a hummingbird-pollinated Salvia species?

PubMed Central

Aximoff, Izar Araujo; Freitas, Leandro

2010-01-01

Background and Aims The period between the beginning of anthesis and flower senescence modulates the transport of pollen by pollinators among conspecific flowers, and its length may therefore influence reproductive success. This study evaluated whether floral longevity favours pollen removal from the anthers over fecundity (seed set) in an ornithophilous species that does not undergo pollen limitation. Methods Field investigations were conducted on floral longevity, nectar production, pollinator behaviour, and variations in fruit set (FS), mean number of seeds per fruit (MSF) and pollen removal by hummingbirds (PR) during the anthesis of Salvia sellowiana in south-east Brazil. Key Results Anthesis of flowers exposed to pollinators lasted 4 d, as well as on flowers with pollen removed from the anthers or deposited on the stigma. The longevity of bagged flowers was significantly higher (approx. 9 d). FS and PR reached 87·2 and 90 %, respectively, in natural conditions. PR increased gradually over the period of anthesis; however, FS and MSF reached their maxima in the first hours of anthesis. Nectar production was continuous, but the secretion rate was reduced after pollination. The removal of nectar from non-pollinated flowers stimulated its production. Conclusions The longevity of anthesis in S. sellowiana seems to be related to the mechanism of gradual dispensing of pollen, resulting in greater male reproductive success. This is in agreement with the pollen-donation hypothesis. The small number of ovules (four) of S. sellowiana and the high frequency and the foraging mode of its pollinators may favour the selection for floral longevity driven by male fitness in this system. PMID:20622254

Improved lipids, diastolic pressure and kidney function are potential contributors to familial longevity: a study on 60 Chinese centenarian families.

PubMed

He, Yong-Han; Pu, Shao-Yan; Xiao, Fu-Hui; Chen, Xiao-Qiong; Yan, Dong-Jing; Liu, Yao-Wen; Lin, Rong; Liao, Xiao-Ping; Yu, Qin; Yang, Li-Qin; Yang, Xing-Li; Ge, Ming-Xia; Li, Ying; Jiang, Jian-Jun; Cai, Wang-Wei; Kong, Qing-Peng

2016-02-25

Centenarians are a good healthy aging model. Interestingly, centenarians' offspring are prone to achieve longevity. Here we recruited 60 longevity families and investigated the blood biochemical indexes of family members to seek candidate factors associated with familial longevity. First, associations of blood indexes with age were tested. Second, associations of blood parameters in centenarians (CEN) with their first generation of offspring (F1) and F1 spouses (F1SP) were analyzed. Third, genes involved in regulating target factors were investigated. We found that total cholesterol (TC) and triglyceride (TG) increased with age (20-80 years), but decreased in CEN. Similarly, blood urea nitrogen (BUN) and blood creatinine (BCr) increased with age (20-80 years), but were maintained on a plateau in CEN. Importantly, we first revealed dual changes in blood pressure, i.e., decreased diastolic blood pressure but increased systolic blood pressure in CEN, which associated with altered CST3 expression. Genetic analysis revealed a significant association of blood uric acid (BUA) and BCr in CEN with F1 but not with F1SP, suggesting they may be heritable traits. Taken together, our results suggest serum lipids, kidney function and especially diastolic pressure rather than systolic pressure were improved in CEN or their offspring, suggesting these factors may play an important role in familial longevity.

Longevity expectations in the pension fund, insurance, and employee benefits industries.

PubMed

Zhavoronkov, Alex

2015-01-01

Considerable progress has been made in many areas of biomedical science since the 1960s, suggesting likely increases in life expectancy and decreases in morbidity and mortality in the adult population. These changes may pose substantial risks to the pensions and benefits industries. While there is no significant statistical evidence demonstrating rapid decreases in mortality rates, there are conflicting opinions among demographers and biogerontologists on the biological limits of the human lifespan and trends in life expectancy. We administered a survey of the International Employee Benefits Association (IEBA), a large, international industry group. Industry professionals employed by consulting (35%), insurance (24%), pension (14%), and other (27%) companies responded to 32 questions. Respondents showed reasonably conservative views on the future of longevity and retirement, including that for women. The respondents formed their personal longevity expectations based on their family history and, to a lesser degree, on the actuarial life tables. Most of the sample expressed no desire to life past age 100 years, even if the enabling technologies required to maintain a healthy youthful state were available, and only a few respondents in the sample expressed a desire to live for the maximum period (at least) offered by the survey question. The majority of the respondents would not undergo any invasive procedures, and only 56% of the respondents would opt for noninvasive therapies to extend their healthy lifespans to 150 years of age if these were available.

Is There a Role for Oligosaccharides in Seed Longevity? An Assessment of Intracellular Glass Stability1

PubMed Central

Buitink, Julia; Hemminga, Marcus A.; Hoekstra, Folkert A.

2000-01-01

We examined whether oligosaccharides extend seed longevity by increasing the intracellular glass stability. For that purpose, we used a spin probe technique to measure the molecular mobility and glass transition temperature of the cytoplasm of impatiens (Impatiens walleriana) and bell pepper (Capsicum annuum) seeds that were osmo-primed to change oligosaccharide content and longevity. Using saturation transfer electron paramagnetic resonance spectroscopy, we found that the rotational correlation time of the polar spin probe 3-carboxy-proxyl in the cytoplasm decreased, together with longevity, as a function of increasing seed water content, suggesting that longevity may indeed be regulated by cytoplasmic mobility. Osmo-priming of the seeds resulted in considerable decreases in longevity and oligosaccharide content, while the sucrose content increased. No difference in the glass transition temperature was found between control and primed impatiens seeds at the same temperature and water content. Similarly, there was no difference in the rotational motion of the spin probe in the cytoplasm between control and primed impatiens and bell pepper seeds. We therefore conclude that oligosaccharides in seeds do not affect the stability of the intracellular glassy state, and that the reduced longevity after priming is not the result of increased molecular mobility in the cytoplasm. PMID:10759518

Haploinsufficiency of myostatin protects against aging-related declines in muscle function and enhances the longevity of mice.

PubMed

Mendias, Christopher L; Bakhurin, Konstantin I; Gumucio, Jonathan P; Shallal-Ayzin, Mark V; Davis, Carol S; Faulkner, John A

2015-08-01

The molecular mechanisms behind aging-related declines in muscle function are not well understood, but the growth factor myostatin (MSTN) appears to play an important role in this process. Additionally, epidemiological studies have identified a positive correlation between skeletal muscle mass and longevity. Given the role of myostatin in regulating muscle size, and the correlation between muscle mass and longevity, we tested the hypotheses that the deficiency of myostatin would protect oldest-old mice (28-30 months old) from an aging-related loss in muscle size and contractility, and would extend the maximum lifespan of mice. We found that MSTN(+/-) and MSTN(-/-) mice were protected from aging-related declines in muscle mass and contractility. While no differences were detected between MSTN(+/+) and MSTN(-/-) mice, MSTN(+/-) mice had an approximately 15% increase in maximal lifespan. These results suggest that targeting myostatin may protect against aging-related changes in skeletal muscle and contribute to enhanced longevity. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Factor Analysis of Linear Type Traits and Their Relation with Longevity in Brazilian Holstein Cattle

PubMed Central

Kern, Elisandra Lurdes; Cobuci, Jaime Araújo; Costa, Cláudio Napolis; Pimentel, Concepta Margaret McManus

2014-01-01

In this study we aimed to evaluate the reduction in dimensionality of 20 linear type traits and more final score in 14,943 Holstein cows in Brazil using factor analysis, and indicate their relationship with longevity and 305 d first lactation milk production. Low partial correlations (−0.19 to 0.38), the medium to high Kaiser sampling mean (0.79) and the significance of the Bartlett sphericity test (p<0.001), indicated correlations between type traits and the suitability of these data for a factor analysis, after the elimination of seven traits. Two factors had autovalues greater than one. The first included width and height of posterior udder, udder texture, udder cleft, loin strength, bone quality and final score. The second included stature, top line, chest width, body depth, fore udder attachment, angularity and final score. The linear regression of the factors on several measures of longevity and 305 d milk production showed that selection considering only the first factor should lead to improvements in longevity and 305 milk production. PMID:25050015

Rejuvenation of Gene Expression Pattern of Aged Human Skin by Broadband Light Treatment: A Pilot Study

PubMed Central

Chang, Anne Lynn S; Bitter, Patrick H; Qu, Kun; Lin, Meihong; Rapicavoli, Nicole A; Chang, Howard Y

2013-01-01

Studies in model organisms suggest that aged cells can be functionally rejuvenated, but whether this concept applies to human skin is unclear. Here we apply 3′-end sequencing for expression quantification (“3-seq”) to discover the gene expression program associated with human photoaging and intrinsic skin aging (collectively termed “skin aging”), and the impact of broadband light (BBL) treatment. We find that skin aging was associated with a significantly altered expression level of 2,265 coding and noncoding RNAs, of which 1,293 became “rejuvenated” after BBL treatment; i.e., they became more similar to their expression level in youthful skin. Rejuvenated genes (RGs) included several known key regulators of organismal longevity and their proximal long noncoding RNAs. Skin aging is not associated with systematic changes in 3′-end mRNA processing. Hence, BBL treatment can restore gene expression pattern of photoaged and intrinsically aged human skin to resemble young skin. In addition, our data reveal, to our knowledge, a previously unreported set of targets that may lead to new insights into the human skin aging process. PMID:22931923

[AGING, HEALTH AND ACTIVE LONGEVITY: SEMANTIC CONTEXT OF THEIR MENTIONING IN SOCIAL NETWORKS].

PubMed

Grigoryeva, I A; Bikkulov, A S

2015-01-01

Traditional media play a large role in shaping the image of oldsters as weak and sick members of society, while the gerontologists say the health of the elderly is quite specific. In a study of the views of the Internet audience, we tried to find out what this IT-competent part of society thinks on aging, what meanings they associate with aging and active longevity.

Oviposition, Life Cycle, and Longevity of the Leaf-Cutting Ant Acromyrmex rugosus rugosus.

PubMed

Verza, Sandra S; Mussury, Rosilda M; Camargo, Roberto S; Andrade, Ana Paula P; Forti, Luiz C

2017-08-04

Studies related to the demography of individual members from ant colonies have received little attention, although they are the basis to understanding the population dynamics of colonies. Thus, the objective of this work was to study the queen oviposition rate and the duration of the life cycle and longevity of Acromyrmex rugosus rugosus workers. To determine the oviposition rate, queens from three colonies were individually placed in plastic containers, and the eggs laid were quantified over a 96 h period. The development of the immature forms was observed every 24 h, with which the duration of each stage of development was determined. To verify the longevity of workers, the newly emerged adults were marked and daily observations were made. According to the results, there is variation in the development time of immature forms within the colony itself and between colonies. In addition, the number of eggs deposited was also inconstant in the three colonies, ranging from 5 to 119 eggs per day, while the longevity of workers varied from 3 to 7 months. Occasionally, it was found that the workers feed on the eggs produced by the queen; besides, there was a disappearance of larvae and pupae during the research, indicating a possibility of the practice of cannibalism in this species.

Controversies in cancer and the mind: effects of psychosocial support.

PubMed

Sampson, Wallace

2002-12-01

In the last decades of the twentieth century, interest in effects of consciousness on health and illness generated several lines of investigation into effects on cancer. Animal studies showed sensitivity of some cancers to hormonal and stressful influences. However, those findings did not translate into effects on humans, nor did they lead to advances in understanding of human cancer. The proposal that emotional state or stress, mediated through psycho-neuro-immunologic mechanisms would affect cancer generation or growth, resulted in conflicting information. Major surveys found no relationship. The proposal of a cancer personality (Type C) also was not confirmed. Initial observations that depression and stress affected human cancer seem to have best been explained by misinterpretations of cause and effect. By the mid 1990s, a remaining thesis--effect of psychosocial support on longevity and the course of cancer--was yet to be resolved. Initial positive results, especially findings in two popularly quoted studies, were not confirmed; they seem to have been due to inadequate numbers (chance) or to artifacts in study design or implementation. Psychosocial support may result in better adjustment and quality of life, but it does not directly affect the evolution of human cancer. Copyright 2002, Elsevier Science (USA). All rights reserved.

The Effect of Decomposition on the Efficacy of Biometrics for Positive Identification.

PubMed

Sauerwein, Kelly; Saul, Tiffany B; Steadman, Dawnie Wolfe; Boehnen, Chris B

2017-11-01

Biometrics, unique measurable physiological and behavioral characteristics, are used to identify individuals in a variety of scenarios, including forensic investigations. However, data on the longevity of these indicators are incomplete. This study demonstrated that iris and fingerprint biometric data can be obtained up to four days postmortem in warmer seasons and 50 + days in the winter. It has been generally believed, but never studied, that iris recognition is only obtainable within the first 24 hours after death. However, this study showed that they remain viable for longer (2-34 days) depending upon the environmental conditions. Temperature, precipitation, insects, and scavenger activity were the primary factors affecting the retention of biometrics in decomposing human remains. While this study is an initial step in determining the utility of physiological biometrics across postmortem time, biometric research has the potential to make important contributions to human identification and the law enforcement, military, and medicolegal communities. © 2017 American Academy of Forensic Sciences.

AVPR1A alleles are pleiotropic sources of variation in age at puberty and reproductive longevity in sows

USDA-ARS?s Scientific Manuscript database

Age at puberty is a moderately heritable trait and an early indicator of sow reproductive longevity. Gilts that express first estrus early in life are characterized by improved reproductive longevity and lifetime productivity. These traits are dependent on the function of the hypothalamic-pituitary-...

Is there a trade-off between longevity and quality of life in Grossman's pure investment model?

PubMed

Eisenring, C

2000-12-01

The question is posed whether an individual maximizes lifetime or trades off longevity for quality of life in Grossman's pure investment (PI)-model. It is shown that the answer critically hinges on the assumed production function for healthy time. If the production function for healthy time produces a trade-off between life-span and quality of life, one has to solve a sequence of fixed time problems. The one offering maximal intertemporal utility determines optimal longevity. Comparative static results of optimal longevity for a simplified version of the PI-model are derived. The obtained results predict that higher initial endowments of wealth and health, a rise in the wage rate, or improvements in the technology of producing healthy time, all increase the optimal length of life. On the other hand, optimal longevity is decreasing in the depreciation and interest rate. From a technical point of view, the paper illustrates that a discrete time equivalent to the transversality condition for optimal longevity employed in continuous optimal control models does not exist. Copyright 2000 John Wiley & Sons, Ltd.

Fine-scale spatial climate variation and drought mediate the likelihood of reburning.

PubMed

Parks, Sean A; Parisien, Marc-André; Miller, Carol; Holsinger, Lisa M; Baggett, Larry Scott

2018-03-01

In many forested ecosystems, it is increasingly recognized that the probability of burning is substantially reduced within the footprint of previously burned areas. This self-limiting effect of wildland fire is considered a fundamental emergent property of ecosystems and is partly responsible for structuring landscape heterogeneity (i.e., mosaics of different age classes), thereby reducing the likelihood of uncharacteristically large fires in regions with active fire regimes. However, the strength and longevity of this self-limiting phenomenon is not well understood in most fire-prone ecosystems. In this study, we quantify the self-limiting effect in terms of its strength and longevity for five fire-prone study areas in western North America and investigate how each measure varies along a spatial climatic gradient and according to temporal (i.e., annual) climatic variation. Results indicate that the longevity (i.e., number of years) of the self-limiting effect ranges between 15 yr in the warm and dry study area in the southwestern United States to 33 yr in the cold, northern study areas in located in northwestern Montana and the boreal forest of Canada. We also found that spatial climatic variation has a strong influence on wildland fire's self-limiting capacity. Specifically, the self-limiting effect within each study area was stronger and lasted longer in areas with low mean moisture deficit (i.e., wetter and cooler settings) compared to areas with high mean moisture deficit (warmer and drier settings). Last, our findings show that annual climatic variation influences wildland fire's self-limiting effect: drought conditions weakened the strength and longevity of the self-limiting effect in all study areas, albeit at varying magnitudes. Overall, our study provides support for the idea that wildland fire contributes to spatial heterogeneity in fuel ages that subsequently mediate future fire sizes and effects. However, our findings show that the strength and longevity of the self-limiting effect varies considerably according to spatial and temporal climatic variation, providing land and fire managers relevant information for effective planning and management of fire and highlighting that fire itself is an important factor contributing to fire-free intervals. © 2017 by the Ecological Society of America.

Drugs that modulate aging: the promising yet difficult path ahead.

PubMed

Kennedy, Brian K; Pennypacker, Juniper K

2014-05-01

Once a backwater in medical sciences, aging research has emerged and now threatens to take the forefront. This dramatic change of stature is driven from 3 major events. First and foremost, the world is rapidly getting old. Never before have we lived in a demographic environment like today, and the trends will continue such that 20% percent of the global population of 9 billion will be over the age of 60 by 2050. Given current trends of sharply increasing chronic disease incidence, economic disaster from the impending silver tsunami may be ahead. A second major driver on the rise is the dramatic progress that aging research has made using invertebrate models such as worms, flies, and yeast. Genetic approaches using these organisms have led to hundreds of aging genes and, perhaps surprisingly, strong evidence of evolutionary conservation among longevity pathways between disparate species, including mammals. Current studies suggest that this conservation may extend to humans. Finally, small molecules such as rapamycin and resveratrol have been identified that slow aging in model organisms, although only rapamycin to date impacts longevity in mice. The potential now exists to delay human aging, whether it is through known classes of small molecules or a plethora of emerging ones. But how can a drug that slows aging become approved and make it to market when aging is not defined as a disease. Here, we discuss the strategies to translate discoveries from aging research into drugs. Will aging research lead to novel therapies toward chronic disease, prevention of disease or be targeted directly at extending lifespan? Copyright © 2014 Mosby, Inc. All rights reserved.

Fasting: molecular mechanisms and clinical applications.

PubMed

Longo, Valter D; Mattson, Mark P

2014-02-04

Fasting has been practiced for millennia, but, only recently, studies have shed light on its role in adaptive cellular responses that reduce oxidative damage and inflammation, optimize energy metabolism, and bolster cellular protection. In lower eukaryotes, chronic fasting extends longevity, in part, by reprogramming metabolic and stress resistance pathways. In rodents intermittent or periodic fasting protects against diabetes, cancers, heart disease, and neurodegeneration, while in humans it helps reduce obesity, hypertension, asthma, and rheumatoid arthritis. Thus, fasting has the potential to delay aging and help prevent and treat diseases while minimizing the side effects caused by chronic dietary interventions. Copyright © 2014 Elsevier Inc. All rights reserved.

Cognition, interaction and ageing: an Internet workshops exploratory study.

PubMed

Xavier, André; Sales, Márcia; Ramos, Luiz; Anção, Meide; Sigulem, Daniel

2004-01-01

Gerontology is known more and more as an interdisciplinary and functional knowledge. Geriatrics as one of its branches intends to make possible longevity with health. World population ageing occurs along with important economical and social inequalities for elder people, which are likely to be more affected by deficiencies (physical and/or cognitive) than younger groups. With the purpose of minimizing these deficiencies, Internet Workshops were accomplished, with a retired group of senior persons. This research was developed to bring together principles of Human-Computer Interaction, informatics, accessibility and gerontology in order to promote Digital Inclusion to this growing population and a methodology to virtual cognitive rehabilitation.

Gender, marital status and longevity.

PubMed

Tatangelo, Gemma; McCabe, Marita; Campbell, Stephen; Szoeke, Cassandra

2017-06-01

Most studies report a positive relationship between marital status and health, with findings consistent across cultures and countries. Gender effects are significant, with men demonstrating greater health benefit than women. The vast majority of the research has examined heterosexual marriages, yet there has been rapid evolution in society of cohabitation patterns, who can marry, and roles in marriage. In this review, we summarise research findings and discuss important future challenges. Broader work looking at the impact of social connectedness, loneliness and support on survival should be supported. Human relationships are crucial to our health and wellbeing - caring and support promote significantly better health outcomes. Copyright © 2017 Elsevier B.V. All rights reserved.

Raymond Pearl and the shaping of human biology.

