Visual Search Across the Life Span

ERIC Educational Resources Information Center

Hommel, Bernhard; Li, Karen Z. H.; Li, Shu-Chen

2004-01-01

Gains and losses in visual search were studied across the life span in a representative sample of 298 individuals from 6 to 89 years of age. Participants searched for single-feature and conjunction targets of high or low eccentricity. Search was substantially slowed early and late in life, age gradients were more pronounced in conjunction than in…

Teaching the Psychology of Aging: A Life-Span Perspective.

ERIC Educational Resources Information Center

Seltzer, Mildred M.

There is a vast body of literature devoted to an examination of life-span development. Several authors have described the characteristics of the life-span approach and have distinguished it from more traditional forms of psychology. Emphasis has been placed on the multidirectional and multidimensional nature of development and change, as well as…

Pyrophosphate Supplementation Prevents Chronic and Acute Calcification in ABCC6-Deficient Mice.

PubMed

Pomozi, Viola; Brampton, Christopher; van de Wetering, Koen; Zoll, Janna; Calio, Bianca; Pham, Kevin; Owens, Jesse B; Marh, Joel; Moisyadi, Stefan; Váradi, András; Martin, Ludovic; Bauer, Carolin; Erdmann, Jeanette; Aherrahrou, Zouhair; Le Saux, Olivier

2017-06-01

Soft tissue calcification occurs in several common acquired pathologies, such as diabetes and hypercholesterolemia, or can result from genetic disorders. ABCC6, a transmembrane transporter primarily expressed in liver and kidneys, initiates a molecular pathway inhibiting ectopic calcification. ABCC6 facilitates the cellular efflux of ATP, which is rapidly converted into pyrophosphate (PPi), a major calcification inhibitor. Heritable mutations in ABCC6 underlie the incurable calcification disorder pseudoxanthoma elasticum and some cases of generalized arterial calcification of infancy. Herein, we determined that the administration of PPi and the bisphosphonate etidronate to Abcc6 -/- mice fully inhibited the acute dystrophic cardiac calcification phenotype, whereas alendronate had no significant effect. We also found that daily injection of PPi to Abcc6 -/- mice over several months prevented the development of pseudoxanthoma elasticum-like spontaneous calcification, but failed to reverse already established lesions. Furthermore, we found that the expression of low amounts of the human ABCC6 in liver of transgenic Abcc6 -/- mice, resulting in only a 27% increase in plasma PPi levels, led to a major reduction in acute and chronic calcification phenotypes. This proof-of-concept study shows that the development of both acute and chronic calcification associated with ABCC6 deficiency can be prevented by compensating PPi deficits, even partially. Our work indicates that PPi substitution represents a promising strategy to treat ABCC6-dependent calcification disorders. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Adaptive prolonged postreproductive life span in killer whales.

PubMed

Foster, Emma A; Franks, Daniel W; Mazzi, Sonia; Darden, Safi K; Balcomb, Ken C; Ford, John K B; Croft, Darren P

2012-09-14

Prolonged life after reproduction is difficult to explain evolutionarily unless it arises as a physiological side effect of increased longevity or it benefits related individuals (i.e., increases inclusive fitness). There is little evidence that postreproductive life spans are adaptive in nonhuman animals. By using multigenerational records for two killer whale (Orcinus orca) populations in which females can live for decades after their final parturition, we show that postreproductive mothers increase the survival of offspring, particularly their older male offspring. This finding may explain why female killer whales have evolved the longest postreproductive life span of all nonhuman animals.

Learning From Leaders: Life-span Trends in Olympians and Supercentenarians

PubMed Central

Berthelot, Geoffroy; Marck, Adrien; Noirez, Philippe; Latouche, Aurélien; Toussaint, Jean-François

2015-01-01

Life-span trends progression has worldwide practical implications as it may affect the sustainability of modern societies. We aimed to describe the secular life-span trends of populations with a propensity to live longer—Olympians and supercentenarians—under two hypotheses: an ongoing life-span extension versus a biologic “probabilistic barrier” limiting further progression. In a study of life-span densities (total number of life durations per birth date), we analyzed 19,012 Olympians and 1,205 supercentenarians deceased between 1900 and 2013. Among most Olympians, we observed a trend toward increased life duration. This trend, however, decelerates at advanced ages leveling off with the upper values with a perennial gap between Olympians and supercentenarians during the whole observation period. Similar tendencies are observed among supercentenarians, and over the last years, a plateau attests to a stable longevity pattern among the longest-lived humans. The common trends between Olympians and supercentenarians indicate similar mortality pressures over both populations that increase with age, scenario better explained by a biologic “barrier” forecast. PMID:25143003

Increased Expression of Plasma-Induced ABCC1 mRNA in Cystic Fibrosis.

PubMed

Ideozu, Justin E; Zhang, Xi; Pan, Amy; Ashrafi, Zainub; Woods, Katherine J; Hessner, Martin J; Simpson, Pippa; Levy, Hara

2017-08-11

The ABCC1 gene is structurally and functionally related to the cystic fibrosis transmembrane conductance regulator gene ( CFTR ). Upregulation of ABCC1 is thought to improve lung function in patients with cystic fibrosis (CF); the mechanism underlying this effect is unknown. We analyzed the ABCC1 promoter single nucleotide polymorphism (SNP rs504348), plasma-induced ABCC1 mRNA expression levels, and ABCC1 methylation status and their correlation with clinical variables among CF subjects with differing CFTR mutations. We assigned 93 CF subjects into disease severity groups and genotyped SNP rs504348. For 23 CF subjects and 7 healthy controls, donor peripheral blood mononuclear cells (PBMCs) stimulated with plasma underwent gene expression analysis via qRT-PCR. ABCC1 promoter methylation was analyzed in the same 23 CF subjects. No significant correlation was observed between rs504348 genotypes and CF disease severity, but pancreatic insufficient CF subjects showed increased colonization with any form of Pseudomonas aeruginosa (OR = 3.125, 95% CI: 1.192-8.190) and mucoid P. aeruginosa (OR = 5.075, 95% CI: 1.307-28.620) compared to the pancreatic sufficient group. A significantly higher expression of ABCC1 mRNA was induced by CF plasma compared to healthy control plasma ( p < 0.001). CF subjects with rs504348 (CC/CG) also had higher mRNA expression compared to those with the ancestral GG genotype ( p < 0.005). ABCC1 promoter was completely unmethylated; therefore, we did not detect any association between methylation and CF disease severity. In silico predictions suggested that histone modifications are crucial for regulating ABCC1 expression in PBMCs. Our results suggest that ABCC1 expression has a role in CFTR activity thereby increasing our understanding of the molecular underpinnings of the clinical heterogeneity in CF.

Working memory and inhibitory control across the life span: Intrusion errors in the Reading Span Test.

PubMed

Robert, Christelle; Borella, Erika; Fagot, Delphine; Lecerf, Thierry; de Ribaupierre, Anik

2009-04-01

The aim of this study was to examine to what extent inhibitory control and working memory capacity are related across the life span. Intrusion errors committed by children and younger and older adults were investigated in two versions of the Reading Span Test. In Experiment 1, a mixed Reading Span Test with items of various list lengths was administered. Older adults and children recalled fewer correct words and produced more intrusions than did young adults. Also, age-related differences were found in the type of intrusions committed. In Experiment 2, an adaptive Reading Span Test was administered, in which the list length of items was adapted to each individual's working memory capacity. Age groups differed neither on correct recall nor on the rate of intrusions, but they differed on the type of intrusions. Altogether, these findings indicate that the availability of attentional resources influences the efficiency of inhibition across the life span.

Exploratory and problem-solving consumer behavior across the life span.

PubMed

Lesser, J A; Kunkel, S R

1991-09-01

Different cognitive functioning, social, and personality changes appear to occur systematically during the adult life span. This article synthesizes research on life span changes in order to develop age-specific models of shopping behavior. The models are tested within a naturalistic field study of shoppers.

Blade life span, structural investment, and nutrient allocation in giant kelp.

PubMed

Rodriguez, Gabriel E; Reed, Daniel C; Holbrook, Sally J

2016-10-01

The turnover of plant biomass largely determines the amount of energy flowing through an ecosystem and understanding the processes that regulate turnover has been of interest to ecologists for decades. Leaf life span theory has proven useful in explaining patterns of leaf turnover in relation to resource availability, but the predictions of this theory have not been tested for macroalgae. We measured blade life span, size, thickness, nitrogen content, pigment content, and maximum photosynthetic rate (P max) in the giant kelp (Macrocystis pyrifera) along a strong resource (light) gradient to test whether the predictions of leaf life span theory applied to this alga. We found that shorter blade life spans and larger blade areas were associated with increased light availability. In addition, nitrogen and P max decreased with blade age, and their decrease was greater in shorter lived blades. These observations are generally consistent with patterns observed for higher plants and the prevailing theory of leaf life span. By contrast, variation observed in pigments of giant kelp was inconsistent with that predicted by leaf life span theory, as blades growing in the most heavily shaded portion of the forest had the lowest chlorophyll content. This result may reflect the dual role of macroalgal blades in carbon fixation and nutrient absorption and the ability of giant kelp to modify blade physiology to optimize the acquisition of light and nutrients. Thus, the marine environment may place demands on resource acquisition and allocation that have not been previously considered with respect to leaf life span optimization.

Individual differences in personality change across the adult life span.

PubMed

Schwaba, Ted; Bleidorn, Wiebke

2018-06-01

A precise and comprehensive description of personality continuity and change across the life span is the bedrock upon which theories of personality development are built. Little research has quantified the degree to which individuals deviate from mean-level developmental trends. In this study, we addressed this gap by examining individual differences in personality trait change across the life span. Data came from a nationally representative sample of 9,636 Dutch participants who provided Big Five self-reports at five assessment waves across 7 years. We divided our sample into 14 age groups (ages 16-84 at initial measurement) and estimated latent growth curve models to describe individual differences in personality change across the study period for each trait and age group. Across the adult life span, individual differences in personality change were small but significant until old age. For Openness, Conscientiousness, Extraversion, and Agreeableness, individual differences in change were most pronounced in emerging adulthood and decreased throughout midlife and old age. For Emotional Stability, individual differences in change were relatively consistent across the life span. These results inform theories of life span development and provide future directions for research on the causes and conditions of personality change. © 2017 Wiley Periodicals, Inc.

Comparative transcriptional profiling identifies takeout as a gene that regulates life span

PubMed Central

Bauer, Johannes; Antosh, Michael; Chang, Chengyi; Schorl, Christoph; Kolli, Santharam; Neretti, Nicola; Helfand, Stephen L.

2010-01-01

A major challenge in translating the positive effects of dietary restriction (DR) for the improvement of human health is the development of therapeutic mimics. One approach to finding DR mimics is based upon identification of the proximal effectors of DR life span extension. Whole genome profiling of DR in Drosophila shows a large number of changes in gene expression, making it difficult to establish which changes are involved in life span determination as opposed to other unrelated physiological changes. We used comparative whole genome expression profiling to discover genes whose change in expression is shared between DR and two molecular genetic life span extending interventions related to DR, increased dSir2 and decreased Dmp53 activity. We find twenty-one genes shared among the three related life span extending interventions. One of these genes, takeout, thought to be involved in circadian rhythms, feeding behavior and juvenile hormone binding is also increased in four other life span extending conditions: Rpd3, Indy, chico and methuselah. We demonstrate takeout is involved in longevity determination by specifically increasing adult takeout expression and extending life span. These studies demonstrate the power of comparative whole genome transcriptional profiling for identifying specific downstream elements of the DR life span extending pathway. PMID:20519778

Learning From Leaders: Life-span Trends in Olympians and Supercentenarians.

PubMed

Antero-Jacquemin, Juliana da Silva; Berthelot, Geoffroy; Marck, Adrien; Noirez, Philippe; Latouche, Aurélien; Toussaint, Jean-François

2015-08-01

Life-span trends progression has worldwide practical implications as it may affect the sustainability of modern societies. We aimed to describe the secular life-span trends of populations with a propensity to live longer-Olympians and supercentenarians-under two hypotheses: an ongoing life-span extension versus a biologic "probabilistic barrier" limiting further progression. In a study of life-span densities (total number of life durations per birth date), we analyzed 19,012 Olympians and 1,205 supercentenarians deceased between 1900 and 2013. Among most Olympians, we observed a trend toward increased life duration. This trend, however, decelerates at advanced ages leveling off with the upper values with a perennial gap between Olympians and supercentenarians during the whole observation period. Similar tendencies are observed among supercentenarians, and over the last years, a plateau attests to a stable longevity pattern among the longest-lived humans. The common trends between Olympians and supercentenarians indicate similar mortality pressures over both populations that increase with age, scenario better explained by a biologic "barrier" forecast. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America.

Understanding retirement: the promise of life-span developmental frameworks.

PubMed

Löckenhoff, Corinna E

2012-09-01

The impending retirement of large population cohorts creates a pressing need for practical interventions to optimize outcomes at the individual and societal level. This necessitates comprehensive theoretical models that acknowledge the multi-layered nature of the retirement process and shed light on the dynamic mechanisms that drive longitudinal patterns of adjustment. The present commentary highlights ways in which contemporary life-span developmental frameworks can inform retirement research, drawing on the specific examples of Bronfenbrenner's Ecological Model, Baltes and Baltes Selective Optimization with Compensation Framework, Schulz and Heckhausen's Motivational Theory of Life-Span Development, and Carstensen's Socioemotional Selectivity Theory. Ultimately, a life-span developmental perspective on retirement offers not only new interpretations of known phenomena but may also help to identify novel directions for future research as well as promising pathways for interventions.

Developmental Regulation across the Life Span: Toward a New Synthesis

ERIC Educational Resources Information Center

Haase, Claudia M.; Heckhausen, Jutta; Wrosch, Carsten

2013-01-01

How can individuals regulate their own development to live happy, healthy, and productive lives? Major theories of developmental regulation across the life span have been proposed (e.g., dual-process model of assimilation and accommodation; motivational theory of life-span development; model of selection, optimization, and compensation), but they…

Connecting Life Span Development with the Sociology of the Life Course: A New Direction.

PubMed

Gilleard, Chris; Higgs, Paul

2016-04-01

The life course has become a topic of growing interest within the social sciences. Attempts to link this sub-discipline with life span developmental psychology have been called for but with little sign of success. In this paper, we seek to address three interlinked issues concerning the potential for a more productive interchange between life course sociology and life span psychology. The first is to try to account for the failure of these two sub-disciplines to achieve any deepening engagement with each other, despite the long-expressed desirability of that goal; the second is to draw attention to the scope for enriching the sociology of the life course through Erik Erikson's model of life span development; and the last is the potential for linking Eriksonian theory with current debates within mainstream sociology about the processes involved in 'individualisation' and 'self-reflexivity' as an alternative entry point to bring together these two fields of work.

Connecting Life Span Development with the Sociology of the Life Course: A New Direction

PubMed Central

Gilleard, Chris; Higgs, Paul

2015-01-01

The life course has become a topic of growing interest within the social sciences. Attempts to link this sub-discipline with life span developmental psychology have been called for but with little sign of success. In this paper, we seek to address three interlinked issues concerning the potential for a more productive interchange between life course sociology and life span psychology. The first is to try to account for the failure of these two sub-disciplines to achieve any deepening engagement with each other, despite the long-expressed desirability of that goal; the second is to draw attention to the scope for enriching the sociology of the life course through Erik Erikson’s model of life span development; and the last is the potential for linking Eriksonian theory with current debates within mainstream sociology about the processes involved in ‘individualisation’ and ‘self-reflexivity’ as an alternative entry point to bring together these two fields of work. PMID:27041774

Divergent evolution of life span associated with mitochondrial DNA evolution.

PubMed

Stojković, Biljana; Sayadi, Ahmed; Đorđević, Mirko; Jović, Jelena; Savković, Uroš; Arnqvist, Göran

2017-01-01

Mitochondria play a key role in ageing. The pursuit of genes that regulate variation in life span and ageing have shown that several nuclear-encoded mitochondrial genes are important. However, the role of mitochondrial encoded genes (mtDNA) is more controversial and our appreciation of the role of mtDNA for the evolution of life span is limited. We use replicated lines of seed beetles that have been artificially selected for long or short life for >190 generations, now showing dramatic phenotypic differences, to test for a possible role of mtDNA in the divergent evolution of ageing and life span. We show that these divergent selection regimes led to the evolution of significantly different mtDNA haplotype frequencies. Selection for a long life and late reproduction generated positive selection for one specific haplotype, which was fixed in most such lines. In contrast, selection for reproduction early in life led to both positive selection as well as negative frequency-dependent selection on two different haplotypes, which were both present in all such lines. Our findings suggest that the evolution of life span was in part mediated by mtDNA, providing support for the emerging general tenet that adaptive evolution of life-history syndromes may involve mtDNA. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Characterization of Zebrafish Abcc4 as an Efflux Transporter of Organochlorine Pesticides

PubMed Central

Lu, Xing; Long, Yong; Lin, Li; Sun, Rongze; Zhong, Shan; Cui, Zongbin

2014-01-01

DDT and lindane are highly toxic organochlorine pesticides and posing adverse effects on the environment and public health due to their frequent usage in developing countries. ABCC4/MRP4 is an organic anion transporter that mediates cellular efflux of a wide range of exogenous and endogenous compounds such as cyclic nucleotides and anti-cancer drugs; however, it remains unclear whether ABCC4 and its orthologs function in the detoxification of organochlorine pesticides. Here, we demonstrated the roles of zebrafish Abcc4 in cellular efflux of DDT and lindane. Zebrafish abcc4 was maternally expressed in the oocytes and its transcripts were detected in the lens, pancreas, gills, liver, intestine and bladder of developing embryos and in adult tissues examined. DDT and lindane were able to induce the expression of abcc4 gene and overexpression of Abcc4 significantly decreased the cytotoxicity and accumulation of DDT and lindane in LLC-PK1 cells and developing embryos. In contrast, overexpression of an Abcc4-G1188D mutant abolished its transporter function without effects on its substrate binding activity, and sensitized LLC-PK1 cells and developing embryos to toxic pesticides. Moreover, glutathione (GSH) was involved in the efflux of cellular pesticides and ATPase activity in developing embryos can be induced by DDT or lindane. Thus, zebrafish Abcc4 plays crucial roles in cellular efflux of organochlorine pesticides and can be used a potential molecular marker for the monitor of DDT and lindane contamination in the aquatic environment. PMID:25478949

Getting together: Social contact frequency across the life span.

PubMed

Sander, Julia; Schupp, Jürgen; Richter, David

2017-08-01

Frequent social interactions are strongly linked to positive affect, longevity, and good health. Although there has been extensive research on changes in the size of social networks over time, little attention has been given to the development of contact frequency across the life span. In this cohort-sequential longitudinal study, we examined intraindividual changes in the frequency of social contact with family and nonfamily members, and potential moderators of these changes. The data come from the 1998, 2003, 2008, and 2013 waves of the German Socio-Economic Panel (SOEP) study (N = 36,716; age range: 17-85 years). Using latent growth curve analysis, we found that the frequency of in-person contact with family members remained relatively stable across the life span. In contrast, the frequency of visits to and from nonfamily members (neighbors, friends, and acquaintances) declined following a cubic trajectory and dropped below the frequency of family visits when respondents were in their mid-30s. Relationship status and gender had a slight effect on both of these relationship trajectories. Subjective current health status and employment status influenced the life span trajectory of nonfamily social contact only. Changes of residence and the birth of a child, both of which constitute major turning points in the life course, did not affect the life span trajectory of either family or nonfamily in-person contact. The findings are discussed here in the context of earlier findings and in relation to socioemotional selectivity and social convoy theory and the evolutionary life history approach. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Heterozygous ABCC8 mutations are a cause of MODY.

PubMed

Bowman, P; Flanagan, S E; Edghill, E L; Damhuis, A; Shepherd, M H; Paisey, R; Hattersley, A T; Ellard, S

2012-01-01

The ABCC8 gene encodes the sulfonylurea receptor 1 (SUR1) subunit of the pancreatic beta cell ATP-sensitive potassium (K(ATP)) channel. Inactivating mutations cause congenital hyperinsulinism (CHI) and activating mutations cause transient neonatal diabetes (TNDM) or permanent neonatal diabetes (PNDM) that can usually be treated with sulfonylureas. Sulfonylurea sensitivity is also a feature of HNF1A and HNF4A MODY, but patients referred for genetic testing with clinical features of these types of diabetes do not always have mutations in the HNF1A/4A genes. Our aim was to establish whether mutations in the ABCC8 gene cause MODY that is responsive to sulfonylurea therapy. We sequenced the ABCC8 gene in 85 patients with a BMI <30 kg/m², no family history of neonatal diabetes and who were deemed sensitive to sulfonylureas by the referring clinician or were sulfonylurea-treated. All had tested negative for mutations in the HNF1A and HNF4A genes. ABCC8 mutations were found in seven of the 85 (8%) probands. Four patients were heterozygous for previously reported mutations and four novel mutations, E100K, G214R, Q485R and N1245D, were identified. Only four probands fulfilled MODY criteria, with two diagnosed after 25 years and one patient, who had no family history of diabetes, as a result of a proven de novo mutation. ABCC8 mutations can cause MODY in patients whose clinical features are similar to those with HNF1A/4A MODY. Therefore, sequencing of ABCC8 in addition to the known MODY genes should be considered if such features are present, to facilitate optimal clinical management of these patients.

Life-span perspective of personality in dementia.

PubMed

Kolanowski, A M; Whall, A L

1996-01-01

To propose an alternative view of personality change in dementia by presenting existing evidence for the continuity of personality. As the population continues to age, dementing illnesses will account for a greater proportion of morbidity and mortality; the care of these people will have a significant effect on the health care system. Life-span perspective of personality continuity. SCOPE METHOD: Review of current literature on personality in dementia using Medline, 1980-1994; CINAHL, 1990-1994; and Psych Lit., 1980-1994. Although there are systematic shifts in personality with dementia, individuals tend to maintain their unique pattern of premorbid personality traits. The personalities of dementia patients seem to reflect adaptive patterns that served them in the past. Use of a life-span perspective can enhance individualized care for demented patients and advance theory development.

78. VIEW SHOWING PLACEMENT OF LIFE SPAN SHOE ON PIER ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

78. VIEW SHOWING PLACEMENT OF LIFE SPAN SHOE ON PIER 6, LOOKING NORTH, March 5, 1935 - Sacramento River Bridge, Spanning Sacramento River at California State Highway 275, Sacramento, Sacramento County, CA

The pharmacogenetics of body odor: as easy as ABCC?

PubMed

Brown, Sara

2013-07-01

ABCC11 genotype affects apocrine secretory cell function and determines individual body odor phenotype. Rodriguez et al. have applied genetic epidemiology using predetermined phenotype data to demonstrate an association between a single-nucleotide polymorphism (rs17822931) and the human behavior of deodorant application. Individuals with the ABCC11 genotype predicting a nonodorous phenotype report a significantly lower frequency of deodorant use.

Sensorimotor Synchronization across the Life Span

ERIC Educational Resources Information Center

Drewing, Knut; Aschersleben, Gisa; Li, Shu-Chen

2006-01-01

The present study investigates the contribution of general processing resources as well as other more specific factors to the life-span development of sensorimotor synchronization and its component processes. Within a synchronization tapping paradigm, a group of 286 participants, 6 to 88 years of age, were asked to synchronize finger taps with…

ABCC6 knockdown in HepG2 cells induces a senescent-like cell phenotype.