PubMed

Little, Michael A; Garruto, Ralph M

2010-02-01

Raymond Pearl (1879-1940) was a significant figure in the field of biology. He founded the journal Human Biology and almost single-handedly promoted and established the scientific discipline of human biology. His scientific versatility was one of his most important features during the first four decades of the 20th century, and he played a major role in developing the fields of biodemography, human population biology, human life-cycle and life span approaches, fertility, growth, the biology of longevity and senescence, and mortality. He was one of the earliest biologists to combine biometric analyses and experimental studies to explore the dimensions of human biology. Pearl also was broadly educated in the arts, music, literature, history, the classics, and science. His writing was sophisticated and often witty, and his views were sometimes provocative and controversial. His network of colleagues and friends among the literary and science worlds was substantial. The following biographical memoir of Raymond Pearl is designed to commemorate the 80th anniversary of the founding of his journal Human Biology and is a tribute to this great scientist. Pearl's sudden death at age 61 truncated a scientific career that was one of the most productive of the 20th century.

Daughters increase longevity of fathers, but daughters and sons equally reduce longevity of mothers.

PubMed

Jasienska, Grazyna; Nenko, Ilona; Jasienski, Michal

2006-01-01

Reproduction is energetically and physiologically expensive, and an individual investing resources into producing offspring should suffer costs such as deterioration in health condition and possibly shorter life span. Since the energetic and nutritional demands of pregnancy and breastfeeding render reproductive costs much higher in women than in men, women with a large number of children should show signs of deterioration in condition, while men with large families should not. However, whether reproductive costs reduce longevity in women is still questionable, and in men this issue has not been adequately addressed. In addition, since sons are energetically more expensive to produce than daughters, having sons should have a more pronounced negative impact on maternal longevity than having daughters. Here we document a striking disparity in the impact of children on the life span of mothers and fathers in a Polish rural population. We show for the first time that number of daughters was positively related to a longer life span of their fathers, increasing their longevity on average by 74 weeks per daughter born, while number of sons did not have a significant effect on paternal longevity. In contrast, in women, the number of daughters and number of sons reduced maternal longevity and did so to the same extent, on average by 95 weeks per son or daughter, indicating that for women, the costs of having sons and daughters are similar.

Chemical genetic screen identifies lithocholic acid as an anti-aging compound that extends yeast chronological life span in a TOR-independent manner, by modulating housekeeping longevity assurance processes.

PubMed

Goldberg, Alexander A; Richard, Vincent R; Kyryakov, Pavlo; Bourque, Simon D; Beach, Adam; Burstein, Michelle T; Glebov, Anastasia; Koupaki, Olivia; Boukh-Viner, Tatiana; Gregg, Christopher; Juneau, Mylène; English, Ann M; Thomas, David Y; Titorenko, Vladimir I

2010-07-01

In chronologically aging yeast, longevity can be extended by administering a caloric restriction (CR) diet or some small molecules. These life-extending interventions target the adaptable target of rapamycin (TOR) and cAMP/protein kinase A (cAMP/PKA) signaling pathways that are under the stringent control of calorie availability. We designed a chemical genetic screen for small molecules that increase the chronological life span of yeast under CR by targeting lipid metabolism and modulating housekeeping longevity pathways that regulate longevity irrespective of the number of available calories. Our screen identifies lithocholic acid (LCA) as one of such molecules. We reveal two mechanisms underlying the life-extending effect of LCA in chronologically aging yeast. One mechanism operates in a calorie availability-independent fashion and involves the LCA-governed modulation of housekeeping longevity assurance pathways that do not overlap with the adaptable TOR and cAMP/PKA pathways. The other mechanism extends yeast longevity under non-CR conditions and consists in LCA-driven unmasking of the previously unknown anti-aging potential of PKA. We provide evidence that LCA modulates housekeeping longevity assurance pathways by suppressing lipid-induced necrosis, attenuating mitochondrial fragmentation, altering oxidation-reduction processes in mitochondria, enhancing resistance to oxidative and thermal stresses, suppressing mitochondria-controlled apoptosis, and enhancing stability of nuclear and mitochondrial DNA.

Bigheaded carps : a biological synopsis and environmental risk assessment

USGS Publications Warehouse

Kolar, Cindy S.; Chapman, Duane C.; Courtenay, Walter R.; Housel, Christine M.; Williams, James D.; Jennings, Dawn P.

2007-01-01

Includes information on taxonomy and distinguishing characteristics, hybrids, native and introduced ranges, temperature and salinity tolerances, fecundity, sexual maturity and mating behavior, spawning, early development, feeding habits, growth rate and longevity, response to physical stimuli, associated diseases and parasites, human uses, environmental effects, potential range, population control measures. Summarizes United States federal and state regulations, and assesses the risk posed by these species in the United States.

Central insulin-like growth factor-1 (IGF-1) restores whole-body insulin action in a model of age-related insulin resistance and IGF-1 decline.

PubMed

Huffman, Derek M; Farias Quipildor, Gabriela; Mao, Kai; Zhang, Xueying; Wan, Junxiang; Apontes, Pasha; Cohen, Pinchas; Barzilai, Nir

2016-02-01

Low insulin-like growth factor-1 (IGF-1) signaling is associated with improved longevity, but is paradoxically linked with several age-related diseases in humans. Insulin-like growth factor-1 has proven to be particularly beneficial to the brain, where it confers protection against features of neuronal and cognitive decline. While aging is characterized by central insulin resistance in the face of hyperinsulinemia, the somatotropic axis markedly declines in older humans. Thus, we hypothesized that increasing IGF-1 in the brain may prove to be a novel therapeutic alternative to overcome central insulin resistance and restore whole-body insulin action in aging. Utilizing hyperinsulinemic-euglycemic clamps, we show that old insulin-resistant rats with age-related declines in IGF-1 level demonstrate markedly improved whole-body insulin action, when treated with central IGF-1, as compared to central vehicle or insulin (P < 0.05). Furthermore, central IGF-1, but not insulin, suppressed hepatic glucose production and increased glucose disposal rates in aging rats (P < 0.05). Taken together, IGF-1 action in the brain and periphery provides a 'balance' between its beneficial and detrimental actions. Therefore, we propose that strategies aimed at 'tipping the balance' of IGF-1 action centrally are the optimal approach to achieve healthy aging and longevity in humans. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Battery longevity in cardiac resynchronization therapy implantable cardioverter defibrillators.

PubMed

Alam, Mian Bilal; Munir, Muhammad Bilal; Rattan, Rohit; Flanigan, Susan; Adelstein, Evan; Jain, Sandeep; Saba, Samir

2014-02-01

Cardiac resynchronization therapy (CRT) implantable cardioverter defibrillators (ICDs) deliver high burden ventricular pacing to heart failure patients, which has a significant effect on battery longevity. The aim of this study was to investigate whether battery longevity is comparable for CRT-ICDs from different manufacturers in a contemporary cohort of patients. All the CRT-ICDs implanted at our institution from 1 January 2008 to 31 December 2010 were included in this analysis. Baseline demographic and clinical data were collected on all patients using the electronic medical record. Detailed device information was collected on all patients from scanned device printouts obtained during routine follow-up. The primary endpoint was device replacement for battery reaching the elective replacement indicator (ERI). A total of 646 patients (age 69 ± 13 years), implanted with CRT-ICDs (Boston Scientific 173, Medtronic 416, and St Jude Medical 57) were included in this analysis. During 2.7 ± 1.5 years follow-up, 113 (17%) devices had reached ERI (Boston scientific 4%, Medtronic 25%, and St Jude Medical 7%, P < 0.001). The 4-year survival rate of device battery was significantly worse for Medtronic devices compared with devices from other manufacturers (94% for Boston scientific, 67% for Medtronic, and 92% for St Jude Medical, P < 0.001). The difference in battery longevity by manufacturer was independent of pacing burden, lead parameters, and burden of ICD therapy. There are significant discrepancies in CRT-ICD battery longevity by manufacturer. These data have important implications on clinical practice and patient outcomes.

Safety and efficiency of ventricular pacing prevention with an AAI-DDD changeover mode in patients with sinus node disease or atrioventricular block: impact on battery longevity-a sub-study of the ANSWER trial.

PubMed

Stockburger, Martin; Defaye, Pascal; Boveda, Serge; Stancak, Branislav; Lazarus, Arnaud; Sipötz, Johann; Nardi, Stefano; Rolando, Mara; Moreno, Javier

2016-05-01

This ANSWER (EvaluAtioN of the SafeR mode in patients With a dual chambER pacemaker indication) sub-study assesses safety and effectiveness of SafeR™ and the impact of ventricular pacing (VP) prevention on anticipated device longevity and replacement rate. Patients implanted for atrioventricular block (AVB, n = 310) or sinus node dysfunction (SND, n = 336) were randomly assigned to SafeR (n = 314) or DDD (n = 318) and followed for 36 months. Safety, median VP, estimated device longevity (mean difference, 95% confidence interval [CI]), and anticipated replacement rates were analysed by pacing mode and implant indication. No difference in mortality, syncope, or mode intolerance was observed between randomization groups regardless of the indication. Ventricular pacing on SafeR vs. DDD was 11.5 vs. 93.6% in the overall population (P < 0.001), 89.2 vs. 83.8% in permanent AVB (P = 0.944), 53.5 vs. 98.2% in intermittent AVB (P < 0.001), and 2.2 vs. 84.7% in SND (P < 0.001). Anticipated median device longevity increased on SafeR by 14 [Q1 10; Q3 17] months [10; 17] (P < 0.001) in the overall population, 9 months [-5; 22] (P = 0.193) in permanent AVB, 14 months [8; 19] (P < 0.001) in intermittent AVB, and 14 months [9; 19] (P < 0.001) in SND. In intermittent AVB and SND, prolonged estimated battery longevity translated into the prevention of one anticipated replacement in at least 23% of patients. SafeR was effective in reducing VP in intermittent AVB and in SND. No effect was observed in permanent AVB. No safety issue was observed. Ventricular pacing reduction by SafeR translated into relevant estimated prolongation of device longevity and anticipated reduction of required replacements. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Automatic remote monitoring utilizing daily transmissions: transmission reliability and implantable cardioverter defibrillator battery longevity in the TRUST trial.

PubMed

Varma, Niraj; Love, Charles J; Schweikert, Robert; Moll, Philip; Michalski, Justin; Epstein, Andrew E

2018-04-01

Benefits of automatic remote home monitoring (HM) among implantable cardioverter defibrillator (ICD) patients may require high transmission frequency. However, transmission reliability and effects on battery longevity remain uncertain. We hypothesized that HM would have high transmission success permitting punctual guideline based follow-up, and improve battery longevity. This was tested in the prospective randomized TRUST trial. Implantable cardioverter defibrillator patients were randomized post-implant 2:1 to HM (n = 908) (transmit daily) or to Conventional in-person monitoring [conventional management (CM), n = 431 (HM disabled)]. In both groups, five evaluations were scheduled every 3 months for 15 months. Home Monitoring technology performance was assessed by transmissions received vs. total possible, and number of scheduled HM checks failing because of missed transmissions. Battery longevity was compared in HM vs. CM at 15 months, and again in HM 3 years post-implant using continuously transmitted data. Transmission success per patient was 91% (median follow-up of 434 days). Overall, daily HM transmissions were received in 315 795 of a potential 363 450 days (87%). Only 55/3759 (1.46%) of unsuccessful scheduled evaluations in HM were attributed to transmission loss. Shock frequency and pacing percentage were similar in HM vs. CM. Fifteen month battery longevity was 12% greater in HM (93.2 ± 8.8% vs. 83.5 ± 6.0% CM, P < 0.001). In extended follow-up of HM patients, estimated battery longevity was 50.9 ± 9.1% (median 52%) at 36 months. Automatic remote HM demonstrated robust transmission reliability. Daily transmission load may be sustained without reducing battery longevity. Home Monitoring conserves battery longevity and tracks long term device performance. ClinicalTrials.gov; NCT00336284.

A Novel 3-Hydroxysteroid Dehydrogenase That Regulates Reproductive Development and Longevity

PubMed Central

Wollam, Joshua; Magner, Daniel B.; Magomedova, Lilia; Rass, Elisabeth; Shen, Yidong; Rottiers, Veerle; Habermann, Bianca; Cummins, Carolyn L.; Antebi, Adam

2012-01-01

Endogenous small molecule metabolites that regulate animal longevity are emerging as a novel means to influence health and life span. In C. elegans, bile acid-like steroids called the dafachronic acids (DAs) regulate developmental timing and longevity through the conserved nuclear hormone receptor DAF-12, a homolog of mammalian sterol-regulated receptors LXR and FXR. Using metabolic genetics, mass spectrometry, and biochemical approaches, we identify new activities in DA biosynthesis and characterize an evolutionarily conserved short chain dehydrogenase, DHS-16, as a novel 3-hydroxysteroid dehydrogenase. Through regulation of DA production, DHS-16 controls DAF-12 activity governing longevity in response to signals from the gonad. Our elucidation of C. elegans bile acid biosynthetic pathways reveals the possibility of novel ligands as well as striking biochemical conservation to other animals, which could illuminate new targets for manipulating longevity in metazoans. PMID:22505847

Visceral adipose tissue modulates mammalian longevity

PubMed Central

Muzumdar, Radhika; Allison, David B.; Huffman, Derek M.; Ma, Xiaohui; Atzmon, Gil; Einstein, Francine H.; Fishman, Sigal; Poduval, Aruna D.; McVei, Theresa; Keith, Scott W.; Barzilai, Nir

2008-01-01

Summary Caloric restriction (CR) can delay many age-related diseases and extend lifespan, while an increase in adiposity is associated with enhanced disease risk and accelerated aging. Among the various fat depots, the accrual of visceral fat (VF) is a common feature of aging, and has been shown to be the most detrimental on metabolic syndrome of aging in humans. We have previously demonstrated that surgical removal of VF in rats improves insulin action; thus, we set out to determine if VF removal affects longevity. We prospectively studied lifespan in three groups of rats: ad libitum-fed (AL-fed), CR (Fed 60% of AL) and a group of AL-fed rats with selective removal of VF at 5 months of age (VF-removed rats). We demonstrate that compared to AL-fed rats, VF-removed rats had a significant increase in mean (p < 0.001) and maximum lifespan (p < 0.04) and significant reduction in the incidence of severe renal disease (p < 0.01). CR rats demonstrated the greatest mean and maximum lifespan (p < 0.001) and the lowest rate of death as compared to AL-fed rats (0.13). Taken together, these observations provide the most direct evidence to date that a reduction in fat mass, specifically VF, may be one of the possible underlying mechanisms of the anti-aging effect of CR. PMID:18363902

Walking four times weekly for at least 15 min is associated with longevity in a cohort of very elderly people.

PubMed

Fortes, Cristina; Mastroeni, Simona; Sperati, Alessandra; Pacifici, Roberta; Zuccaro, PierGiorgio; Francesco, Forastiere; Agabiti, Nerina; Piras, Giovanna; Amleto, D'Amicis; Ebrahim, Shah

2013-03-01

This study investigated the role of walking outdoors on longevity, controlling for individual and other life-style factors as possible confounders. A 10-year cohort study was conducted with 152 self-caring and mobile, mean age 80 years, were enrolled in the study. Information on socio-demographic characteristics, clinical and biochemical data, diet, physical activity, smoking, depression status, cognitive status and anthropometrics measurements, were obtained for all participants. Cox proportional-hazards models were used to determine independent predictors of longevity. During the 10-years of follow-up, 96 (63%) died. Old age, chronic diseases, smoking, depression, CD4/CD8 ratio and coffee consumption were significantly predictors of mortality. Over-all survival was highest for subjects walking at open air for 4 times weekly for at least 15 min in comparison to subjects walking less than 4 times weekly (40% versus 22%). After adjusting for sex, age, education, chronic diseases, smoking, Body Mass Index and CD4/CD8 ratio, elderly people walking at open air for four times weekly had 40% decreased risk of mortality that individuals who walked less than four times weekly [relative risk (RR)=0.53; 95% confidence interval (CI)=0.32-0.88, p=0.01]. Findings suggest an independent and protective effect of walking on mortality and supports the encouragement of physical activity in advanced age for increasing longevity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Growth hormone, insulin and aging: The benefits of endocrine defects

PubMed Central

Bartke, Andrzej

2012-01-01

Longevity of mice can be increased by spontaneous or experimentally induced mutations that interfere with the biosynthesis or actions of growth hormone (GH), insulin-like growth factor 1 (IGF-1), or insulin in the adipose tissue. The effects of GH resistance and deficiency of GH (along with thyrotropin and prolactin) on aging and lifespan are the most pronounced and best established of these mutations. Potential mechanisms linking these endocrine deficits with delayed aging and extended longevity include increased stress resistance, alterations in insulin and mammalian target of rapamycin (mTOR) signaling and metabolic adjustments. Physiological relationships deduced from the extreme phenotypes of long-lived mouse mutants appear to apply broadly, encompassing genetically normal (“wild-type”) mice and other mammalian species. The role of GH in the control of human aging continues to be hotly debated, but recent data indicate that reduced somatotropic signaling provides protection from cancer and other age-related diseases and may promote old age survival. PMID:20851173

Caloric restriction in the presence of attractive food cues: external cues, eating, and weight.

PubMed

Polivy, Janet; Herman, C Peter; Coelho, Jennifer S

2008-08-06

A growing body of research on caloric restriction (CR) in many species of laboratory animals suggests that underfeeding leads to better health and longevity in the calorically-restricted animal (e.g., see [[34]. J.P. Pinel, S. Assanand and D.R. Lehman, (2000). Hunger, eating and ill health. Am Psychol, 55, 1105-1116.], for a review). Although some objections have been raised by scientists concerned about negative psychological and behavioral sequelae of such restriction, advocates of CR continue to urge people to adopt sharply reduced eating regimes in order to increase their longevity. Yet very few people are even attempting to reap the benefits of such restriction. The present paper explores one factor that may deter many humans from drastically reducing their food consumption--the presence of abundant, attractive food cues in the environment. Research on the influence of food cues on food-related behaviors is reviewed to demonstrate that the presence of food cues makes restriction of intake more difficult.

Non-senescent Hydra tolerates severe disturbances in the nuclear lamina.

PubMed

Klimovich, Alexander; Rehm, Arvid; Wittlieb, Jörg; Herbst, Eva-Maria; Benavente, Ricardo; Bosch, Thomas C G

2018-05-10

The cnidarian Hydra is known for its unlimited lifespan and non-senescence, due to the indefinite self-renewal capacity of its stem cells. While proteins of the Lamin family are recognized as critical factors affecting senescence and longevity in human and mice, their putative role in the extreme longevity and non-senescence in long-living animals remains unknown. Here we analyze the role of a single lamin protein in non-senescence of Hydra . We demonstrate that proliferation of stem cells in Hydra is robust against the disturbance of Lamin expression and localization. While Lamin is indispensable for Hydra , the stem cells tolerate overexpression, downregulation and mislocalization of Lamin, and disturbances in the nuclear envelope structure. This extraordinary robustness may underlie the indefinite self-renewal capacity of stem cells and the non-senescence of Hydra . A relatively low complexity of the nuclear envelope architecture in basal Metazoa might allow for their extreme lifespans, while an increasing complexity of the nuclear architecture in bilaterians resulted in restricted lifespans.

Early-life stress and reproductive cost: A two-hit developmental model of accelerated aging?

PubMed

Shalev, Idan; Belsky, Jay

2016-05-01

Two seemingly independent bodies of research suggest a two-hit model of accelerated aging, one highlighting early-life stress and the other reproduction. The first, informed by developmental models of early-life stress, highlights reduced longevity effects of early adversity on telomere erosion, whereas the second, informed by evolutionary theories of aging, highlights such effects with regard to reproductive cost (in females). The fact that both early-life adversity and reproductive effort are associated with shorter telomeres and increased oxidative stress raises the prospect, consistent with life-history theory, that these two theoretical frameworks currently informing much research are tapping into the same evolutionary-developmental process of increased senescence and reduced longevity. Here we propose a mechanistic view of a two-hit model of accelerated aging in human females through (a) early-life adversity and (b) early reproduction, via a process of telomere erosion, while highlighting mediating biological embedding mechanisms that might link these two developmental aging processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Non-senescent Hydra tolerates severe disturbances in the nuclear lamina

PubMed Central

Rehm, Arvid; Wittlieb, Jörg; Herbst, Eva-Maria; Benavente, Ricardo

2018-01-01

The cnidarian Hydra is known for its unlimited lifespan and non-senescence, due to the indefinite self-renewal capacity of its stem cells. While proteins of the Lamin family are recognized as critical factors affecting senescence and longevity in human and mice, their putative role in the extreme longevity and non-senescence in long-living animals remains unknown. Here we analyze the role of a single lamin protein in non-senescence of Hydra. We demonstrate that proliferation of stem cells in Hydra is robust against the disturbance of Lamin expression and localization. While Lamin is indispensable for Hydra, the stem cells tolerate overexpression, downregulation and mislocalization of Lamin, and disturbances in the nuclear envelope structure. This extraordinary robustness may underlie the indefinite self-renewal capacity of stem cells and the non-senescence of Hydra. A relatively low complexity of the nuclear envelope architecture in basal Metazoa might allow for their extreme lifespans, while an increasing complexity of the nuclear architecture in bilaterians resulted in restricted lifespans. PMID:29754147

Evaluating the Longevity and Hydraulic Performance of Permeable Reactive Barriers at Department of Defense Sites

DTIC Science & Technology

2001-10-01

Draft Final Report Evaluating the Longevity and Hydraulic Performance of Permeable Reactive Barriers at Department of Defense Sites Prepared for...AND SUBTITLE Evaluating the Longevity and Hydraulic Performance of Permeable Reactive Barriers at Department of Defense Sites 5a. CONTRACT NUMBER...34 4.3.2 Hydraulic Performance Evaluation .................................................................... 38 4.3.2.1 Water-Level

AMPK at the Nexus of Energetics and Aging

PubMed Central

Burkewitz, Kristopher; Zhang, Yue; Mair, William B.

2014-01-01

When energy supply is low, organisms respond by slowing aging and increasing resistance to diverse age-related pathologies. Targeting the mechanisms underpinning this response may therefore treat multiple disorders through a single intervention. Here we discuss AMP-activated protein kinase (AMPK) as an integrator and mediator of several pathways and processes linking energetics to longevity. Activated by low energy, AMPK is both pro-longevity and druggable, but its role in some pathologies may not be beneficial. As such, activating AMPK may modulate multiple longevity pathways to promote healthy aging, but unlocking its full potential may require selective targeting towards substrates involved in longevity-assurance. PMID:24726383

Life course analysis of the impact of mammary cancer and pyometra on age-anchored life expectancy in female Rottweilers: Implications for envisioning ovary conservation as a strategy to promote healthy longevity in pet dogs.

PubMed

Waters, D J; Kengeri, S S; Maras, A H; Suckow, C L; Chiang, E C

2017-06-01

Mammary cancer and pyometra are important health hazards associated with ovary conservation in pet dogs. Early ovariohysterectomy may reduce the incidence of these two diseases, but an estimate of the extent to which the development of mammary cancer or pyometra adversely influences overall longevity is missing. As a first step toward addressing this knowledge gap, the results of a historical cohort study of Rottweilers that lived in North America are reported. Questionnaires completed by owners and veterinarians were used to obtain lifetime health and medical information on 242 female Rottweilers, including years of lifetime ovary exposure, age at death, and cause of death. To determine the extent to which longevity was shortened in females that developed these ovary-associated diseases, age-anchored life expectancy-defined as the median number of remaining years until death for females alive at specified ages during the life course-and years of life lost, a measure of premature mortality, were estimated. Mammary carcinoma was diagnosed in 19 (7.9%) females; median age at diagnosis was 8.5 years; case fatality was 37%. Pyometra was diagnosed in 16 (6.6%) females; median age at diagnosis was 5.4 years; case fatality was 7%. Median lifetime ovary exposure for the study population was 4.3 years. Although risk for developing both diseases increased with longer ovary exposure, longer ovary exposure (≥4.3 years) was also associated with an overall longevity advantage-a 33% decrease in mortality, living 17 months longer than females with shorter ovary exposure (P=0.002). Analysis of age-anchored life expectancy showed that at no time points during the life course was the current or future diagnosis of mammary carcinoma or pyometra associated with shortened survival compared to females who never developed these conditions. This lack of longevity disadvantage is an expected result for diseases with late-onset, moderate (<50%) case fatality (mammary carcinoma) or low (<10%) case fatality (pyometra). These findings fail to support the notion that a strategy, such as elective ovariohysterectomy, implemented to reduce the incidence of mammary carcinoma and pyometra will beneficially impact overall longevity. It follows that future efforts to find and implement effective longevity-promoting interventions should look beyond reducing the incidence of a particular disease to considering trade-offs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Studies on the intracellular Ca2+ concentration of thawed dog spermatozoa: influence of Equex from different sources, two thawing diluents and post-thaw incubation in capacitating conditions.

PubMed

Peña, A I; López-Lugilde, L; Barrio, M; Becerra, J J; Quintela, L A; Herradón, P G

2003-02-01

The addition of 0.5% (v/v) of Equex STM Paste (Nova Chemical Sales, Scituate Inc., MA, USA), whose active ingredient is sodium dodecyl sulphate (SDS), to a Tris-egg yolk extender was demonstrated to improve the longevity of frozen-thawed dog spermatozoa during in vitro incubation at 38 degrees C. The aim of the first experiment was to compare the effects of two SDS-containing compounds, Equex STM Paste and Equex Pasta (Minitüb, Tiefenbach, Germany), when added to a Tris-egg yolk based extender, on the post-thaw longevity of dog spermatozoa, as well as on the intracellular Ca2+ concentration of spermatozoa, during post-thaw incubation at 38 degrees C. The post-thaw sperm survival and longevity, as well as the quality of the sperm movement, were significantly better when using Equex STM Paste. Such prolonged sperm longevity, however, was associated to a higher intracellular Ca2+ concentration in a large subpopulation of the live spermatozoa. A second experiment was aimed to evaluate the effects of sperm dilution immediately post-thaw with a Tris buffer containing glucose or fructose. The two Tris buffers were no different for any of the sperm parameters studied. The aim of a third experiment was to evaluate the sperm longevity, motility patterns and intracellular Ca2+ concentration of cryopreserved dog spermatozoa during post-thaw incubation in capacitating conditions [canine capacitating medium (CCM) with or without 5 microg/ml of heparin]. Heparin had no significant effects on any of the sperm parameters evaluated. During the first 8 h of incubation, the majority of the live spermatozoa had a high intracellular Ca2+ content. However, after 8-10 h of incubation, it had significantly declined. The highest proportion of fast motile sperm, and the highest curvilinear velocity, average path velocity and amplitude of lateral head displacement for the total motile sperm were observed during the 2-4-h incubation period. It was concluded that: (a) the addition of 0.5% (v/v) of Equex STM Paste to a Tris-egg yolk based extender significantly improved the post-thaw longevity of dog spermatozoa, but the same concentration of Equex Pasta had no significant beneficial effects; (b) sperm dilution after thawing with a Tris buffer containing glucose or fructose made no difference in post-thaw sperm longevity; (c) the addition of 5 microg/ml of heparin to CCM had no significant capacitating effects on frozen-thawed dog spermatozoa.

Enhanced Longevity by Ibuprofen, Conserved in Multiple Species, Occurs in Yeast through Inhibition of Tryptophan Import

PubMed Central

He, Chong; Tsuchiyama, Scott K.; Nguyen, Quynh T.; Plyusnina, Ekaterina N.; Terrill, Samuel R.; Sahibzada, Sarah; Patel, Bhumil; Faulkner, Alena R.; Shaposhnikov, Mikhail V.; Tian, Ruilin; Tsuchiya, Mitsuhiro; Kaeberlein, Matt; Moskalev, Alexey A.; Kennedy, Brian K.; Polymenis, Michael

2014-01-01

The common non-steroidal anti-inflammatory drug ibuprofen has been associated with a reduced risk of some age-related pathologies. However, a general pro-longevity role for ibuprofen and its mechanistic basis remains unclear. Here we show that ibuprofen increased the lifespan of Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster, indicative of conserved eukaryotic longevity effects. Studies in yeast indicate that ibuprofen destabilizes the Tat2p permease and inhibits tryptophan uptake. Loss of Tat2p increased replicative lifespan (RLS), but ibuprofen did not increase RLS when Tat2p was stabilized or in an already long-lived strain background impaired for aromatic amino acid uptake. Concomitant with lifespan extension, ibuprofen moderately reduced cell size at birth, leading to a delay in the G1 phase of the cell cycle. Similar changes in cell cycle progression were evident in a large dataset of replicatively long-lived yeast deletion strains. These results point to fundamental cell cycle signatures linked with longevity, implicate aromatic amino acid import in aging and identify a largely safe drug that extends lifespan across different kingdoms of life. PMID:25521617

Kidney transplantation: a systematic review of interventional and observational studies of physical activity on intermediate outcomes.

PubMed

Macdonald, Jamie Hugo; Kirkman, Danielle; Jibani, Mahdi

2009-11-01

Kidney transplant patients have decreased quality and longevity of life. Whether exercise can positively affect associated outcomes such as physical functioning, metabolic syndrome, kidney function, and immune function, has only been addressed in relatively small studies. Thus the aim of this systematic review was to determine effects of physical activity level on these intermediate outcomes in kidney transplant patients. We electronically and hand searched to identify 21 studies (6 retrospective assessments of habitual physical activity and 15 intervention studies including 6 controlled trials). After study quality assessment, intermediate outcomes associated with quality and longevity of life were expressed as correlations or percentage changes in addition to effect sizes. Habitual physical activity level was positively associated with quality of life and aerobic fitness and negatively associated with body fat (medium to large effect sizes). Exercise interventions also showed medium to large positive effects on aerobic capacity (10%-114% increase) and muscle strength (10%-22% increase). However, exercise programs had minimal or contradictory effects on metabolic syndrome and immune and kidney function. In kidney transplant patients, physical activity intervention is warranted to enhance physical functioning. Whether exercise impacts on outcomes associated with longevity of life requires further study.

Whole-Genome Sequencing of a Healthy Aging Cohort.

PubMed

Erikson, Galina A; Bodian, Dale L; Rueda, Manuel; Molparia, Bhuvan; Scott, Erick R; Scott-Van Zeeland, Ashley A; Topol, Sarah E; Wineinger, Nathan E; Niederhuber, John E; Topol, Eric J; Torkamani, Ali

2016-05-05

Studies of long-lived individuals have revealed few genetic mechanisms for protection against age-associated disease. Therefore, we pursued genome sequencing of a related phenotype-healthy aging-to understand the genetics of disease-free aging without medical intervention. In contrast with studies of exceptional longevity, usually focused on centenarians, healthy aging is not associated with known longevity variants, but is associated with reduced genetic susceptibility to Alzheimer and coronary artery disease. Additionally, healthy aging is not associated with a decreased rate of rare pathogenic variants, potentially indicating the presence of disease-resistance factors. In keeping with this possibility, we identify suggestive common and rare variant genetic associations implying that protection against cognitive decline is a genetic component of healthy aging. These findings, based on a relatively small cohort, require independent replication. Overall, our results suggest healthy aging is an overlapping but distinct phenotype from exceptional longevity that may be enriched with disease-protective genetic factors. VIDEO ABSTRACT. Copyright © 2016 Elsevier Inc. All rights reserved.

A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice.

PubMed

Roberts, Megan N; Wallace, Marita A; Tomilov, Alexey A; Zhou, Zeyu; Marcotte, George R; Tran, Dianna; Perez, Gabriella; Gutierrez-Casado, Elena; Koike, Shinichiro; Knotts, Trina A; Imai, Denise M; Griffey, Stephen M; Kim, Kyoungmi; Hagopian, Kevork; McMackin, Marissa Z; Haj, Fawaz G; Baar, Keith; Cortopassi, Gino A; Ramsey, Jon J; Lopez-Dominguez, Jose Alberto

2017-09-05

Calorie restriction, without malnutrition, has been shown to increase lifespan and is associated with a shift away from glycolysis toward beta-oxidation. The objective of this study was to mimic this metabolic shift using low-carbohydrate diets and to determine the influence of these diets on longevity and healthspan in mice. C57BL/6 mice were assigned to a ketogenic, low-carbohydrate, or control diet at 12 months of age and were either allowed to live their natural lifespan or tested for physiological function after 1 or 14 months of dietary intervention. The ketogenic diet (KD) significantly increased median lifespan and survival compared to controls. In aged mice, only those consuming a KD displayed preservation of physiological function. The KD increased protein acetylation levels and regulated mTORC1 signaling in a tissue-dependent manner. This study demonstrates that a KD extends longevity and healthspan in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Genomic prediction and genome-wide association analysis of female longevity in a composite beef cattle breed.

PubMed

Hamidi Hay, E; Roberts, A

2017-04-01

Longevity is a highly important trait to the efficiency of beef cattle production. The objective of this study was to evaluate the genomic prediction of longevity and identify genomic regions associated with this trait. The data used in this study consisted of 547 Composite Gene Combination cows (1/2 Red Angus, 1/4 Charolais, 1/4 Tarentaise) born from 2002 to 2011 genotyped with Illumina BovineSNP50 BeadChip. Three models were used to assess genomic prediction: Bayes A, Bayes B and GBLUP using a genomic relationship matrix. To identify genomic regions associated with longevity 2 approaches were adopted: single marker genome wide association and Bayesian approach using GenSel software. The genomic prediction accuracy was low 0.28, 0.25, and 0.22 for Bayes A, Bayes B and GBLUP, respectively. The single-marker genome wide association study (GWAS)identified 5 loci with -value less than 0.05 after false discovery correction: UA-IFASA-7571 on chromosome 19 (58.03 Mb), ARS-BFGL-BAC-15059 on BTA 1 (28.8 Mb), ARS-BFGL-NGS-104159 on BTA3 (29.4 Mb), ARS-BFGL-NGS-32882 on BTA9 (104.07 Mb) and ARS-BFGL-NGS-32883 on BTA25 (33.77 Mb). The Bayesian GWAS yielded 4 genomic regions overlapping with the single marker GWAS results. The region with the highest percentage of genomic variance (3.73%) was detected on chromosome 19. Both GWAS approaches adopted in this study showed evidence for association with various chromosomal locations.

Evolutionary conservation of regulated longevity assurance mechanisms

PubMed Central

McElwee, Joshua J; Schuster, Eugene; Blanc, Eric; Piper, Matthew D; Thomas, James H; Patel, Dhaval S; Selman, Colin; Withers, Dominic J; Thornton, Janet M; Partridge, Linda; Gems, David

2007-01-01

Background To what extent are the determinants of aging in animal species universal? Insulin/insulin-like growth factor (IGF)-1 signaling (IIS) is an evolutionarily conserved (public) regulator of longevity; yet it remains unclear whether the genes and biochemical processes through which IIS acts on aging are public or private (that is, lineage specific). To address this, we have applied a novel, multi-level cross-species comparative analysis to compare gene expression changes accompanying increased longevity in mutant nematodes, fruitflies and mice with reduced IIS. Results Surprisingly, there is little evolutionary conservation at the level of individual, orthologous genes or paralogous genes under IIS regulation. However, a number of gene categories are significantly enriched for genes whose expression changes in long-lived animals of all three species. Down-regulated categories include protein biosynthesis-associated genes. Up-regulated categories include sugar catabolism, energy generation, glutathione-S-transferases (GSTs) and several other categories linked to cellular detoxification (that is, phase 1 and phase 2 metabolism of xenobiotic and endobiotic toxins). Protein biosynthesis and GST activity have recently been linked to aging and longevity assurance, respectively. Conclusion These processes represent candidate, regulated mechanisms of longevity-control that are conserved across animal species. The longevity assurance mechanisms via which IIS acts appear to be lineage-specific at the gene level (private), but conserved at the process level (or semi-public). In the case of GSTs, and cellular detoxification generally, this suggests that the mechanisms of aging against which longevity assurance mechanisms act are, to some extent, lineage specific. PMID:17612391

Carbon Dioxide Methanation for Human Exploration of Mars: A Look at Catalyst Longevity and Activity Using Supported Ruthenium

NASA Technical Reports Server (NTRS)

Petersen, Elspeth M.; Meier, Anne J.; Tessonnier, Jean-Philippe

2018-01-01

Overarching Purpose: To design a carbon dioxide methanation/Sabatier reaction catalyst able to withstand variable conditions including fluctuations in bed temperature and feed flow rates for 480 days of remote operation to produce seven tons of methane. Current Study Purpose: Examine supported Ruthenium as a carbon dioxide methanation catalyst to determine the effects support properties have on the active phase by studying activity and selectivity. Objective: The remote operation of the Mars ISRU (In Situ Resources Utilization) lander to produce rocket fuel prior to crew arrival on the planet to power an ascent vehicle. Constraints: Long-term operation (480 days); Variable conditions: Feed gas flow rates, Feed gas flow ratios, Reactor bed temperature.

Longevity expectations in the pension fund, insurance, and employee benefits industries

PubMed Central

Zhavoronkov, Alex

2015-01-01

Considerable progress has been made in many areas of biomedical science since the 1960s, suggesting likely increases in life expectancy and decreases in morbidity and mortality in the adult population. These changes may pose substantial risks to the pensions and benefits industries. While there is no significant statistical evidence demonstrating rapid decreases in mortality rates, there are conflicting opinions among demographers and biogerontologists on the biological limits of the human lifespan and trends in life expectancy. We administered a survey of the International Employee Benefits Association (IEBA), a large, international industry group. Industry professionals employed by consulting (35%), insurance (24%), pension (14%), and other (27%) companies responded to 32 questions. Respondents showed reasonably conservative views on the future of longevity and retirement, including that for women. The respondents formed their personal longevity expectations based on their family history and, to a lesser degree, on the actuarial life tables. Most of the sample expressed no desire to life past age 100 years, even if the enabling technologies required to maintain a healthy youthful state were available, and only a few respondents in the sample expressed a desire to live for the maximum period (at least) offered by the survey question. The majority of the respondents would not undergo any invasive procedures, and only 56% of the respondents would opt for noninvasive therapies to extend their healthy lifespans to 150 years of age if these were available. PMID:25653568

[Effect of physical activity on longevity].

PubMed

Wilczek, Mateusz M; Krupienicz, Andrzej

2016-11-25

Multiple population studies have reported a positive correlation between higher levels of physical activity (PA) and longer lifespan. It has been generally accepted that it occurs due to PA having a direct effect on longevity. However, this idea is negated by experiments on animal models and an observational study on a twin cohort published recently by Karvinen et al. This unique study includes a pairwise comparison of monozygotic twins discordant for PA, therefore eliminating any influence of genetic factors on both mortality and tendency to take up exercise. The intriguing lack of differences in lifespan in such pairs implies that PA is not an important life prolonging factor. This discovery casts doubt on the validity of PA recommendations found in numerous medical guidelines. Nevertheless, the mentioned results apply only to the plain PA - longevity relation. They do not consider health benefits of PA, for which solid evidence exists. In particular, PA clearly reduces the risk of obesity-related diseases. This may indirectly yet significantly affect the length and quality of life, even if the direct relationship between PA and lifespan will be proven false in further research. © 2016 MEDPRESS.

Placing Intelligence into an Evolutionary Framework or How "g" Fits into the "r-K" Matrix of Life-History Traits Including Longevity

ERIC Educational Resources Information Center

Rushton, J. Philippe

2004-01-01

First, I describe why intelligence (Spearman's "g") can only be fully understood through "r-K" theory, which places it into an evolutionary framework along with brain size, longevity, maturation speed, and several other life-history traits. The "r-K" formulation explains why IQ predicts longevity and also why the gap in mortality rates between…

Plasticity of floral longevity and floral display in the self-compatible biennial Sabatia angularis (Gentianaceae): untangling the role of multiple components of pollination.

PubMed

Spigler, Rachel B

2017-01-01

Plasticity of floral traits in response to pollination can enable plants to maximize opportunities for pollen import and export under poor pollination conditions, while minimizing costs under favourable ones. Both floral longevity and display are key traits influencing pollination. While pollination-induced flower wilting is widely documented, we lack an understanding of the multifactorial complexity of this response, including the influence of other pollination components, costs of extended longevity and subsequent impacts on floral display. Plasticity of floral longevity was experimentally evaluated in Sabatia angularis in response to multiple pollination factors: pollen addition, removal, and source (self, single-donor outcross, multiple-donor outcross) and timing of pollination. Effects of pollen quantity were further evaluated by exploiting variation in autonomous self-pollen deposition. Delayed pollination costs were tested comparing seed set from early versus late pollinations. Finally, I compared floral display metrics (peak floral display, time to peak flower, flowering duration, mean flowering rate) between experimentally pollinated and control plants. Floral longevity was highly plastic in response to pollen addition and its timing, and the response was dose-dependent but insensitive to pollen source. Pollen removal tended to extend floral longevity, but only insofar as it precluded pollination-induced wilting via autonomous self-pollination. Under delayed pollination, the wilting response was faster and no cost was detected. Pollination further led to reduced peak floral displays and condensed flowering periods. Floral longevity and display plasticity could optimize fitness in S. angularis, a species prone to pollen limitation and high inbreeding depression. Under pollinator scarcity, extended floral longevities offer greater opportunities for pollen receipt and export at no cost to seed set, reproductive assurance via autonomous self-pollination and larger, more attractive floral displays. Under high pollinator availability, shortened longevities lead to smaller displays that should lower the risk of geitonogamy. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Exercise, APOE genotype, and the evolution of the human lifespan

PubMed Central

Raichlen, David A.; Alexander, Gene E.