PubMed

Miglionico, Rocchina; Ostuni, Angela; Armentano, Maria Francesca; Milella, Luigi; Crescenzi, Elvira; Carmosino, Monica; Bisaccia, Faustino

2017-01-01

Pseudoxanthoma elasticum (PXE) is characterized by progressive ectopic mineralization of elastic fibers in dermal, ocular and vascular tissues. No effective treatment exists. It is caused by inactivating mutations in the gene encoding for the ATP-binding cassette, sub-family C member 6 transporter (ABCC6), which is mainly expressed in the liver. The ABCC6 substrate (s) and the PXE pathomechanism remain unknown. Recent studies have shown that overexpression of ABCC6 in HEK293 cells results in efflux of ATP, which is rapidly converted into nucleoside monophosphates and pyrophosphate (PPi). Since the latter inhibits mineralization, it was proposed that the absence of circulating PPi in PXE patients results in the characteristic ectopic mineralization. These studies also demonstrated that the presence of ABCC6 modifies cell secretory activity and suggested that ABCC6 can change the cell phenotype. Stable ABCC6 knockdown HepG2 clones were generated using small hairpin RNA (shRNA) technology. The intracellular glutathione and ROS levels were determined. Experiments using cell cycle analysis, real-time PCR and western blot were performed on genes involved in the senescence phenotype. To shed light on the physiological role of ABCC6, we focused on the phenotype of HepG2 cells that lack ABCC6 activity. Interestingly, we found that ABCC6 knockdown HepG2 cells show: 1) intracellular reductive stress; 2) cell cycle arrest in G1 phase; 3) upregulation of p21 Cip p53 independent; and 4) downregulation of lamin A/C. These findings show that the absence of ABCC6 profoundly changes the HepG2 phenotype, suggesting that the PXE syndrome is a complex metabolic disease that is not exclusively related to the absence of pyrophosphate in the bloodstream.

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

Targeted Ablation of the Abcc6 Gene Results in Ectopic Mineralization of Connective Tissues

PubMed Central

Klement, John F.; Matsuzaki, Yasushi; Jiang, Qiu-Jie; Terlizzi, Joseph; Choi, Hae Young; Fujimoto, Norihiro; Li, Kehua; Pulkkinen, Leena; Birk, David E.; Sundberg, John P.; Uitto, Jouni

2005-01-01

Pseudoxanthoma elasticum (PXE), characterized by connective tissue mineralization of the skin, eyes, and cardiovascular system, is caused by mutations in the ABCC6 gene. ABCC6 encodes multidrug resistance-associated protein 6 (MRP6), which is expressed primarily in the liver and kidneys. Mechanisms producing ectopic mineralization as a result of these mutations remain unclear. To elucidate this complex disease, a transgenic mouse was generated by targeted ablation of the mouse Abcc6 gene. Abcc6 null mice were negative for Mrp6 expression in the liver, and complete necropsies revealed profound mineralization of several tissues, including skin, arterial blood vessels, and retina, while heterozygous animals were indistinguishable from the wild-type mice. Particularly striking was the mineralization of vibrissae, as confirmed by von Kossa and alizarin red stains. Electron microscopy revealed mineralization affecting both elastic structures and collagen fibers. Mineralization of vibrissae was noted as early as 5 weeks of age and was progressive with age in Abcc6−/− mice but was not observed in Abcc6+/− or Abcc6+/+ mice up to 2 years of age. A total body computerized tomography scan of Abcc6−/− mice revealed mineralization in skin and subcutaneous tissue as well as in the kidneys. These data demonstrate aberrant mineralization of soft tissues in PXE-affected organs, and, consequently, these mice recapitulate features of this complex disease. PMID:16135817

Regulation of hepatic ABCC transporters by xenobiotics and in disease states

PubMed Central

Gu, Xinsheng; Manautou, Jose E.

2015-01-01

The subfamily of ABCC transporters consists of 13 members in mammals, including the multidrug resistance-associated proteins (MRPs), sulfonylurea receptors (SURs), and the cystic fibrosis transmembrane conductance regulator (CFTR). These proteins play roles in chemical detoxification, disposition, and normal cell physiology. ABCC transporters are expressed differentially in the liver and are regulated at the transcription and translation level. Their expression and function are also controlled by post-translational modification and membrane-trafficking events. These processes are tightly regulated. Information about alterations in the expression of hepatobiliary ABCC transporters could provide important insights into the pathogenesis of diseases and disposition of xenobiotics. In this review, we describe the regulation of hepatic ABCC transporters in humans and rodents by a variety of xenobiotics, under disease states and in genetically modified animal models deficient in transcription factors, transporters, and cell-signaling molecules. PMID:20233023

Paternal smoking habits affect the reproductive life span of daughters.

PubMed

Fukuda, Misao; Fukuda, Kiyomi; Shimizu, Takashi; Nobunaga, Miho; Andersen, Elisabeth Wreford; Byskov, Anne Grete; Andersen, Claus Yding

2011-06-30

The present study assessed whether the smoking habits of fathers around the time of conception affected the period in which daughters experienced menstrual cycles (i.e., the reproductive life span). The study revealed that the smoking habits of the farther shortened the daughters' reproductive life span compared with daughters whose fathers did not smoke. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The Rate of Source Memory Decline across the Adult Life Span

ERIC Educational Resources Information Center

Cansino, Selene; Estrada-Manilla, Cinthya; Hernandez-Ramos, Evelia; Martinez-Galindo, Joyce Graciela; Torres-Trejo, Frine; Gomez-Fernandez, Tania; Ayala-Hernandez, Mariana; Osorio, David; Cedillo-Tinoco, Melisa; Garces-Flores, Lissete; Gomez-Melgarejo, Sandra; Beltran-Palacios, Karla; Guadalupe Garcia-Lazaro, Haydee; Garcia-Gutierrez, Fabiola; Cadena-Arenas, Yadira; Fernandez-Apan, Luisa; Bartschi, Andrea; Resendiz-Vera, Julieta; Rodriguez-Ortiz, Maria Dolores

2013-01-01

Previous studies have suggested that the ability to remember contextual information related to specific episodic experiences declines with advancing age; however, the exact moment in the adult life span when this deficit begins is still controversial. Source memory for spatial information was tested in a life span sample of 1,500 adults between…

Sex differences in life span: Females homozygous for the X chromosome do not suffer the shorter life span predicted by the unguarded X hypothesis.

PubMed

Brengdahl, Martin; Kimber, Christopher M; Maguire-Baxter, Jack; Friberg, Urban

2018-03-01

Life span differs between the sexes in many species. Three hypotheses to explain this interesting pattern have been proposed, involving different drivers: sexual selection, asymmetrical inheritance of cytoplasmic genomes, and hemizygosity of the X(Z) chromosome (the unguarded X hypothesis). Of these, the unguarded X has received the least experimental attention. This hypothesis suggests that the heterogametic sex suffers a shortened life span because recessive deleterious alleles on its single X(Z) chromosome are expressed unconditionally. In Drosophila melanogaster, the X chromosome is unusually large (∼20% of the genome), providing a powerful model for evaluating theories involving the X. Here, we test the unguarded X hypothesis by forcing D. melanogaster females from a laboratory population to express recessive X-linked alleles to the same degree as males, using females exclusively made homozygous for the X chromosome. We find no evidence for reduced life span or egg-to-adult viability due to X homozygozity. In contrast, males and females homozygous for an autosome both suffer similar, significant reductions in those traits. The logic of the unguarded X hypothesis is indisputable, but our results suggest that the degree to which recessive deleterious X-linked alleles depress performance in the heterogametic sex appears too small to explain general sex differences in life span. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

Spatial abilities across the adult life span.

PubMed

Borella, Erika; Meneghetti, Chiara; Ronconi, Lucia; De Beni, Rossana

2014-02-01

The study investigates age-related effects across the adult life span on spatial abilities (testing subabilities based on a distinction between spatial visualization, mental rotation, and perspective taking) and spatial self-assessments. The sample consisted of 454 participants (223 women and 231 men) from 20 to 91 years of age. Results showed nonlinear age-related effects for spatial visualization and perspective taking but linear effects for mental rotation; few or no age-related effects were found for spatial self-assessments. Working memory accounted for only a small proportion of the variance in all spatial tasks and had no effect on spatial self-assessments. Overall, our findings suggest that the influence of age on spatial skills across the adult life span is considerable, but the effects of age change as a function of the spatial task considered, and the effect on spatial self-assessment is more marginal.

Arsenic tolerance in Arabidopsis is mediated by two ABCC-type phytochelatin transporters

PubMed Central

Song, Won-Yong; Park, Jiyoung; Mendoza-Cózatl, David G.; Suter-Grotemeyer, Marianne; Shim, Donghwan; Hörtensteiner, Stefan; Geisler, Markus; Weder, Barbara; Rea, Philip A.; Rentsch, Doris; Schroeder, Julian I.; Lee, Youngsook; Martinoia, Enrico

2010-01-01

Arsenic is an extremely toxic metalloid causing serious health problems. In Southeast Asia, aquifers providing drinking and agricultural water for tens of millions of people are contaminated with arsenic. To reduce nutritional arsenic intake through the consumption of contaminated plants, identification of the mechanisms for arsenic accumulation and detoxification in plants is a prerequisite. Phytochelatins (PCs) are glutathione-derived peptides that chelate heavy metals and metalloids such as arsenic, thereby functioning as the first step in their detoxification. Plant vacuoles act as final detoxification stores for heavy metals and arsenic. The essential PC–metal(loid) transporters that sequester toxic metal(loid)s in plant vacuoles have long been sought but remain unidentified in plants. Here we show that in the absence of two ABCC-type transporters, AtABCC1 and AtABCC2, Arabidopsis thaliana is extremely sensitive to arsenic and arsenic-based herbicides. Heterologous expression of these ABCC transporters in phytochelatin-producing Saccharomyces cerevisiae enhanced arsenic tolerance and accumulation. Furthermore, membrane vesicles isolated from these yeasts exhibited a pronounced arsenite [As(III)]–PC2 transport activity. Vacuoles isolated from atabcc1 atabcc2 double knockout plants exhibited a very low residual As(III)–PC2 transport activity, and interestingly, less PC was produced in mutant plants when exposed to arsenic. Overexpression of AtPCS1 and AtABCC1 resulted in plants exhibiting increased arsenic tolerance. Our findings demonstrate that AtABCC1 and AtABCC2 are the long-sought and major vacuolar PC transporters. Modulation of vacuolar PC transporters in other plants may allow engineering of plants suited either for phytoremediation or reduced accumulation of arsenic in edible organs. PMID:21078981

A CRTCal link between energy and life span.

PubMed

Brunet, Anne

2011-04-06

Cutting down calories prolongs life, but how this works remains largely unknown. A recent study in Nature (Mair et al., 2011) shows that life span extension triggered by the energy-sensing protein kinase AMPK is mediated by an evolutionarily conserved transcriptional circuit involving CRTC-1 and CREB. Copyright © 2011 Elsevier Inc. All rights reserved.

Sibling Communication Functions across the Life-Span.

ERIC Educational Resources Information Center

Myers, Scott A.; Smith, Ronda L.; Sonnier, Michelle F.

An investigation examined whether perceived use of sibling functional communication skills differed across the life-span. Participants were recruited through university students enrolled in an introductory communication course at a southern university. All students received extra credit for recruiting two participants. Potential participants were…

Herbal Supplement Extends Life Span Under Some Environmental Conditions and Boosts Stress Resistance

PubMed Central

Villeponteau, Bryant; Matsagas, Kennedy; Nobles, Amber C.; Rizza, Cristina; Horwitz, Marc; Benford, Gregory; Mockett, Robin J.

2015-01-01

Genetic studies indicate that aging is modulated by a great number of genetic pathways. We have used Drosophila longevity and stress assays to test a multipath intervention strategy. To carry out this strategy, we supplemented the flies with herbal extracts (SC100) that are predicted to modulate the expression of many genes involved in aging and stress resistance, such as mTOR, NOS, NF-KappaB, and VEGF. When flies were housed in large cages with SC100 added, daily mortality rates of both male and female flies were greatly diminished in mid to late life. Surprisingly, SC100 also stabilized midlife mortality rate increases so as to extend the maximum life span substantially beyond the limits previously reported for D. melanogaster. Under these conditions, SC100 also promoted robust resistance to partial starvation stress and to heat stress. Fertility was the same initially in both treated and control flies, but it became significantly higher in treated flies at older ages as the fertility of control flies declined. Mean and maximum life spans of flies in vials at the same test site were also extended by SC100, but the life spans were short in absolute terms. In contrast, at an independent test site where stress was minimized, the flies exhibited much longer mean life spans, but the survival curves became highly rectangular and the effects of SC100 on both mean and maximum life spans declined greatly or were abolished. The data indicate that SC100 is a novel herbal mix with striking effects on enhancing Drosophila stress resistance and life span in some environments, while minimizing mid to late life mortality rates. They also show that the environment and other factors can have transformative effects on both the length and distribution of survivorship, and on the ability of SC100 to extend the life span. PMID:25879540

Hyperinsulinemic hypoglycemia evolving to gestational diabetes and diabetes mellitus in a family carrying the inactivating ABCC8 E1506K mutation.

PubMed

Vieira, Teresa C; Bergamin, Carla S; Gurgel, Lucimary C; Moisés, Regina S

2010-11-01

Congenital hyperinsulinism of infancy (CHI) is the most common cause of hypoglycemia in newborns and infants. Several molecular mechanisms are involved in the development of CHI, but the most common genetic defects are inactivating mutations of the ABCC8 or KCNJ11 genes. The classical treatment for CHI has been pancreatectomy that eventually leads to diabetes. More recently, conservative treatment has been attempted in some cases, with encouraging results. Whether or not the patients with heterozygous ABCC8 mutations submitted to conservative treatment may spontaneously develop type 2 diabetes in the long run, is a controversial issue. Here, we report a family carrying the dominant heterozygous germ line E1506K mutation in ABCC8 associated with persistent hypoglycemia in the newborn period and diabetes in adulthood. The mutation occurred as a de novo germ line mutation in the mother of the index patient. Her hypoglycemic symptoms as a child occurred after the fourth year of life and were very mild, but she developed glucose metabolism impairment in adulthood. On the other hand, in her daughter, the clinical manifestations of the disease occurred in the neonatal period and were more severe, leading to episodes of tonic-clonic seizures that were well controlled with octreotide or diazoxide. Our data corroborate the hypothesis that the dominant E1506K ABCC8 mutation, responsible for CHI, predisposes to the development of glucose intolerance and diabetes later in life. © 2009 John Wiley & Sons A/S.

Studying the replicative life span of yeast cells.

PubMed

Sinclair, David A

2013-01-01

The budding yeast Saccharomyces cerevisiae is a useful model for elucidating the pathways that control life span and the influence of environmental factors, such as calorie restriction (CR). For 75 years, CR has been studied for its ability to delay diseases of aging in mammals, from cancer to cardiovascular disease (McCay et al., Nutr Rev 33:241-243, 1975). In many other species, reducing calorie intake extends life span, including unicellular organisms (Jiang et al., FASEB J 14:2135-2137, 2000; Lin et al., Science 289:2126-2128, 2000), invertebrates (Rogina and Helfand, Proc Natl Acad Sci U S A 101:15998-16003, 2004), and rodents (Martín-Montalvo et al., Oncogene 30:505-520, 2011). Here we describe how to calorically restrict yeast cells, the methods used to determine the replicative life span (RLS) of budding yeast cells, how to selectively kill daughter cells using the mother enrichment program (MEP), how to measure recombination frequency at the rDNA locus, how to isolate large quantities of old cells, and how to analyze the circular forms of DNA known as extrachromosomal rDNA circles (ERCs), a cause of aging in S. cerevisiae (Petes, Cell 19:765-774, 1980; Sinclair and Guarente, Cell 91:1033-1042, 1997; Defossez et al., Mol Cell 3:447-455, 1999).

Qualitative Exploration of Acculturation and Life-Span Issues of Elderly Asian Americans

ERIC Educational Resources Information Center

Lee, Jee Hyang; Heo, Nanseol; Lu, Junfei; Portman, Tarrell Awe Agahe

2013-01-01

Awareness of aging issues across diverse populations begins the journey toward counselors becoming culturally competent across client life spans. Understanding the life-span experiences of cultural groups is important for helping professionals. The purpose of this research was to gain insight into the qualitative experiences of Asian American…

Karanjin interferes with ABCB1, ABCC1, and ABCG2.

PubMed

Michaelis, Martin; Rothweiler, Florian; Nerreter, Thomas; Sharifi, Mohsen; Ghafourian, Taravat; Cinatl, Jindrich

2014-01-01

The prominent ATP-binding cassette (ABC) transporters ABCB1, ABCC1, and ABCG2 are involved in substance transport across physiological barriers and therefore in drug absorption, distribution, and elimination. They also mediate multi-drug resistance in cancer cells. Different flavonoids are known to interfere with different ABC transporters. Here, the effect of the furanoflavonol karanjin, a potential drug with antiglycaemic, gastroprotective, antifungal, and antibacterial effects, was investigated on ABCB1, ABCC1, and ABCG2-mediated drug transport in comparison to the flavonoids apigenin, genistein, and naringenin. Cells expressing the relevant transporters (ABCB1: UKF-NB-3(ABCB1), UKF-NB-3(r)VCR¹⁰; ABCC1: G62, PC-3(r)VCR²⁰; ABCG2: UKF-NB-3(ABCG2)) were used in combination with specific fluorescent and cytotoxic ABC transporter substrates and ABC transporter inhibitors to study ABC transporter function. Moreover, the effects of the investigated flavonoids were determined on the ABC transporter ATPase activities. Karanjin interfered with drug efflux mediated by ABCB1, ABCC1, and ABCG2 and enhanced the ATPase activity of all three transporters. Moreover, karanjin exerted more pronounced effects than the control flavonoids apigenin, genistein, and naringenin on all three transporters. Most notably, karanjin interfered with ABCB1 at low concentrations being about 1 µM. Taken together, these findings should be taken into account during further consideration of karanjin as a potential drug for different therapeutic indications. The effects on ABCB1, ABCC1, and ABCG2 may affect the pharmacokinetics of co-administered drugs.

Does Dietary Restriction Reduce Life Span in Male Fruit-feeding Butterflies?

PubMed Central

Molleman, Freerk; Ding, Jimin; Boggs, Carol L.; Carey, James R.; Arlet, Małgorzata E.

2009-01-01

Male life history and resource allocation is not frequently studied in aging and life span research. Here we verify that males of long-lived fruit-feeding butterfly species have reduced longevity on restricted diets (Beck 2007 Oecologia), in contrast to the common finding of longevity extension in dietary restriction experiments in Drosophila and some other organisms. Males of some of the most long-lived species of fruit-feeding butterflies were collected from Kibale Forest, Uganda, and kept on diets of either sugar or mashed banana. Seven out of eight species had non-significantly longer life spans on mashed banana diets. Data analysis using a time-varying Cox-model with species as covariate showed that males had reduced survival on the sugar diet during the first 35 days of captive life, but the effect was absent or reversed at more advanced ages. These results challenge the generality of dietary restriction as a way to extend life span in animals. We argue that such studies on males are promising tools for better understanding life history evolution and aging because males display a wider variety of tactics for obtaining reproductive success than females. PMID:19580860

Spatial Abilities across the Adult Life Span

ERIC Educational Resources Information Center

Borella, Erika; Meneghetti, Chiara; Ronconi, Lucia; De Beni, Rossana

2014-01-01

The study investigates age-related effects across the adult life span on spatial abilities (testing subabilities based on a distinction between spatial visualization, mental rotation, and perspective taking) and spatial self-assessments. The sample consisted of 454 participants (223 women and 231 men) from 20 to 91 years of age. Results showed…

Suppression of the ATP-binding cassette transporter ABCC4 impairs neuroblastoma tumour growth and sensitises to irinotecan in vivo.

PubMed

Murray, Jayne; Valli, Emanuele; Yu, Denise M T; Truong, Alan M; Gifford, Andrew J; Eden, Georgina L; Gamble, Laura D; Hanssen, Kimberley M; Flemming, Claudia L; Tan, Alvin; Tivnan, Amanda; Allan, Sophie; Saletta, Federica; Cheung, Leanna; Ruhle, Michelle; Schuetz, John D; Henderson, Michelle J; Byrne, Jennifer A; Norris, Murray D; Haber, Michelle; Fletcher, Jamie I

2017-09-01

The ATP-binding cassette transporter ABCC4 (multidrug resistance protein 4, MRP4) mRNA level is a strong predictor of poor clinical outcome in neuroblastoma which may relate to its export of endogenous signalling molecules and chemotherapeutic agents. We sought to determine whether ABCC4 contributes to development, growth and drug response in neuroblastoma in vivo. In neuroblastoma patients, high ABCC4 protein levels were associated with reduced overall survival. Inducible knockdown of ABCC4 strongly inhibited the growth of human neuroblastoma cells in vitro and impaired the growth of neuroblastoma xenografts. Loss of Abcc4 in the Th-MYCN transgenic neuroblastoma mouse model did not impact tumour formation; however, Abcc4-null neuroblastomas were strongly sensitised to the ABCC4 substrate drug irinotecan. Our findings demonstrate a role for ABCC4 in neuroblastoma cell proliferation and chemoresistance and provide rationale for a strategy where inhibition of ABCC4 should both attenuate the growth of neuroblastoma and sensitise tumours to ABCC4 chemotherapeutic substrates. Copyright © 2017 Elsevier Ltd. All rights reserved.

ω-6 Polyunsaturated fatty acids extend life span through the activation of autophagy

PubMed Central

O'Rourke, Eyleen J.; Kuballa, Petric; Xavier, Ramnik; Ruvkun, Gary

2013-01-01

Adaptation to nutrient scarcity depends on the activation of metabolic programs to efficiently use internal reserves of energy. Activation of these programs in abundant food regimens can extend life span. However, the common molecular and metabolic changes that promote adaptation to nutritional stress and extend life span are mostly unknown. Here we present a response to fasting, enrichment of ω-6 polyunsaturated fatty acids (PUFAs), which promotes starvation resistance and extends Caenorhabditis elegans life span. Upon fasting, C. elegans induces the expression of a lipase, which in turn leads to an enrichment of ω-6 PUFAs. Supplementing C. elegans culture media with these ω-6 PUFAs increases their resistance to starvation and extends their life span in conditions of food abundance. Supplementation of C. elegans or human epithelial cells with these ω-6 PUFAs activates autophagy, a cell recycling mechanism that promotes starvation survival and slows aging. Inactivation of C. elegans autophagy components reverses the increase in life span conferred by supplementing the C. elegans diet with these fasting-enriched ω-6 PUFAs. We propose that the salubrious effects of dietary supplementation with ω-3/6 PUFAs (fish oils) that have emerged from epidemiological studies in humans may be due to a similar activation of autophagic programs. PMID:23392608

Functional diversification of sea urchin ABCC1 (MRP1) by alternative splicing.

PubMed

Gökirmak, Tufan; Campanale, Joseph P; Reitzel, Adam M; Shipp, Lauren E; Moy, Gary W; Hamdoun, Amro

2016-06-01

The multidrug resistance protein (MRP) family encodes a diverse repertoire of ATP-binding cassette (ABC) transporters with multiple roles in development, disease, and homeostasis. Understanding MRP evolution is central to unraveling their roles in these diverse processes. Sea urchins occupy an important phylogenetic position for understanding the evolution of vertebrate proteins and have been an important invertebrate model system for study of ABC transporters. We used phylogenetic analyses to examine the evolution of MRP transporters and functional approaches to identify functional forms of sea urchin MRP1 (also known as SpABCC1). SpABCC1, the only MRP homolog in sea urchins, is co-orthologous to human MRP1, MRP3, and MRP6 (ABCC1, ABCC3, and ABCC6) transporters. However, efflux assays revealed that alternative splicing of exon 22, a region critical for substrate interactions, could diversify functions of sea urchin MRP1. Phylogenetic comparisons also indicate that while MRP1, MRP3, and MRP6 transporters potentially arose from a single transporter in basal deuterostomes, alternative splicing appears to have been the major mode of functional diversification in invertebrates, while duplication may have served a more important role in vertebrates. These results provide a deeper understanding of the evolutionary origins of MRP transporters and the potential mechanisms used to diversify their functions in different groups of animals. Copyright © 2016 the American Physiological Society.

Functional diversification of sea urchin ABCC1 (MRP1) by alternative splicing

PubMed Central

Gökirmak, Tufan; Campanale, Joseph P.; Reitzel, Adam M.; Shipp, Lauren E.; Moy, Gary W.