2014-01-01

Humans have exceptionally long lifespans compared with other mammals. However, our longevity evolved when our ancestors had two copies of the apolipoprotein E (APOE) ε4 allele, a genotype that leads to a high risk of Alzheimer’s disease (AD), cardiovascular disease, and increased mortality. How did human aging evolve within this genetic constraint? Drawing from neuroscience, anthropology, and brain-imaging research, we propose the hypothesis that the evolution of increased physical activity approximately 2 million years ago served to reduce the amyloid plaque and vascular burden of APOE ε4, relaxing genetic constraints on aging. This multidisciplinary approach links human evolution with health and provides a complementary perspective on aging and neurodegenerative disease that may help identify key mechanisms and targets for intervention. PMID:24690272

Nutrition and lifestyle in healthy aging: the telomerase challenge.

PubMed

Boccardi, Virginia; Paolisso, Giuseppe; Mecocci, Patrizia

2016-01-01

Nutrition and lifestyle, known to modulate aging process and age-related diseases, might also affect telomerase activity. Short and dysfunctional telomeres rather than average telomere length are associated with longevity in animal models, and their rescue by telomerase maybe sufficient to restore cell and organismal viability. Improving telomerase activation in stem cells and potentially in other cells by diet and lifestyle interventions may represent an intriguing way to promote health-span in humans.

Age and growth in the Australian freshwater mussel, Westralunio carteri , with an evaluation of the fluorochrome calcein for validating the assumption of annulus formation

Treesearch

Michael W. Klunzinger; Stephen J. Beatty; David L. Morgan; Alan J. Lymbery; Wendell R. Haag

2014-01-01

Growth and longevity of freshwater mussels (Unionida) are important for defining life-history strategies and assessing vulnerability to human impacts. We used mark–recapture and analysis of shell rings to investigate age and growth of the hyriid, Westralunio carteri, at 5 sites in southwestern Australia. We tested the utility of the in situ marker...

Generation of Recombinant Human AChE OP-Scavengers with Extended Circulatory Longevity

DTIC Science & Technology

2006-11-01

PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Avigdor Shafferman Ph.D. 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail: avigdor...glycans of rHuAChE, and in particular the distal termini of these glycan 8 projections , constitute a major factor in determining the circulatory...experiments funded by sources other than the USAMRMC contract, since they may have a major impact on the present project . Section III focuses on the

Phenotypic plasticity and longevity in plants and animals: cause and effect?

PubMed

Borges, Renee M

2009-10-01

Immobile plants and immobile modular animals outlive unitary animals. This paper discusses competing but not necessarily mutually exclusive theories to explain this extreme longevity, especially from the perspective of phenotypic plasticity. Stem cell immortality, vascular autonomy, and epicormic branching are some important features of the phenotypic plasticity of plants that contribute to their longevity. Monocarpy versus polycarpy can also influence the kind of senescent processes experienced by plants. How density-dependent phenomena affecting the establishment of juveniles in these immobile organisms can influence the evolution of senescence, and consequently longevity, is reviewed and discussed. Whether climate change scenarios will favour long-lived or short-lived organisms, with their attendant levels of plasticity, is also presented.

Biological and Host Range Studies with Bagous affinis, An Indian Weevil that Destroys Hydrilla Tubers. Aquatic Plant Control Research Program.

DTIC Science & Technology

1994-12-01

three times with newly emerged adults and three times with adults at least a month old. Treatments were (a) four hydrilla sprigs, (b) four hydrilla...Methods conducted to determine if feeding on nonhost plants stimulated the develop- ment of flight muscles. Newly emerged females were held in a plastic...Fecundity and adult longevity A fecundity and adult longevity test was conducted with newly emerged adults. Adults were held initially with moist paper

Ecological correlates of ex situ seed longevity: a comparative study on 195 species.

PubMed

Probert, Robin J; Daws, Matthew I; Hay, Fiona R

2009-07-01

Extended seed longevity in the dry state is the basis for the ex situ conservation of 'orthodox' seeds. However, even under identical storage conditions there is wide variation in seed life-span between species. Here, the effects of seed traits and environmental conditions at the site of collection on seed longevity is explored for195 wild species from 71 families from environments ranging from cold deserts to tropical forests. Seeds were rapidly aged at elevated temperature and relative humidity (either 45 degrees C and 60% RH or 60 degrees C and 60% RH) and regularly sampled for germination. The time taken in storage for viability to fall to 50% (p(50)) was determined using Probit analysis and used as a measure of relative seed longevity between species. Across species, p(50) at 45 degrees C and 60% RH varied from 0.1 d to 771 d. Endospermic seeds were, in general, shorter lived than non-endospermic seeds and seeds from hot, dry environments were longer lived than those from cool, wet conditions. These relationships remained significant when controlling for the effects of phylogenetic relatedness using phylogenetically independent contrasts. Seed mass and oil content were not correlated with p(50). The data suggest that the endospermic seeds of early angiosperms which evolved in forest understorey habitats are short-lived. Extended longevity presumably evolved as a response to climatic change or the invasion of drier areas. The apparent short-lived nature of endospermic seeds from cool wet environments may have implications for re-collection and re-testing strategies in ex situ conservation.

Bud-bank and tiller dynamics of co-occurring C3 caespitose grasses in mixed-grass prairie.

PubMed

Ott, Jacqueline P; Hartnett, David C

2015-09-01

Tiller recruitment from the belowground bud bank of caespitose grasses influences their ability to monopolize local resources and, hence, their genet fitness. Differences in bud production and outgrowth among tiller types within a genet and among species may explain co-occurrence of caespitose grasses. This study aimed to characterize genet bud-bank and tiller production and dynamics in two co-occurring species and compare their vegetative reproductive strategies. Bud-bank and tiller dynamics of Hesperostipa comata and Nassella viridula, dominant C3 caespitose grasses in the northern mixed-grass prairie of North America, were assessed throughout an annual cycle. The two species showed similar strategies, maintaining polycyclic tillers and thus creating mixed-age genet bud banks comprising multiple bud cohorts produced in different years. Vegetative tillers produced the majority of buds, whereas flowering tillers contributed little to the bud bank. Buds lived for at least 2 yr and were maintained in multiple developmental stages throughout the year. Because bud longevity rarely exceeded tiller longevity, tiller longevity drove turnover within the bud bank. Tiller population dynamics, more than bud production per tiller, determined the differential contribution of tiller types to the bud bank. Nassella viridula had higher bud production per tiller, a consistent annual tiller recruitment density, and greater longevity of buds on senesced and flowering tillers than H. comata. Co-occurring C3 caespitose grasses had similar bud-bank and tiller dynamics contributing to genet persistence but differed in bud characteristics that could affect genet longevity and species coexistence. © 2015 Botanical Society of America.

Anticancer effect of triterpenes from Ganoderma lucidum in human prostate cancer cells.

PubMed

Qu, Lijun; Li, Sumei; Zhuo, Yumin; Chen, Jianfan; Qin, Xiaoping; Guo, Guoqing

2017-12-01

Ganoderma lucidum , within the Polyporaceae family of Basidiomycota, is a popular traditional remedy medicine used in Asia to promote health and longevity. Compounds extracted from G. lucidum have revealed anticancer, antioxidant and liver protective effects. G. lucidum has been associated with prostate cancer cells. G. lucidum extracts contain numerous bioactive components; however, the exact functional monomer is unknown and the role of triterpenes from G. lucidum (GLT) in prostate cancer remain obscure. The present study investigated the effects of GLT on cell viability, migration, invasion and apoptosis in DU-145 human prostate cancer cells. The results demonstrated that a high dose (2 mg/ml) of GLT inhibits cell viability in a dose- and time-dependent manner by the regulation of matrix metalloproteases. Furthermore, GLT induced apoptosis of DU-145 cells. In general, GLT exerts its effect on cancer cells via numerous mechanisms and may have potential therapeutic use for the prevention and treatment of cancer.

Demography of human supercentenarians.

PubMed

Coles, L Stephen

2004-06-01

An international committee of demographers has created a carefully documented list of worldwide living supercentenarians (> or =110 years old) that has been published by the Los Angeles Gerontology Research Group on its web site and updated on a weekly basis for the past 6 years [see "snapshot" for the year 2003 in the Appendix]. What can be learned by studying this distinguished group of individuals? Also, what are the implications for understanding the fundamental biological limits to human longevity and maximum life span? Our conclusion: Although everyone agrees that average life expectancy has systematically advanced linearly over the last century, it is not realistic to expect that this pace can continue indefinitely. Our data suggest that, without the invention of some new unknown form of medical breakthrough, the Guinness Book of World Records benchmark established by French woman Jeanne Calment of 122 years, set back in 1997, will be exceedingly difficult to break in our lifetime.

The Energy Maintenance Theory of Aging: Maintaining Energy Metabolism to Allow Longevity.

PubMed

Chaudhari, Snehal N; Kipreos, Edward T

2018-06-14

Fused, elongated mitochondria are more efficient in generating ATP than fragmented mitochondria. In diverse C. elegans longevity pathways, increased levels of fused mitochondria are associated with lifespan extension. Blocking mitochondrial fusion in these animals abolishes their extended longevity. The long-lived C. elegans vhl-1 mutant is an exception that does not have increased fused mitochondria, and is not dependent on fusion for longevity. Loss of mammalian VHL upregulates alternate energy generating pathways. This suggests that mitochondrial fusion facilitates longevity in C. elegans by increasing energy metabolism. In diverse animals, ATP levels broadly decreases with age. Substantial evidence supports the theory that increasing or maintaining energy metabolism promotes the survival of older animals. Increased ATP levels in older animals allow energy-intensive repair and homeostatic mechanisms such as proteostasis that act to prevent cellular aging. These observations support the emerging paradigm that maintaining energy metabolism promotes the survival of older animals. © 2018 WILEY Periodicals, Inc.

Feedback regulation via AMPK and HIF-1 mediates ROS-dependent longevity in Caenorhabditis elegans

PubMed Central

Hwang, Ara B.; Ryu, Eun-A; Artan, Murat; Chang, Hsin-Wen; Kabir, Mohammad Humayun; Nam, Hyun-Jun; Lee, Dongyeop; Yang, Jae-Seong; Kim, Sanguk; Mair, William B.; Lee, Cheolju; Lee, Siu Sylvia; Lee, Seung-Jae

2014-01-01

Mild inhibition of mitochondrial respiration extends the lifespan of many species. In Caenorhabditis elegans, reactive oxygen species (ROS) promote longevity by activating hypoxia-inducible factor 1 (HIF-1) in response to reduced mitochondrial respiration. However, the physiological role and mechanism of ROS-induced longevity are poorly understood. Here, we show that a modest increase in ROS increases the immunity and lifespan of C. elegans through feedback regulation by HIF-1 and AMP-activated protein kinase (AMPK). We found that activation of AMPK as well as HIF-1 mediates the longevity response to ROS. We further showed that AMPK reduces internal levels of ROS, whereas HIF-1 amplifies the levels of internal ROS under conditions that increase ROS. Moreover, mitochondrial ROS increase resistance to various pathogenic bacteria, suggesting a possible association between immunity and long lifespan. Thus, AMPK and HIF-1 may control immunity and longevity tightly by acting as feedback regulators of ROS. PMID:25288734

The Ratio of Macronutrients, Not Caloric Intake, Dictates Cardiometabolic Health, Aging, and Longevity in Ad Libitum-Fed Mice

PubMed Central

Solon-Biet, Samantha M.; McMahon, Aisling C.; Ballard, J. William O.; Ruohonen, Kari; Wu, Lindsay E.; Cogger, Victoria C.; Warren, Alessandra; Huang, Xin; Pichaud, Nicolas; Melvin, Richard G.; Gokarn, Rahul; Khalil, Mamdouh; Turner, Nigel; Cooney, Gregory J.; Sinclair, David A.; Raubenheimer, David; Le Couteur, David G.; Simpson, Stephen J.

2016-01-01

Summary The fundamental questions of what represents a macronutritionally balanced diet and how this maintains health and longevity remain unanswered. Here, the Geometric Framework, a state-space nutritional modeling method, was used to measure interactive effects of dietary energy, protein, fat, and carbohydrate on food intake, cardiometabolic phenotype, and longevity in mice fed one of 25 diets ad libitum. Food intake was regulated primarily by protein and carbohydrate content. Longevity and health were optimized when protein was replaced with carbohydrate to limit compensatory feeding for protein and suppress protein intake. These consequences are associated with hepatic mammalian target of rapamycin (mTOR) activation and mitochondrial function and, in turn, related to circulating branched-chain amino acids and glucose. Calorie restriction achieved by high-protein diets or dietary dilution had no beneficial effects on lifespan. The results suggest that longevity can be extended in ad libitum-fed animals by manipulating the ratio of macronutrients to inhibit mTOR activation. PMID:24606899

Longevity and mortality of owned dogs in England.

PubMed

O'Neill, D G; Church, D B; McGreevy, P D; Thomson, P C; Brodbelt, D C

2013-12-01

Improved understanding of longevity represents a significant welfare opportunity for the domestic dog, given its unparalleled morphological diversity. Epidemiological research using electronic patient records (EPRs) collected from primary veterinary practices overcomes many inherent limitations of referral clinic, owner questionnaire and pet insurance data. Clinical health data from 102,609 owned dogs attending first opinion veterinary practices (n=86) in central and southeast England were analysed, focusing on 5095 confirmed deaths. Of deceased dogs with information available, 3961 (77.9%) were purebred, 2386 (47.0%) were female, 2528 (49.8%) were neutered and 1105 (21.7%) were insured. The overall median longevity was 12.0 years (IQR 8.9-14.2). The longest-lived breeds were the Miniature poodle, Bearded collie, Border collie and Miniature dachshund, while the shortest-lived were the Dogue de Bordeaux and Great Dane. The most frequently attributed causes of death were neoplastic, musculoskeletal and neurological disorders. The results of multivariable modelling indicated that longevity in crossbred dogs exceeded purebred dogs by 1.2 years (95% confidence interval 0.9-1.4; P<0.001) and that increasing bodyweight was negatively correlated with longevity. The current findings highlight major breed differences for longevity and support the concept of hybrid vigour in dogs. Copyright © 2013 Elsevier Ltd. All rights reserved.

Longevity effect of a polysaccharide from Chlorophytum borivilianum on Caenorhabditis elegans and Saccharomyces cerevisiae

PubMed Central

Pannakal, Steve Thomas; Jäger, Sibylle; Duranton, Albert; Tewari, Amit; Saha, Subarna; Radhakrishnan, Aneesha; Roy, Nita; Kuntz, Jean François; Fermas, Soraya; Mellor, Jane; Breton, Lionel

2017-01-01

The traditional Indian medicine, Ayurveda, provides insights and practical solutions towards a healthy life style. Rasayana is a branch of Ayurveda known for preserving and promoting health, enhancing the quality of life and delaying the aging process. In the traditional knowledge, the Rasayana herb, Chlorophytum borivilianum (C. borivilanum) is regarded as a general health promoting tonic that delays aging and increases lifespan, cognitive function and physical strength. Aging is a complex and multifactorial physiological phenomenon that manifests itself over a wide range of biological systems, tissues, and functions. Longevity is an obvious marker of physiological aging. Simple model systems such as the single-cell budding yeast Saccharomyces cerevisiae (S. cerevisiae) and the nematode, Caenorhabditis elegans (C. elegans) are widely used to study the aging process and longevity. Here, we show that a polysaccharide fraction obtained from C. borivilianum increases the lifespan of S. cerevisiae and C. elegans, using an automated screening platform (ChronoscreenTM). Chemical analysis of this extract revealed a low molecular weight polysaccharide of 1000 Da, predominantly comprising Glu1→6Glu linkage. This polysaccharide showed significant dose-dependent extension of the median lifespan of S. cerevisiae by up to 41% and of the median lifespan of C. elegans by up to 10%. Taking cue from these results and the traditionally described benefits of Rasayanas on skin rejuvenation, we tested in vitro the polysaccharide for potential skin benefits. In a keratinocyte culture, we observed that this polysaccharide increased cell proliferation significantly, and induced synthesis of hyaluronic acid (HA), a well-known extracellular matrix component. Furthermore, when added to culture medium of human reconstructed epidermis, we observed an enhanced production of epidermal markers, e.g. CD44 and HA that are otherwise diminished in aged skin. Together, these results suggest that in addition to life-span extension of S. cerevisiae and C. elegans, a polysaccharide from the Rasayana herb, C. borivilianum may have beneficial effects on skin aging parameters. PMID:28727758

Environmental control and control of the environment: the basis of longevity in bivalves.

PubMed

Abele, Doris; Philipp, Eva

2013-01-01

Longevity and ageing are two sides of a coin, leaving the question open as to which one is the cause and which one the effect. At the individual level, the physiological rate of ageing determines the length of life (= individual longevity, as long as death results from old age and not from disease or other impacts). Individual longevity depends on the direct influence of environmental conditions with respect to nutrition, and the possibility for and timing of reproduction, as well as on the energetic costs animals invest in behavioural and physiological stress defence. All these environmental effectors influence hormonal and cellular signalling pathways that modify the individual physiological condition, the reproductive strategy, and the rate of ageing. At the species level, longevity (= maximum lifespan) is the result of an evolutionary process and, thus, largely determined by the species' behavioural and physiological adaptations to its ecological niche. Specifically, reproductive and breeding strategies have to be optimized in relation to local environmental conditions in different habitats. As a result of adaptive and evolutionary processes, species longevity is genetically underpinned, not necessarily by a few ageing genes, but by an evolutionary process that has hierarchically shaped and optimized species genomes to function in a specific niche or environmental system. Importantly, investigations and reviews attempting to unravel the mechanistic basis of the ageing process need to differentiate clearly between the evolutionary process shaping longevity at the species level and the regulatory mechanisms that alter the individual rate of ageing. Copyright © 2012 S. Karger AG, Basel.

Mating and male pheromone kill Caenorhabditis males through distinct mechanisms.

PubMed

Shi, Cheng; Runnels, Alexi M; Murphy, Coleen T

2017-03-14

Differences in longevity between sexes is a mysterious yet general phenomenon across great evolutionary distances. To test the roles of responses to environmental cues and sexual behaviors in longevity regulation, we examined Caenorhabditis male lifespan under solitary, grouped, and mated conditions. We find that neurons and the germline are required for male pheromone-dependent male death. Hermaphrodites with a masculinized nervous system secrete male pheromone and are susceptible to male pheromone killing. Male pheromone-mediated killing is unique to androdioecious Caenorhabditis , and may reduce the number of males in hermaphroditic populations; neither males nor females of gonochoristic species are susceptible to male pheromone killing. By contrast, mating-induced death, which is characterized by germline-dependent shrinking, glycogen loss, and ectopic vitellogenin expression, utilizes distinct molecular pathways and is shared between the sexes and across species. The study of sex- and species-specific regulation of aging reveals deeply conserved mechanisms of longevity and population structure regulation.

Predator-induced demographic shifts in coral reef fish assemblages

USGS Publications Warehouse

Ruttenberg, B.I.; Hamilton, S.L.; Walsh, S.M.; Donovan, M.K.; Friedlander, A.; DeMartini, E.; Sala, E.; Sandin, S.A.

2011-01-01

In recent years, it has become apparent that human impacts have altered community structure in coastal and marine ecosystems worldwide. Of these, fishing is one of the most pervasive, and a growing body of work suggests that fishing can have strong effects on the ecology of target species, especially top predators. However, the effects of removing top predators on lower trophic groups of prey fishes are less clear, particularly in highly diverse and trophically complex coral reef ecosystems. We examined patterns of abundance, size structure, and age-based demography through surveys and collection-based studies of five fish species from a variety of trophic levels at Kiritimati and Palmyra, two nearby atolls in the Northern Line Islands. These islands have similar biogeography and oceanography, and yet Kiritimati has ~10,000 people with extensive local fishing while Palmyra is a US National Wildlife Refuge with no permanent human population, no fishing, and an intact predator fauna. Surveys indicated that top predators were relatively larger and more abundant at unfished Palmyra, while prey functional groups were relatively smaller but showed no clear trends in abundance as would be expected from classic trophic cascades. Through detailed analyses of focal species, we found that size and longevity of a top predator were lower at fished Kiritimati than at unfished Palmyra. Demographic patterns also shifted dramatically for 4 of 5 fish species in lower trophic groups, opposite in direction to the top predator, including decreases in average size and longevity at Palmyra relative to Kiritimati. Overall, these results suggest that fishing may alter community structure in complex and non-intuitive ways, and that indirect demographic effects should be considered more broadly in ecosystem-based management. ?? 2011 Ruttenberg et al.

Predator-Induced Demographic Shifts in Coral Reef Fish Assemblages

PubMed Central

Ruttenberg, Benjamin I.; Hamilton, Scott L.; Walsh, Sheila M.; Donovan, Mary K.; Friedlander, Alan; DeMartini, Edward; Sala, Enric; Sandin, Stuart A.

2011-01-01

In recent years, it has become apparent that human impacts have altered community structure in coastal and marine ecosystems worldwide. Of these, fishing is one of the most pervasive, and a growing body of work suggests that fishing can have strong effects on the ecology of target species, especially top predators. However, the effects of removing top predators on lower trophic groups of prey fishes are less clear, particularly in highly diverse and trophically complex coral reef ecosystems. We examined patterns of abundance, size structure, and age-based demography through surveys and collection-based studies of five fish species from a variety of trophic levels at Kiritimati and Palmyra, two nearby atolls in the Northern Line Islands. These islands have similar biogeography and oceanography, and yet Kiritimati has ∼10,000 people with extensive local fishing while Palmyra is a US National Wildlife Refuge with no permanent human population, no fishing, and an intact predator fauna. Surveys indicated that top predators were relatively larger and more abundant at unfished Palmyra, while prey functional groups were relatively smaller but showed no clear trends in abundance as would be expected from classic trophic cascades. Through detailed analyses of focal species, we found that size and longevity of a top predator were lower at fished Kiritimati than at unfished Palmyra. Demographic patterns also shifted dramatically for 4 of 5 fish species in lower trophic groups, opposite in direction to the top predator, including decreases in average size and longevity at Palmyra relative to Kiritimati. Overall, these results suggest that fishing may alter community structure in complex and non-intuitive ways, and that indirect demographic effects should be considered more broadly in ecosystem-based management. PMID:21698165

The comparison of species longevity and size evolution in fossilized dinosaurs vs. fossilized mammals

NASA Astrophysics Data System (ADS)

Baeza, E.; Srinath, A.; Hernandez, A.; Heim, N.; Payne, J.

2016-12-01

For over 200 million years, two animal groups have been competing for dominance over Earth: the reptiles, (in this case, dinosaurs), and the mammals. At the beginning of the Triassic, mammals were small, rat-like creatures that were dwarfed by the dinosaurs. Dinosaurs progressively continued to grow larger throughout the Jurassic and Cretaceous periods, thus outweighing and outliving the current mammals. But at the end of the Cretaceous, the K-T mass extinction occurred, and that wiped out the dinosaurs from the face of the Earth. After the disappearance of dinosaurs, mammals started to grow larger to fill the niches that the dinosaurs left open. With this evolution in mammals, would they be able to match or even beat the dinosaur's previous records? To judge that, we need to utilize two significant factors to help judge our answer. The two factors that set them apart were body mass and longevity. Documenting the body mass shows us how much the animal weighed compared to other species. The heaviest animal in our data set weighed 77 tons. The other factor is longevity, which indicates how long a certain species has existed on a geologic time scale. The longest living animal species in our data set lived for over 20 million years. With all the data we have analyzed, we have conducted research on this subject to find out how terrestrial mammals contrasted dinosaurs in the terms of body mass and species longevity. Our research brought us to the conclusion that mammals could not overtake the body mass and longevity of dinosaurs. Although mammals came pretty close to overlapping the dinosaurs' body masses, they were just below them marginally. We had a similar pattern in longevity, where we found out that heavier animals tended to have longer longevity, therefore the dinosaurs came out on top. Additionally, we did another contrast between Mesozoic and Cenozoic mammals, where Cenozoic mammals were larger, but both had similar longevities.

Reduced insulin-like growth factor-I serum levels in formerly obese women subjected to laparoscopic-adjustable gastric banding or diet-induced long-term caloric restriction.

PubMed

Mitterberger, Maria C; Mattesich, Monika; Klaver, Elise; Piza-Katzer, Hildegunde; Zwerschke, Werner

2011-11-01

Life-span extension in laboratory rodents induced by long-term caloric restriction correlates with decreased serum insulin-like growth factor-I (IGF-I) levels. Reduced activity of the growth hormone/IGF-I signaling system slows aging and increases longevity in mutant mouse models. In the present study, we show that long-term caloric restriction achieved by two different interventions for 4 years, either laparoscopic-adjustable gastric banding or reducing diet, leads to reduced IGF-I serum levels in formerly obese women relative to normal-weight women eating ad libitum. Moreover, we present evidence that the long-term caloric restriction interventions reduce fasting growth hormone serum levels. The present study indicates that the activity of the growth hormone/IGF-I axis is reduced in long-term calorically restricted formerly obese humans. Furthermore, our findings suggest that the duration and severity of the caloric restriction intervention are important for the outcome on the growth hormone/IGF-I axis in humans.

Reforming the politics of animal research.

PubMed

Levin, Lisa Hara; Reppy, William A

2015-07-01

An unfortunate tension exists between the biomedical research and animal welfare/rights communities. We believe that despite the mistrust between these groups, there are individuals on both sides of the controversy who seek to better understand the other. We recommend an update of institutional policies that will better inform the public about the use of non-human animals in biomedical research and improve a dialogue on such use between concerned individuals who either support or oppose non-human animal-based biomedical research. Such interactions may well determine the longevity of using non-human animals as experimental subjects. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds

PubMed Central

Bonkowski, Michael S.; Sinclair, David A.

2016-01-01

The sirtuins (SIRT1–7) are a family of nicotinamide adenine dinucleotide (NAD+)-dependent deacylases with remarkable abilities to prevent diseases and even reverse aspects of ageing. Mice engineered to express additional copies of SIRT1 or SIRT6, or treated with sirtuin-activating compounds (STACs) such as resveratrol and SRT2104 or with NAD+ precursors, have improved organ function, physical endurance, disease resistance and longevity. Trials in non-human primates and in humans have indicated that STACs may be safe and effective in treating inflammatory and metabolic disorders, among others. These advances have demonstrated that it is possible to rationally design molecules that can alleviate multiple diseases and possibly extend lifespan in humans. PMID:27552971

Evaluation of quality of life, physical, and mental aspects in longevous patients with chronic kidney disease.

PubMed

Martini, Adriana; Ammirati, Adriano; Garcia, Carlos; Andrade, Carolina; Portela, Odete; Cendoroglo, Maysa S; Sesso, Ricardo

2018-04-01

The diagnosis of chronic kidney disease (CKD) in elderly individuals has been increasing. The objective of this study was to evaluate physical, mental and social aspects in longevous elderly patients with CKD. Eighty patients with CKD (stage 4 and 5, not on dialysis) and 60 longevous elderly (≥ 80 years) paired by gender and age living in the community were evaluated. Physical, cognitive, social and quality of life aspects were analyzed according to the following scales: Charlson comorbidity index, Medical Outcomes Study Short Form 36-Item (SF-36), Medical Outcomes Study, Boston Naming Test, verbal fluency test (animal naming), sit-to-stand test, gait speed, and the Mini-Mental state examination. Compared to the control group, the CKD group had a higher mean in the comorbidities index (3.5 ± 1.2 vs. 1.0 ± 1, respectively, p < 0.001). In the multivariate analysis, the CKD group presented worse performance in the SF-36 dimensions: 'physical functioning,' 'general health,' 'emotional functioning,' 'vitality,' and physical component summary. On the other hand, they presented better results for the 'mental health' dimension, in addition to lower  social support, worse verbal fluency and worse results on the sit-to-stand test. Longevous patients with stage 4 or 5 CKD presented worse evaluation in several domains of physical and emotional functioning, lower social support and evidence of worse cognitive performance. These aspects should be taken into account in order to improve the care provided to these patients, improve their quality of life and prevent their morbidity.

Centenarian Rates and Life Expectancy Related to the Death Rates of Multiple Sclerosis, Asthma, and Rheumatoid Arthritis and the Incidence of Type 1 Diabetes in Children.

PubMed

Lens-Pechakova, Lilia S

2016-02-01

The autoimmune diseases are among the 10 leading causes of death for women and the number two cause of chronic illness in America as well as a predisposing factor for cardiovascular diseases and cancer. Patients of some autoimmune diseases have shown a shorter life span and are a model of accelerated immunosenescence. Conversely, centenarians are used as a model of successful aging and have shown several immune parameters that are better preserved and lower levels of autoantibodies. The study reported here focused on clarifying the connection between longevity and some autoimmune and allergic diseases in 29 developed Organisation for Economic Co-operation and Development (OECD) countries, because multidisciplinary analyses of the accelerated or delayed aging data could show a distinct relationship pattern, help to identify common factors, and determine new important factors that contribute to longevity and healthy aging. The relationships between the mortality rates data of multiple sclerosis (MS), rheumatoid arthritis (RA), asthma, the incidence of type 1 diabetes (T1D) from one side and centenarian rates (two sets) as well as life expectancy data from the other side were assessed using regression models and Pearson correlation coefficients. The data obtained correspond to an inverse linear correlation with different degrees of linearity. This is the first observation of a clear tendency of diminishing centenarian rates or life expectancy in countries having higher death rates of asthma, MS, and RA and a higher incidence of T1D in children. The conclusion is that most probably there are common mechanistic pathways and factors affecting the above diseases and at the same time but in the opposite direction the processes of longevity. Further study, comparing genetic data, mechanistic pathways, and other factors connected to autoimmune diseases with those of longevity could clarify the processes involved, so as to promote longevity and limit the expansion of those diseases in the younger and older population.

Safety and efficiency of ventricular pacing prevention with an AAI-DDD changeover mode in patients with sinus node disease or atrioventricular block: impact on battery longevity—a sub-study of the ANSWER trial

PubMed Central

Stockburger, Martin; Defaye, Pascal; Boveda, Serge; Stancak, Branislav; Lazarus, Arnaud; Sipötz, Johann; Nardi, Stefano; Rolando, Mara; Moreno, Javier

2016-01-01

Abstract Aims This ANSWER (EvaluAtioN of the SafeR mode in patients With a dual chambER pacemaker indication) sub-study assesses safety and effectiveness of SafeR™ and the impact of ventricular pacing (VP) prevention on anticipated device longevity and replacement rate. Methods and results Patients implanted for atrioventricular block (AVB, n = 310) or sinus node dysfunction (SND, n = 336) were randomly assigned to SafeR (n = 314) or DDD (n = 318) and followed for 36 months. Safety, median VP, estimated device longevity (mean difference, 95% confidence interval [CI]), and anticipated replacement rates were analysed by pacing mode and implant indication. No difference in mortality, syncope, or mode intolerance was observed between randomization groups regardless of the indication. Ventricular pacing on SafeR vs. DDD was 11.5 vs. 93.6% in the overall population (P < 0.001), 89.2 vs. 83.8% in permanent AVB (P = 0.944), 53.5 vs. 98.2% in intermittent AVB (P < 0.001), and 2.2 vs. 84.7% in SND (P < 0.001). Anticipated median device longevity increased on SafeR by 14 [Q1 10; Q3 17] months [10; 17] (P < 0.001) in the overall population, 9 months [−5; 22] (P = 0.193) in permanent AVB, 14 months [8; 19] (P < 0.001) in intermittent AVB, and 14 months [9; 19] (P < 0.001) in SND. In intermittent AVB and SND, prolonged estimated battery longevity translated into the prevention of one anticipated replacement in at least 23% of patients. Conclusion SafeR was effective in reducing VP in intermittent AVB and in SND. No effect was observed in permanent AVB. No safety issue was observed. Ventricular pacing reduction by SafeR translated into relevant estimated prolongation of device longevity and anticipated reduction of required replacements. PMID:26612882

Evaluating the Longevity and Hydraulic Performance of Permeable Reactive Barriers at Department of Defense Sites

DTIC Science & Technology

2002-04-24

F inal Repor t Evaluating the Longevity and Hydraulic Performance of Permeable Reactive Barriers at Department of Defense Sites P1·epared for... Hydraulic Performance of Permeable Reactive Barriers at Department of Defense Sites Prepared for Project Officer: Charles Reeter Naval Facilities...SUBTITLE 5a. CONTRACT NUMBER Evaluating the Longevity and Hydraulic Performance of Permeable Reactive N4 7408-95-D-0730/0087 Barriers at Department of

Comparative studies of the influence of relative humidity and temperature on the longevity and fecundity of the parasitoid, Cotesia flavipes.

PubMed

G D, Emana

2007-01-01

The parasitoid, Cotesia flavipes (Cameron) (Hymenoptera: Braconidae), was introduced for biological control of the stemborer, Chilo partellus (Swinhoe) (Lepidoptera: Crambidae), in eastern and southern African countries. The parasitoid became firmly established in Ethiopia, with varying density and distribution in various regions of the country indicating that there are factors regulating the success of the parasitoid. From previous studies, it was known that the population of the parasitoid released, the type of host, and temperature highly affect some of the biological parameters of the parasitoid. The current studies were undertaken to understand the individual and interactive effect of temperature and relative humidity on the longevity and fecundity of C. flavipes. The study was conducted on C. flavipes collected from the Melkassa Agricultural Research Center Experimental Field, Ethiopia. C. flavipes was reared in the laboratory on C. partellus feeding on pieces of sorghum stem. The longevity experiment was conducted at 10, 20, 30 and 40 degrees C, while the fecundity experiment was conducted at 20, 25, 28 and 30 degrees C. For both experiments 40-50%, 60-70% and 80-90% relative humidity regimes were used. The results obtained indicate that the interactive effect of temperature and relative humidity significantly affected the longevity, the number of oocytes, and fecundity of C. flavipes implying that the two factors play an important role in the success of the parasitoid as a biocontrol agent against C. partellus. The results obtained suggests the importance of the selection of target release sites for maximum efficiency of the parasitoid, which can have a positive impact on the on-going augmentative release of C. flavipes in Ethiopia.

Favorable glucose tolerance and lower prevalence of metabolic syndrome in offspring without diabetes mellitus of nonagenarian siblings: the Leiden longevity study.

PubMed

Rozing, Maarten P; Westendorp, Rudi G J; de Craen, Anton J M; Frölich, Marijke; de Goeij, Moniek C M; Heijmans, Bastiaan T; Beekman, Marian; Wijsman, Carolien A; Mooijaart, Simon P; Blauw, Gerard-Jan; Slagboom, P Eline; van Heemst, Diana

2010-03-01

To explore measures of metabolic syndrome and glucose metabolism in families with exceptional longevity. Case-control study. A university hospital in Leiden, the Netherlands. One hundred twenty-one offspring of nonagenarian siblings, who were enriched for familial factors promoting longevity, and 113 of their partners. No subject had diabetes mellitus. Prevalence of metabolic syndrome was determined according to the criteria of the Third Report of the National Cholesterol Education Program. Glucose tolerance was assessed according to a 2-hour oral glucose tolerance test. The offspring of nonagenarians siblings had a lower prevalence of metabolic syndrome (P=.03), similar body composition, lower mean fasting blood glucose levels (4.99 vs 5.16 mmol/L; P=.01), lower mean fasting insulin levels (5.81 vs 6.75 mU/L; P=.04), a higher mean homeostasis model assessment of insulin sensitivity (0.78 vs 0.65; P=.02), and a more-favorable glucose tolerance (mean area under the receiver operating characteristic curve for glucose (13.2 vs 14.3; P=.007) than their partners. No significant differences were observed between the offspring and their partners in beta-cell function (insulogenic index 13.6 vs 12.5; P=.38). Despite similar body composition, the offspring of nonagenarian siblings showed a lower prevalence of metabolic syndrome and better glucose tolerance than their partners, centralizing the role of favorable glucose metabolism in familial longevity.

Economic trade-offs between genetic improvement and longevity in dairy cattle.

PubMed

De Vries, A

2017-05-01

Genetic improvement in sires used for artificial insemination (AI) is increasing faster compared with a decade ago. The genetic merit of replacement heifers is also increasing faster and the genetic lag with older cows in the herd increases. This may trigger greater cow culling to capture this genetic improvement. On the other hand, lower culling rates are often viewed favorably because the costs and environmental effects of maintaining herd size are generally lower. Thus, there is an economic trade-off between genetic improvement and longevity in dairy cattle. The objective of this study was to investigate the principles, literature, and magnitude of these trade-offs. Data from the Council on Dairy Cattle Breeding show that the estimated breeding value of the trait productive life has increased for 50 yr but the actual time cows spend in the herd has not increased. The average annual herd cull rate remains at approximately 36% and cow longevity is approximately 59 mo. The annual increase in average estimated breeding value of the economic index lifetime net merit of Holstein sires is accelerating from $40/yr when the sire entered AI around 2002 to $171/yr for sires that entered AI around 2012. The expectation is therefore that heifers born in 2015 are approximately $50 more profitable per lactation than heifers born in 2014. Asset replacement theory shows that assets should be replaced sooner when the challenging asset is technically improved. Few studies have investigated the direct effects of genetic improvement on optimal cull rates. A 35-yr-old study found that the economically optimal cull rates were in the range of 25 to 27%, compared with the lowest possible involuntary cull rate of 20%. Only a small effect was observed of using the best surviving dams to generate the replacement heifer calves. Genetic improvement from sires had little effect on the optimal cull rate. Another study that optimized culling decisions for individual cows also showed that the effect of changes in genetic improvement of milk revenue minus feed cost on herd longevity was relatively small. Reduced involuntary cull rates improved profitability, but also increased optimal voluntary culling. Finally, an economically optimal culling model with prices from 2015 confirmed that optimal annual cull rates were insensitive to heifer prices and therefore insensitive to genetic improvement in heifers. In conclusion, genetic improvement is important but does not warrant short cow longevity. Economic cow longevity continues to depends more on cow depreciation than on accelerated genetic improvements in heifers. This is confirmed by old and new studies. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The iFly Tracking System for an Automated Locomotor and Behavioural Analysis of Drosophila melanogaster

PubMed Central

Kohlhoff, Kai J.; Jahn, Thomas R.; Lomas, David A.; Dobson, Christopher M.; Crowther, Damian C.; Vendruscolo, Michele

2016-01-01

The use of animal models in medical research provides insights into molecular and cellular mechanisms of human disease, and helps identify and test novel therapeutic strategies. Drosophila melanogaster – the common fruit fly – is one of the most established model organisms, as its study can be performed more readily and with far less expense than for other model animal systems, such as mice, fish, or indeed primates. In the case of fruit flies, standard assays are based on the analysis of longevity and basic locomotor functions. Here we present the iFly tracking system, which enables to increase the amount of quantitative information that can be extracted from these studies, and to reduce significantly the duration and costs associated with them. The iFly system uses a single camera to simultaneously track the trajectories of up to 20 individual flies with about 100μm spatial and 33ms temporal resolution. The statistical analysis of fly movements recorded with such accuracy makes it possible to perform a rapid and fully automated quantitative analysis of locomotor changes in response to a range of different stimuli. We anticipate that the iFly method will reduce very considerably the costs and the duration of the testing of genetic and pharmacological interventions in Drosophila models, including an earlier detection of behavioural changes and a large increase in throughput compared to current longevity and locomotor assays. PMID:21698336

Systemic Age-Associated DNA Hypermethylation of ELOVL2 Gene: In Vivo and In Vitro Evidences of a Cell Replication Process.