2016-01-01

The multidrug resistance protein (MRP) family encodes a diverse repertoire of ATP-binding cassette (ABC) transporters with multiple roles in development, disease, and homeostasis. Understanding MRP evolution is central to unraveling their roles in these diverse processes. Sea urchins occupy an important phylogenetic position for understanding the evolution of vertebrate proteins and have been an important invertebrate model system for study of ABC transporters. We used phylogenetic analyses to examine the evolution of MRP transporters and functional approaches to identify functional forms of sea urchin MRP1 (also known as SpABCC1). SpABCC1, the only MRP homolog in sea urchins, is co-orthologous to human MRP1, MRP3, and MRP6 (ABCC1, ABCC3, and ABCC6) transporters. However, efflux assays revealed that alternative splicing of exon 22, a region critical for substrate interactions, could diversify functions of sea urchin MRP1. Phylogenetic comparisons also indicate that while MRP1, MRP3, and MRP6 transporters potentially arose from a single transporter in basal deuterostomes, alternative splicing appears to have been the major mode of functional diversification in invertebrates, while duplication may have served a more important role in vertebrates. These results provide a deeper understanding of the evolutionary origins of MRP transporters and the potential mechanisms used to diversify their functions in different groups of animals. PMID:27053522

Life span effects of Hypericum perforatum extracts on Caenorhabditis elegans under heat stress.

PubMed

Kılıçgün, Hasan; Göksen, Gülden

2012-10-01

The beneficial effects of antioxidants in plants are mainly extrapolated from in vitro studies or short-term dietary supplementation studies. Due to cost and duration, relatively little is known about whether dietary antioxidants are beneficial in whole animals' life span or not. To address this question, under heat stress (35°C), Hypericum perforatum was extracted with petroleum ether and the nematodes Caenorhabditis elegans exposed to three different extract concentrations (1mg/mL, 0.1mg/mL, 0.01mg/mL) of H. perforatum. We report that Hypericum perforatum extracts did not increase life span and slow aging related increase in C. elegans. Moreover, one fraction (1mg/mL) increased declines of C. elegans life span and thermotolerance. Given this mounting evidence for life span role of H. perforatum in the presence of heat stress in vivo, the question whether H. perforatum acts as a prooxidant or an antioxidant in vivo under heat stress arises.

Life span effects of Hypericum perforatum extracts on Caenorhabditis elegans under heat stress

PubMed Central

Kılıçgün, Hasan; Göksen, Gülden

2012-01-01

Background: The beneficial effects of antioxidants in plants are mainly extrapolated from in vitro studies or short-term dietary supplementation studies. Due to cost and duration, relatively little is known about whether dietary antioxidants are beneficial in whole animals’ life span or not. Materials and Methods: To address this question, under heat stress (35°C), Hypericum perforatum was extracted with petroleum ether and the nematodes Caenorhabditis elegans exposed to three different extract concentrations (1mg/mL, 0.1mg/mL, 0.01mg/mL) of H. perforatum. Results: We report that Hypericum perforatum extracts did not increase life span and slow aging related increase in C. elegans. Moreover, one fraction (1mg/mL) increased declines of C. elegans life span and thermotolerance. Conclusion: Given this mounting evidence for life span role of H. perforatum in the presence of heat stress in vivo, the question whether H. perforatum acts as a prooxidant or an antioxidant in vivo under heat stress arises. PMID:24082638

Attitudes Toward Death Across the Life Span.

ERIC Educational Resources Information Center

Maiden, Robert; Walker, Gail

To understand the change and development of people's attitudes toward death over the life span, a 62-item attitude questionnaire on death and dying was administered to 90 adults. Participants included five females and five males in each of nine age categories: 18-20, 20-24, 25-29, 30-34, 35-39, 40-49, 50-59, 60-64, and 65 or older. Participants…

Life-span extension by a metacaspase in the yeast Saccharomyces cerevisiae.

PubMed

Hill, Sandra Malmgren; Hao, Xinxin; Liu, Beidong; Nyström, Thomas

2014-06-20

Single-cell species harbor ancestral structural homologs of caspase proteases, although the evolutionary benefit of such apoptosis-related proteins in unicellular organisms is unclear. Here, we found that the yeast metacaspase Mca1 is recruited to the insoluble protein deposit (IPOD) and juxtanuclear quality-control compartment (JUNQ) during aging and proteostatic stress. Elevating MCA1 expression counteracted accumulation of unfolded proteins and aggregates and extended life span in a heat shock protein Hsp104 disaggregase- and proteasome-dependent manner. Consistent with a role in protein quality control, genetic interaction analysis revealed that MCA1 buffers against deficiencies in the Hsp40 chaperone YDJ1 in a caspase cysteine-dependent manner. Life-span extension and aggregate management by Mca1 was only partly dependent on its conserved catalytic cysteine, which suggests that Mca1 harbors both caspase-dependent and independent functions related to life-span control. Copyright © 2014, American Association for the Advancement of Science.

Influence of resveratrol on oxidative stress resistance and life span in Caenorhabditis elegans.

PubMed

Chen, Wei; Rezaizadehnajafi, Leila; Wink, Michael

2013-05-01

Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a polyphenol from red wine, has been reported to be beneficial in cases of ageing-related cardiovascular and neurodegenerative diseases owing to its property to reduce oxidative stress. Previous studies on the longevity promoting effect of resveratrol have been partly inconclusive, therefore we set out to investigate whether resveratrol at least promoted longevity in Caenorhabditis elegans under acute oxidative stress conditions. C. elegans was cultured under standard conditions with or without resveratrol. After exposure to juglone-induced acute oxidative stress, the survival rate and hsp-16.2::GFP expression were measured. The influence of resveratrol on life span was recorded also under oxidative stress induced by high glucose concentrations in the growth medium. No extension of the normal life span of C. elegans was observed either in liquid or solid growth media containing different concentrations of resveratrol. However, resveratrol alleviated juglone-induced lethal oxidative stress, and significantly prolonged the life span of C. elegans under conditions of acute oxidative damage and oxidative stress caused by high concentrations of glucose. Resveratrol, as an antioxidant, ameliorated oxidative stress in vivo but did not extend the life span of C. elegans under normal conditions. However, resveratrol did extend life span under conditions of oxidative stress. © 2013 The Authors. JPP © 2013 Royal Pharmaceutical Society.

How long will my mouse live? Machine learning approaches for prediction of mouse life span.

PubMed

Swindell, William R; Harper, James M; Miller, Richard A

2008-09-01

Prediction of individual life span based on characteristics evaluated at middle-age represents a challenging objective for aging research. In this study, we used machine learning algorithms to construct models that predict life span in a stock of genetically heterogeneous mice. Life-span prediction accuracy of 22 algorithms was evaluated using a cross-validation approach, in which models were trained and tested with distinct subsets of data. Using a combination of body weight and T-cell subset measures evaluated before 2 years of age, we show that the life-span quartile to which an individual mouse belongs can be predicted with an accuracy of 35.3% (+/-0.10%). This result provides a new benchmark for the development of life-span-predictive models, but improvement can be expected through identification of new predictor variables and development of computational approaches. Future work in this direction can provide tools for aging research and will shed light on associations between phenotypic traits and longevity.

Friendship in childhood and adulthood: lessons across the life span.

PubMed

Sherman, A M; de Vries, B; Lansford, J E

2000-01-01

Friendship occupies an important place in the growing body of literature in child development and gerontological research. As such, it may be useful for researchers from both fields to consider what can be learned from work carried out in each tradition. Therefore, we present a selected review of topics in friendship research across the life span. Through discussion of the value of friendship, the development of friendship, challenges to friendship, the gendered nature of friendship, and the connection between friends and family, points of commonality and contrast are identified. We conclude by presenting possible avenues for future investigation for researchers interested in friendship at any point in the life span.

Mitochondrial Reactive Oxygen Species Trigger Hypoxia-Inducible Factor-Dependent Extension of the Replicative Life Span during Hypoxia▿

PubMed Central

Bell, Eric L.; Klimova, Tatyana A.; Eisenbart, James; Schumacker, Paul T.; Chandel, Navdeep S.

2007-01-01

Physiological hypoxia extends the replicative life span of human cells in culture. Here, we report that hypoxic extension of replicative life span is associated with an increase in mitochondrial reactive oxygen species (ROS) in primary human lung fibroblasts. The generation of mitochondrial ROS is necessary for hypoxic activation of the transcription factor hypoxia-inducible factor (HIF). The hypoxic extension of replicative life span is ablated by a dominant negative HIF. HIF is sufficient to induce telomerase reverse transcriptase mRNA and telomerase activity and to extend replicative life span. Furthermore, the down-regulation of the von Hippel-Lindau tumor suppressor protein by RNA interference increases HIF activity and extends replicative life span under normoxia. These findings provide genetic evidence that hypoxia utilizes mitochondrial ROS as signaling molecules to activate HIF-dependent extension of replicative life span. PMID:17562866

Causes and consequences of variation in conifer leaf life-span

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reich, P.B.; Koike, T.; Gower, S.T.

1995-07-01

Species with mutually supporting traits, such as high N{sub mass}, SLA, and A{sub mass}, and short leaf life-span, tend to inhabit either generally resource-rich environments or spatial and/or temporal microhabitats that are resource-rich in otherwise more limited habitats (e.g., {open_quotes}precipitation{close_quotes} ephemerals in warm deserts or spring ephemerals in the understory of temperate deciduous forests). In contrast, species with long leaf life-span often support foliage with low SLA, N{sub mass}, and A{sub mass}, and often grow in low-temperature limited, dry, and/or nutrient-poor environments. The contrast between evergreen and deciduous species, and the implications that emerge from such comparisons, can be consideredmore » a paradigm of modern ecological theory. However, based on the results of Reich et al. (1992) and Gower et al. (1993), coniferous species with foliage that persists for 9-10 years are likely to assimilate and allocate carbon and nutrients differently than other evergreen conifers that retain foliage for 2-3 years. Thus, attempts to contrast ecophysiological or ecosystem characteristics of evergreen versus deciduous life forms may be misleading, and pronounced differences among evergreen conifers may be ignored. Clearly, the deciduous-evergreen contrast, although useful in several ways, should be viewed from the broader perspective of a gradient in leaf life-span.« less

Yeast MRX deletions have short chronological life span and more triacylglycerols.

PubMed

Kanagavijayan, Dhanabalan; Rajasekharan, Ram; Srinivasan, Malathi

2016-02-01

Saccharomyces cerevisiae is an excellent model organism for lipid research. Here, we have used yeast haploid RAdiation Damage (RAD) deletion strains to study life span and lipid storage patterns. RAD genes are mainly involved in DNA repair mechanism and hence, their deletions have resulted in shorter life span. Viable RAD mutants were screened for non-polar lipid content, and some of the mutants showed significantly high amounts of triacylglycerol (TAG) and steryl ester, besides short chronological life span. Among these, RAD50, MRE11 and XRS2 form a complex, MRX that is involved in homologous recombination that showed an increase in the amount of TAG. Microarray data of single MRX deletions revealed that besides DNA damage signature genes, lipid metabolism genes are also differentially expressed. Lipid biosynthetic genes (LPP1, SLC1) were upregulated and lipid hydrolytic gene (TGL3) was downregulated. We observed that rad50Δ, mre11Δ, xrs2Δ and mrxΔ strains have high number of lipid droplets (LDs) with fragmented mitochondria. These mutants have a short chronological life span compared to wild type. Aged wild-type cells also accumulated TAG with LDs of ∼2.0 μm in diameter. These results suggest that TAG accumulation and big size LDs could be possible markers for premature or normal aging. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Emotional Egocentricity Bias Across the Life-Span.

PubMed

Riva, Federica; Triscoli, Chantal; Lamm, Claus; Carnaghi, Andrea; Silani, Giorgia

2016-01-01

In our daily lives, we often have to quickly estimate the emotions of our conspecifics in order to have successful social interactions. While this estimation process seems quite easy when we are ourselves in a neutral or equivalent emotional state, it has recently been shown that in case of incongruent emotional states between ourselves and the others, our judgments can be biased. This phenomenon, introduced to the literature with the term Emotional Egocentricity Bias (EEB), has been found to occur in young adults and, to a greater extent, in children. However, how the EEB changes across the life-span from adolescence to old age has been largely unexplored. In this study, we recruited 114 female participants subdivided in four cohorts (adolescents, young adults, middle-aged adults, older adults) to examine EEB age-related changes. Participants were administered with a recently developed paradigm which, by making use of visuo-tactile stimulation that elicits conflicting feelings in paired participants, allows the valid and reliable exploration of the EEB. Results highlighted a U-shape relation between age and EEB, revealing enhanced emotional egocentricity in adolescents and older adults compared to young and middle-aged adults. These results are in line with the neuroscientific literature which has recently shown that overcoming the EEB is associated with a greater activation of a portion of the parietal lobe, namely the right Supramarginal Gyrus (rSMG). This is an area that reaches full maturation by the end of adolescence and goes through an early decay. Thus, the age-related changes of the EEB could be possibly due to the life-span development of the rSMG. This study is the first one to show the quadratic relation between age and the EEB and set a milestone for further research exploring the neural correlates of the life-span development of the EEB. Future studies are needed in order to generalize these results to the male population and to explore gender

Structural covariance networks across the life span, from 6 to 94 years of age.

PubMed

DuPre, Elizabeth; Spreng, R Nathan

2017-10-01

Structural covariance examines covariation of gray matter morphology between brain regions and across individuals. Despite significant interest in the influence of age on structural covariance patterns, no study to date has provided a complete life span perspective-bridging childhood with early, middle, and late adulthood-on the development of structural covariance networks. Here, we investigate the life span trajectories of structural covariance in six canonical neurocognitive networks: default, dorsal attention, frontoparietal control, somatomotor, ventral attention, and visual. By combining data from five open-access data sources, we examine the structural covariance trajectories of these networks from 6 to 94 years of age in a sample of 1,580 participants. Using partial least squares, we show that structural covariance patterns across the life span exhibit two significant, age-dependent trends. The first trend is a stable pattern whose integrity declines over the life span. The second trend is an inverted-U that differentiates young adulthood from other age groups. Hub regions, including posterior cingulate cortex and anterior insula, appear particularly influential in the expression of this second age-dependent trend. Overall, our results suggest that structural covariance provides a reliable definition of neurocognitive networks across the life span and reveal both shared and network-specific trajectories.

Structural covariance networks across the life span, from 6 to 94 years of age

PubMed Central

DuPre, Elizabeth; Spreng, R. Nathan

2017-01-01

Structural covariance examines covariation of gray matter morphology between brain regions and across individuals. Despite significant interest in the influence of age on structural covariance patterns, no study to date has provided a complete life span perspective—bridging childhood with early, middle, and late adulthood—on the development of structural covariance networks. Here, we investigate the life span trajectories of structural covariance in six canonical neurocognitive networks: default, dorsal attention, frontoparietal control, somatomotor, ventral attention, and visual. By combining data from five open-access data sources, we examine the structural covariance trajectories of these networks from 6 to 94 years of age in a sample of 1,580 participants. Using partial least squares, we show that structural covariance patterns across the life span exhibit two significant, age-dependent trends. The first trend is a stable pattern whose integrity declines over the life span. The second trend is an inverted-U that differentiates young adulthood from other age groups. Hub regions, including posterior cingulate cortex and anterior insula, appear particularly influential in the expression of this second age-dependent trend. Overall, our results suggest that structural covariance provides a reliable definition of neurocognitive networks across the life span and reveal both shared and network-specific trajectories. PMID:29855624

Advanced Biomedical Computing Center (ABCC) | DSITP

Cancer.gov

The Advanced Biomedical Computing Center (ABCC), located in Frederick Maryland (MD), provides HPC resources for both NIH/NCI intramural scientists and the extramural biomedical research community. Its mission is to provide HPC support, to provide collaborative research, and to conduct in-house research in various areas of computational biology and biomedical research.

Explanatory style across the life span: evidence for stability over 52 years.

PubMed

Burns, M O; Seligman, M E

1989-03-01

Analyzed explanatory style across the life span. 30 Ss whose average age was 72 responded to questions about their current life and provided diaries or letters written in their youth, an average of 52 years earlier. A blind content analysis of explanatory style derived from these 2 sources revealed that explanatory style for negative events was stable throughout adult life (r = .54, p less than .002). In contrast, there appeared to be no stability of explanatory style for positive events between the same 2 time periods. These results suggest that explanatory style for negative events may persist across the life span and may constitute an enduring risk factor for depression, low achievement, and physical illness.

Holistic life-span health outcomes among elite intercollegiate student-athletes.

PubMed

Sorenson, Shawn C; Romano, Russell; Scholefield, Robin M; Martin, Brandon E; Gordon, James E; Azen, Stanley P; Schroeder, E Todd; Salem, George J

2014-01-01

Competitive sports are recognized as having unique health benefits and risks, and the effect of sports on life-span health among elite athletes has received increasing attention. However, supporting scientific data are sparse and do not represent modern athletes. To assess holistic life-span health and health-related quality-of-life (HRQL) among current and former National Collegiate Athletic Association student-athletes (SAs). Cross-sectional study. A large Division I university. Population-based sample of 496 university students and alumni (age 17-84 years), including SAs and an age-matched and sex-matched nonathlete (NA) control group. Participants completed anonymous, self-report questionnaires. We measured the Short-Form 12 (SF-12) physical and mental component HRQL scores and cumulative lifetime experience and relative risk of treatment for joint, cardiopulmonary, and psychosocial health concerns. Older alumni (age 43+ years) SAs reported greater joint health concerns than NAs (larger joint summary scores; P = .04; Cohen d = 0.69; probability of clinically important difference [pCID] = 77%; treatment odds ratio [OR] = 14.0, 95% confidence interval [CI] = 1.6, 126). Joint health for current and younger alumni SAs was similar to that for NAs. Older alumni reported greater cardiopulmonary health concerns than younger alumni (summary score P < .001; d = 1.05; pCID = 85%; OR = 5.8, 95% CI = 2.0, 16) and current students (P < .001; d = 2.25; pCID >99.5%; OR = 7.1, 95% CI = 3.3, 15), but the risk was similar for SAs and NAs. Current SAs demonstrated evidence of better psychosocial health (summary score P = .006; d = -0.52; pCID = 40%) and mental component HRQL (P = .008; d = 0.50; pCID = 48%) versus NAs but similar psychosocial treatment odds (OR = 0.87, 95% CI = 0.39, 1.9). Psychosocial health and mental component HRQL were similar between alumni SAs and NAs. No differences were observed between SAs and NAs in physical component HRQL. The SAs demonstrated

The Writing Process: Effects of Life-Span Development on Imaging.

ERIC Educational Resources Information Center

Shock, Diane Hahn

A qualitative study focused on incubation and illumination within the act of writing to determine if life-span development affects image production during these creative, cognitive acts. Sixteen subjects of both sexes from four age groups represented major developmental stages in the life cycle. The research design provided two 90-minute sessions…

From menarche to menopause: the fertile life span of celiac women.

PubMed

Santonicola, Antonella; Iovino, Paola; Cappello, Carmelina; Capone, Pietro; Andreozzi, Paolo; Ciacci, Carolina

2011-10-01

We evaluated menopause-associated disorders and fertile life span in women with celiac disease (CD) under untreated conditions and after long-term treatment with a gluten-free diet. The participants were 33 women with CD after menopause (untreated CD group), 25 celiac women consuming a gluten-free diet at least 10 years before menopause (treated CD group), and 45 healthy volunteers (control group). The Menopause Rating Scale questionnaire was used to gather information on menopause-associated disorders. The International Physical Activity Questionnaire was used to acquire information on physical activity. Untreated celiac women had a shorter duration of fertile life span than did the control women because of an older age of menarche and a younger age of menopause (P < 0.01). The scores for hot flushes, muscle/joint problems, and irritability were higher in untreated celiac women than in the control women (higher by 49.4%, 121.4%, and 58.6%, respectively; P < 0.05). In comparison with untreated CD, long-lasting treatment of CD was not associated with a significant difference in the duration of fertile life span, but was only associated with a significant reduction in muscle/joint problems (a reduction of 47.1%; P < 0.05). Late menarche and early menopause causes a shorter fertile period in untreated celiac women compared with control women. A gluten-free diet that started at least 10 years before menopause prolongs the fertile life span of celiac women. The perception of intensity of hot flushes and irritability is more severe in untreated celiac women than in controls. Low physical exercise and/or poorer quality of life frequently reported by untreated celiac women might be the cause of reduced discomfort tolerance, thus increasing the subjective perception of menopausal symptoms.

Multidrug Resistance Proteins (MRPs/ABCCs) in Cancer Chemotherapy and Genetic Diseases

PubMed Central

Chen, Zhe-Sheng; Tiwari, Amit K.

2011-01-01

The ATP-binding cassette (ABC) transporters are a superfamily of membrane proteins that are best known for their ability to transport a wide variety of exogenous and endogenous substances across membranes against a concentration gradient via ATP hydrolysis. There are seven subfamilies of human ABC transporters, one of the largest being the ‘C’ subfamily (gene symbol ABCC). Nine ABCC subfamily members, the so-called Multidrug Resistance Proteins (MRPs) 1-9, have been implicated in mediating multidrug resistance in tumor cells to varying degrees as the efflux extrude chemotherapeutic compounds (or their metabolites) from malignant cells. Some of the MRPs are also known to either influence drug disposition in normal tissues or modulate the elimination of drugs (or their metabolites) via hepatobiliary or renal excretory pathways. In addition, the cellular efflux of physiologically important organic anions such as leukotriene C4 and cAMP is mediated by one or more of the MRPs. Finally, mutations in several MRPs are associated with human genetic disorders. In this review article, the current biochemical and physiological knowledge of MRP1-MRP9 in cancer chemotherapy and human genetic disease is summarized. The mutations in MRP2/ABCC2 leading to conjugated hyperbilirubinemia (Dubin-Johnson syndrome) and in MRP6/ABCC6 leading to the connective tissue disorder Pseudoxanthoma elasticum are also discussed. PMID:21740521

Life-span development of self-esteem and its effects on important life outcomes.

PubMed

Orth, Ulrich; Robins, Richard W; Widaman, Keith F

2012-06-01

We examined the life-span development of self-esteem and tested whether self-esteem influences the development of important life outcomes, including relationship satisfaction, job satisfaction, occupational status, salary, positive and negative affect, depression, and physical health. Data came from the Longitudinal Study of Generations. Analyses were based on 5 assessments across a 12-year period of a sample of 1,824 individuals ages 16 to 97 years. First, growth curve analyses indicated that self-esteem increases from adolescence to middle adulthood, reaches a peak at about age 50 years, and then decreases in old age. Second, cross-lagged regression analyses indicated that self-esteem is best modeled as a cause rather than a consequence of life outcomes. Third, growth curve analyses, with self-esteem as a time-varying covariate, suggested that self-esteem has medium-sized effects on life-span trajectories of affect and depression, small to medium-sized effects on trajectories of relationship and job satisfaction, a very small effect on the trajectory of health, and no effect on the trajectory of occupational status. These findings replicated across 4 generations of participants--children, parents, grandparents, and their great-grandparents. Together, the results suggest that self-esteem has a significant prospective impact on real-world life experiences and that high and low self-esteem are not mere epiphenomena of success and failure in important life domains. 2012 APA, all rights reserved

ABCC3 as a marker for multidrug resistance in non-small cell lung cancer

PubMed Central

Zhao, Yanbin; Lu, Hailing; Yan, An; Yang, Yanmei; Meng, Qingwei; Sun, Lichun; Pang, Hui; Li, Chunhong; Dong, Xiaoqun; Cai, Li

2013-01-01

Multidrug resistance (MDR) contributes to the failure of chemotherapy and high mortality in non-small cell lung cancer (NSCLC). We aim to identify MDR genes that predict tumor response to chemotherapy. 199 NSCLC fresh tissue samples were tested for chemosensitivity by MTT assay. cDNA microarray was done with 5 samples with highest resistance and 6 samples with highest sensitivity. Expression of ABCC3 mRNA and protein was detected by real-time PCR and immunohistochemisty, respectively. The association between gene expression and overall survival (OS) was examined using Cox proportional hazard regression. 44 genes were upregulated and 168 downregulated in the chemotherapy-resistant group. ABCC3 was one of the most up-regulated genes in the resistant group. ABCC3-positive expression correlated with lymph node involvement, advanced TNM stage, more malignant histological type, multiple-resistance to anti-cancer drugs, and reduced OS. ABCC3 expression may serve as a marker for MDR and predictor for poor clinical outcome of NSCLC. PMID:24176985

A Holistic Model for Wellness and Prevention over the Life Span.

ERIC Educational Resources Information Center

Witmer, J. Melvin; Sweeney, Thomas J.

1992-01-01

Presents integrated paradigm for wellness and prevention over the life span for purpose of theory building, research, clinical application, education, advocacy, and consciousness raising. Model described includes 11 characteristics desirable for optimal health and functioning. Notes characteristics are expressed through five life tasks of…

The Social Context of Managing Diabetes across the Life Span

PubMed Central

Wiebe, Deborah J.; Helgeson, Vicki; Berg, Cynthia A.