PubMed

Bacalini, Maria Giulia; Deelen, Joris; Pirazzini, Chiara; De Cecco, Marco; Giuliani, Cristina; Lanzarini, Catia; Ravaioli, Francesco; Marasco, Elena; van Heemst, Diana; Suchiman, H Eka D; Slieker, Roderick; Giampieri, Enrico; Recchioni, Rina; Mercheselli, Fiorella; Salvioli, Stefano; Vitale, Giovanni; Olivieri, Fabiola; Spijkerman, Annemieke M W; Dollé, Martijn E T; Sedivy, John M; Castellani, Gastone; Franceschi, Claudio; Slagboom, Pieternella E; Garagnani, Paolo

2017-08-01

Epigenetic remodeling is one of the major features of the aging process. We recently demonstrated that DNA methylation of ELOVL2 and FHL2 CpG islands is highly correlated with age in whole blood. Here we investigated several aspects of age-associated hypermethylation of ELOVL2 and FHL2. We showed that ELOVL2 methylation is significantly different in primary dermal fibroblast cultures from donors of different ages. Using epigenomic data from public resources, we demonstrated that most of the tissues show ELOVL2 and FHL2 hypermethylation with age. Interestingly, ELOVL2 hypermethylation was not found in tissues with very low replication rate. We demonstrated that ELOVL2 hypermethylation is associated with in vitro cell replication rather than with senescence. We confirmed intra-individual hypermethylation of ELOVL2 and FHL2 in longitudinally assessed participants from the Doetinchem Cohort Study. Finally we showed that, although the methylation of the two loci is not associated with longevity/mortality in the Leiden Longevity Study, ELOVL2 methylation is associated with cytomegalovirus status in nonagenarians, which could be informative of a higher number of replication events in a fraction of whole-blood cells. Collectively, these results indicate that ELOVL2 methylation is a marker of cell divisions occurring during human aging. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Evidence of correlated evolution of hypsodonty and exceptional longevity in endemic insular mammals.

PubMed

Jordana, Xavier; Marín-Moratalla, Nekane; DeMiguel, Daniel; Kaiser, Thomas M; Köhler, Meike

2012-08-22

Here, we test whether the increase in tooth height in insular endemics results from the expansion of the dietary niche under resource limitation, as widely considered, or whether it represents an investment in dental durability in response to the selection for extended longevity under low levels of extrinsic mortality. We tested these hypotheses in the extremely hypsodont fossil bovid Myotragus balearicus from the Balearic Islands, an ideal model to study the evolutionary trends on islands. Dental abrasion was significantly lower in the insular bovid than in highly hypsodont continental artiodactyls, suggesting that feeding habits are not the sole driving force behind increased crown height. However, the estimated longevity for M. balearicus based on dental durability was two times that predicted from body mass. Survivorship curves confirm that an extraordinarily large number of individuals approached the longevity of the species. Our results, hence, provide evidence that hypsodonty in insular endemics is the outcome of selection for increased durability of the permanent dentition in association with an extended lifespan. In the context of insularity, our results lend additional support to the disposable soma theory of ageing confirming the dependency of somatic maintenance and repair on lifespan, and its control by resource availability and extrinsic mortality.

Gadd45 proteins: Relevance to aging, longevity and age-related pathologies

PubMed Central

Moskalev, Alexey A.; Smit-McBride, Zeljka; Shaposhnikov, Mikhail V.; Plyusnina, Ekaterina N.; Zhavoronkov, Alex; Budovsky, Arie; Tacutu, Robi; Fraifeld, Vadim E.

2013-01-01

The Gadd45 proteins have been intensively studied, in view of their important role in key cellular processes. Indeed, the Gadd45 proteins stand at the crossroad of the cell fates by controlling the balance between cell (DNA) repair, eliminating (apoptosis) or preventing the expansion of potentially dangerous cells (cell cycle arrest, cellular senescence), and maintaining the stem cell pool. However, the biogerontological aspects have not thus far received sufficient attention. Here we analyzed the pathways and modes of action by which Gadd45 members are involved in aging, longevity and age-related diseases. Because of their pleiotropic action, a decreased inducibility of Gadd45 members may have far-reaching consequences including genome instability, accumulation of DNA damage, and disorders in cellular homeostasis – all of which may eventually contribute to the aging process and age-related disorders (promotion of tumorigenesis, immune disorders, insulin resistance and reduced responsiveness to stress). Most recently, the dGadd45 gene has been identified as a longevity regulator in Drosophila. Although further wide-scale research is warranted, it is becoming increasingly clear that Gadd45s are highly relevant to aging, age-related diseases (ARDs) and to the control of life span, suggesting them as potential therapeutic targets in ARDs and pro-longevity interventions. PMID:21986581

Evidence of correlated evolution of hypsodonty and exceptional longevity in endemic insular mammals

PubMed Central

Jordana, Xavier; Marín-Moratalla, Nekane; DeMiguel, Daniel; Kaiser, Thomas M.; Köhler, Meike

2012-01-01

Here, we test whether the increase in tooth height in insular endemics results from the expansion of the dietary niche under resource limitation, as widely considered, or whether it represents an investment in dental durability in response to the selection for extended longevity under low levels of extrinsic mortality. We tested these hypotheses in the extremely hypsodont fossil bovid Myotragus balearicus from the Balearic Islands, an ideal model to study the evolutionary trends on islands. Dental abrasion was significantly lower in the insular bovid than in highly hypsodont continental artiodactyls, suggesting that feeding habits are not the sole driving force behind increased crown height. However, the estimated longevity for M. balearicus based on dental durability was two times that predicted from body mass. Survivorship curves confirm that an extraordinarily large number of individuals approached the longevity of the species. Our results, hence, provide evidence that hypsodonty in insular endemics is the outcome of selection for increased durability of the permanent dentition in association with an extended lifespan. In the context of insularity, our results lend additional support to the disposable soma theory of ageing confirming the dependency of somatic maintenance and repair on lifespan, and its control by resource availability and extrinsic mortality. PMID:22535784

Burial increases seed longevity of two Artemisia tridentata (Asteraceae) subspecies

USGS Publications Warehouse

Wijayratne, Upekala C.; Pyke, David A.

2012-01-01

Premise of the study: Seed longevity and persistence in soil seed banks may be especially important for population persistence in ecosystems where opportunities for seedling establishment and disturbance are unpredictable. The fire regime, an important driver of population dynamics in sagebrush steppe ecosystems, has been altered by exotic annual grass invasion. Soil seed banks may play an active role in postfire recovery of the foundation shrub Artemisia tridentata, yet conditions under which seeds persist are largely unknown. Methods: We investigated seed longevity of two Artemisia tridentata subspecies in situ by retrieving seed bags that were placed at varying depths over a 2 yr period. We also sampled naturally dispersed seeds in litter and soil immediately after seed dispersal and before flowering in subsequent seasons to estimate seed persistence. Key results: After 24 mo, seeds buried at least 3 cm below the soil surface retained 30–40% viability whereas viability of seeds on the surface and under litter declined to 0 and Artemisia tridentata has the potential to form a short-term soil seed bank that persists longer than has been commonly assumed, and that burial is necessary for seed longevity. Use of seeding techniques that promote burial of some seeds to aid in formation of a soil seed bank may increase restoration potential.

Influence of the operatory field isolation technique on tooth-colored direct dental restorations.

PubMed

Cajazeira, Marlus Roberto Rodrigues; De Sabóia, Ticiana Medeiros; Maia, Lucianne Cople

2014-06-01

To evaluate, through a systematic review, the influence of the operatory field isolation technique on the longevity of dental restorations performed with tooth-colored materials. An electronic search of the scientific databases (MEDLINE, SCIRUS, VHL and SIGLE) and reference lists of the selected articles was conducted to identify randomized controlled clinical trials with a follow-up period of at least 12 months. The selected articles evaluated the effects of the operatory field isolation techniques (rubber dam or cotton rolls/saliva ejector) on the longevity of direct restorations performed with tooth-colored materials (e.g. resin composites, compomers and glass-ionomer cements) in primary or permanent posterior teeth. The selected studies were analyzed and categorized using a checklist proposed by the National Institute for Health and Clinical Excellence of the United Kingdom. 484 studies were identified on the scientific databases. After applying the exclusion criteria and removal of duplicates, a total of nine studies were considered as potentially eligible. From these, five studies were included in the final analysis by two evaluators. In four studies analyzed, the use of rubber dam did not influence the longevity of restorations in comparison to cotton rolls/saliva ejector. Only two studies were considered as low risk of bias.

The Middle East in 2015: The Impact of Regional Trends in U.S. Strategic Planning

DTIC Science & Technology

2002-07-01

longevity , the activation of a Syrian- Israeli track, or the American election cycle—will eliminate the need to provide economic assistance and investment...to do so. But the movement toward elected, albeit still largely consultative, bodies pioneered by Kuwait has been followed in more modest measure in...The trends described in these chapters reflect an appreciation of demography , the natural laws of economics, history, and the deter- mination of human

The phytochemical glaucarubinone promotes mitochondrial metabolism, reduces body fat, and extends lifespan of Caenorhabditis elegans.

PubMed

Zarse, K; Bossecker, A; Müller-Kuhrt, L; Siems, K; Hernandez, M A; Berendsohn, W G; Birringer, M; Ristow, M

2011-04-01

Naturally occurring compounds that promote energy expenditure and delay aging in model organisms may be of significant interest, since these substances potentially provide pharmaceutical approaches to tackle obesity and promote healthy lifespan in humans. We aimed to test whether pharmaceutical concentrations of glaucarubinone, a cytotoxic and antimalarial quassinoid known from different species of the plant family Simaroubaceae, are capable of affecting metabolism and/or extending lifespan in a nematodal model organism for aging processes, the roundworm Caenorhabditis elegans. Adult C. elegans roundworms, maintained on agar plates, were fed with E. coli strain OP50 bacteria, and glaucarubinone was applied to the agar to test (i) whether it alters respiration rates and mitochondrial activity, (ii) whether it affects body fat content, and (iii) whether it may promote longevity by quantifying survival in the presence and absence of the compound. We have found that glaucarubinone induces oxygen consumption and reduces body fat content of C. elegans. Moreover and consistent with the concept of mitohormesis, glaucarubinone extends C. elegans lifespan when applied at a concentration of 1 or 10 nanomolar. Taken together, glaucarubinone is capable of reducing body fat and promoting longevity in C. elegans, tentatively suggesting that this compound may promote metabolic health and lifespan in mammals and possibly humans. © Georg Thieme Verlag KG Stuttgart · New York.

Migrating microbes: what pathogens can tell us about population movements and human evolution.

PubMed

Houldcroft, Charlotte J; Ramond, Jean-Baptiste; Rifkin, Riaan F; Underdown, Simon J

2017-08-01

The biology of human migration can be observed from the co-evolutionary relationship with infectious diseases. While many pathogens are brief, unpleasant visitors to human bodies, others have the ability to become life-long human passengers. The story of a pathogen's genetic code may, therefore, provide insight into the history of its human host. The evolution and distribution of disease in Africa is of particular interest, because of the deep history of human evolution in Africa, the presence of a variety of non-human primates, and tropical reservoirs of emerging infectious diseases. This study explores which pathogens leave traces in the archaeological record, and whether there are realistic prospects that these pathogens can be recovered from sub-Saharan African archaeological contexts. Three stories are then presented of germs on a journey. The first is the story of HIV's spread on the back of colonialism and the railway networks over the last 150 years. The second involves the spread of Schistosoma mansoni, a parasite which shares its history with the trans-Atlantic slave trade and the origins of fresh-water fishing. Finally, we discuss the tantalising hints of hominin migration and interaction found in the genome of human herpes simplex virus 2. Evidence from modern African pathogen genomes can provide data on human behaviour and migration in deep time and contribute to the improvement of human quality-of-life and longevity.

ARABIDOPSIS THALIANA HOMEOBOX25 Uncovers a Role for Gibberellins in Seed Longevity1[C][W

PubMed Central

Bueso, Eduardo; Muñoz-Bertomeu, Jesús; Campos, Francisco; Brunaud, Veronique; Martínez, Liliam; Sayas, Enric; Ballester, Patricia; Yenush, Lynne; Serrano, Ramón

2014-01-01

Seed longevity is crucial for agriculture and plant genetic diversity, but it is limited by cellular damage during storage. Seeds are protected against aging by cellular defenses and by structures such as the seed coat. We have screened an activation-tagging mutant collection of Arabidopsis (Arabidopsis thaliana) and selected four dominant mutants with improved seed longevity (isl1-1D to isl4-1D) under both natural and accelerated aging conditions. In the isl1-1D mutant, characterized in this work, overexpression of the transcription factor ARABIDOPSIS THALIANA HOMEOBOX25 (ATHB25; At5g65410) increases the expression of GIBBERELLIC ACID3-OXIDASE2, encoding a gibberellin (GA) biosynthetic enzyme, and the levels of GA1 and GA4 are higher (3.2- and 1.4-fold, respectively) in the mutant than in the wild type. The morphological and seed longevity phenotypes of the athb25-1D mutant were recapitulated in transgenic plants with moderate (4- to 6-fold) overexpression of ATHB25. Simultaneous knockdown of ATHB25, ATHB22, and ATHB31 expression decreases seed longevity, as does loss of ATHB25 and ATHB22 function in a double mutant line. Seeds from wild-type plants treated with GA and from a quintuple DELLA mutant (with constitutive GA signaling) are more tolerant to aging, providing additional evidence for a role of GA in seed longevity. A correlation was observed in several genotypes between seed longevity and mucilage formation at the seed surface, suggesting that GA may act by reinforcing the seed coat. This mechanism was supported by the observation of a maternal effect in reciprocal crosses between the wild type and the athb25-1D mutant. PMID:24335333

Factors shaping life history traits of two proovigenic parasitoids.

PubMed

Segoli, Michal; Sun, Shucun; Nava, Dori E; Rosenheim, Jay A

2017-11-23

What shapes the relative investment in reproduction vs. survival of organisms is one of the key questions in life history. Proovigenic insects mature all their eggs prior to emergence and are short lived, providing a unique opportunity to quantify their lifetime investments in the different functions. We investigated the initial eggloads and longevity of two proovigenic parasitoid wasps (Anagrus erythroneurae and Anagrus daanei, (Hymenoptera: Mymaridae) that develop within leafhopper eggs in both agricultural vineyards and natural riparian habitats in Northern California. We collected Vitis spp. leaves containing developing parasitoids from three natural sites (Knight Landing, American River and Putah Creek) and three agricultural vineyards (Solano Farm, Davis Campus and Village Homes). We recorded eggloads at parasitoid emergence and female parasitoid longevity with or without honey-feeding. Theory predicts that parasitoids from vineyards (where hosts are abundant) would have higher initial eggloads and lower longevity compared with parasitoids from riparian habitats (where hosts are scarce). Although host density and parasitoid eggloads were indeed higher in vineyards than in riparian habitats, parasitoid longevity did not follow the predicted pattern. Longevity without feeding differed among field sites, but it was not affected by habitat type (natural vs. agricultural), whereas longevity with feeding was not significantly affected by any of the examined factors. Moreover, longevity was positively, rather than negatively, correlated with eggloads at the individual level, even after correcting for parasitoid body size. The combined results suggest a more complex allocation mechanism than initially predicted, and the possibility of variation in host quality that is independent of size. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Economics and extended longevity: a case study.

PubMed

Gori, G B; Richter, B J; Yu, W K

1984-07-01

Preventive and therapeutic advances have brought life expectancy in the United States to well over 70 years and have shifted mortality causes from acute to chronic diseases, the determinants of which are genetics, lifestyle, the environment, and aging itself. Plausible approaches to chronic disease prevention are likely to increase longevity further, with some foreseeable effects on demographic and economic projections. Primarily, longevity advances would swell forecasts of population size, and would thus have to be met by production advances in order to maintain or improve living standards. This study, a restricted example, considers the probable demographic and economic consequences of a limited prevention program in the context of the Ford Motor Company, based on actual experience and certain expectations up to the year 2000. According to the results, prevention would reduce outlays for life insurance, disability, and health care, but would also generate the higher costs of extending pension plans. Undoubtedly, prevention will continue to be highly ranked in society's pursuit of happiness, and society must prepare to meet its effects with appropriate social and economic policies.

Psychosocial Factors Associated with Longevity in the United States: Age Differences between the Old and Oldest-Old in the Health and Retirement Study

PubMed Central

Ailshire, Jennifer A.; Crimmins, Eileen M.

2011-01-01

Recent growth in the number of adults surviving to advanced ages raises questions about the quality of life associated with increased longevity. Psychosocial factors have received relatively little attention in research on quality of life among the oldest-old. This study uses nationally representative data on older US adults to examine how social relationships, feelings of loneliness, and satisfaction with life and the aging experience differ between the oldest-old, those who have survived to age 90 or older, and older adults in their 70s. We find that the oldest-old are able to maintain social relationships with family and friends and receive more social support than younger elderly adults. Yet, the oldest-old are more likely to feel lonely due to their greater rates of widowhood. Satisfaction with life was higher among the oldest-old, but the oldest-old had more negative perceptions of the aging experience. Psychosocial dimensions of longevity should be considered in research on quality of life among the oldest-old. PMID:22028969

Psychosocial Factors Associated with Longevity in the United States: Age Differences between the Old and Oldest-Old in the Health and Retirement Study.

PubMed

Ailshire, Jennifer A; Crimmins, Eileen M

2011-01-01

Recent growth in the number of adults surviving to advanced ages raises questions about the quality of life associated with increased longevity. Psychosocial factors have received relatively little attention in research on quality of life among the oldest-old. This study uses nationally representative data on older US adults to examine how social relationships, feelings of loneliness, and satisfaction with life and the aging experience differ between the oldest-old, those who have survived to age 90 or older, and older adults in their 70s. We find that the oldest-old are able to maintain social relationships with family and friends and receive more social support than younger elderly adults. Yet, the oldest-old are more likely to feel lonely due to their greater rates of widowhood. Satisfaction with life was higher among the oldest-old, but the oldest-old had more negative perceptions of the aging experience. Psychosocial dimensions of longevity should be considered in research on quality of life among the oldest-old.

Improved Cell Sensitivity and Longevity in a Rapid Impedance-based Toxicity Sensor

DTIC Science & Technology

2009-01-06

sensitivity and longevity in a rapid impedance-based toxicity sensor† Improved cell sensitivity and longevityTheresa M. Curtis,a** Joel Tabb,a Lori...Romeo,a Steven J. Schwager,b Mark W. Widderc* and William H. van der Schaliec ABSTRACT: A number of toxicity sensors for testing field water using a...range of eukaryotic cell types have been proposed, but it has been difficult to identify sensors with both appropriate sensitivity to toxicants and the

Larval food quantity affects development time, survival and adult biological traits that influence the vectorial capacity of Anopheles darlingi under laboratory conditions.

PubMed

Araújo, Maisa da-Silva; Gil, Luiz Herman S; e-Silva, Alexandre de-Almeida

2012-08-02

The incidence of malaria in the Amazon is seasonal and mosquito vectorial capacity parameters, including abundance and longevity, depend on quantitative and qualitative aspects of the larval diet. Anopheles darlingi is a major malaria vector in the Amazon, representing >95% of total Anopheles population present in the Porto Velho region. Despite its importance in the transmission of the Plasmodium parasite, knowledge of the larval biology and ecology is limited. Studies regarding aspects of adult population ecology are more common than studies on larval ecology. However, in order develop effective control strategies and laboratory breeding conditions for this species, more data on the factors affecting vector biology is needed. The aim of the present study is to assess the effects of larval food quantity on the vectorial capacity of An. darling under laboratory conditions. Anopheles darlingi was maintained at 28°C, 80% humidity and exposed to a daily photoperiod of 12 h. Larvae were divided into three experimental groups that were fed either a low, medium, or high food supply (based on the food amounts consumed by other species of culicids). Each experiment was replicated for six times. A cohort of adults were also exposed to each type of diet and assessed for several biological characteristics (e.g. longevity, bite frequency and survivorship), which were used to estimate the vectorial capacity of each experimental group. The group supplied with higher food amounts observed a reduction in development time while larval survival increased. In addition to enhanced longevity, increasing larval food quantity was positively correlated with increasing frequency of bites, longer blood meal duration and wing length, resulting in greater vectorial capacity. However, females had greater longevity than males despite having smaller wings. Overall, several larval and adult biological traits were significantly affected by larval food availability. Greater larval food supply led to enhance larval and production and larger mosquitoes with longer longevity and higher biting frequency. Thus, larval food availability can alter important biological traits that influence the vectorial capacity of An. darlingi.

Permanent epicardial pacing in pediatric patients: 12-year experience at a single center.