2016-01-01

Diabetes self-management is crucial to maintaining quality of life and preventing long-term complications, and occurs daily in the context of close interpersonal relationships. This article examines how social relationships are central to meeting the complex demands of managing type 1 and type 2 diabetes across the life span. The social context of diabetes management includes multiple resources, including family (parents, spouses), peers, romantic partners, and health care providers. We discuss how these social resources change across the life span, focusing on childhood and adolescence, emerging adulthood, and adulthood and aging. We review how diabetes both affects and is affected by key social relationships at each developmental period. Despite high variability in how the social context is conceptualized and measured across studies, findings converge on the characteristics of social relationships that facilitate or undermine diabetes management across the life span. These characteristics are consistent with both Interpersonal Theory and Self-Determination Theory, two organizing frameworks that we utilize to explore social behaviors that are related to diabetes management. Involvement and support from one’s social partners, particularly family members, is consistently associated with good diabetes outcomes when characterized by warmth, collaboration and acceptance. Under-involvement and interactions characterized by conflict and criticism are consistently associated with poor diabetes outcomes. Intrusive involvement that contains elements of social control may undermine diabetes management, particularly when it impinges on self-efficacy. Implications for future research directions and for interventions that promote the effective use of the social context to improve diabetes self-management are discussed. PMID:27690482

Experimental evolution reveals antagonistic pleiotropy in reproductive timing but not life span in Caenorhabditis elegans.

PubMed

Anderson, Jennifer L; Reynolds, Rose M; Morran, Levi T; Tolman-Thompson, Julie; Phillips, Patrick C

2011-12-01

Many mutations that dramatically extend life span in model organisms come with substantial fitness costs. Although these genetic manipulations provide valuable insight into molecular modulators of life span, it is currently unclear whether life-span extension is unavoidably linked to fitness costs. To examine this relationship, we evolved a genetically heterogeneous population of Caenorhabditis elegans for 47 generations, selecting for early fecundity. We asked whether an increase in early fecundity would necessitate a decrease in longevity or late fecundity (antagonistic pleiotropy). Caenorhabditis elegans experimentally evolved for increased early reproduction and decreased late reproduction but suffered no total fitness or life-span costs. Given that antagonistic pleiotropy among these traits has been previously demonstrated in some cases, we conclude that the genetic constraint is not absolute, that is, it is possible to uncouple longevity from early fecundity using genetic variation segregating within and among natural populations.

Virtual screening of ABCC1 transporter nucleotidebinding domains as a therapeutic target in multidrug resistant cancer

PubMed Central

Rungsardthong, Kanin; Mares- Sámano, Sergio; Penny, Jeffrey

2012-01-01

ABCC1 is a member of the ATP-binding Cassette super family of transporters, actively effluxes xenobiotics from cells. Clinically, ABCC1 expression is linked to cancer multidrug resistance. Substrate efflux is energised by ATP binding and hydrolysis at the nucleotide-binding domains (NBDs) and inhibition of these events may help combat drug resistance. The aim of this study is to identify potential inhibitors of ABCC1 through virtual screening of National Cancer Institute (NCI) compounds. A threedimensional model of ABCC1 NBD2 was generated using MODELLER whilst the X-ray crystal structure of ABCC1 NBD1 was retrieved from the Protein Data Bank. A pharmacophore hypothesis was generated based on flavonoids known to bind at the NBDs using PHASE, and used to screen the NCI database. GLIDE was employed in molecular docking studies for all hit compounds identified by pharmacophore screening. The best potential inhibitors were identified as compounds possessing predicted binding affinities greater than ATP. Approximately 5% (13/265) of the hit compounds possessed lower docking scores than ATP in ABCC1 NBD1 (NSC93033, NSC662377, NSC319661, NSC333748, NSC683893, NSC226639, NSC94231, NSC55979, NSC169121, NSC166574, NSC73380, NSC127738, NSC115534), whereas approximately 7% (7/104) of docked NCI compounds were predicted to possess lower docking scores than ATP in ABCC1 NBD2 (NSC91789, NSC529483, NSC211168, NSC318214, NSC116519, NSC372332, NSC526974). Analyses of docking orientations revealed P-loop residues of each NBD and the aromatic amino acids Trp653 (NBD1) and Tyr1302 (NBD2) were key in interacting with high-affinity compounds. On the basis of docked orientation and docking score the compounds identified may be potential inhibitors of ABCC1 and require further pharmacological analysis. Abbreviations ABC - ATP-binding cassette, DHS - dehydrosilybin, MDR - multidrug resistance, NBD - nucleotide-binding domain, PDB - protein data bank. PMID:23144549

Holistic Life-Span Health Outcomes Among Elite Intercollegiate Student–Athletes

PubMed Central

Sorenson, Shawn C.; Romano, Russell; Scholefield, Robin M.; Martin, Brandon E.; Gordon, James E.; Azen, Stanley P.; Schroeder, E. Todd; Salem, George J.

2014-01-01

Context: Competitive sports are recognized as having unique health benefits and risks, and the effect of sports on life-span health among elite athletes has received increasing attention. However, supporting scientific data are sparse and do not represent modern athletes. Objective: To assess holistic life-span health and health-related quality-of-life (HRQL) among current and former National Collegiate Athletic Association student–athletes (SAs). Design: Cross-sectional study. Setting: A large Division I university. Patients or Other Participants: Population-based sample of 496 university students and alumni (age 17–84 years), including SAs and an age-matched and sex-matched nonathlete (NA) control group. Main Outcome Measure(s): Participants completed anonymous, self-report questionnaires. We measured the Short-Form 12 (SF-12) physical and mental component HRQL scores and cumulative lifetime experience and relative risk of treatment for joint, cardiopulmonary, and psychosocial health concerns. Results: Older alumni (age 43+ years) SAs reported greater joint health concerns than NAs (larger joint summary scores; P = .04; Cohen d = 0.69; probability of clinically important difference [pCID] = 77%; treatment odds ratio [OR] = 14.0, 95% confidence interval [CI] = 1.6, 126). Joint health for current and younger alumni SAs was similar to that for NAs. Older alumni reported greater cardiopulmonary health concerns than younger alumni (summary score P < .001; d = 1.05; pCID = 85%; OR = 5.8, 95% CI = 2.0, 16) and current students (P < .001; d = 2.25; pCID >99.5%; OR = 7.1, 95% CI = 3.3, 15), but the risk was similar for SAs and NAs. Current SAs demonstrated evidence of better psychosocial health (summary score P = .006; d = −0.52; pCID = 40%) and mental component HRQL (P = .008; d = 0.50; pCID = 48%) versus NAs but similar psychosocial treatment odds (OR = 0.87, 95% CI = 0.39, 1.9). Psychosocial health and mental component HRQL were similar between alumni SAs and NAs

Health span approximates life span among many supercentenarians: compression of morbidity at the approximate limit of life span.

PubMed

Andersen, Stacy L; Sebastiani, Paola; Dworkis, Daniel A; Feldman, Lori; Perls, Thomas T

2012-04-01

We analyze the relationship between age of survival, morbidity, and disability among centenarians (age 100-104 years), semisupercentenarians (age 105-109 years), and supercentenarians (age 110-119 years). One hundred and four supercentenarians, 430 semisupercentenarians, 884 centenarians, 343 nonagenarians, and 436 controls were prospectively followed for an average of 3 years (range 0-13 years). The older the age group, generally, the later the onset of diseases, such as cancer, cardiovascular disease, dementia, and stroke, as well as of cognitive and functional decline. The hazard ratios for these individual diseases became progressively less with older and older age, and the relative period of time spent with disease was lower with increasing age group. We observed a progressive delay in the age of onset of physical and cognitive function impairment, age-related diseases, and overall morbidity with increasing age. As the limit of human life span was effectively approached with supercentenarians, compression of morbidity was generally observed.

Health Span Approximates Life Span Among Many Supercentenarians: Compression of Morbidity at the Approximate Limit of Life Span

PubMed Central

Andersen, Stacy L.; Sebastiani, Paola; Dworkis, Daniel A.; Feldman, Lori

2012-01-01

We analyze the relationship between age of survival, morbidity, and disability among centenarians (age 100–104 years), semisupercentenarians (age 105–109 years), and supercentenarians (age 110–119 years). One hundred and four supercentenarians, 430 semisupercentenarians, 884 centenarians, 343 nonagenarians, and 436 controls were prospectively followed for an average of 3 years (range 0–13 years). The older the age group, generally, the later the onset of diseases, such as cancer, cardiovascular disease, dementia, and stroke, as well as of cognitive and functional decline. The hazard ratios for these individual diseases became progressively less with older and older age, and the relative period of time spent with disease was lower with increasing age group. We observed a progressive delay in the age of onset of physical and cognitive function impairment, age-related diseases, and overall morbidity with increasing age. As the limit of human life span was effectively approached with supercentenarians, compression of morbidity was generally observed. PMID:22219514

Women's Spirituality across the Life Span: Implications for Counseling

ERIC Educational Resources Information Center

Briggs, Michele Kielty; Dixon, Andrea L.

2013-01-01

Women's spirituality has unique characteristics that are often ignored within the spirituality literature. The authors review the literature on women's spirituality to reveal the major themes women have identified as relevant to their spiritual journeys across the life span. Implications for counseling and ideas for practice are included after…

ABCC6 does not transport vitamin K3-glutathione conjugate from the liver: relevance to pathomechanisms of pseudoxanthoma elasticum.

PubMed

Fülöp, Krisztina; Jiang, Qiujie; Wetering, Koen V D; Pomozi, Viola; Szabó, Pál T; Arányi, Tamás; Sarkadi, Balázs; Borst, Piet; Uitto, Jouni; Váradi, András

2011-11-25

Vitamin K is a cofactor required for gamma-glutamyl carboxylation of several proteins regulating blood clotting, bone formation and soft tissue mineralization. Vitamin K3 is an important intermediate during conversion of the dietary vitamin K1 to the most abundant vitamin K2 form. It has been suggested that ABCC6 may have a role in transporting vitamin K or its derivatives from the liver to the periphery. This activity is missing in pseudoxanthoma elasticum, a genetic disorder caused by mutations in ABCC6 characterized by abnormal soft tissue mineralization. Here we examined the efflux of the glutathione conjugate of vitamin K3 (VK3GS) from the liver in wild type and Abcc6(-/-) mice, and in transport assays in vitro. We found in liver perfusion experiments that VK3GS is secreted into the inferior vena cava, but we observed no significant difference between wild type and Abcc6(-/-) animals. We overexpressed the human ABCC6 transporter in Sf9 insect and MDCKII cells and assayed its vitamin K3-conjugate transport activity in vitro. We found no measurable transport of VK3GS by ABCC6, whereas ABCC1 transported this compound at high rate in these assays. These results show that VK3GS is not the essential metabolite transported by ABCC6 from the liver and preventing the symptoms of pseudoxanthoma elasticum. Copyright © 2011 Elsevier Inc. All rights reserved.

Increasing cell culture population doublings for long-term growth of finite life span human cell cultures

DOEpatents

Stampfer, Martha R.; Garbe, James C.

2016-06-28

Cell culture media formulations for culturing human epithelial cells are herein described. Also described are methods of increasing population doublings in a cell culture of finite life span human epithelial cells and prolonging the life span of human cell cultures. Using the cell culture media disclosed alone and in combination with addition to the cell culture of a compound associated with anti-stress activity achieves extended growth of pre-stasis cells and increased population doublings and life span in human epithelial cell cultures.

Increasing cell culture population doublings for long-term growth of finite life span human cell cultures

DOEpatents

Stampfer, Martha R; Garbe, James C

2015-02-24

Cell culture media formulations for culturing human epithelial cells are herein described. Also described are methods of increasing population doublings in a cell culture of finite life span human epithelial cells and prolonging the life span of human cell cultures. Using the cell culture media disclosed alone and in combination with addition to the cell culture of a compound associated with anti-stress activity achieves extended growth of pre-stasis cells and increased population doublings and life span in human epithelial cell cultures.

Mice Producing Reduced Levels of Insulin-Like Growth Factor Type 1 Display an Increase in Maximum, but not Mean, Life Span

PubMed Central

2014-01-01

Reduced signaling through the IGF type 1 (IGF-1) receptor increases life span in multiple invertebrate organisms. Studies on mammalian longevity suggest that reducing levels of IGF-1 may also increase life span. However, the data are conflicting and complicated by the physiology of the mammalian neuroendocrine system. We have performed life-span analysis on mice homozygous for an insertion in the Igf1 gene. These mice produce reduced levels of IGF-1 and display a phenotype consistent with a significant decrease in IGF-1. Life-span analysis was carried out at three independent locations. Although the life-span data varied between sites, the maximum life span of the IGF-1-deficient mice was significantly increased and age-specific mortality rates were reduced in the IGF-1-deficient mice; however, mean life span did not differ except at one site, where mean life span was increased in female IGF-1-deficient animals. Early life mortality was noted in one cohort of IGF-1-deficient mice. The results are consistent with a significant role for IGF-1 in the modulation of life span but contrast with the published life-span data for the hypopituitary Ames and Snell dwarf mice and growth hormone receptor null mice, indicating that a reduction in IGF-1 alone is insufficient to increase both mean and maximal life span in mice. PMID:23873963

Effect of habitat preference on frond life span in three Cyathea tree ferns

NASA Astrophysics Data System (ADS)

Chiu, Tzu Yun; Wang, Hsiang Hua; Lun Kuo, Yao; Kume, Tomonori

2013-04-01

It has been reported that plants living in various geographical areas had different physiological forms, as factors of microenvironment have strong impacts on physiological characters. However, the physiological characters of fronds have been scarcely reported in ferns. In this study, we investigated physiological differences in response to the habitat preference in the three tree ferns in northeast Taiwan, Cyathea lepifera, C. spinulosa, and C. podophylla, prefer to open site, edge of forest, and interior forest, respectively. The canopy openness above the individuals of C. lepifera, C. spinulosa and C. podophylla were 29.2 ± 14.10 , 7.0 ± 3.07 and 5.0 ± 2.24 %, respectively. Among three species, C. podophylla had the longest frond life span (13.0 ± 4.12 months) than the two others (C. lepifera (6.8 ± 1.29 months) and C. spinulosa (7.3 ±1.35 months). Our result supported the general patterns that shade intolerant species have a shorter leaf life span than shade tolerant species. The maximum net CO2 assimilation of C. lepifera, C. spinulosa and C. podophylla were 11.46 ± 1.34, 8.27 ± 0.69, and 6.34 ± 0.54 μmol CO2 m-2 s-1, respectively. As well, C. lepifera had the highest photosynthetic light saturation point (LSP), while C. podophylla had the lowest LSP among these three tree ferns. These suggested that C. lepifera could be more efficient for capturing and utilizing light resources under the larger canopy openness condition than the other two species. We also found that frond C : N ratio were positively correlated with frond life span among species. C. podophylla, with the longest frond life span, had the highest frond C : N ratio (22.17 ± 1.95), which was followed by C. spinulosa (18.58 ± 1.37) and C. lepifera (18.68 ± 2.63) with shorter frond life span. The results were consistent to the theory that the fronds and leaves of shade intolerant species have high photosynthetic abilities with low C : N ratio. Key words: Canopy openness, frond life span

Genetic heterogeneity of pseudoxanthoma elasticum: the Chinese signature profile of ABCC6 and ENPP1 mutations.

PubMed

Jin, Liang; Jiang, Qiujie; Wu, Zhengsheng; Shao, Changxia; Zhou, Yong; Yang, Luting; Uitto, Jouni; Wang, Gang

2015-05-01

Pseudoxanthoma elasticum (PXE), an autosomal recessive disorder characterized by ectopic mineralization, is caused by mutations in the ABCC6 gene. We examined clinically 29 Chinese PXE patients from unrelated families, so far the largest cohort of Asian PXE patients. In a subset of 22 patients, we sequenced ABCC6 and another candidate gene, ENPP1, and conducted pathogenicity analyses for each variant. We identified a total of 17 distinct mutations in ABCC6, 15 of them being, to our knowledge, previously unreported, including 5 frameshift and 10 missense variants. In addition, a missense mutation in combination with a recurrent nonsense mutation in ENPP1 was discovered in a pediatric PXE case. No cases with p.R1141X or del23-29 mutations, common in Caucasian patient populations, were identified. The 10 missense mutations in ABCC6 were expressed in the mouse liver via hydrodynamic tail-vein injections. One mutant protein showed cytoplasmic accumulation indicating abnormal subcellular trafficking, while the other nine mutants showed correct plasma membrane location. These nine mutations were further investigated for their pathogenicity using a recently developed zebrafish mRNA rescue assay. Minimal rescue of the morpholino-induced phenotype was achieved with eight of the nine mutant human ABCC6 mRNAs tested, implying pathogenicity. This study demonstrates that the Chinese PXE population harbors unique ABCC6 mutations. These genetic data have implications for allele-specific therapy currently being developed for PXE.

Regionally clustered ABCC8 polymorphisms in a prospective cohort predict cerebral oedema and outcome in severe traumatic brain injury.

PubMed

Jha, Ruchira Menka; Koleck, Theresa A; Puccio, Ava M; Okonkwo, David O; Park, Seo-Young; Zusman, Benjamin E; Clark, Robert S B; Shutter, Lori A; Wallisch, Jessica S; Empey, Philip E; Kochanek, Patrick M; Conley, Yvette P

2018-04-19

ABCC8 encodes sulfonylurea receptor 1, a key regulatory protein of cerebral oedema in many neurological disorders including traumatic brain injury (TBI). Sulfonylurea-receptor-1 inhibition has been promising in ameliorating cerebral oedema in clinical trials. We evaluated whether ABCC8 tag single-nucleotide polymorphisms predicted oedema and outcome in TBI. DNA was extracted from 485 prospectively enrolled patients with severe TBI. 410 were analysed after quality control. ABCC8 tag single-nucleotide polymorphisms (SNPs) were identified (Hapmap, r 2 >0.8, minor-allele frequency >0.20) and sequenced (iPlex-Gold, MassArray). Outcomes included radiographic oedema, intracranial pressure (ICP) and 3-month Glasgow Outcome Scale (GOS) score. Proxy SNPs, spatial modelling, amino acid topology and functional predictions were determined using established software programs. Wild-type rs7105832 and rs2237982 alleles and genotypes were associated with lower average ICP (β=-2.91, p=0.001; β=-2.28, p=0.003) and decreased radiographic oedema (OR 0.42, p=0.012; OR 0.52, p=0.017). Wild-type rs2237982 also increased favourable 3-month GOS (OR 2.45, p=0.006); this was partially mediated by oedema (p=0.03). Different polymorphisms predicted 3-month outcome: variant rs11024286 increased (OR 1.84, p=0.006) and wild-type rs4148622 decreased (OR 0.40, p=0.01) the odds of favourable outcome. Significant tag and concordant proxy SNPs regionally span introns/exons 2-15 of the 39-exon gene. This study identifies four ABCC8 tag SNPs associated with cerebral oedema and/or outcome in TBI, tagging a region including 33 polymorphisms. In polymorphisms predictive of oedema, variant alleles/genotypes confer increased risk. Different variant polymorphisms were associated with favourable outcome, potentially suggesting distinct mechanisms. Significant polymorphisms spatially clustered flanking exons encoding the sulfonylurea receptor site and transmembrane domain 0/loop 0 (juxtaposing the channel pore

Getting Together: Social Contact Frequency across the Life Span

ERIC Educational Resources Information Center

Sander, Julia; Schupp, Jürgen; Richter, David

2017-01-01

Frequent social interactions are strongly linked to positive affect, longevity, and good health. Although there has been extensive research on changes in the size of social networks over time, little attention has been given to the development of contact frequency across the life span. In this cohort-sequential longitudinal study, we examined…

Characterization and analyses of multidrug resistance-associated protein 1 (MRP1/ABCC1) polymorphisms in Chinese population

PubMed Central

Yin, Ji-Ye; Huang, Qiong; Yang, Youyun; Zhang, Jian-Ting; Zhong, Mei-Zuo; Zhou, Hong-Hao; Liu, Zhao-Qian

2009-01-01

Multidrug resistance (MDR) is one of the major obstacles for successful cancer chemotherapy. Over-expression of ATP-binding cassette (ABC) transporters such as MRP1/ABCC1 has been suggested to cause MDR. In this study, we explored the distribution frequencies of four common single nucleotide polymorphisms (SNPs) of MRP1/ABCC1 in a mainland Chinese population and investigated whether these SNPs affect the expression and function of the MRP1/ABCC1. We found that the allelic frequencies of Cys43Ser (128G>C), Thr73Ile (218C>T), Arg723Gln (2168G>A) and Arg1058Gln (3173G>A) in mainland Chinese were 0.5%, 1.4%, 5.8% and 0.5%, respectively. These four SNPs were recreated by site-directed mutagenesis and tested for their effect on MRP1/ABCC1 expression and MDR function in HEK293 and CHO-K1 cells lines. We found that none of these mutations had any effect on MRP1/ABCC1 expression and trafficking, but that Arg723Gln mutation significantly reduced MRP1/ABCC1-mediated resistance to daunorubicin, doxorubicin, etoposide, vinblastine and vincristine. The Cys43Ser mutation did not affect all tested drugs resistance. On the other hand, the Thr73Ile mutation reduced resistance to methotrexate and etoposide while the Arg1058Gln mutation increased the response of two anthracycline drugs and etoposide in HEK293 and CHO-K1 cells as well as vinblastine and methotrexate in CHO-K1 cells. We conclude that the allelic frequency of the Arg723Gln mutation is relatively higher than other SNPs in mainland Chinese population and therefore this mutation significantly reduces MRP1/ABCC1 activity in MDR. PMID:19214144

Foraging across the life span: is there a reduction in exploration with aging?

PubMed Central

Mata, Rui; Wilke, Andreas; Czienskowski, Uwe

2013-01-01

Does foraging change across the life span, and in particular, with aging? We report data from two foraging tasks used to investigate age differences in search in external environments as well as internal search in memory. Overall, the evidence suggests that foraging behavior may undergo significant changes across the life span across internal and external search. In particular, we find evidence of a trend toward reduced exploration with increased age. We discuss these findings in light of theories that postulate a link between aging and reductions in novelty seeking and exploratory behavior. PMID:23616741

From Children to Adults: Motor Performance across the Life-Span

PubMed Central

Leversen, Jonas S. R.; Haga, Monika; Sigmundsson, Hermundur

2012-01-01

The life-span approach to development provides a theoretical framework to examine the general principles of life-long development. This study aims to investigate motor performance across the life span. It also aims to investigate if the correlations between motor tasks increase with aging. A cross-sectional design was used to describe the effects of aging on motor performance across age groups representing individuals from childhood to young adult to old age. Five different motor tasks were used to study changes in motor performance within 338 participants (7–79 yrs). Results showed that motor performance increases from childhood (7–9) to young adulthood (19–25) and decreases from young adulthood (19–25) to old age (66–80). These results are mirroring results from cognitive research. Correlation increased with increasing age between two fine motor tasks and two gross motor tasks. We suggest that the findings might be explained, in part, by the structural changes that have been reported to occur in the developing and aging brain and that the theory of Neural Darwinism can be used as a framework to explain why these changes occur. PMID:22719958

Neuromodulation of Behavioral and Cognitive Development across the Life Span

ERIC Educational Resources Information Center

Li, Shu-Chen

2012-01-01

Among other mechanisms, behavioral and cognitive development entail, on the one hand, contextual scaffolding and, on the other hand, neuromodulation of adaptive neurocognitive representations across the life span. Key brain networks underlying cognition, emotion, and motivation are innervated by major transmitter systems (e.g., the catecholamines…

Spectrum of genetic variation at the ABCC6 locus in South Africans: Pseudoxanthoma elasticum patients and healthy individuals.

PubMed

Ramsay, Michèle; Greenberg, Tarryn; Lombard, Zane; Labrum, Robyn; Lubbe, Steven; Aron, Shaun; Marais, Anna-Susan; Terry, Sharon; Bercovitch, Lionel; Viljoen, Denis

2009-06-01

Pseudoxanthoma elasticum (PXE) is an autosomal recessive metabolic disorder with ectopic mineralization in the skin, eyes and cardiovascular system. PXE is caused by mutations in ABCC6. To examine 54 unrelated South African PXE patients for ABCC6 PXE causing mutations. Patients were screened for mutations in ABCC6 using two strategies. The first involved a comprehensive screening of all the ABCC6 exons and flanking regions by dHPLC or sequencing whereas the second involved screening patients only for the common PXE mutations. The ABCC6 gene was screened in ten white and ten black healthy unrelated South Africans in order to examine the level of common non-PXE associated variation. The Afrikaner founder mutation, R1339C, was present in 0.41 of white ABCC6 PXE alleles, confirming the founder effect and its presence in both Afrikaans- (34/63 PXE alleles) and English-speakers (4/28). Eleven mutations were detected in the white patients (of European origin), including two nonsense mutations, 6 missense mutations, two frameshift mutations and a large deletion mutation. The five "Coloured" patients (of mixed Khoisan, Malay, European and African origin) included three compound heterozygotes with R1339C as one of the mutations. The three black patients (sub-Saharan African origin) were all apparent homozygotes for the R1314W mutation. Blacks showed a trend towards a higher degree of neurtral variation (18 variants) when compared to whites (12 variants). Delineation of the ABCC6 mutation profile in South African PXE patients will be used as a guide for molecular genetic testing in a clinical setting and for genetic counselling.

miR-133b down-regulates ABCC1 and enhances the sensitivity of CRC to anti-tumor drugs.

PubMed

Chen, Miao; Li, Daojiang; Gong, Ni; Wu, Hao; Su, Chen; Xie, Canbin; Xiang, Hong; Lin, Changwei; Li, Xiaorong

2017-08-08

Multidrug resistance (MDR) is the main cause of failed chemotherapy treatments. Therefore, preventing MDR is pivotal in treating colorectal cancer (CRC). In a previous study miR-133b was shown to be a tumor suppressor. Additionally, in CRC cells transfected with miR-133b, ATP-binding cassette (ABC) subfamily C member 1(ABCC1) was shown to be significantly down regulated. Whether miR-133b also enhances the chemosensitivity of drugs used to treat CRC by targeting ABCC1 is still unclear. Here, we utilized flow cytometry and high-performance liquid chromatography (HPLC) analysis to identify the ability of miR-133b to reserve MDR in CRC. We then used a dual-luciferase reporter assay to validate that miR-133b targets ABCC1. Further in vivo experiments were designed to validate the method in which miR-133b reversed MDR in CRC cells. The results demonstrated that the level of miR-133b was down-regulated and the expression of ABCC1 was up-regulated in drug-resistant CRC cells compared to non-drug-resistant CRC cells. The restoration of miR-133b expression in CRC drug-resistant cells in vitro resulted in reduced IC50s to chemotherapeutic drugs, significantly induced G1 accumulation, inhibited growth and promoted necrosis in combination with either 5-fluorouracil (5-FU) or vincristine (VCR), and decreased the expression of ABCC1. The dual-luciferase assay demonstrated that miR-133b directly targets ABCC1. The combination of agomiRNA-133b with chemotherapeutic drugs in vivo inhibited tumor growth induced by CRC drug-resistant cells. A xenograft from the in vivo model resulted in up-regulated levels of miR-133b and down-regulated levels of ABCC1. Therefore, miR-133b enhances the chemosensitivity of CRC cells to anti-tumor drugs by directly down-regulating ABCC1. This discovery provides a therapeutic strategy in which miR-133b is used as a potential sensitizer for drug-resistant CRC.

Redesign of a Life Span Development Course Using Fink's Taxonomy

ERIC Educational Resources Information Center

Fallahi, Carolyn R.

2008-01-01

This study compared a traditional lecture-based life span development course to the same course redesigned using Fink's (2003) taxonomy of significant learning. The goals, activities, and feedback within the course corresponded to Fink's 6 taxa (knowledge, application, integration, human dimension, caring, learning how to learn). Undergraduates in…

Target of Rapamycin Signaling Regulates Metabolism, Growth, and Life Span in Arabidopsis[W][OA

PubMed Central

Ren, Maozhi; Venglat, Prakash; Qiu, Shuqing; Feng, Li; Cao, Yongguo; Wang, Edwin; Xiang, Daoquan; Wang, Jinghe; Alexander, Danny; Chalivendra, Subbaiah; Logan, David; Mattoo, Autar; Selvaraj, Gopalan; Datla, Raju

2012-01-01

Target of Rapamycin (TOR) is a major nutrition and energy sensor that regulates growth and life span in yeast and animals. In plants, growth and life span are intertwined not only with nutrient acquisition from the soil and nutrition generation via photosynthesis but also with their unique modes of development and differentiation. How TOR functions in these processes has not yet been determined. To gain further insights, rapamycin-sensitive transgenic Arabidopsis thaliana lines (BP12) expressing yeast FK506 Binding Protein12 were developed. Inhibition of TOR in BP12 plants by rapamycin resulted in slower overall root, leaf, and shoot growth and development leading to poor nutrient uptake and light energy utilization. Experimental limitation of nutrient availability and light energy supply in wild-type Arabidopsis produced phenotypes observed with TOR knockdown plants, indicating a link between TOR signaling and nutrition/light energy status. Genetic and physiological studies together with RNA sequencing and metabolite analysis of TOR-suppressed lines revealed that TOR regulates development and life span in Arabidopsis by restructuring cell growth, carbon and nitrogen metabolism, gene expression, and rRNA and protein synthesis. Gain- and loss-of-function Ribosomal Protein S6 (RPS6) mutants additionally show that TOR function involves RPS6-mediated nutrition and light-dependent growth and life span in Arabidopsis. PMID:23275579

Like cognitive function, decision making across the life span shows profound age-related changes.

PubMed

Tymula, Agnieszka; Rosenberg Belmaker, Lior A; Ruderman, Lital; Glimcher, Paul W; Levy, Ifat

2013-10-15

It has long been known that human cognitive function improves through young adulthood and then declines across the later life span. Here we examined how decision-making function changes across the life span by measuring risk and ambiguity attitudes in the gain and loss domains, as well as choice consistency, in an urban cohort ranging in age from 12 to 90 y. We identified several important age-related patterns in decision making under uncertainty: First, we found that healthy elders between the ages of 65 and 90 were strikingly inconsistent in their choices compared with younger subjects. Just as elders show profound declines in cognitive function, they also show profound declines in choice rationality compared with their younger peers. Second, we found that the widely documented phenomenon of ambiguity aversion is specific to the gain domain and does not occur in the loss domain, except for a slight effect in older adults. Finally, extending an earlier report by our group, we found that risk attitudes across the life span show an inverted U-shaped function; both elders and adolescents are more risk-averse than their midlife counterparts. Taken together, these characterizations of decision-making function across the life span in this urban cohort strengthen the conclusions of previous reports suggesting a profound impact of aging on cognitive function in this domain.

Endosomal protein sorting and autophagy genes contribute to the regulation of yeast life span.

PubMed

Longo, Valter D; Nislow, Corey; Fabrizio, Paola

2010-11-01

Accumulating evidence from various organisms points to a role for autophagy in the regulation of life span. By performing a genome-wide screen to identify novel life span determinants in Saccharomyces cerevisiae, we have obtained further insights into the autophagy-related and -unrelated degradation processes that may be important for preventing cellular senescence. The generation of multivesicular bodies and their fusion with the vacuole in the endosomal pathway emerged as novel cell functions involved in yeast chronological survival and longevity extension.

"Pull and push back" concepts of longevity and life span extension.

PubMed

Muradian, Khachik

2013-12-01

The negative relation between metabolism and life span is a fundamental gerontological discovery well documented in a variety of ontogenetic and phylogenetic models. But how the long-lived species and populations sustain lower metabolic rate and, in more general terms, what is the efficient way to decline the metabolism? The suggested 'pull and push back' hypothesis assumes that decreased Po2 (hypoxia) and/or increased [Formula: see text] (hypercapnia) may create preconditions for the declined metabolic and aging rates. However, wider implementation of such ideas is compromised because of little advances in modification of the metabolic rate. Artificial atmosphere with controlled [Formula: see text] and [Formula: see text] could be a promising approach because of the minimal external invasions and involvement of the backward and forward loops ensuring physiological self-regulation of the metabolic perturbations. General considerations and existing data indicate that manipulations of [Formula: see text] may be more efficient in life span extension than [Formula: see text]. Thus, maximum life span of mammals positively correlates with the blood [Formula: see text] and HCO3 (-) but not with [Formula: see text]. Yet, proportional decease of the body [Formula: see text] and increase of [Formula: see text] seems the most optimal regime ensuring lower losses of the energy equivalents. Furthermore, especially rewarding results could be expected when such changes are modeled without major external invasions using the animals' inner capacity to consume O2 and generate CO2, as it is typical for the extreme longevity.

Reading through the Life Span: Individual Differences in Psycholinguistic Effects

ERIC Educational Resources Information Center

Davies, Rob A. I.; Arnell, Ruth; Birchenough, Julia M. H.; Grimmond, Debbie; Houlson, Sam

2017-01-01

The effects of psycholinguistic variables are critical to the evaluation of theories about the cognitive reading system. However, reading research has tended to focus on the impact of key variables on average performance. We report the first investigation examining variation in psycholinguistic effects across the life span, from childhood into old…

ABCC1, an ATP Binding Cassette Protein from Grape Berry, Transports Anthocyanidin 3-O-Glucosides[W][OA

PubMed Central

Francisco, Rita Maria; Regalado, Ana; Ageorges, Agnès; Burla, Bo J.; Bassin, Barbara; Eisenach, Cornelia; Zarrouk, Olfa; Vialet, Sandrine; Marlin, Thérèse; Chaves, Maria Manuela; Martinoia, Enrico; Nagy, Réka

2013-01-01

Accumulation of anthocyanins in the exocarp of red grapevine (Vitis vinifera) cultivars is one of several events that characterize the onset of grape berry ripening (véraison). Despite our thorough understanding of anthocyanin biosynthesis and regulation, little is known about the molecular aspects of their transport. The participation of ATP binding cassette (ABC) proteins in vacuolar anthocyanin transport has long been a matter of debate. Here, we present biochemical evidence that an ABC protein, ABCC1, localizes to the tonoplast and is involved in the transport of glucosylated anthocyanidins. ABCC1 is expressed in the exocarp throughout berry development and ripening, with a significant increase at véraison (i.e., the onset of ripening). Transport experiments using microsomes isolated from ABCC1-expressing yeast cells showed that ABCC1 transports malvidin 3-O-glucoside. The transport strictly depends on the presence of GSH, which is cotransported with the anthocyanins and is sensitive to inhibitors of ABC proteins. By exposing anthocyanin-producing grapevine root cultures to buthionine sulphoximine, which reduced GSH levels, a decrease in anthocyanin concentration is observed. In conclusion, we provide evidence that ABCC1 acts as an anthocyanin transporter that depends on GSH without the formation of an anthocyanin-GSH conjugate. PMID:23723325

Metabotypes with properly functioning mitochondria and anti-inflammation predict extended productive life span in dairy cows

PubMed Central

Huber, K.; Dänicke, S.; Rehage, J.; Sauerwein, H.; Otto, W.; Rolle-Kampczyk, U.; von Bergen, M.

2016-01-01

The failure to adapt metabolism to the homeorhetic demands of lactation is considered as a main factor in reducing the productive life span of dairy cows. The so far defined markers of production performance and metabolic health in dairy cows do not predict the length of productive life span satisfyingly. This study aimed to identify novel pathways and biomarkers related to productive life in dairy cows by means of (targeted) metabolomics. In a longitudinal study from 42 days before up to 100 days after parturition, we identified metabolites such as long-chain acylcarnitines and biogenic amines associated with extended productive life spans. These metabolites are mainly secreted by the liver and depend on the functionality of hepatic mitochondria. The concentrations of biogenic amines and some acylcarnitines differed already before the onset of lactation thus indicating their predictive potential for continuation or early ending of productive life. PMID:27089826

Metabotypes with properly functioning mitochondria and anti-inflammation predict extended productive life span in dairy cows.

PubMed

Huber, K; Dänicke, S; Rehage, J; Sauerwein, H; Otto, W; Rolle-Kampczyk, U; von Bergen, M

2016-04-19

The failure to adapt metabolism to the homeorhetic demands of lactation is considered as a main factor in reducing the productive life span of dairy cows. The so far defined markers of production performance and metabolic health in dairy cows do not predict the length of productive life span satisfyingly. This study aimed to identify novel pathways and biomarkers related to productive life in dairy cows by means of (targeted) metabolomics. In a longitudinal study from 42 days before up to 100 days after parturition, we identified metabolites such as long-chain acylcarnitines and biogenic amines associated with extended productive life spans. These metabolites are mainly secreted by the liver and depend on the functionality of hepatic mitochondria. The concentrations of biogenic amines and some acylcarnitines differed already before the onset of lactation thus indicating their predictive potential for continuation or early ending of productive life.

Sustained Attention Across the Life Span in a Sample of 10,000: Dissociating Ability and Strategy.

PubMed

Fortenbaugh, Francesca C; DeGutis, Joseph; Germine, Laura; Wilmer, Jeremy B; Grosso, Mallory; Russo, Kathryn; Esterman, Michael

2015-09-01

Normal and abnormal differences in sustained visual attention have long been of interest to scientists, educators, and clinicians. Still lacking, however, is a clear understanding of how sustained visual attention varies across the broad sweep of the human life span. In the present study, we filled this gap in two ways. First, using an unprecedentedly large 10,430-person sample, we modeled age-related differences with substantially greater precision than have prior efforts. Second, using the recently developed gradual-onset continuous performance test (gradCPT), we parsed sustained-attention performance over the life span into its ability and strategy components. We found that after the age of 15 years, the strategy and ability trajectories saliently diverge. Strategy becomes monotonically more conservative with age, whereas ability peaks in the early 40s and is followed by a gradual decline in older adults. These observed life-span trajectories for sustained attention are distinct from results of other life-span studies focusing on fluid and crystallized intelligence. © The Author(s) 2015.

Novel mutation in ABCC6 gene in a Japanese pedigree with pseudoxanthoma elasticum and retinitis pigmentosa.

PubMed

Yoshida, S; Honda, M; Yoshida, A; Nakao, S; Goto, Y; Nakamura, T; Fujisawa, K; Ishibashi, T

2005-02-01

To report a novel mutation of the ABCC6 gene in a Japanese family that had a case of pseudoxanthoma elasticum (PXE) another with PXE and retinitis pigmentosa. Ophthalmologic examinations were performed, and the ABCC6 gene was analysed by direct genomic sequencing. Fundus examinations of the 48-year-old proband disclosed angioid streaks and a peud'orange appearance of the retina of the both eyes, whereas both of his 25- and 20-year-old daughters had pigmentary degeneration and angioid streaks. In the sibilings, the mixed cone-rod ERG was almost nondetectable, whereas that of the proband was well-preserved. Molecular genetic analysis revealed that the proband has a homozygous nonsense mutation at the 595 bp in the ABCC6, and the siblings were heterozygous for the same mutation. This mutation was not detected in Japanese subjects in the JSNP database (http://snp.ims.u-tokyo.ac.jp/). Our results demonstrated an association between a novel mutation in the ABCC6 gene and PXE in a Japanese family.

The importance of adult life-span perspective in explaining variations in political ideology.

PubMed

Sedek, Grzegorz; Kossowska, Malgorzata; Rydzewska, Klara

2014-06-01

As a comment on Hibbing et al.'s paper, we discuss the evolution of political and social views from more liberal to more conservative over the span of adulthood. We show that Hibbing et al.'s theoretical model creates a false prediction from this developmental perspective, as increased conservatism in the adult life-span trajectory is accompanied by the avoidance of negative bias.

Overexpression of PtABCC1 contributes to mercury tolerance and accumulation in Arabidopsis and poplar.

PubMed

Sun, Liping; Ma, Yifeng; Wang, Huihong; Huang, Weipeng; Wang, Xiaozhu; Han, Li; Sun, Wanmei; Han, Erqin; Wang, Bangjun

2018-03-18

Mercury (Hg) is a highly biotoxic heavy metal that contaminates the environment. Phytoremediation is a green technology for environmental remediation and is used to clean up Hg contaminated soil in recent years. In this study, we isolated an ATP-binding cassette (ABC) transporter gene PtABCC1 from Populus trichocarpa and overexpressed it in Arabidopsis and poplar. The transgenic plants conferred higher Hg tolerance than wild type (WT) plants, and overexpression of PtABCC1 could lead to 26-72% or 7-160% increase of Hg accumulation in Arabidopsis or poplar plants, respectively. These results demonstrated that PtABCC1 plays a crucial role in enhancing tolerance and accumulation to Hg in plants, which provides a promising way for phytoremediation of Hg contamination. Copyright © 2018 Elsevier Inc. All rights reserved.

ABCC1 is related to the protection of the distal nephron against hyperosmolality and high sodium environment: possible implications for cancer chemotherapy.

PubMed

Fonseca, Leonardo M; Alvarez, Adriana B; Rodrigues, Rachel C; Santos, Diego H F; Lopes, Anibal G; Capella, Marcia A M

2013-01-01

Glutathione (GSH) plays an important role in protecting cells against oxidative damage. ABCC1 protein transports GSH. Although this protein is largely studied in cancer, due to multidrug resistance phenotype, its role in the tubular cells of the kidney is unknown. The goal of this study was to find out whether ABCC1 has a role in protecting cells from the distal nephron against the stress caused by high medullar osmolality. MA104 cells were treated with high concentrations of sodium chloride, urea, or both to raise the osmolality of the culture medium. Cell viability was accessed by MTT and trypan blue assays. ABCC1 expression and extrusion of carboxi-fluorescein (CF), a fluorescent ABCC1 substrate, were measured by flow cytometry. Incubation of MA104 cells in a high sodium concentration medium resulted in changes in cell granularity and altered expression and activity of ABCC1. Urea did not alter ABCC1 expression or activity, but reversed the observed NaCl effects. High sodium concentrations also had a negative effect on cell viability and urea also protected cells against this effect. Our findings demonstrate that ABCC1 plays a significant role in the protection of kidney epithelial cells against the stress caused by high sodium environment present in renal medulla.

Age Differences in Five Personality Domains across the Life Span

ERIC Educational Resources Information Center

Allemand, Mathias; Zimprich, Daniel; Hendriks, A. A. Jolijn

2008-01-01

The present study addresses the issue of age differences in 5 personality domains across the life span in a cross-sectional study. In contrast to most previous studies, the present study follows a methodologically more rigorous approach to warrant that age-related differences in personality structure and mean level can be meaningfully compared. It…

Leaf life span and the mobility of "non-mobile" mineral nutrients - the case of boron in conifers

Treesearch

Pedro J. Aphalo; Anna W. Schoettle; Tarja Lehto

2002-01-01

Nutrient conservation is considered important for the adaptation of plants to infertile environments. The importance of leaf life spans in controlling mean residence time of nutrients in plants has usually been analyzed in relation to nutrients that can be retranslocated within the plant. Longer leaf life spans increase the mean residence time of all mineral...

Weight concern across the life-span: relationship to self-esteem and feminist identity.

PubMed

Tiggemann, M; Stevens, C

1999-07-01

The aim of this study was to investigate the correlates of weight concern across the life-span. Questionnaires assessing weight concern, self-esteem, and feminist attitudes were completed in their homes by 180 women aged between 18 and 60 years. It was found that there was a negative relationship between weight concern and self-esteem for 30 to 49-year-old women, but not for younger or older women. A similar pattern held for feminist attitudes. Among 30 to 49-year-old women, a strong feminist orientation related to a lesser concern with weight. It was concluded that the meaning and experience of body weight and size change across the life-span.

Life-span extension by caloric restriction is determined by type and level of food reduction and by reproductive mode in Brachionus manjavacas (Rotifera).

PubMed

Gribble, Kristin E; Welch, David B Mark

2013-04-01

We measured life span and fecundity of three reproductive modes in a clone of the monogonont rotifer Brachionus manjavacas subjected to chronic caloric restriction (CCR) over a range of food concentrations or to intermittent fasting (IF). IF increased life span 50%-70% for all three modes, whereas CCR increased life span of asexual females derived from sexually or asexually produced eggs, but not that of sexual females. The main effect of CR on both asexual modes was to delay death at young ages, rather than to prevent death at middle ages or to greatly extend maximum life span; in contrast CR in sexual females greatly increased the life span of a few long-lived individuals. Lifetime fecundity did not decrease with CCR, suggesting a lack of resource allocation trade-off between somatic maintenance and reproduction. Multiple outcomes for a clonal lineage indicate that different responses are established through epigenetic programming, whereas differences in life-span allocations suggest that multiple genetic mechanisms mediate life-span extension.

Life-Span Extension in Mice by Preweaning Food Restriction and by Methionine Restriction in Middle Age

PubMed Central

Sun, Liou; Sadighi Akha, Amir A.; Miller, Richard A.

2009-01-01

Life span can be extended in rodents by restricting food availability (caloric restriction [CR]) or by providing food low in methionine (Meth-R). Here, we show that a period of food restriction limited to the first 20 days of life, via a 50% enlargement of litter size, shows extended median and maximal life span relative to mice from normal sized litters and that a Meth-R diet initiated at 12 months of age also significantly increases longevity. Furthermore, mice exposed to a CR diet show changes in liver messenger RNA patterns, in phosphorylation of Erk, Jnk2, and p38 kinases, and in phosphorylation of mammalian target of rapamycin and its substrate 4EBP1, HE-binding protein 1 that are not observed in liver from age-matched Meth-R mice. These results introduce new protocols that can increase maximal life span and suggest that the spectrum of metabolic changes induced by low-calorie and low-methionine diets may differ in instructive ways. PMID:19414512

Psychosocial stressors and the short life spans of legendary jazz musicians.

PubMed

Patalano, F

2000-04-01

Mean age at death of 168 legendary jazz musicians and 100 renowned classical musicians were compared to examine whether psychosocial stressors such as severe substance abuse, haphazard working conditions, lack of acceptance of jazz as an art form in the United States, marital and family discord, and a vagabond life style may have contributed to shortened life spans for the jazz musicians. Analysis indicated that the jazz musicians died at an earlier age (57.2 yr.) than the classical musicians (73.3 yr.).

The life span-prolonging effect of sirtuin-1 is mediated by autophagy.

PubMed

Morselli, Eugenia; Maiuri, Maria Chiara; Markaki, Maria; Megalou, Evgenia; Pasparaki, Angela; Palikaras, Konstantinos; Criollo, Alfredo; Galluzzi, Lorenzo; Malik, Shoaib Ahmad; Vitale, Ilio; Michaud, Mickael; Madeo, Frank; Tavernarakis, Nektarios; Kroemer, Guido

2010-01-01

The life span of various model organisms can be extended by caloric restriction as well as by autophagy-inducing pharmacological agents. Life span-prolonging effects have also been observed in yeast cells, nematodes and flies upon the overexpression of the deacetylase Sirtuin-1. Intrigued by these observations and by the established link between caloric restriction and Sirtuin-1 activation, we decided to investigate the putative implication of Sirtuin-1 in the response of human cancer cells and Caenorhabditis elegans to multiple triggers of autophagy. Our data indicate that the activation of Sirtuin-1 (by the pharmacological agent resveratrol and/or genetic means) per se ignites autophagy, and that Sirtuin-1 is required for the autophagic response to nutrient deprivation, in both human and nematode cells, but not for autophagy triggered by downstream signals such as the inhibition of mTOR or p53. Since the life spanextending effects of Sirtuin-1 activators are lost in autophagy-deficient C. elegans, our results suggest that caloric restriction and resveratrol extend longevity, at least in experimental settings, by activating autophagy.

Influence of Domain Knowledge on Monitoring Performance across the Life Span

ERIC Educational Resources Information Center

Löffler, Elisabeth; von der Linden, Nicole; Schneider, Wolfgang

2016-01-01

Two studies were conducted to investigate effects of domain knowledge on metacognitive monitoring across the life span in materials of different complexity. Participants from 4 age groups (3rd-grade children, adolescents, younger and older adults) were compared using an expert-novice paradigm. In Study 1, soccer experts' and novices'…

Dietary restriction in two rotifer species: the effect of the length of food deprivation on life span and reproduction.