PubMed

Kwak, Jae Gun; Kim, Soo-Jin; Song, Jin Young; Choi, Eun Young; Lee, Sang Yoon; Shim, Woo Sup; Lee, Chang-Ha; Lee, Cheul; Park, Chun Soo

2012-02-01

Permanent cardiac pacing is not often done in children, and when done is usually accomplished through epicardial pacing. We reviewed a 12-year experience with the implantation of epicardial pacemakers by our clinical group. Fifty-three patients who underwent their first implantation of an epicardial pacemaker before the age of 18 years and between 1997 and 2009 were included in our study. The mean age of the patients at the time of first pacemaker implantation was 5.7±4.8 years. Indications for pacemaker implantation included postoperative or congenital atrioventricular block and sinus node dysfunction. The patients underwent 105 operations for the replacement of pacemaker pulse generators and 75 operations for the replacement of pacemaker leads. The most commonly used generator mode was the rate-responsive accelerometer-based (DDDR) mode, which was used in 40.9% of the patients. We used more non-steroid-eluting leads (70.1%) than steroid-eluting leads (29.1%). The overall duration of follow-up in the study was 8.0±4.5 years (range, 2.1 months to approximately 17.0 years). Freedom from the need for generator replacement was 98.0%, 60.7%, and 11.1% at 1, 5, and 8 years, respectively. A tendency toward early generator exhaustion was observed among younger patients (p=0.058). The generator mode used for pacing did not significantly affect generator longevity. Freedom from the need for lead replacement was 98.3%, 83.8%, and 63.6% at 1, 5, and 10 years, respectively. The mean longevity of the leads used in the study was 10.8±0.8 years. Neither patient age at the time of lead implantation nor type of lead significantly affected lead longevity. Lead longevity was sufficiently long and did not vary significantly according to type of lead. Generator longevity was not affected by lead type, generator mode, or patient age at the time of pacemaker implantation. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

The Fruit Fly Drosophila melanogaster as a Model for Aging Research.

PubMed

Brandt, Annely; Vilcinskas, Andreas

2013-01-01

: Average human life expectancy is increasing and so is the impact on society of aging and age-related diseases. Here we highlight recent advances in the diverse and multidisciplinary field of aging research, focusing on the fruit fly Drosophila melanogaster, an excellent model system in which to dissect the genetic and molecular basis of the aging processes. The conservation of human disease genes in D. melanogaster allows the functional analysis of orthologues implicated in human aging and age-related diseases. D. melanogaster models have been developed for a variety of age-related processes and disorders, including stem cell decline, Alzheimer's disease, and cardiovascular deterioration. Understanding the detailed molecular events involved in normal aging and age-related diseases could facilitate the development of strategies and treatments that reduce their impact, thus improving human health and increasing longevity.

Heritability and factors associated with number of harness race starts in the Spanish Trotter horse population.

PubMed

Solé, M; Valera, M; Gómez, M D; Sölkner, J; Molina, A; Mészáros, G

2017-05-01

Longevity/durability is a relevant trait in racehorses. Genetic analysis and knowledge of factors that influence number of harness race starts would be advantageous for both horse welfare and the equine industry. To perform a genetic analysis on harness racing using number of races as a measure of longevity/durability and to identify factors associated with career length in Spanish Trotter Horses (STH). Longitudinal study. Performance data (n = 331,970) on the STH population for harness racing at national level between 1990 and 2014 were used. A grouped data model was fitted to assess factors influencing the risk of ending harness racing career and to estimate the heritability and breeding values for total number of harness races starts as an indicator of horses' longevity and durability. The model included sex, age at first race and first start earnings as time-independent effects, and the calendar year, driver, trainer, racetrack category and season of competition as time-dependent effects. Across the whole dataset, the average number of harness races horses achieved in Spain was 54.7 races, and this was associated with the horses' sex, age at first race and first start earnings, calendar year, driver, racetrack category, and season. The heritability estimated (0.17 ± 0.01) for number of harness race starts indicates that a beneficial response to direct genetic selection can be expected. Data on horses' health status were not available. Horses' total number of harness race starts is a promising tool for genetic analysis and the evaluation of racing longevity and durability. The estimated heritability provides evidence to support the application of genetic selection of total career number of races to improve longevity/durability of STH. © 2016 EVJ Ltd.

Physiological responding to stress in middle-aged males enriched for longevity: a social stress study.

PubMed

Jansen, Steffy W M; van Heemst, Diana; van der Grond, Jeroen; Westendorp, Rudi; Oei, Nicole Y L

2016-01-01

Individuals enriched for familial longevity display a lower prevalence of age-related diseases, such as cardiovascular- and metabolic diseases. Since these diseases are associated with stress and increased cortisol levels, one of the underlying mechanisms that may contribute to healthy longevity might be a more adaptive response to stress. To investigate this, male middle-aged offspring from long-lived families (n = 31) and male non-offspring (with no familial history of longevity) (n = 26) were randomly allocated to the Trier Social Stress Test or a control condition in an experimental design. Physiological (cortisol, blood pressure, heart rate) and subjective responses were measured during the entire procedure. The results showed that Offspring had lower overall cortisol levels compared to Non-offspring regardless of condition, and lower absolute cortisol output (AUCg) during stress compared to Non-Offspring, while the increase (AUCi) did not differ between groups. In addition, systolic blood pressure in Offspring was lower compared to Non-offspring during the entire procedure. At baseline, Offspring had significantly lower systolic blood pressure and reported less subjective stress than Non-offspring and showed a trend towards lower heart rate. Offspring from long-lived families might thus be less stressed prior to potentially stressful events and consequently show overall lower levels in physiological responses. Although attenuated physiological responding cannot be ruled out, lower starting points and a lower peak level in physiological responding when confronted with an actual stressor, might already limit damage due to stress over a lifetime. Lower physiological responding may also contribute to the lower prevalence of cardiovascular diseases and other stress-related diseases in healthy longevity.

Device Longevity in a Contemporary Cohort of ICD/CRT-D Patients Undergoing Device Replacement.

PubMed

Zanon, Francesco; Martignani, Cristian; Ammendola, Ernesto; Menardi, Endrj; Narducci, Maria Lucia; DE Filippo, Paolo; Santamaria, Matteo; Campana, Andrea; Stabile, Giuseppe; Potenza, Domenico Rosario; Pastore, Gianni; Iori, Matteo; LA Rosa, Concetto; Biffi, Mauro

2016-07-01

The longevity of defibrillators (ICD) is extremely important from both a clinical and economic perspective. We studied the reasons for device replacement, the longevity of removed ICD, and the existence of possible factors associated with shorter service life. Consecutive patients who underwent ICD replacement from March 2013 to May 2015 in 36 Italian centers were included in this analysis. Data on replaced devices were collected. A total of 953 patients were included in this analysis. In 813 (85%) patients the reason for replacement was battery depletion, while 88 (9%) devices were removed for clinical reasons and the remaining 52 because of system failure (i.e., lead or ICD generator failure or a safety advisory indication). The median service life was 5.9 years (25th-75th percentile, 4.9-6.9) for single- and dual-chamber ICD and 4.9 years (25th-75th percentile, 4.0-5.7) for CRT-D. On multivariate analysis, the factors CRT-D device, SC/DC ICD generator from Biotronik, percentage of ventricular pacing, and the occurrence of a system failure were positively associated with a replacement procedure. By contrast, the device from Boston Scientific was an independent protective factor against replacement. Considerable differences were seen in battery duration in both ICD and CRT-D. Specifically, Biotronik devices showed the shortest longevity among ICD and Boston Scientific showed the longest longevity among CRT-D (log-rank test, P < 0.001 for pairwise comparisons). Several factors were associated with shorter service life of ICD devices: CRT-D, occurrence of system failure and percentage of ventricular pacing. Our results confirmed significant differences among manufacturers. © The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals, Inc.

Ecological correlates of ex situ seed longevity: a comparative study on 195 species

PubMed Central

Probert, Robin J.; Daws, Matthew I.; Hay, Fiona R.

2009-01-01

Background and Aims Extended seed longevity in the dry state is the basis for the ex situ conservation of ‘orthodox’ seeds. However, even under identical storage conditions there is wide variation in seed life-span between species. Here, the effects of seed traits and environmental conditions at the site of collection on seed longevity is explored for195 wild species from 71 families from environments ranging from cold deserts to tropical forests. Methods Seeds were rapidly aged at elevated temperature and relative humidity (either 45°C and 60% RH or 60°C and 60% RH) and regularly sampled for germination. The time taken in storage for viability to fall to 50% (p50) was determined using Probit analysis and used as a measure of relative seed longevity between species. Key Results Across species, p50 at 45°C and 60% RH varied from 0·1 d to 771 d. Endospermic seeds were, in general, shorter lived than non-endospermic seeds and seeds from hot, dry environments were longer lived than those from cool, wet conditions. These relationships remained significant when controlling for the effects of phylogenetic relatedness using phylogenetically independent contrasts. Seed mass and oil content were not correlated with p50. Conclusions The data suggest that the endospermic seeds of early angiosperms which evolved in forest understorey habitats are short-lived. Extended longevity presumably evolved as a response to climatic change or the invasion of drier areas. The apparent short-lived nature of endospermic seeds from cool wet environments may have implications for re-collection and re-testing strategies in ex situ conservation. PMID:19359301

Differential role of molten globule and protein folding in distinguishing unique features of botulinum neurotoxin.

PubMed

Kumar, Raj; Kukreja, Roshan V; Cai, Shuowei; Singh, Bal R

2014-06-01

Botulinum neurotoxins (BoNTs) are proteins of great interest not only because of their extreme toxicity but also paradoxically for their therapeutic applications. All the known serotypes (A-G) have varying degrees of longevity and potency inside the neuronal cell. Differential chemical modifications such as phosphorylation and ubiquitination have been suggested as possible mechanisms for their longevity, but the molecular basis of the longevity remains unclear. Since the endopeptidase domain (light chain; LC) of toxin apparently survives inside the neuronal cells for months, it is important to examine the structural features of this domain to understand its resistance to intracellular degradation. Published crystal structures (both botulinum neurotoxins and endopeptidase domain) have not provided adequate explanation for the intracellular longevity of the domain. Structural features obtained from spectroscopic analysis of LCA and LCB were similar, and a PRIME (PReImminent Molten Globule Enzyme) conformation appears to be responsible for their optimal enzymatic activity at 37°C. LCE, on the other hand, was although optimally active at 37°C, but its active conformation differed from the PRIME conformation of LCA and LCB. This study establishes and confirms our earlier finding that an optimally active conformation of these proteins in the form of PRIME exists for the most poisonous poison, botulinum neurotoxin. There are substantial variations in the structural and functional characteristics of these active molten globule related structures among the three BoNT endopeptidases examined. These differential conformations of LCs are important in understanding the fundamental structural features of proteins, and their possible connection to intracellular longevity could provide significant clues for devising new countermeasures and effective therapeutics. Copyright © 2014 Elsevier B.V. All rights reserved.

Dopa decarboxylase (Ddc) affects variation in Drosophila longevity.

PubMed

De Luca, Maria; Roshina, Nataliya V; Geiger-Thornsberry, Gretchen L; Lyman, Richard F; Pasyukova, Elena G; Mackay, Trudy F C

2003-08-01

Mutational analyses in model organisms have shown that genes affecting metabolism and stress resistance regulate life span, but the genes responsible for variation in longevity in natural populations are largely unidentified. Previously, we mapped quantitative trait loci (QTLs) affecting variation in longevity between two Drosophila melanogaster strains. Here, we show that the longevity QTL in the 36E;38B cytogenetic interval on chromosome 2 contains multiple closely linked QTLs, including the Dopa decarboxylase (Ddc) locus. Complementation tests to mutations show that Ddc is a positional candidate gene for life span in these strains. Linkage disequilibrium (LD) mapping in a sample of 173 alleles from a single population shows that three common molecular polymorphisms in Ddc account for 15.5% of the genetic contribution to variance in life span from chromosome 2. The polymorphisms are in strong LD, and the effects of the haplotypes on longevity suggest that the polymorphisms are maintained by balancing selection. DDC catalyzes the final step in the synthesis of the neurotransmitters, dopamine and serotonin. Thus, these data implicate variation in the synthesis of bioamines as a factor contributing to natural variation in individual life span.

A C. elegans Thermosensory Circuit Regulates Longevity through crh-1/CREB-Dependent flp-6 Neuropeptide Signaling.

PubMed

Chen, Yen-Chih; Chen, Hung-Jhen; Tseng, Wei-Chin; Hsu, Jiun-Min; Huang, Tzu-Ting; Chen, Chun-Hao; Pan, Chun-Liang

2016-10-24

Sensory perception, including thermosensation, shapes longevity in diverse organisms, but longevity-modulating signals from the sensory neurons are largely obscure. Here we show that CRH-1/CREB activation by CMK-1/CaMKI in the AFD thermosensory neuron is a key mechanism that maintains lifespan at warm temperatures in C. elegans. In response to temperature rise and crh-1 activation, the AFD neurons produce and secrete the FMRFamide neuropeptide FLP-6. Both CRH-1 and FLP-6 are necessary and sufficient for longevity at warm temperatures. Our data suggest that FLP-6 targets the AIY interneurons and engages DAF-9 sterol hormone signaling. Moreover, we show that FLP-6 signaling downregulates ins-7/insulin-like peptide and several insulin pathway genes, whose activity compromises lifespan. Our work illustrates how temperature experience is integrated by the thermosensory circuit to generate neuropeptide signals that remodel insulin and sterol hormone signaling and reveals a neuronal-endocrine circuit driven by thermosensation to promote temperature-specific longevity. Copyright © 2016 Elsevier Inc. All rights reserved.

Long-time aging in 3 mol.% yttria-stabilized tetragonal zirconia polycrystals at human body temperature.

PubMed

Keuper, Melanie; Berthold, Christoph; Nickel, Klaus Georg

2014-02-01

We present new findings on the low-temperature degradation of yttria-stabilized zirconia at 37°C over several years and at high and low partial pressures of water. With the aid of focused ion beam cross-section confirmation studies we are able to show an extensive linear, continuous degradation without retardation, even at low temperatures and low water pressures. The characteristic layer growth and its inferred rate constant imply a lifetime of tens of years under simple tension and open the possibility of studying the longevity of these ceramics more rigorously. In addition, we show reproducibility complications of accelerated aging tests by the use of different autoclaves and possible implications for standardized procedures. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Short communication: Development of a direct in vivo screening model to identify potential probiotic bacteria using Caenorhabditis elegans.

PubMed

Park, M R; Yun, H S; Son, S J; Oh, S; Kim, Y

2014-11-01

Caenorhabditis elegans is an accepted model host to study host-bacteria interactions in the gut, in addition to being a simple model with which to study conserved aspects of biological signaling pathways in intestinal environments, because these nematode worms have similar intestinal cells to those of humans. Here, we used C. elegans to develop a new in vivo screening system for potential probiotic lactic acid bacteria (LAB). Initially, critical colonization ability of LAB strains isolated from Korean infant feces was screened in the worm intestinal tract over a period of 5 d. Furthermore, we investigated host health-promoting activities, including longevity-extending effects and immune-enhancing activities against foodborne pathogen infection. We identified 4 LAB strains that were highly persistent in the nematode gut and that significantly prolonged the longevity of C. elegans and improved the survival of C. elegans in response to infection by Staphylococcus aureus. The 4 LAB strains we identified showed resistance to acid and bile conditions, assimilated cholesterol, and were able to attach to a mucus layer. The 4 LAB isolates were identified as Lactobacillus plantarum using 16S rRNA sequencing analysis. Taken together, we developed a direct in vivo screening system using C. elegans to study host health-promoting LAB. Our system is simple, rapid, cost-effective, and reliable, and we anticipate that this system will result in the discovery of many more potential probiotic bacteria for dairy foods. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Cross-Resistance and Resistance Longevity as Induced by Bean Leaf Beetle, Cerotoma trifurcata and Soybean Looper, Pseudoplusia includens herbivory on Soybean

PubMed Central

Srinivas, P.; Danielson, Stephen D.; Smith, C. Michael; Foster, John E.

2001-01-01

Cross-resistance, and longevity of resistance, induced by the bean leaf beetle, Cerotoma trifurcata, was studied IN the soybean PI 227687 that exhibited induced response in earlier studies. Bean leaf beetle adults and soybean looper, Pseudoplusia includens, larvae were used to induce resistance and to determine beetle feeding preference. Beetles were collected from soybean fields 2 to 5 days prior to the feeding preference test. The level of cross-resistance induced by soybean looper herbivory to subsequent bean leaf beetle feeding was higher when compared to cross-resistance induced by bean leaf beetle herbivory against subsequent feeding by soybean looper. Further, herbivory by the bean leaf beetle also induced resistance against soybean looper feeding. In the longevity study, leaflets from treated plants were collected 5, 10, 12, 14, 16, 20 and 25 days after initiation of feeding. Pairwise comparisons of leaflets from plants treated by bean leaf beetle herbivory with untreated plants revealed that induced responses were highest 14 and lowest 25 days after initiation of feeding. On other sampling days, levels of induced response varied with the sampling day. PMID:15455065

Experimental evolution of female traits under different levels of intersexual conflict in Drosophila melanogaster.

PubMed

Nandy, B; Gupta, V; Udaykumar, N; Samant, M A; Sen, S; Prasad, N G

2014-02-01

A number of studies have documented the evolution of female resistance to mate-harm in response to the alteration of intersexual conflict in the populations. However, the life-history consequence of such evolution is still a subject of debate. In this study, we subjected replicate populations of Drosophila melanogaster to different levels of sexual conflict (generated by altering the operational sex ratio) for over 45 generations. Our results suggest that females from populations experiencing higher level of intersexual conflict evolved increased resistance to mate-harm, in terms of both longevity and progeny production. Females from the populations with low conflict were significantly heavier at eclosion and were more susceptible to mate-harm in terms of progeny production under continuous exposure to the males. However, these females produced more progeny upon single mating and had significantly higher longevity in absence of any male exposure-a potential evidence of trade-offs between resistance-related traits and other life-history traits, such as fecundity and longevity. We also report tentative evidence, suggesting an increased male cost of interacting with more resistant females. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

Prolongevity effects of a botanical with oregano and cranberry extracts in Mexican fruit flies: examining interactions of diet restriction and age.

PubMed

Zou, Sige; Carey, James R; Liedo, Pablo; Ingram, Donald K; Yu, Binbing

2012-04-01

Botanicals rich with phytochemicals have numerous health benefits. Dietary restriction (DR) extends lifespan in diverse species. We previously demonstrated that an oregano-cranberry (OC) mixture can promote longevity in the Mexican Fruit fly (Mexfly, Anastrepha ludens Loew). However, little is known about the interaction between botanicals and DR, and the age-dependent effect of botanicals on lifespan and reproduction. Here we investigated these issues by feeding Mexflies a full or DR diet supplemented with or without 2% OC. Lifespan and daily egg production of individual flies were recorded. The effect of short-term OC supplementation was evaluated by implementing the supplementation at three age intervals-young, middle, and old age. We found that OC increased lifespan of Mexflies on the full or DR diet when compared to their respective controls. OC increased reproduction of females on the full diet and, to a lesser extent, on the DR diet. Short-term OC supplementation was not sufficient to extend lifespan for males at all three age intervals nor for females at young and old age intervals. However, OC supplementation at the middle age interval was sufficient to extend lifespan in females, while only OC supplementation at the young age interval increased reproduction in females. Our findings suggest that OC extends lifespan and promotes reproduction partly through DR-independent pathways, and short-term supplementation have varied impact on longevity and reproduction. This also suggests a positive interaction between non-genetic interventions in promoting longevity and provides guidance for using botanicals as aging interventions in humans.