PubMed

Weithoff, Guntram

2007-08-01

According to resource allocation theory, animals face a trade off between the allocation of resources into reproduction and into individual growth/maintenance. This trade off is reinforced when food conditions decline. It is well established in biological research that many animals increase their life span when food is in suboptimal supply for growth and/or reproduction. Such a situation of reduced food availability is called dietary restriction. An increase in life span under dietary restricted conditions is seen as a strategy to tolerate periods of food shortage so that the animals can start reproduction again when food is in greater supply. In this study, the effect of dietary restriction on life span and reproduction in two rotifer species, Cephalodella sp. and Elosa worallii, was investigated using life table experiments. The food concentration under dietary restricted conditions was below the threshold for population growth. It was (1) tested whether the rotifers start reproduction again after food replenishment, and (2) estimated whether the time scale of dietary restricted conditions is relevant for the persistence of a population in the field. Only E. worallii responded to dietary restriction with an increase in life span at the expense of reproduction. After replenishment of food, E. worallii started to reproduce again within 1 day. With an increase in the duration of dietary restricted conditions of up to 15 days, which is longer than the median life span of E. worallii under food saturation, the life span increased and the life time reproduction decreased. These results suggest that in a temporally (or spatially) variable environment, some rotifer populations can persist even during long periods of severe food deprivation.

Demography of Genotypes: Failure of the Limited Life-Span Paradigm in Drosophila melanogaster

NASA Astrophysics Data System (ADS)

Curtsinger, James W.; Fukui, Hidenori H.; Townsend, David R.; Vaupel, James W.

1992-10-01

Experimental systems that are amenable to genetic manipulation can be used to address fundamental questions about genetic and nongenetic determinants of longevity. Analysis of large cohorts of ten genotypes of Drosophila melanogaster raised under conditions that favored extended survival has revealed variation between genotypes in both the slope and location of age-specific mortality curves. More detailed examination of a single genotype showed that the mortality trajectory was best fit by a two-stage Gompertz model, with no age-specific increase in mortality rates beyond 30 days after emergence. These results are contrary to the limited life-span paradigm, which postulates well-defined, genotype-specific limits on life-span and brief periods of intense and rapidly accelerating mortality rates at the oldest ages.

Life-Span Extension by Caloric Restriction Is Determined by Type and Level of Food Reduction and by Reproductive Mode in Brachionus manjavacas (Rotifera)

PubMed Central

2013-01-01

We measured life span and fecundity of three reproductive modes in a clone of the monogonont rotifer Brachionus manjavacas subjected to chronic caloric restriction (CCR) over a range of food concentrations or to intermittent fasting (IF). IF increased life span 50%–70% for all three modes, whereas CCR increased life span of asexual females derived from sexually or asexually produced eggs, but not that of sexual females. The main effect of CR on both asexual modes was to delay death at young ages, rather than to prevent death at middle ages or to greatly extend maximum life span; in contrast CR in sexual females greatly increased the life span of a few long-lived individuals. Lifetime fecundity did not decrease with CCR, suggesting a lack of resource allocation trade-off between somatic maintenance and reproduction. Multiple outcomes for a clonal lineage indicate that different responses are established through epigenetic programming, whereas differences in life-span allocations suggest that multiple genetic mechanisms mediate life-span extension. PMID:22904096

Life-Span Differences in the Uses and Gratifications of Tablets: Implications for Older Adults

PubMed Central

Magsamen-Conrad, Kate; Dowd, John; Abuljadail, Mohammad; Alsulaiman, Saud; Shareefi, Adnan

2015-01-01

This study extends Uses and Gratifications theory by examining the uses and gratifications of a new technological device, the tablet computer, and investigating the differential uses and gratifications of tablet computers across the life-span. First, we utilized a six-week tablet training intervention to adapt and extend existing measures to the tablet as a technological device. Next, we used paper-based and online surveys (N=847), we confirmed four main uses of tablets: 1) Information Seeking, 2) Relationship Maintenance, 3) Style, 4) Amusement and Killing time, and added one additional use category 5) Organization. We discovered differences among the five main uses of tablets across the life-span, with older adults using tablets the least overall. Builders, Boomers, GenX and GenY all reported the highest means for information seeking. Finally, we used a structural equation model to examine how uses and gratifications predicts hours of tablet use. The study provides limitations and suggestions for future research and marketers. In particular, this study offers insight to the relevancy of theory as it applies to particular information and communication technologies and consideration of how different periods in the life-span affect tablet motivations. PMID:26113769

Life-Span Differences in the Uses and Gratifications of Tablets: Implications for Older Adults.

PubMed

Magsamen-Conrad, Kate; Dowd, John; Abuljadail, Mohammad; Alsulaiman, Saud; Shareefi, Adnan

2015-11-01

This study extends Uses and Gratifications theory by examining the uses and gratifications of a new technological device, the tablet computer, and investigating the differential uses and gratifications of tablet computers across the life-span. First, we utilized a six-week tablet training intervention to adapt and extend existing measures to the tablet as a technological device. Next, we used paper-based and online surveys ( N =847), we confirmed four main uses of tablets: 1) Information Seeking, 2) Relationship Maintenance, 3) Style, 4) Amusement and Killing time, and added one additional use category 5) Organization. We discovered differences among the five main uses of tablets across the life-span, with older adults using tablets the least overall. Builders, Boomers, GenX and GenY all reported the highest means for information seeking. Finally, we used a structural equation model to examine how uses and gratifications predicts hours of tablet use. The study provides limitations and suggestions for future research and marketers. In particular, this study offers insight to the relevancy of theory as it applies to particular information and communication technologies and consideration of how different periods in the life-span affect tablet motivations.

Increased iron supplied through Fet3p results in replicative life span extension of Saccharomyces cerevisiae under conditions requiring respiratory metabolism.

PubMed

Botta, Gabriela; Turn, Christina S; Quintyne, Nicholas J; Kirchman, Paul A

2011-10-01

We have previously shown that copper supplementation extends the replicative life span of Saccharomyces cerevisiae when grown under conditions forcing cells to respire. We now show that copper's effect on life span is through Fet3p, a copper containing enzyme responsible for high affinity transport of iron into yeast cells. Life span extensions can also be obtained by supplementing the growth medium with 1mM ferric chloride. Extension by high iron levels is still dependent on the presence of Fet3p. Life span extension by iron or copper requires growth on media containing glycerol as the sole carbon source, which forces yeast to respire. Yeast grown on glucose containing media supplemented with iron show no extension of life span. The iron associated with cells grown in media supplemented with copper or iron is 1.4-1.8 times that of cells grown without copper or iron supplementation. As with copper supplementation, iron supplementation partially rescues the life span of superoxide dismutase mutants. Cells grown with copper supplementation display decreased production of superoxide as measured by dihydroethidium staining. Copyright © 2011 Elsevier Inc. All rights reserved.

Physical Performance Across the Adult Life Span: Correlates With Age and Physical Activity.

PubMed

Hall, Katherine S; Cohen, Harvey J; Pieper, Carl F; Fillenbaum, Gerda G; Kraus, William E; Huffman, Kim M; Cornish, Melissa A; Shiloh, Andrew; Flynn, Christy; Sloane, Richard; Newby, L Kristin; Morey, Miriam C

2017-04-01

A number of large-scale population studies have provided valuable information about physical performance in aged individuals; however, there is little information about trajectories of function and associations with age across the adult life span. We developed a mobility-focused physical performance screener designed to be appropriate for the adult life span. The physical performance battery includes measures of mobility, strength, endurance, and balance. Physical activity (PA) was assessed with accelerometry. We examined age-related trends in physical performance and PA, and the relationship between physical performance and PA across the age range (30-90+), by decade, in 775 participants enrolled in the study 2012-2014. Physical performance was worse with increasing age decade. Although men performed better than women across all ages, the decrement by age group was similar between genders. Worsening physical performance was observed as early as the fifth decade for chair stands and balance and in the sixth decade for gait speed and aerobic endurance. The number and strength of significant associations between physical performance and PA increased with greater age: the greatest number of significant associations was seen in the 60-79 age groups, with fewer reported in the 30-59 and 80-90+ age groups. More PA was associated with better physical function. These results emphasize the importance of a life span approach to studies of function and aging. This work points to the need for a physical performance screener that spans across adulthood as a clinical tool for identifying functional decline. © 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.

Human multidrug resistance protein 8 (MRP8/ABCC11), an apical efflux pump for steroid sulfates, is an axonal protein of the CNS and peripheral nervous system.

PubMed

Bortfeld, M; Rius, M; König, J; Herold-Mende, C; Nies, A T; Keppler, D

2006-01-01

Dehydroepiandrosterone 3-sulfate and other neurosteroids are synthesized in the CNS and peripheral nervous system where they may modulate neuronal excitability by interacting with ligand-gated ion channels. For this modulatory activity, neurosteroids have to be locally released from either neurons or glial cells. We here identify the integral membrane protein ABCC11 (multidrug resistance protein 8) as an ATP-dependent efflux pump for steroid sulfates, including dehydroepiandrosterone 3-sulfate, and localize it to axons of the human CNS and peripheral nervous system. ABCC11 mRNA was detected in human brain by real-time polymerase chain reaction. Antibodies raised against ABCC11 served to detect the protein in brain by immunoblotting and immunofluorescence microscopy. ABCC11 was preferentially found in the white matter of the brain and co-localized with neurofilaments indicating that it is an axonal protein. Additionally, ABCC11 was localized to axons of the peripheral nervous system. For functional studies, ABCC11 was expressed in polarized Madin-Darby canine kidney cells where it was sorted to the apical membrane. This apical sorting is in accordance with the localization of ABCC11 to the axonal membrane of neurons. Inside-out plasma membrane vesicles containing recombinant ABCC11 mediated ATP-dependent transport of dehydroepiandrosterone 3-sulfate with a Km value of 21 microM. This transport function together with the localization of the ABCC11 protein in vicinity to GABAA receptors is consistent with a role of ABCC11 in dehydroepiandrosterone 3-sulfate release from neurons to sites of dehydroepiandrosterone 3-sulfate-mediated receptor modulation. Our findings may provide a basis for the characterization of mutations in the human ABCC11 gene and their linkage with neurological disorders.

Materialism across the life span: An age-period-cohort analysis.

PubMed

Jaspers, Esther D T; Pieters, Rik G M

2016-09-01

This research examined the development of materialism across the life span. Two initial studies revealed that (a) lay beliefs were that materialism declines with age and (b) previous research findings also implied a modest, negative relationship between age and materialism. Yet, previous research has considered age only as a linear control variable, thereby precluding the possibility of more intricate relationships between age and materialism. Moreover, prior studies have relied on cross-sectional data and thus confound age and cohort effects. To improve on this, the main study used longitudinal data from 8 waves spanning 9 years of over 4,200 individuals (16 to 90 years) to examine age effects on materialism while controlling for cohort and period effects. Using a multivariate multilevel latent growth model, it found that materialism followed a curvilinear trajectory across the life span, with the lowest levels at middle age and higher levels before and after that. Thus, in contrast to lay beliefs, materialism increased in older age. Moreover, age effects on materialism differed markedly between 3 core themes of materialism: acquisition centrality, possession-defined success, and acquisition as the pursuit of happiness. In particular, acquisition centrality and possession-defined success were higher at younger and older age. Independent of these age effects, older birth cohorts were oriented more toward possession-defined success, whereas younger birth cohorts were oriented more toward acquisition centrality. The economic downturn since 2008 led to a decrease in acquisition as the pursuit of happiness and in desires for personal growth, but to an increase in desires for achievement. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

The BTK Inhibitor Ibrutinib (PCI-32765) Overcomes Paclitaxel Resistance in ABCB1- and ABCC10-Overexpressing Cells and Tumors.

PubMed

Zhang, Hui; Patel, Atish; Wang, Yi-Jun; Zhang, Yun-Kai; Kathawala, Rishil J; Qiu, Long-Hui; Patel, Bhargav A; Huang, Li-Hua; Shukla, Suneet; Yang, Dong-Hua; Ambudkar, Suresh V; Fu, Li-Wu; Chen, Zhe-Sheng

2017-06-01

Paclitaxel is one of the most widely used antineoplastic drugs in the clinic. Unfortunately, the occurrence of cellular resistance has limited its efficacy and application. The ATP-binding cassette subfamily B member 1 (ABCB1/P-glycoprotein) and subfamily C member 10 (ABCC10/MRP7) are the major membrane protein transporters responsible for the efflux of paclitaxel, constituting one of the most important mechanisms of paclitaxel resistance. Here, we demonstrated that the Bruton tyrosine kinase inhibitor, ibrutinib, significantly enhanced the antitumor activity of paclitaxel by antagonizing the efflux function of ABCB1 and ABCC10 in cells overexpressing these transporters. Furthermore, we demonstrated that the ABCB1 or ABCC10 protein expression was not altered after treatment with ibrutinib for up to 72 hours using Western blot analysis. However, the ATPase activity of ABCB1 was significantly stimulated by treatment with ibrutinib. Molecular docking analysis suggested the binding conformation of ibrutinib within the large cavity of the transmembrane region of ABCB1. Importantly, ibrutinib could effectively enhance paclitaxel-induced inhibition on the growth of ABCB1- and ABCC10-overexpressing tumors in nude athymic mice. These results demonstrate that the combination of ibrutinib and paclitaxel can effectively antagonize ABCB1- or ABCC10-mediated paclitaxel resistance that could be of great clinical interest. Mol Cancer Ther; 16(6); 1021-30. ©2017 AACR . ©2017 American Association for Cancer Research.

Post-dauer life span of Caenorhabditis elegans dauer larvae can be modified by X-irradiation.

PubMed

Onodera, Akira; Yanase, Sumino; Ishii, Takamasa; Yasuda, Kayo; Miyazawa, Masaki; Hartman, Philip S; Ishii, Naoaki

2010-01-01

The time spent as a dauer larva does not affect adult life span in Caenorhabditis elegans, as if aging is suspended in this quiescent developmental stage. We now report that modest doses X-irradiation of dauer larvae increased their post-dauer longevity. Post-irradiation incubation of young dauer larvae did not modify this beneficial effect of radiation. Conversely, holding dauer larvae prior to irradiation rendered them refractory to this X-radiation-induced response. We present a model to explain these results. These experiments demonstrate that dauer larvae provide an excellent opportunity to study mechanisms by which X irradiation can extend life span.

Partner preferences across the life span: online dating by older adults.

PubMed

Alterovitz, Sheyna Sears-Roberts; Mendelsohn, Gerald A

2009-06-01

Stereotypes of older adults as withdrawn or asexual fail to recognize that romantic relationships in later life are increasingly common. The authors analyzed 600 Internet personal ads from 4 age groups: 20-34, 40-54, 60-74, and 75+ years. Predictions from evolutionary theory held true in later life, when reproduction is no longer a concern. Across the life span, men sought physical attractiveness and offered status-related information more than women; women were more selective than men and sought status more than men. With age, men desired women increasingly younger than themselves, whereas women desired older men until ages 75 and over, when they sought men younger than themselves. (c) 2009 APA, all rights reserved.

Implication of Ca2+ in the regulation of replicative life span of budding yeast.

PubMed

Tsubakiyama, Ryohei; Mizunuma, Masaki; Gengyo, Anri; Yamamoto, Josuke; Kume, Kazunori; Miyakawa, Tokichi; Hirata, Dai

2011-08-19

In eukaryotic cells, Ca(2+)-triggered signaling pathways are used to regulate a wide variety of cellular processes. Calcineurin, a highly conserved Ca(2+)/calmodulin-dependent protein phosphatase, plays key roles in the regulation of diverse biological processes in organisms ranging from yeast to humans. We isolated a mutant of the SIR3 gene, implicated in the regulation of life span, as a suppressor of the Ca(2+) sensitivity of zds1Δ cells in the budding yeast Saccharomyces cerevisiae. Therefore, we investigated a relationship between Ca(2+) signaling and life span in yeast. Here we show that Ca(2+) affected the replicative life span (RLS) of yeast. Increased external and intracellular Ca(2+) levels caused a reduction in their RLS. Consistently, the increase in calcineurin activity by either the zds1 deletion or the constitutively activated calcineurin reduced RLS. Indeed, the shortened RLS of zds1Δ cells was suppressed by the calcineurin deletion. Further, the calcineurin deletion per se promoted aging without impairing the gene silencing typically observed in short-lived sir mutants, indicating that calcineurin plays an important role in a regulation of RLS even under normal growth condition. Thus, our results indicate that Ca(2+) homeostasis/Ca(2+) signaling are required to regulate longevity in budding yeast.

Life Span Evolution in Eusocial Workers—A Theoretical Approach to Understanding the Effects of Extrinsic Mortality in a Hierarchical System

PubMed Central

Kramer, Boris H.; Schaible, Ralf

2013-01-01

While the extraordinary life span of queens and division of labor in eusocial societies have been well studied, it is less clear which selective forces act on the short life span of workers. The disparity of life span between the queen and the workers is linked to a basic issue in sociobiology: How are the resources in a colony allocated between colony maintenance and reproduction? Resources for somatic maintenance of the colony can either be invested into quality or quantity of workers. Here, we present a theoretical optimization model that uses a hierarchical trade-off within insect colonies and extrinsic mortality to explain how different aging phenotypes could have evolved to keep resources secure in the colony. The model points to the significance of two factors. First, any investment that would generate a longer intrinsic life span for workers is lost if the individual dies from external causes while foraging. As a consequence, risky environments favor the evolution of workers with a shorter life span. Second, shorter-lived workers require less investment than long-lived ones, allowing the colony to allocate these resources to sexual reproduction or colony growth. PMID:23596527

Corrigendum: Childhood Adversity, Self-Esteem, and Diurnal Cortisol Profiles Across the Life Span.

PubMed

2018-01-01

Original article: Zilioli, S., Slatcher, R. B., Chi, P., Li, X., Zhao, J., & Zhao, G. (2016). Childhood adversity, self-esteem, and diurnal cortisol profiles across the life span. Psychological Science, 27, 1249-1265. doi:10.1177/0956797616658287.

Quantifying the Structure of Free Association Networks across the Life Span

ERIC Educational Resources Information Center

Dubossarsky, Haim; De Deyne, Simon; Hills, Thomas T.

2017-01-01

We investigate how the mental lexicon changes over the life span using free association data from over 8,000 individuals, ranging from 10 to 84 years of age, with more than 400 cue words per age group. Using network analysis, with words as nodes and edges defined by the strength of shared associations, we find that associative networks evolve in a…

eRapa Restores A Normal Life Span in a FAP Mouse Model

PubMed Central

Hasty, Paul; Livi, Carolina B.; Dodds, Sherry G.; Jones, Diane; Strong, Randy; Javors, Martin; Fischer, Kathleen E.; Sloane, Lauren; Murthy, Kruthi; Hubbard, Gene; Sun, Lishi; Hurez, Vincent; Curiel, Tyler J.; Sharp, Zelton Dave

2014-01-01

Mutation of a single copy of the adenomatous polyposis coli (APC) gene results in familial adenomatous polyposis (FAP), which confers an extremely high risk for colon cancer. ApcMin/+ mice exhibit multiple intestinal neoplasia (MIN) that causes anemia and death from bleeding by 6 months. Mechanistic target of rapamycin complex 1 (mTORC1) inhibitors were shown to improve ApcMin/+ mouse survival when administered by oral gavage or added directly to the chow, but these mice still died from neoplasia well short of a natural life span. The National Institute of Aging Intervention Testing Program showed that enterically targeted rapamycin (eRapa) extended life span for wild type genetically heterogeneous mice in part by inhibiting age-associated cancer. We hypothesized that eRapa would be effective in preventing neoplasia and extend survival of ApcMin/+ mice. We show that eRapa improved survival for ApcMin/+ mice in a dose-dependent manner. Remarkably, and in contrast to previous reports, most of the ApcMin/+ mice fed 42 ppm eRapa lived beyond the median life span reported for wild type syngeneic mice. Furthermore, chronic eRapa did not cause detrimental immune effects in mouse models of cancer, infection or autoimmunity; thus, assuaging concerns that chronic rapamycin treatment suppresses immunity. Our studies suggest that a novel formulation (enteric targeting) of a well-known and widely used drug (rapamycin) can dramatically improve its efficacy in targeted settings. eRapa or other mTORC1 inhibitors could serve as effective cancer preventatives for people with FAP without suppressing the immune system, thus reducing the dependency on surgery as standard therapy. PMID:24282255

Amino acid sources in the adult diet do not affect life span and fecundity in the fruit-feeding butterfly Bicyclus anynana.

PubMed

Molleman, Freerk; Ding, Jimin; Wang, Jane-Ling; Brakefield, Paul M; Carey, James R; Zwaan, Bas J

2008-08-01

1. In tropical forests, the adults of many butterfly species feed on fruits rather than nectar from flowers and have long life spans. Rotting fruit and nectar differ from each other in many respects, including sources of amino acids and microbial life. If amino acids in the adult diet can be used for reproduction, this may have facilitated the evolution of extended life spans in this guild.2. This issue was addressed by investigating effects of banana, yeast, and amino acids in the adult diet of the fruit-feeding butterfly Bicyclus anynana (Lepidoptera) on longevity and female reproductive output in two experiments.3. Results showed that in the fruit-feeding butterfly B. anynana: (i) banana juice, but not sliced banana or added amino acids extend life span compared with a sugar solution of similar composition; (ii) compared with this sugar solution, other cohorts (banana juice-amino acid enriched) did not have significantly higher reproductive outputs; (iii) yeast does not represent a valuable source of nutrients; (iv) caloric restriction may cause decreased life span and rate of reproduction; and (v) increased rates of reproduction have a life span cost.

Age Stereotypes and Self-Views Revisited: Patterns of Internalization and Projection Processes Across the Life Span.

PubMed

Kornadt, Anna E; Voss, Peggy; Rothermund, Klaus

2017-07-01

We investigated processes of age stereotype internalization into the self and projection of self-views onto age stereotypes from a life-span perspective, taking age-related differences in the relevance of life domains into account. Age stereotypes and self-views in eight life domains were assessed in a sample of N = 593 persons aged 30-80 years (T1) at two time points that were separated by a 4-year time interval. We estimated cross-lagged projection and internalization effects in multigroup structural equation models. Internalization and projection effects were contingent on age group and life domain: Internalization effects were strongest in the young and middle-aged groups and emerged in the domains family, personality, work, and leisure. Projection effects in different domains were most pronounced for older participants. Our findings suggest that the internalization of age stereotypes is triggered by domain-specific expectations of impending age-related changes and transitions during certain phases of the life span. Projection processes, however, seem to occur in response to changes that have already been experienced by the individual. Our study demonstrates the dynamic interrelation of age stereotypes and self-views across the life course and highlights the importance of a differentiated, life-span perspective for the understanding of these mechanisms. © The Author 2015. 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.

Silencing of ABCC13 transporter in wheat reveals its involvement in grain development, phytic acid accumulation and lateral root formation.

PubMed

Bhati, Kaushal Kumar; Alok, Anshu; Kumar, Anil; Kaur, Jagdeep; Tiwari, Siddharth; Pandey, Ajay Kumar

2016-07-01

Low phytic acid is a trait desired in cereal crops and can be achieved by manipulating the genes involved either in its biosynthesis or its transport in the vacuoles. Previously, we have demonstrated that the wheat TaABCC13 protein is a functional transporter, primarily involved in heavy metal tolerance, and a probable candidate gene to achieve low phytate wheat. In the current study, RNA silencing was used to knockdown the expression of TaABCC13 in order to evaluate its functional importance in wheat. Transgenic plants with significantly reduced TaABCC13 transcripts in either seeds or roots were selected for further studies. Homozygous RNAi lines K1B4 and K4G7 exhibited 34-22% reduction of the phytic acid content in the mature grains (T4 seeds). These transgenic lines were defective for spike development, as characterized by reduced grain filling and numbers of spikelets. The seeds of transgenic wheat had delayed germination, but the viability of the seedlings was unaffected. Interestingly, early emergence of lateral roots was observed in TaABCC13-silenced lines as compared to non-transgenic lines. In addition, these lines also had defects in metal uptake and development of lateral roots in the presence of cadmium stress. Our results suggest roles of TaABCC13 in lateral root initiation and enhanced sensitivity towards heavy metals. Taken together, these data demonstrate that wheat ABCC13 is functionally important for grain development and plays an important role during detoxification of heavy metals. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

ABCC6 and Pseudoxanthoma Elasticum: The Face of a Rare Disease from Genetics to Advocacy

PubMed Central

Moitra, Karobi; Garcia, Sonia; Etoundi, Clementine; Cooper, Donna; Roland, Anna; Dixon, Patrice; Reyes, Sandra; Turan, Sevilay; Dean, Michael

2017-01-01

Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder characterized by the mineralization of connective tissues in the body. Primary manifestation of PXE occurs in the tissues of the skin, eyes, and cardiovascular system. PXE is primarily caused by mutations in the ABCC6 gene. The ABCC6 gene encodes the trans-membrane protein ABCC6, which is highly expressed in the kidneys and liver. PXE has high phenotypic variability, which may possibly be affected by several modifier genes. Disease advocacy organizations have had a pivotal role in bringing rare disease research to the forefront and in helping to sustain research funding for rare genetic diseases in order to help find a treatment for these diseases, pseudoxanthoma elasticum included. Because of these initiatives, individuals affected by these conditions benefit by being scientifically informed about their condition, having an effective support mechanism, and also by contributing to scientific research efforts and banking of biological samples. This rapid progress would not have been possible without the aid of disease advocacy organizations such as PXE International. PMID:28696355

Shorter Life Span of Microorganisms and Plants as a Consequence of Shielded Magnetic Environment

NASA Astrophysics Data System (ADS)

Dobrota, C.; Piso, I. M.; Bathory, D.

The geomagnetic field is an essential environmental factor for life and health on this planet. In order to survey how magnetic fields affect the life span and the nitrogenase (an iron-sulphur enzyme) activity of Azotobacter chroococcum as well as the life span, the main organic synthesis and the water balance of plants (22 species), the biological tests were incubated under shielded magnetic field and also in normal geo-magnetic environment. The shielding level was about 10-6 of the terrestrial magnetic field.Life cycles of all organisms require the co-ordinated control of a complex set of interlocked physiological processes and metabolic pathways. Such processes are likely to be regulated by a large number of genes. Our researches suggest that the main point in biological structures, which seems to be affected by the low magnetic environment, is the water molecule. Magnetic field induces a molecular alignment. Under shielded conditions, unstructured water molecules with fewer hydrogen bonds, which are producing a more reactive environment, are occurring. As compared to control, the life span of both microorganisms and plants was shorter in shielded environment. A higher nitrogenase affinity for the substrate was recorded in normal geo-magnetic field compared to low magnetic field. The synthesis of carbohydrates, lipids, proteins and enzymes was modified under experimental conditions. The stomatal conductance was higher between 158 and 300% in shielded environment indicating an important water loss from the plant cells.Our results support the idea that the shielded magnetic environment induces different reactions depending on the time of exposure and on the main metabolic pathways of the cells.

Deleting the 14-3-3 protein Bmh1 extends life span in Saccharomyces cerevisiae by increasing stress response.

PubMed

Wang, Chen; Skinner, Craig; Easlon, Erin; Lin, Su-Ju

2009-12-01

Enhanced stress response has been suggested to promote longevity in many species. Calorie restriction (CR) and conserved nutrient-sensing target of rapamycin (TOR) and protein kinase A (PKA) pathways have also been suggested to extend life span by increasing stress response, which protects cells from age-dependent accumulation of oxidative damages. Here we show that deleting the yeast 14-3-3 protein, Bmh1, extends chronological life span (CLS) by activating the stress response. 14-3-3 proteins are highly conserved chaperone-like proteins that play important roles in many cellular processes. bmh1Delta-induced heat resistance and CLS extension require the general stress-response transcription factors Msn2, Msn4, and Rim15. The bmh1Delta mutant also displays a decreased reactive oxygen species level and increased heat-shock-element-driven transcription activity. We also show that BMH1 genetically interacts with CR and conserved nutrient-sensing TOR- and PKA-signaling pathways to regulate life span. Interestingly, the level of phosphorylated Ser238 on Bmh1 increases during chronological aging, which is delayed by CR or by reduced TOR activities. In addition, we demonstrate that PKA can directly phosphorylate Ser238 on Bmh1. The status of Bmh1 phosphorylation is therefore likely to play important roles in life-span regulation. Together, our studies suggest that phosphorylated Bmh1 may cause inhibitory effects on downstream longevity factors, including stress-response proteins. Deleting Bmh1 may eliminate the inhibitory effects of Bmh1 on these longevity factors and therefore extends life span.

Life-Span Issues in the Fair and Non-Discriminatory Evaluation of Workers.

ERIC Educational Resources Information Center

Alexander, Ralph A.; Barrett, Gerald V.

Until recently, older workers have not been recognized as a group requiring special attention in the area of fair employment practices. Thus, progress has been slow towards the development of valid and reliable indices of performance which are applicable across the life span. Research shows that many measures of employee evaluation provide no…

Atomic Bomb Survivors Life-Span Study

PubMed Central

Dobrzyński, Ludwik

2015-01-01

The atomic bomb survivors life-span study (LSS) is often claimed to support the linear no-threshold hypothesis (LNTH) of radiation carcinogenesis. This paper shows that this claim is baseless. The LSS data are equally or better described by an s-shaped dependence on radiation exposure with a threshold of about 0.3 Sievert (Sv) and saturation level at about 1.5 Sv. A Monte-Carlo simulation of possible LSS outcomes demonstrates that, given the weak statistical power, LSS cannot provide support for LNTH. Even if the LNTH is used at low dose and dose rates, its estimation of excess cancer mortality should be communicated as 2.5% per Sv, i.e., an increase of cancer mortality from about 20% spontaneous mortality to about 22.5% per Sv, which is about half of the usually cited value. The impact of the “neutron discrepancy problem” – the apparent difference between the calculated and measured values of neutron flux in Hiroshima – was studied and found to be marginal. Major revision of the radiation risk assessment paradigm is required. PMID:26673526

Life-span extension by dietary restriction is mediated by NLP-7 signaling and coelomocyte endocytosis in C. elegans.

PubMed

Park, Sang-Kyu; Link, Christopher D; Johnson, Thomas E

2010-02-01

Recent studies have shown that the rate of aging can be modulated by diverse interventions. Dietary restriction is the most widely used intervention to promote longevity; however, the mechanisms underlying the effect of dietary restriction remain elusive. In a previous study, we identified two novel genes, nlp-7 and cup-4, required for normal longevity in Caenorhabditis elegans. nlp-7 is one of a set of neuropeptide-like protein genes; cup-4 encodes an ion-channel involved in endocytosis by coelomocytes. Here, we assess whether nlp-7 and cup-4 mediate longevity increases by dietary restriction. RNAi of nlp-7 or cup-4 significantly reduces the life span of the eat-2 mutant, a genetic model of dietary restriction, but has no effect on the life span of long-lived mutants resulting from reduced insulin/IGF-1 signaling or dysfunction of the mitochondrial electron transport chain. The life-span extension observed in wild-type N2 worms by dietary restriction using bacterial dilution is prevented significantly in nlp-7 and cup-4 mutants. RNAi knockdown of genes encoding candidate receptors of NLP-7 and genes involved in endocytosis by coelomocytes also specifically shorten the life span of the eat-2 mutant. We conclude that two novel pathways, NLP-7 signaling and endocytosis by coelomocytes, are required for life extension under dietary restriction in C. elegans.

Life-span development of visual working memory: when is feature binding difficult?

PubMed

Cowan, Nelson; Naveh-Benjamin, Moshe; Kilb, Angela; Saults, J Scott

2006-11-01

We asked whether the ability to keep in working memory the binding between a visual object and its spatial location changes with development across the life span more than memory for item information. Paired arrays of colored squares were identical or differed in the color of one square, and in the latter case, the changed color was unique on that trial (item change) or was duplicated elsewhere in the array (color-location binding change). Children (8-10 and 11-12 years old) and older adults (65-85 years old) showed deficits relative to young adults. These were only partly simulated by dividing attention in young adults. The older adults had an additional deficiency, specifically in binding information, which was evident only when item- and binding-change trials were mixed together. In that situation, the older adults often overlooked the more subtle, binding-type changes. Some working memory processes related to binding undergo life-span development in an inverted-U shape, whereas other, bias- and salience-related processes that influence the use of binding information seem to develop monotonically.

Reduced Ssy1-Ptr3-Ssy5 (SPS) signaling extends replicative life span by enhancing NAD+ homeostasis in Saccharomyces cerevisiae.

PubMed

Tsang, Felicia; James, Christol; Kato, Michiko; Myers, Victoria; Ilyas, Irtqa; Tsang, Matthew; Lin, Su-Ju

2015-05-15

Attenuated nutrient signaling extends the life span in yeast and higher eukaryotes; however, the mechanisms are not completely understood. Here we identify the Ssy1-Ptr3-Ssy5 (SPS) amino acid sensing pathway as a novel longevity factor. A null mutation of SSY5 (ssy5Δ) increases replicative life span (RLS) by ∼50%. Our results demonstrate that several NAD(+) homeostasis factors play key roles in this life span extension. First, expression of the putative malate-pyruvate NADH shuttle increases in ssy5Δ cells, and deleting components of this shuttle, MAE1 and OAC1, largely abolishes RLS extension. Next, we show that Stp1, a transcription factor of the SPS pathway, directly binds to the promoter of MAE1 and OAC1 to regulate their expression. Additionally, deletion of SSY5 increases nicotinamide riboside (NR) levels and phosphate-responsive (PHO) signaling activity, suggesting that ssy5Δ increases NR salvaging. This increase contributes to NAD(+) homeostasis, partially ameliorating the NAD(+) deficiency and rescuing the short life span of the npt1Δ mutant. Moreover, we observed that vacuolar phosphatase, Pho8, is partially required for ssy5Δ-mediated NR increase and RLS extension. Together, our studies present evidence that supports SPS signaling is a novel NAD(+) homeostasis factor and ssy5Δ-mediated life span extension is likely due to concomitantly increased mitochondrial and vacuolar function. Our findings may contribute to understanding the molecular basis of NAD(+) metabolism, cellular life span, and diseases associated with NAD(+) deficiency and aging. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

ABCC6 Gene Analysis in 20 Japanese Patients with Angioid Streaks Revealing Four Frequent and Two Novel Variants and Pseudodominant Inheritance

PubMed Central

Negishi, Yuya; Mizobuchi, Kei; Urashima, Mitsuyoshi; Nakano, Tadashi

2017-01-01

Purpose To report the spectrum of ABCC6 variants in Japanese patients with angioid streaks (AS). Patients and Methods This was a single-center cohort study. The medical records of 20 patients with AS from 18 unrelated Japanese families were retrospectively reviewed. Screening of the ABCC6 gene (exons 1 to 31) was performed using PCR-based Sanger sequencing. Results Eight ABCC6 variants were identified as candidate disease-causing variants. These eight variants included five known variants (p.Q378X, p.R419Q, p.V848CfsX83, p.R1114C, and p.R1357W), one previously reported variant (p.N428S) of unknown significance, and two novel variants (c.1939C>T [p.H647Y] and c.3374C>T [p.S1125F]); the three latter variants were determined to be variants of significance. The following four variants were frequently identified: p.V848CfsX83 (14/40 alleles, 35.0%), p.Q378X (7/40 alleles, 17.5%), p.R1357W (6/40 alleles, 15.0%), and p.R419Q (4/40 alleles, 10.0%). The ABCC6 variants were identified in compound heterozygous or homozygous states in 13 of 18 probands. Two families showed a pseudodominant inheritance pattern. Pseudoxanthoma elasticum was seen in 15 of 17 patients (88.2%) who underwent dermatological examination. Conclusions We identified disease-causing ABCC6 variants that were in homozygous or compound heterozygous states in 13 of 18 families (72.2%). Our results indicated that ABCC6 variants play a significant role in patients with AS in the Japanese population. PMID:28912966

Life span and reproductive cost explain interspecific variation in the optimal onset of reproduction.

PubMed

Mourocq, Emeline; Bize, Pierre; Bouwhuis, Sandra; Bradley, Russell; Charmantier, Anne; de la Cruz, Carlos; Drobniak, Szymon M; Espie, Richard H M; Herényi, Márton; Hötker, Hermann; Krüger, Oliver; Marzluff, John; Møller, Anders P; Nakagawa, Shinichi; Phillips, Richard A; Radford, Andrew N; Roulin, Alexandre; Török, János; Valencia, Juliana; van de Pol, Martijn; Warkentin, Ian G; Winney, Isabel S; Wood, Andrew G; Griesser, Michael

2016-02-01

Fitness can be profoundly influenced by the age at first reproduction (AFR), but to date the AFR-fitness relationship only has been investigated intraspecifically. Here, we investigated the relationship between AFR and average lifetime reproductive success (LRS) across 34 bird species. We assessed differences in the deviation of the Optimal AFR (i.e., the species-specific AFR associated with the highest LRS) from the age at sexual maturity, considering potential effects of life history as well as social and ecological factors. Most individuals adopted the species-specific Optimal AFR and both the mean and Optimal AFR of species correlated positively with life span. Interspecific deviations of the Optimal AFR were associated with indices reflecting a change in LRS or survival as a function of AFR: a delayed AFR was beneficial in species where early AFR was associated with a decrease in subsequent survival or reproductive output. Overall, our results suggest that a delayed onset of reproduction beyond maturity is an optimal strategy explained by a long life span and costs of early reproduction. By providing the first empirical confirmations of key predictions of life-history theory across species, this study contributes to a better understanding of life-history evolution. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Life-Span Development of Visual Working Memory: When Is Feature Binding Difficult?

ERIC Educational Resources Information Center

Cowan, Nelson; Naveh-Benjamin, Moshe; Kilb, Angela; Saults, J. Scott

2006-01-01

We asked whether the ability to keep in working memory the binding between a visual object and its spatial location changes with development across the life span more than memory for item information. Paired arrays of colored squares were identical or differed in the color of one square, and in the latter case, the changed color was unique on…

Improvement/Maintenance and Reorientation as Central Features of Coping with Major Life Change and Loss: Contributions of Three Life-Span Theories

ERIC Educational Resources Information Center

Boerner, Kathrin; Jopp, Daniela

2007-01-01

This article focuses on the common and unique contributions of three major life-span theories in addressing improvement/maintenance and reorientation, which represent central processes of coping with major life change and loss. For this purpose, we review and compare the dual-process model of assimilative and accommodative coping, the model of…

Life-Span Exposure to Low Doses of Aspartame Beginning during Prenatal Life Increases Cancer Effects in Rats

PubMed Central

Soffritti, Morando; Belpoggi, Fiorella; Tibaldi, Eva; Esposti, Davide Degli; Lauriola, Michelina

2007-01-01

Background In a previous study conducted at the Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation (CMCRC/ERF), we demonstrated for the first time that aspartame (APM) is a multipotent carcinogenic agent when various doses are administered with feed to Sprague-Dawley rats from 8 weeks of age throughout the life span. Objective The aim of this second study is to better quantify the carcinogenic risk of APM, beginning treatment during fetal life. Methods We studied groups of 70–95 male and female Sprague-Dawley rats administered APM (2,000, 400, or 0 ppm) with feed from the 12th day of fetal life until natural death. Results Our results show a) a significant dose-related increase of malignant tumor–bearing animals in males (p < 0.01), particularly in the group treated with 2,000 ppm APM (p < 0.01); b) a significant increase in incidence of lymphomas/leukemias in males treated with 2,000 ppm (p < 0.05) and a significant dose-related increase in incidence of lymphomas/leukemias in females (p < 0.01), particularly in the 2,000-ppm group (p < 0.01); and c) a significant dose-related increase in incidence of mammary cancer in females (p < 0.05), particularly in the 2,000-ppm group (p < 0.05). Conclusions The results of this carcinogenicity bioassay confirm and reinforce the first experimental demonstration of APM’s multipotential carcinogenicity at a dose level close to the acceptable daily intake for humans. Furthermore, the study demonstrates that when life-span exposure to APM begins during fetal life, its carcinogenic effects are increased. PMID:17805418

Loss of the clock protein PER2 shortens the erythrocyte life span in mice.

PubMed

Sun, Qi; Zhao, Yue; Yang, Yunxia; Yang, Xiao; Li, Minghui; Xu, Xi; Wen, Dan; Wang, Junsong; Zhang, Jianfa

2017-07-28

Cell proliferation and release from the bone marrow have been demonstrated to be controlled by circadian rhythms in both humans and mice. However, it is unclear whether local circadian clocks in the bone marrow influence physiological functions and life span of erythrocytes. Here, we report that loss of the clock gene Per2 significantly decreased erythrocyte life span. Mice deficient in Per2 were more susceptible to acute stresses in the erythrocytes, becoming severely anemic upon phenylhydrazine, osmotic, and H 2 O 2 challenges. 1 H NMR-based metabolomics analysis revealed that the Per2 depletion causes significant changes in metabolic profiles of erythrocytes, including increased lactate and decreased ATP levels compared with wild-type mice. The lower ATP levels were associated with hyperfunction of Na + /K + -ATPase activity in Per2 -null erythrocytes, and inhibition of Na + /K + -ATPase activity by ouabain efficiently rescued ATP levels. Per2 -null mice displayed increased levels of Na + /K + -ATPase α1 (ATP1A1) in the erythrocyte membrane, and transfection of Per2 cDNA into the erythroleukemic cell line TF-1 inhibited Atp1a1 expression. Furthermore, we observed that PER2 regulates Atp1a1 transcription through interacting with trans-acting transcription factor 1 (SP1). Our findings reveal that Per2 function in the bone marrow is required for the regulation of life span in circulating erythrocytes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Effects of a Short Strategy Training on Metacognitive Monitoring across the Life-Span

ERIC Educational Resources Information Center

von der Linden, Nicole; Löffler, Elisabeth; Schneider, Wolfgang

2015-01-01

The present study was conducted to explore the potential positive influence of a short strategy training on metacognitive monitoring competencies covering a life-span approach. Participants of four age groups (3rd-grade children, adolescents, younger and older adults) concluded a paired-associate learning task. Additionally, they gave delayed…

ABCC5 Transporter is a Novel Type 2 Diabetes Susceptibility Gene in European and African American Populations

PubMed Central

Direk, Kenan; Lau, Winston; Small, Kerrin S; Maniatis, Nikolas; Andrew, Toby

2014-01-01

Numerous functional studies have implicated PARL in relation to type 2 diabetes (T2D). We hypothesised that conflicting human association studies may be due to neighbouring causal variants being in linkage disequilibrium (LD) with PARL. We conducted a comprehensive candidate gene study of the extended LD genomic region that includes PARL and transporter ABCC5 using three data sets (two European and one African American), in relation to healthy glycaemic variation, visceral fat accumulation and T2D disease. We observed no evidence for previously reported T2D association with Val262Leu or PARL using array and fine-map genomic and expression data. By contrast, we observed strong evidence of T2D association with ABCC5 (intron 26) for European and African American samples (P = 3E−07) and with ABCC5 adipose expression in Europeans [odds ratio (OR) = 3.8, P = 2E−04]. The genomic location estimate for the ABCC5 functional variant, associated with all phenotypes and expression data (P = 1E−11), was identical for all samples (at Chr3q 185,136 kb B36), indicating that the risk variant is an expression quantitative trait locus (eQTL) with increased expression conferring risk of disease. That the association with T2D is observed in populations of disparate ancestry suggests the variant is a ubiquitous risk factor for T2D. PMID:25117150

Genome-wide screen in Saccharomyces cerevisiae identifies vacuolar protein sorting, autophagy, biosynthetic, and tRNA methylation genes involved in life span regulation.

PubMed

Fabrizio, Paola; Hoon, Shawn; Shamalnasab, Mehrnaz; Galbani, Abdulaye; Wei, Min; Giaever, Guri; Nislow, Corey; Longo, Valter D

2010-07-15

The study of the chronological life span of Saccharomyces cerevisiae, which measures the survival of populations of non-dividing yeast, has resulted in the identification of homologous genes and pathways that promote aging in organisms ranging from yeast to mammals. Using a competitive genome-wide approach, we performed a screen of a complete set of approximately 4,800 viable deletion mutants to identify genes that either increase or decrease chronological life span. Half of the putative short-/long-lived mutants retested from the primary screen were confirmed, demonstrating the utility of our approach. Deletion of genes involved in vacuolar protein sorting, autophagy, and mitochondrial function shortened life span, confirming that respiration and degradation processes are essential for long-term survival. Among the genes whose deletion significantly extended life span are ACB1, CKA2, and TRM9, implicated in fatty acid transport and biosynthesis, cell signaling, and tRNA methylation, respectively. Deletion of these genes conferred heat-shock resistance, supporting the link between life span extension and cellular protection observed in several model organisms. The high degree of conservation of these novel yeast longevity determinants in other species raises the possibility that their role in senescence might be conserved.

Psychopathology in Williams Syndrome: The Effect of Individual Differences across the Life Span

ERIC Educational Resources Information Center

Dodd, Helen F.; Porter, Melanie A.

2009-01-01

This research aimed to comprehensively explore psychopathology in Williams syndrome (WS) across the life span and evaluate the relationship between psychopathology and age category (child or adult), gender, and cognitive ability. The parents of 50 participants with WS, ages 6-50 years, were interviewed using the Schedule for Affective Disorders…

MAPK Signaling Pathway Alters Expression of Midgut ALP and ABCC Genes and Causes Resistance to Bacillus thuringiensis Cry1Ac Toxin in Diamondback Moth

PubMed Central

Wu, Qingjun; Wang, Shaoli; Xie, Wen; Zhu, Xun; Baxter, Simon W.; Zhou, Xuguo; Jurat-Fuentes, Juan Luis; Zhang, Youjun

2015-01-01

Insecticidal crystal toxins derived from the soil bacterium Bacillus thuringiensis (Bt) are widely used as biopesticide sprays or expressed in transgenic crops to control insect pests. However, large-scale use of Bt has led to field-evolved resistance in several lepidopteran pests. Resistance to Bt Cry1Ac toxin in the diamondback moth, Plutella xylostella (L.), was previously mapped to a multigenic resistance locus (BtR-1). Here, we assembled the 3.15 Mb BtR-1 locus and found high-level resistance to Cry1Ac and Bt biopesticide in four independent P. xylostella strains were all associated with differential expression of a midgut membrane-bound alkaline phosphatase (ALP) outside this locus and a suite of ATP-binding cassette transporter subfamily C (ABCC) genes inside this locus. The interplay between these resistance genes is controlled by a previously uncharacterized trans-regulatory mechanism via the mitogen-activated protein kinase (MAPK) signaling pathway. Molecular, biochemical, and functional analyses have established ALP as a functional Cry1Ac receptor. Phenotypic association experiments revealed that the recessive Cry1Ac resistance was tightly linked to down-regulation of ALP, ABCC2 and ABCC3, whereas it was not linked to up-regulation of ABCC1. Silencing of ABCC2 and ABCC3 in susceptible larvae reduced their susceptibility to Cry1Ac but did not affect the expression of ALP, whereas suppression of MAP4K4, a constitutively transcriptionally-activated MAPK upstream gene within the BtR-1 locus, led to a transient recovery of gene expression thereby restoring the susceptibility in resistant larvae. These results highlight a crucial role for ALP and ABCC genes in field-evolved resistance to Cry1Ac and reveal a novel trans-regulatory signaling mechanism responsible for modulating the expression of these pivotal genes in P. xylostella. PMID:25875245

SCN1A, ABCC2 and UGT2B7 gene polymorphisms in association with individualized oxcarbazepine therapy.

PubMed

Ma, Chun-Lai; Wu, Xun-Yi; Jiao, Zheng; Hong, Zhen; Wu, Zhi-Yuan; Zhong, Ming-Kang

2015-01-01

Associations between the effects of SCN1A, SCN2A, ABCC2 and UGT2B7 genetic polymorphisms and oxcarbazepine (OXC) maintenance doses in Han Chinese epileptic patients were investigated. Genetic polymorphisms were detected in 184 epileptic patients receiving OXC monotherapy by high-resolution melting curve and TaqMan method. Carriers of the SCN1A IVS5-91G>A, UGT2B7 c.802T>C and ABCC2 c.1249G>A variant alleles required significantly higher OXC maintenance doses than noncarriers (p < 0.05). Corresponding relative ln (concentration-dose ratios) values for SCN1A IVS5-91 variants differed by the genotypic order GG > GA > AA. SCN1A, UGT2B7 and ABCC2 genetic polymorphisms are associated with OXC maintenance doses and may be useful for the personalization of OXC therapy in epileptic patients. Further studies are needed. Original submitted 6 June 2014; Revision submitted 5 September 2014.