The beneficial effects of dietary restriction on learning are distinct from its effects on longevity and mediated by depletion of a neuroinhibitory metabolite

PubMed Central

Vohra, Mihir; Lemieux, George A.; Lin, Lin

2017-01-01

In species ranging from humans to Caenorhabditis elegans, dietary restriction (DR) grants numerous benefits, including enhanced learning. The precise mechanisms by which DR engenders benefits on processes related to learning remain poorly understood. As a result, it is unclear whether the learning benefits of DR are due to myriad improvements in mechanisms that collectively confer improved cellular health and extension of organismal lifespan or due to specific neural mechanisms. Using an associative learning paradigm in C. elegans, we investigated the effects of DR as well as manipulations of insulin, mechanistic target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), and autophagy pathways—processes implicated in longevity—on learning. Despite their effects on a vast number of molecular effectors, we found that the beneficial effects on learning elicited by each of these manipulations are fully dependent on depletion of kynurenic acid (KYNA), a neuroinhibitory metabolite. KYNA depletion then leads, in an N-methyl D-aspartate receptor (NMDAR)-dependent manner, to activation of a specific pair of interneurons with a critical role in learning. Thus, fluctuations in KYNA levels emerge as a previously unidentified molecular mechanism linking longevity and metabolic pathways to neural mechanisms of learning. Importantly, KYNA levels did not alter lifespan in any of the conditions tested. As such, the beneficial effects of DR on learning can be attributed to changes in a nutritionally sensitive metabolite with neuromodulatory activity rather than indirect or secondary consequences of improved health and extended longevity. PMID:28763436

Exceptional longevity and exceptionally high metabolic rates in anthropoid primates are linked to a major modification of the ubiquinone reduction site of cytochrome b.

PubMed

Rottenberg, Hagai

2014-10-01

The maximal lifespan of Anthropoid primates (monkeys, apes and humans) exceed the lifespan of most other mammals of equal body mass. Unexpectedly, their exceptional longevity is associated with exceptionally high metabolic rates, in apparent contradiction to the Free Radical Theory of Aging. It was therefore suggested that in anthropoid primates (and several other taxa of mammals and birds) the mitochondrial electron transport complexes evolved to modify the relationship between basal electron transport and superoxide generation to allow for the evolution of exceptional longevity. Cytochrome b, the core protein of the bc1 complex is a major source of superoxide. The amino-acid sequence of cytochrome b evolved much faster in anthropoid than in prosimian primates, and most other mammals, resulting in a large change in the amino-acids composition of the protein. As a result of these changes cytochrome b in anthropoid primates is significantly less hydrophobic and contains more polar residues than other primates and most other mammals. Most of these changes are clustered around the reduction site of uboiquinone. In particular a key positively charged residue, arginine 313, that interacts with propionate D of heme bH, and thus raises its redox potential, is substituted in anthropoid primates with the neutral residue glutamine, most likely resulting in a lower redox potential of heme bH and faster reduction of ubiquinone at high proton motive force. It is suggested that these changes contribute to the observed increased rates of basal metabolism and reduce the rates of superoxide production, thus allowing for increased lifespan.

Hormetic efficacy of rutin to promote longevity in Drosophila melanogaster.

PubMed

Chattopadhyay, Debarati; Chitnis, Atith; Talekar, Aishwarya; Mulay, Prajakta; Makkar, Manyata; James, Joel; Thirumurugan, Kavitha

2017-06-01

Hormetins are compounds that mediate hormesis by being beneficial at low doses but detrimental at high doses. Recent studies have highlighted that many compounds that extended lifespan in model organisms did so by mediating hormesis. Rutin is a glycosylate conjugate of quercetin and rutinose and is abundant in citrus fruits and buckwheat seeds. Rutin possess ROS scavenging, anti-cancer, cardio-protective, skin-regenerative and neuro-protective properties. Drosophila melanogaster is an attractive model organism for longevity studies owing to its homology of organ and cellular-pathways with mammals. In this study, we aimed to understand the effect of rutin on extending longevity in Drosophila melanogaster. Male and female flies were administered with a range of rutin doses (100-800 µM) to analyse whether rutin mediated lifespan-extension by hormesis. Effect of rutin on physiological parameters like food intake, fecundity, climbing activity, development and resistance to various stresses was also studied. Lifespan assays showed that rutin at 200 and 400 µM significantly extended median lifespan in both male and female flies beyond which flies exhibited drastically reduced longevity. Increase in survival at 400 µM was associated with reduced food intake and fecundity. Flies exhibited improved climbing capability with both 200 and 400 µM rutin. Flies fed with 100 and 200 µM rutin exhibited enhanced survival upon exposure to oxidative stress with 400 µM rutin exhibiting no improvement in median lifespan following oxidative stress. Analysis of endogenous peroxide upon treatment with rutin (100-400 µM) with or without 5% H 2 O 2 showed elevated levels of endogenous peroxide with 400 µM rutin whereas no increase in hydrogen peroxide level was observed with rutin at 100 and 200 µM. Finally, gene expression studies in male flies revealed that rutin treatment at 200 and/or 400 µM elevated transcript levels of dFoxO, MnSod, Cat, dTsc1, dTsc2, Thor, dAtg1, dAtg5 and dAtg7 and reduced transcript levels of dTor. Collectively, rutin at 200 and 400 µM improved longevity in flies; 200 µM rutin acted as a mild stressor to prolong lifespan in flies by mediating hormesis whereas 400 µM, being a high dose for best positive effects.

Life-span of in vitro differentiated Plasmodium falciparum gametocytes.

PubMed

Gebru, Tamirat; Lalremruata, Albert; Kremsner, Peter G; Mordmüller, Benjamin; Held, Jana

2017-08-11

The sexual stages (gametocytes) of Plasmodium falciparum do not directly contribute to the pathology of malaria but are essential for transmission of the parasite from the human host to the mosquito. Mature gametocytes circulate in infected human blood for several days and their circulation time has been modelled mathematically from data of previous in vivo studies. This is the first time that longevity of gametocytes is studied experimentally in vitro. The in vitro longevity of P. falciparum gametocytes of 1 clinical isolate and 2 laboratory strains was assessed by three different methods: microscopy, flow cytometry and reverse transcription quantitative real-time PCR (RT-qPCR). Additionally, the rate of gametocytogenesis of the used P. falciparum strains was compared. The maximum in vitro lifespan of P. falciparum gametocytes reached almost 2 months (49 days by flow cytometry, 46 days by microscopy, and at least 52 days by RT-qPCR) from the starting day of gametocyte culture to death of last parasite in the tested strains with an average 50% survival rate of 6.5, 2.6 and 3.5 days, respectively. Peak gametocytaemia was observed on average 19 days after initiation of gametocyte culture followed by a steady decline due to natural decay of the parasites. The rate of gametocytogenesis was highest in the NF54 strain. Plasmodium falciparum mature gametocytes can survive up to 16-32 days (at least 14 days for mature male gametocytes) in vitro in absence of the influence of host factors. This confirms experimentally a previous modelling estimate that used molecular tools for gametocyte detection in treated patients. The survival time might reflect the time the parasite can be transmitted to the mosquito after clearance of asexual parasites. These results underline the importance of efficient transmission blocking agents in the fight against malaria.

Healthy and happy in Europe? On the association between happiness and life expectancy over time.

PubMed

Bjørnskov, Christian

2008-04-01

This paper revisits the standard finding in individual-level studies that happiness leads to longevity. It does so in a cross-country time-series analysis in which the use of a random effects estimator controls for most relevant time-invariant factors. The findings suggest that happiness is negatively associated with longevity at the national level, and suggests a potential indirect transmission channel, as national happiness is negatively associated with public health expenditures. The paper concludes by discussing the implications of the results for public policy and future research.

Is there a link between aging and microbiome diversity in exceptional mammalian longevity?

PubMed Central

Hughes, Graham M.; Leech, John; Puechmaille, Sébastien J.; Lopez, Jose V.

2018-01-01

A changing microbiome has been linked to biological aging in mice and humans, suggesting a possible role of gut flora in pathogenic aging phenotypes. Many bat species have exceptional longevity given their body size and some can live up to ten times longer than expected with little signs of aging. This study explores the anal microbiome of the exceptionally long-lived Myotis myotis bat, investigating bacterial composition in both adult and juvenile bats to determine if the microbiome changes with age in a wild, long-lived non-model organism, using non-lethal sampling. The anal microbiome was sequenced using metabarcoding in more than 50 individuals, finding no significant difference between the composition of juvenile and adult bats, suggesting that age-related microbial shifts previously observed in other mammals may not be present in Myotis myotis. Functional gene categories, inferred from metabarcoding data, expressed in the M. myotis microbiome were categorized identifying pathways involved in metabolism, DNA repair and oxidative phosphorylation. We highlight an abundance of ‘Proteobacteria’ relative to other mammals, with similar patterns compared to other bat microbiomes. Our results suggest that M. myotis may have a relatively stable, unchanging microbiome playing a role in their extended ‘health spans’ with the advancement of age, and suggest a potential link between microbiome and sustained, powered flight. PMID:29333342

Regulation of longevity by FGF21: Interaction between energy metabolism and stress responses.

PubMed

Salminen, Antero; Kaarniranta, Kai; Kauppinen, Anu

2017-08-01

Fibroblast growth factor 21 (FGF21) is a hormone-like member of FGF family which controls metabolic multiorgan crosstalk enhancing energy expenditure through glucose and lipid metabolism. In addition, FGF21 acts as a stress hormone induced by endoplasmic reticulum stress and dysfunctions of mitochondria and autophagy in several tissues. FGF21 also controls stress responses and metabolism by modulating the functions of somatotropic axis and hypothalamic-pituitary-adrenal (HPA) pathway. FGF21 is a potent longevity factor coordinating interactions between energy metabolism and stress responses. Recent studies have revealed that FGF21 treatment can alleviate many age-related metabolic disorders, e.g. atherosclerosis, obesity, type 2 diabetes, and some cardiovascular diseases. In addition, transgenic mice overexpressing FGF21 have an extended lifespan. However, chronic metabolic and stress-related disorders involving inflammatory responses can provoke FGF21 resistance and thus disturb healthy aging process. First, we will describe the role of FGF21 in interorgan energy metabolism and explain how its functions as a stress hormone can improve healthspan. Next, we will examine both the induction of FGF21 expression via the integrated stress response and the molecular mechanism through which FGF21 enhances healthy aging. Finally, we postulate that FGF21 resistance, similarly to insulin resistance, jeopardizes human healthspan and accelerates the aging process. Copyright © 2017 Elsevier B.V. All rights reserved.

Anthropology and the study of menopause: evolutionary, developmental, and comparative perspectives.

PubMed

Sievert, Lynnette Leidy

2014-10-01

This work aims to consider how the discipline of anthropology contributes to the study of menopause through evolutionary, developmental, and comparative perspectives. This study was a review of skeletal and ethnographic evidence for menopause and postreproductive life in humans' distant past, hypotheses for the evolution of menopause and long postreproductive life, variation in age at menopause with focus on childhood environments, and the study of variation in symptom experience across populations. Longevity, rather than capacity for menopause, sets humans apart from other primates. Skeletal evidence demonstrates that some Neanderthals and archaic Homo sapiens lived to the age at menopause and that at least one third of women in traditional foraging populations live beyond menopause. The evolutionary reasons for why women experience a long postreproductive life continue to be debated. A developmental perspective suggests that early childhood may be a critical time for the environment to irreversibly influence the number of oocytes or rate of follicular atresia and, ultimately, age at menopause. A comparative perspective examines symptom experience at midlife through participant observation, qualitative interviews, and quantitative instruments to gain a holistic understanding of the meaning, experience, and sociocultural context of menopause. An evolutionary perspective suggests that menopause is not a recent phenomenon among humans. A developmental perspective focuses on the influence of early childhood on ovarian function. A comparative perspective expands clinical norms and provides knowledge about the range of human variations.

Dafadine inhibits DAF-9 to promote dauer formation and longevity of Caenorhabditis elegans.

PubMed

Luciani, Genna M; Magomedova, Lilia; Puckrin, Rachel; Urbanus, Malene L; Wallace, Iain M; Giaever, Guri; Nislow, Corey; Cummins, Carolyn L; Roy, Peter J

2011-11-06

The DAF-9 cytochrome P450 is a key regulator of dauer formation, developmental timing and longevity in the nematode Caenorhabditis elegans. Here we describe the first identified chemical inhibitor of DAF-9 and the first reported small-molecule tool that robustly induces dauer formation in typical culture conditions. This molecule (called dafadine) also inhibits the mammalian ortholog of DAF-9(CYP27A1), suggesting that dafadine can be used to interrogate developmental control and longevity in other animals.

Circulating miRNAs and miRNA shuttles as biomarkers: Perspective trajectories of healthy and unhealthy aging.

PubMed

Olivieri, Fabiola; Capri, Miriam; Bonafè, Massimiliano; Morsiani, Cristina; Jung, Hwa Jin; Spazzafumo, Liana; Viña, Jose; Suh, Yousin

2017-07-01

Human aging is a lifelong process characterized by a continuous trade-off between pro-and anti-inflammatory responses, where the best-adapted and/or remodeled genetic/epigenetic profile may develop a longevity phenotype. Centenarians and their offspring represent such a phenotype and their comparison to patients with age-related diseases (ARDs) is expected to maximize the chance to unravel the genetic makeup that better associates with healthy aging trajectories. Seemingly, such comparison is expected to allow the discovery of new biomarkers of longevity together with risk factor for the most common ARDs. MicroRNAs (miRNAs) and their shuttles (extracellular vesicles in particular) are currently conceived as those endowed with the strongest ability to provide information about the trajectories of healthy and unhealthy aging. We review the available data on miRNAs in aging and underpin the evidence suggesting that circulating miRNAs (and cognate shuttles), especially those involved in the regulation of inflammation (inflamma-miRs) may constitute biomarkers capable of reliably depicting healthy and unhealthy aging trajectories. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Connecting prosocial behavior to improved physical health: Contributions from the neurobiology of parenting.

PubMed

Brown, Stephanie L; Brown, R Michael

2015-08-01

Although a growing body of evidence suggests that giving to (helping) others is linked reliably to better health and longevity for the helper, little is known about causal mechanisms. In the present paper we use a recently developed model of caregiving motivation to identify possible neurophysiological mechanisms. The model describes a mammalian neurohormonal system that evolved to regulate maternal care, but over time may have been recruited to support a wide variety of helping behaviors in humans and other social animals. According to the model, perception of need or distress in others activates caregiving motivation, which in turn, can facilitate helping behavior. Motivational regulation is governed by the medial preoptic area of the hypothalamus, interacting with certain other brain regions, hormones, and neuromodulators (especially oxytocin and progesterone). Consideration of neurohormonal circuitry and related evidence raises the possibility that it is these hormones, known to have stress-buffering and restorative properties, that are responsible, at least in part, for health and longevity benefits associated with helping others. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Mass-Longevity Triangle: Pareto Optimality and the Geometry of Life-History Trait Space

PubMed Central

Szekely, Pablo; Korem, Yael; Moran, Uri; Mayo, Avi; Alon, Uri

2015-01-01

When organisms need to perform multiple tasks they face a fundamental tradeoff: no phenotype can be optimal at all tasks. This situation was recently analyzed using Pareto optimality, showing that tradeoffs between tasks lead to phenotypes distributed on low dimensional polygons in trait space. The vertices of these polygons are archetypes—phenotypes optimal at a single task. This theory was applied to examples from animal morphology and gene expression. Here we ask whether Pareto optimality theory can apply to life history traits, which include longevity, fecundity and mass. To comprehensively explore the geometry of life history trait space, we analyze a dataset of life history traits of 2105 endothermic species. We find that, to a first approximation, life history traits fall on a triangle in log-mass log-longevity space. The vertices of the triangle suggest three archetypal strategies, exemplified by bats, shrews and whales, with specialists near the vertices and generalists in the middle of the triangle. To a second approximation, the data lies in a tetrahedron, whose extra vertex above the mass-longevity triangle suggests a fourth strategy related to carnivory. Each animal species can thus be placed in a coordinate system according to its distance from the archetypes, which may be useful for genome-scale comparative studies of mammalian aging and other biological aspects. We further demonstrate that Pareto optimality can explain a range of previous studies which found animal and plant phenotypes which lie in triangles in trait space. This study demonstrates the applicability of multi-objective optimization principles to understand life history traits and to infer archetypal strategies that suggest why some mammalian species live much longer than others of similar mass. PMID:26465336

Effect of dystocia on subsequent reproductive performance and functional longevity in Holstein cows.

PubMed

Ghavi Hossein-Zadeh, N

2016-10-01

The objective of this study was to evaluate the effect of dystocia on the reproductive performance and functional longevity in Iranian Holsteins. Data consisted of 1 467 064 lactation records of 581 421 Holstein cows from 3083 herds which were collected by the Animal Breeding Center of Iran from April 1987 to February 2014. Reproduction traits in this study included interval from first to second calving, days open and days from first calving to first service. The generalized linear model was used for the statistical analysis of reproductive traits. Survival analysis was performed using the Weibull proportional hazards models to analyse the impact of dystocia on functional longevity. The incidence of dystocia had an adverse effect on the reproductive performance of dairy cows. Therefore, reproductive traits deteriorated along with increase in dystocia score (p < 0.05). The culling risk was increased along with increase in the score of dystocia (p < 0.0001). The greatest culling risk was observed in primiparous cows, small herds and low-yielding cows (p < 0.0001). Also, the lowest culling risk was found for cows calving at the youngest age (<27 months), and cows with age at first calving >33 months had the greatest risk (p < 0.0001). The results of current study indicated that dystocia had important negative effects on the reproductive performance and functional longevity in dairy cows, and it should be avoided as much as possible to provide a good perspective in the scope of economic and animal welfare issues in dairy herds. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Educational attainment and longevity: results from the REGARDS U.S. national cohort study of blacks and whites.

PubMed

Kaplan, Robert M; Howard, Virginia J; Safford, Monika M; Howard, George

2015-05-01

Educational attainment may be an important determinant of life expectancy. However, few studies have prospectively evaluated the relationship between educational attainment and life expectancy using adjustments for other social, behavioral, and biological factors. The data were from the REasons for Geographic and Racial Differences in Stroke study that enrolled 30,239 black and white adults (≥45 years) between 2003 and 2007. Demographic and cardiovascular risk information was collected and participants were followed for health outcomes. Educational attainment was categorized as less than high school education, high school graduate, some college, or college graduate. Proportional hazards analysis was used to characterize survival by level of education. Educational attainment and follow-up data were available on 29,657 (98%) of the participants. Over 6.3 years of follow-up, 3673 participants died. There was a monotonically increasing risk of death with lower levels of educational attainment. The same monotonic relationship held with adjustments for age, race, sex, cardiovascular risk factors, and health behaviors. The unadjusted hazard ratio for those without a high school education in comparison with college graduates was 2.89 (95% CI = 2.64-3.18). Although adjustment for income, health behaviors, and cardiovascular risk factors attenuated the relationship, the same consistent pattern was observed after adjustment. The relationship between educational attainment and longevity was similar for black and white participants. The monotonic relationship between educational attainment and longevity was observed for all age groups, except for those aged 85 years or more. Educational attainment is a significant predictor of longevity. Other factors including age, race, income, health behaviors, and cardiovascular risk factors only partially explain the relationship. Published by Elsevier Inc.

Enhancing longevity of Plasmodium vivax and P. falciparum sporozoites after dissection from mosquito salivary glands.

PubMed

Lupton, Emily J; Roth, Alison; Patrapuvich, Rapatbhorn; Maher, Steve P; Singh, Naresh; Sattabongkot, Jetsumon; Adams, John H

2015-04-01

The pre-erythrocytic stages of Plasmodium vivax and Plasmodium falciparum remain challenging for experimental research in part due to limited access to sporozoites. An important factor limiting availability is the laboratory support required for producing infected mosquitoes and the ephemeral nature of isolated extracellular sporozoites. This study was undertaken to investigate methods to improve the availability of this limited resource by extending the longevity of the extracellular sporozoites after mosquito dissection. Our goal in this study was to determine whether buffer conditions more closely mimicking the insect microenvironment could prolong longevity of ex vivo P. vivax and P. falciparum sporozoites. The study compared the current standard dissection buffer RPMI1640 to Hank's Balanced Salt Solution with 1g/L glucose (HBSS-1) or 2g/L glucose (HBSS-2) and Grace's Insect Medium for ability to extend longevity of ex vivo P. vivax and P. falciparum sporozoites. The effect of each buffer on sporozoite viability was evaluated by measuring sporozoite gliding motility at 0, 4, 8, and 24h post-dissection from mosquito salivary glands. Comparisons of mean gliding percentages of ex vivo sporozoites in the different buffers and time points found that RPMI and Grace's both showed strong gliding at 0h. In contrast, by 4h post-dissection sporozoites in RPMI consistently had the lowest gliding activity, whereas sporozoites in Grace's had significantly more gliding compared to all other buffers at almost all time points. Our results indicate that P. vivax and P. falciparum sporozoites maintained in insect media rather than the standard dissection buffer RPMI and HBSS retain viability better over time. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.