Spontaneous locomotor activity and life span. A test of the rate of living theory in Drosophila melanogaster.

PubMed

Lints, F A; Le Bourg, E; Lints, C V

1984-01-01

The spontaneous locomotor activity and life span of approximately 600 individuals of both sexes and of three widely different genotypes of Drosophila melanogaster have been measured. Neither at the individual nor at the populational level could a significant correlation between spontaneous locomotor activity and life span be found. The results are discussed in relation with Pearl's [The rate of living, London University Press, London 1928] rate of living theory. That theory has been tested in relation with environmental temperature, oxygen consumption and activity. It is shown that the theory has received no definite confirmation until now.

Two-carbon metabolites, polyphenols and vitamins influence yeast chronological life span in winemaking conditions

PubMed Central

2012-01-01

Background Viability in a non dividing state is referred to as chronological life span (CLS). Most grape juice fermentation happens when Saccharomyces cerevisiae yeast cells have stopped dividing; therefore, CLS is an important factor toward winemaking success. Results We have studied both the physical and chemical determinants influencing yeast CLS. Low pH and heat shorten the maximum wine yeast life span, while hyperosmotic shock extends it. Ethanol plays an important negative role in aging under winemaking conditions, but additional metabolites produced by fermentative metabolism, such as acetaldehyde and acetate, have also a strong impact on longevity. Grape polyphenols quercetin and resveratrol have negative impacts on CLS under winemaking conditions, an unexpected behavior for these potential anti-oxidants. We observed that quercetin inhibits alcohol and aldehyde dehydrogenase activities, and that resveratrol performs a pro-oxidant role during grape juice fermentation. Vitamins nicotinic acid and nicotinamide are precursors of NAD+, and their addition reduces mean longevity during fermentation, suggesting a metabolic unbalance negative for CLS. Moreover, vitamin mix supplementation at the end of fermentation shortens CLS and enhances cell lysis, while amino acids increase life span. Conclusions Wine S. cerevisiae strains are able to sense changes in the environmental conditions and adapt their longevity to them. Yeast death is influenced by the conditions present at the end of wine fermentation, particularly by the concentration of two-carbon metabolites produced by the fermentative metabolism, such as ethanol, acetic acid and acetaldehyde, and also by the grape juice composition, particularly its vitamin content. PMID:22873488

Replication of TPMT and ABCC3 genetic variants highly associated with cisplatin-induced hearing loss in children.

PubMed

Pussegoda, K; Ross, C J; Visscher, H; Yazdanpanah, M; Brooks, B; Rassekh, S R; Zada, Y F; Dubé, M-P; Carleton, B C; Hayden, M R

2013-08-01

Cisplatin is a widely used chemotherapeutic agent for the treatment of solid tumors. A serious complication of cisplatin treatment is permanent hearing loss. The aim of this study was to replicate previous genetic findings in an independent cohort of 155 pediatric patients. Associations were replicated for genetic variants in TPMT (rs12201199, P = 0.0013, odds ratio (OR) 6.1) and ABCC3 (rs1051640, P = 0.036, OR 1.8). A predictive model combining variants in TPMT, ABCC3, and COMT with clinical variables (patient age, vincristine treatment, germ-cell tumor, and cranial irradiation) significantly improved the prediction of hearing-loss development as compared with using clinical risk factors alone (area under the curve (AUC) 0.786 vs. 0.708, P = 0.00048). The novel combination of genetic and clinical factors predicted the risk of hearing loss with a sensitivity of 50.3% and a specificity of 92.7%. These findings provide evidence to support the importance of TPMT, COMT, and ABCC3 in the prediction of cisplatin-induced hearing loss in children.

Replication of TPMT and ABCC3 Genetic Variants Highly Associated With Cisplatin-Induced Hearing Loss in Children

PubMed Central

Pussegoda, K; Ross, CJ; Visscher, H; Yazdanpanah, M; Brooks, B; Rassekh, SR; Zada, YF; Dubé, M-P; Carleton, BC; Hayden, MR

2014-01-01

Cisplatin is a widely used chemotherapeutic agent for the treatment of solid tumors. A serious complication of cisplatin treatment is permanent hearing loss. The aim of this study was to replicate previous genetic findings in an independent cohort of 155 pediatric patients. Associations were replicated for genetic variants in TPMT (rs12201199, P = 0.0013, odds ratio (OR) 6.1) and ABCC3 (rs1051640, P = 0.036, OR 1.8). A predictive model combining variants in TPMT, ABCC3, and COMT with clinical variables (patient age, vincristine treatment, germ-cell tumor, and cranial irradiation) significantly improved the prediction of hearing-loss development as compared with using clinical risk factors alone (area under the curve (AUC) 0.786 vs. 0.708, P = 0.00048). The novel combination of genetic and clinical factors predicted the risk of hearing loss with a sensitivity of 50.3% and a specificity of 92.7%. These findings provide evidence to support the importance of TPMT, COMT, and ABCC3 in the prediction of cisplatin-induced hearing loss in children. PMID:23588304

Oxidative stress and the evolution of sex differences in life span and ageing in the decorated cricket, Gryllodes sigillatus.

PubMed

Archer, Catharine R; Sakaluk, Scott K; Selman, Colin; Royle, Nick J; Hunt, John

2013-03-01

The Free Radical Theory of Ageing (FRTA) predicts that oxidative stress, induced when levels of reactive oxygen species exceed the capacity of antioxidant defenses, causes ageing. Recently, it has also been argued that oxidative damage may mediate important life-history trade-offs. Here, we use inbred lines of the decorated cricket, Gryllodes sigillatus, to estimate the genetic (co)variance between age-dependent reproductive effort, life span, ageing, oxidative damage, and total antioxidant capacity within and between the sexes. The FRTA predicts that oxidative damage should accumulate with age and negatively correlate with life span. We find that protein oxidation is greater in the shorter lived sex (females) and negatively genetically correlated with life span in both sexes. However, oxidative damage did not accumulate with age in either sex. Previously we have shown antagonistic pleiotropy between the genes for early-life reproductive effort and ageing rate in both sexes, although this was stronger in females. In females, we find that elevated fecundity early in life is associated with greater protein oxidation later in life, which is in turn positively correlated with the rate of ageing. Our results provide mixed support for the FRTA but suggest that oxidative stress may mediate sex-specific life-history strategies in G. sigillatus. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

Intermittent Administration of Rapamycin Extends the Life Span of Female C57BL/6J Mice.

PubMed

Arriola Apelo, Sebastian I; Pumper, Cassidy P; Baar, Emma L; Cummings, Nicole E; Lamming, Dudley W

2016-07-01

Inhibition of the mTOR (mechanistic target of rapamycin) signaling pathway by the FDA-approved drug rapamycin promotes life span in numerous model organisms and delays age-related disease in mice. However, the utilization of rapamycin as a therapy for age-related diseases will likely prove challenging due to the serious metabolic and immunological side effects of rapamycin in humans. We recently identified an intermittent rapamycin treatment regimen-2mg/kg administered every 5 days-with a reduced impact on glucose homeostasis and the immune system as compared with chronic treatment; however, the ability of this regimen to extend life span has not been determined. Here, we report for the first time that an intermittent rapamycin treatment regimen starting as late as 20 months of age can extend the life span of female C57BL/6J mice. Our work demonstrates that the anti-aging potential of rapamycin is separable from many of its negative side effects and suggests that carefully designed dosing regimens may permit the safer use of rapamycin and its analogs for the treatment of age-related diseases in humans. © 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.

Gene-based association study of genes linked to hippocampal sclerosis of aging neuropathology: GRN, TMEM106B, ABCC9, and KCNMB2

PubMed Central

Katsumata, Yuriko; Nelson, Peter T.; Ellingson, Sally R.; Fardo, David W.

2017-01-01

Hippocampal sclerosis of aging (HS-Aging) is a common neurodegenerative condition associated with dementia. To learn more about genetic risk of HS-Aging pathology, we tested gene-based associations of the GRN, TMEM106B, ABCC9, and KCNMB2 genes, which were reported to be associated with HS-Aging pathology in previous studies. Genetic data were obtained from the Alzheimer’s Disease Genetics Consortium (ADGC), linked to autopsy-derived neuropathological outcomes from the National Alzheimer’s Coordinating Center (NACC). Of the 3,251 subjects included in the study, 271 (8.3%) were identified as an HS-Aging case. The significant gene-based association between the ABCC9 gene and HS-Aging appeared to be driven by a region in which a significant haplotype-based association was found. We tested this haplotype as an expression Quantitative Trait Locus (eQTL) using two different public-access brain gene expression databases. The HS-Aging pathology protective ABCC9 haplotype was associated with decreased ABCC9 expression, indicating a possible toxic gain of function. PMID:28131462

The Development of Memory Efficiency and Value-Directed Remembering across the Life Span: A Cross-Sectional Study of Memory and Selectivity

ERIC Educational Resources Information Center

Castel, Alan D.; Humphreys, Kathryn L.; Lee, Steve S.; Galvan, Adriana; Balota, David A.; McCabe, David P.

2011-01-01

Although attentional control and memory change considerably across the life span, no research has examined how the ability to strategically remember important information (i.e., value-directed remembering) changes from childhood to old age. The present study examined this in different age groups across the life span (N = 320, 5-96 years old). A…

Blood volume and red cell life span (M113), part C

NASA Technical Reports Server (NTRS)

Johnson, P. C., Jr.

1973-01-01

Prechamber, in-chamber, and postchamber blood samples taken from Skylab simulation crewmembers did not indicate significant shortening of the red cell life span during the mission. This does not suggest that the space simulation environment could not be associated with red cell enzyme changes. It does show that any changes in enzymes were not sufficiently great to significantly shorten red cell survival. There was no evidence of bone marrow erythropoetic suppression nor was there any evidence of increased red cell destruction.

Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium-chain triglyceride oil on life span of genetically heterogeneous mice.

PubMed

Strong, Randy; Miller, Richard A; Astle, Clinton M; Baur, Joseph A; de Cabo, Rafael; Fernandez, Elizabeth; Guo, Wen; Javors, Martin; Kirkland, James L; Nelson, James F; Sinclair, David A; Teter, Bruce; Williams, David; Zaveri, Nurulain; Nadon, Nancy L; Harrison, David E

2013-01-01

The National Institute on Aging Interventions Testing Program (ITP) was established to evaluate agents that are hypothesized to increase life span and/or health span in genetically heterogeneous mice. Each compound is tested in parallel at three test sites. It is the goal of the ITP to publish all results, negative or positive. We report here on the results of lifelong treatment of mice, beginning at 4 months of age, with each of five agents, that is, green tea extract (GTE), curcumin, oxaloacetic acid, medium-chain triglyceride oil, and resveratrol, on the life span of genetically heterogeneous mice. Each agent was administered beginning at 4 months of age. None of these five agents had a statistically significant effect on life span of male or female mice, by log-rank test, at the concentrations tested, although a secondary analysis suggested that GTE might diminish the risk of midlife deaths in females only.

The Use of Digital Technologies across the Adult Life Span in Distance Education

ERIC Educational Resources Information Center

Jelfs, Anne; Richardson, John T. E.

2013-01-01

In June 2010, a survey was carried out to explore access to digital technology, attitudes to digital technology and approaches to studying across the adult life span in students taking courses with the UK Open University. In total, 7000 people were surveyed, of whom more than 4000 responded. Nearly all these students had access to a computer and…

The Development of Attentional Networks: Cross-Sectional Findings from a Life Span Sample

ERIC Educational Resources Information Center

Waszak, Florian; Li, Shu-Chen; Hommel, Bernhard

2010-01-01

Using a population-based sample of 263 individuals ranging from 6 to 89 years of age, we investigated the gains and losses in the abilities to (a) use exogenous cues to shift attention covertly and (b) ignore conflicting information across the life span. The participants' ability to shift visual attention was tested by a typical Posner-type…

Quantification and in situ localisation of abcb1 and abcc9genes in toxicant-exposed sea urchin embryos.

PubMed

Bošnjak, Ivana; Pleić, Ivana Lepen; Borra, Marco; Mladineo, Ivona

2013-12-01

A multixenobiotic resistance (MXR) mechanism mediated by ABC binding cassette (ABC) transport proteins is an efficient chemical defence mechanism in sea urchin embryos. The aim of our work was to evidence whether exposure to sub-lethal doses of specific contaminants (oxybenzone (OXI), mercuric chloride (HgCl2) and trybutiltin (TBT)) would induce MXR transporter activity during embryonic development (from zygote to blastula stage) in purple sea urchin (Paracentrotus lividus) embryos. Further, we present data on molecular identification, transport function, expression levels and gene localisation of two ABC efflux transporters-P-glycoprotein (ABCB1/P-gp) and sulfonylurea-receptor-like protein (ABCC9/SUR-like). Partial cDNA sequences of abcb1 and abcc9 were identified and quantitative PCR (qPCR) evidenced an increase in mRNA transcript levels of both ABC transporters during the two-cell, as well as an overall decrease during the blastulae stage. Calcein-AM efflux activity assay indicated the activation of multidrug resistance-associated protein/ABCC-like transport in the presence of HgCl2 and TBT in exposed blastulae. The in situ hybridisation of the two-cell and blastula stages showed ubiquitous localisation of both transcripts within cells, supporting qPCR data. In conclusion, ABCB1 and ABCC9 are constitutive, as are HgCl2, TBT and OXI-inducible ABC membrane transporters, coexpressed in the zygote, two-cell and blastula stages of the P. lividus. Their ubiquitous cell localisation further fortifies their protective role in early embryonic development.

Effect of Ala-Glu-Asp-Gly peptide on life span and development of spontaneous tumors in female rats exposed to different illumination regimes.

PubMed

Vinogradova, I A; Bukalev, A V; Zabezhinski, M A; Semenchenko, A V; Khavinson, V Kh; Anisimov, V N

2007-12-01

The effects of Ala-Glu-Asp-Gly peptide (Epithalon) on the life span and development of spontaneous tumors were studied in female rats exposed to standard, natural for North-Western Russia, and constant illumination. The mean life span of animals exposed to constant or natural illumination decreased by 13.5 and 25.5%, the maximum by 9 and 7 months, respectively, and spontaneous tumors developed much more rapidly than in animals living under conditions of the standard light regimen. Epithalon (0.1 microg daily 5 times a week from the age of 4 months) did not change the life span of rats living under conditions of standard day/night regimen, while in rats exposed to the natural and constant light it promoted prolongation of the maximum life span by 95 and 24 days, respectively. Epithalon prolonged the mean life span of the last 10% of rats exposed to natural and constant illumination, treated with Epithalon, by 137 and 43 days, respectively. This peptide exhibited virtually no effect on the development of spontaneous tumors in rats exposed to standard and constant illumination, but significantly inhibited their development in rats exposed to natural light.

Body Image across the Life Span in Adult Women: The Role of Self-Objectification.

ERIC Educational Resources Information Center

Tiggemann, Marika; Lynch, Jessica E.

2001-01-01

Investigated body image across life span in cross-section of women ages 20-84 years. Found that although body dissatisfaction remained stable, self-objectification, habitual body monitoring, appearance anxiety, and disordered eating all significantly decreased with age. Self- objectification mediated the relationship between age and disordered…

Ageing in a eusocial insect: molecular and physiological characteristics of life span plasticity in the honey bee

PubMed Central

Münch, D.; Amdam, G. V.; Wolschin, F.

2008-01-01

Summary Commonly held views assume that ageing, or senescence, represents an inevitable, passive, and random decline in function that is strongly linked to chronological age. In recent years, genetic intervention of life span regulating pathways, for example, in Drosophila as well as case studies in non-classical animal models, have provided compelling evidence to challenge these views. Rather than comprehensively revisiting studies on the established genetic model systems of ageing, we here focus on an alternative model organism with a wild type (unselected genotype) characterized by a unique diversity in longevity – the honey bee. Honey bee (Apis mellifera) life span varies from a few weeks to more than 2 years. This plasticity is largely controlled by environmental factors. Thereby, although individuals are closely related genetically, distinct life histories can emerge as a function of social environmental change. Another remarkable feature of the honey bee is the occurrence of reverted behavioural ontogeny in the worker (female helper) caste. This behavioural peculiarity is associated with alterations in somatic maintenance functions that are indicative of reverted senescence. Thus, although intraspecific variation in organismal life span is not uncommon, the honey bee holds great promise for gaining insights into regulatory pathways that can shape the time-course of ageing by delaying, halting or even reversing processes of senescence. These aspects provide the setting of our review. We will highlight comparative findings from Drosophila melanogaster and Caenorhabditis elegans in particular, and focus on knowledge spanning from molecular- to behavioural-senescence to elucidate how the honey bee can contribute to novel insights into regulatory mechanisms that underlie plasticity and robustness or irreversibility in ageing. PMID:18728759

Ageing in a eusocial insect: molecular and physiological characteristics of life span plasticity in the honey bee.

PubMed

Münch, D; Amdam, G V; Wolschin, F

2008-01-01

Commonly held views assume that ageing, or senescence, represents an inevitable, passive, and random decline in function that is strongly linked to chronological age. In recent years, genetic intervention of life span regulating pathways, for example, in Drosophila as well as case studies in non-classical animal models, have provided compelling evidence to challenge these views.Rather than comprehensively revisiting studies on the established genetic model systems of ageing, we here focus on an alternative model organism with a wild type (unselected genotype) characterized by a unique diversity in longevity - the honey bee.Honey bee (Apis mellifera) life span varies from a few weeks to more than 2 years. This plasticity is largely controlled by environmental factors. Thereby, although individuals are closely related genetically, distinct life histories can emerge as a function of social environmental change.Another remarkable feature of the honey bee is the occurrence of reverted behavioural ontogeny in the worker (female helper) caste. This behavioural peculiarity is associated with alterations in somatic maintenance functions that are indicative of reverted senescence. Thus, although intraspecific variation in organismal life span is not uncommon, the honey bee holds great promise for gaining insights into regulatory pathways that can shape the time-course of ageing by delaying, halting or even reversing processes of senescence. These aspects provide the setting of our review.We will highlight comparative findings from Drosophila melanogaster and Caenorhabditis elegans in particular, and focus on knowledge spanning from molecular- to behavioural-senescence to elucidate how the honey bee can contribute to novel insights into regulatory mechanisms that underlie plasticity and robustness or irreversibility in ageing.

Inducible knockdown of pregnancy-associated plasma protein-A gene expression in adult female mice extends life span.

PubMed

Bale, Laurie K; West, Sally A; Conover, Cheryl A

2017-08-01

Pregnancy-associated plasma protein-A (PAPP-A) knockout (KO) mice, generated through homologous recombination in embryonic stem cells, have a significantly increased lifespan compared to wild-type littermates. However, it is unknown whether this longevity advantage would pertain to PAPP-A gene deletion in adult animals. In the present study, we used tamoxifen (Tam)-inducible Cre recombinase-mediated excision of the floxed PAPP-A (fPAPP-A) gene in mice at 5 months of age. fPAPP-A mice, which were either positive (pos) or negative (neg) for Tam-Cre, received Tam treatment with quarterly boosters. Only female mice could be used with this experimental design. fPAPP-A/neg and fPAPP-A/pos mice had similar weights at the start of the experiment and showed equivalent weight gain. We found that fPAPP-A/pos mice had a significant extension of life span (P = 0.005). The median life span was increased by 21% for fPAPP-A/pos compared to fPAPP-A/neg mice. Analysis of mortality in life span quartiles indicated that the proportion of deaths of fPAPP-A/pos mice were lower than fPAPP-A/neg mice at young adult ages (P = 0.002 for 601-800 days) and higher than fPAPP-A/neg mice at older ages (P = 0.004 for >1000 days). Thus, survival curves and age-specific mortality indicate that female mice with knockdown of PAPP-A gene expression as adults have an extended healthy life span. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Dietary supplementation with Lovaza and krill oil shortens the life span of long-lived F1 mice.

PubMed

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

2014-06-01

Marine oils rich in ω-3 polyunsaturated fatty acids have been recommended as a preventive treatment for patients at risk for cardiovascular diseases. These oils also are the third most consumed dietary supplement in the USA. However, evidence for their health benefits is equivocal. We tested the daily, isocaloric administration of krill oil (1.17 g oil/kg diet) and Lovaza (Omacor; 4.40 g/kg diet), a pharmaceutical grade fish oil, beginning at 12 months of age, on the life span and mortality-related pathologies of long-lived, male, B6C3F1 mice. The oils were incorporated into the chemically defined American Institute of Nutrition (AIN)-93 M diet. An equivalent volume of soybean oil was removed. Krill oil was 3 % and Lovaza 11 % of the oil in the diets. When their effects were analyzed together, the marine oils significantly shortened life span by 6.6 % (P = 0.0321; log-rank test) relative to controls. Individually, Lovaza and krill oil non-significantly shortened median life span by 9.8 and 4.7 %, respectively. Lovaza increased the number of enlarged seminal vesicles (7.1-fold). Lovaza and krill oil significantly increased lung tumors (4.1- and 8.2-fold) and hemorrhagic diathesis (3.9- and 3.1-fold). Analysis of serum from treated mice found that Lovaza slightly increased blood urea nitrogen, while krill oil modestly increased bilirubin, triglycerides, and blood glucose levels. Taken together, the results do not support the idea that the consumption of isolated ω-3 fatty acid-rich oils will increase the life span or health of initially healthy individuals.

Attachment and the Processing of Social Information across the Life Span: Theory and Evidence

ERIC Educational Resources Information Center

Dykas, Matthew J.; Cassidy, Jude

2011-01-01

Researchers have used J. Bowlby's (1969/1982, 1973, 1980, 1988) attachment theory frequently as a basis for examining whether experiences in close personal relationships relate to the processing of social information across childhood, adolescence, and adulthood. We present an integrative life-span-encompassing theoretical model to explain the…

Evaluation of Resveratrol, Green Tea Extract, Curcumin, Oxaloacetic Acid, and Medium-Chain Triglyceride Oil on Life Span of Genetically Heterogeneous Mice

PubMed Central

Miller, Richard A.; Astle, Clinton M.; Baur, Joseph A.; de Cabo, Rafael; Fernandez, Elizabeth; Guo, Wen; Javors, Martin; Kirkland, James L.; Nelson, James F.; Sinclair, David A.; Teter, Bruce; Williams, David; Zaveri, Nurulain; Nadon, Nancy L.; Harrison, David E.

2013-01-01

The National Institute on Aging Interventions Testing Program (ITP) was established to evaluate agents that are hypothesized to increase life span and/or health span in genetically heterogeneous mice. Each compound is tested in parallel at three test sites. It is the goal of the ITP to publish all results, negative or positive. We report here on the results of lifelong treatment of mice, beginning at 4 months of age, with each of five agents, that is, green tea extract (GTE), curcumin, oxaloacetic acid, medium-chain triglyceride oil, and resveratrol, on the life span of genetically heterogeneous mice. Each agent was administered beginning at 4 months of age. None of these five agents had a statistically significant effect on life span of male or female mice, by log-rank test, at the concentrations tested, although a secondary analysis suggested that GTE might diminish the risk of midlife deaths in females only. PMID:22451473

In Silico and in Vitro Modeling of Hepatocyte Drug Transport Processes: Importance of ABCC2 Expression Levels in the Disposition of CarboxydichloroflurosceinS⃞

PubMed Central

Howe, Katharine; Gibson, G. Gordon; Coleman, Tanya; Plant, Nick

2009-01-01

The impact of transport proteins in the disposition of chemicals is becoming increasingly evident. Alteration in disposition can cause altered pharmacokinetic and pharmacodynamic parameters, potentially leading to reduced efficacy or overt toxicity. We have developed a quantitative in silico model, based upon literature and experimentally derived data, to model the disposition of carboxydichlorofluroscein (CDF), a substrate for the SLCO1A/B and ABCC subfamilies of transporters. Kinetic parameters generated by the in silico model closely match both literature and experimentally derived kinetic values, allowing this model to be used for the examination of transporter action in primary rat hepatocytes. In particular, we show that the in silico model is suited to the rapid, accurate determination of Ki values, using 3-[[3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl]-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid (MK571) as a prototypical pan-ABCC inhibitor. In vitro-derived data are often used to predict in vivo response, and we have examined how differences in protein expression levels between these systems may affect chemical disposition. We show that ABCC2 and ABCC3 are overexpressed in sandwich culture hepatocytes by 3.5- and 2.3-fold, respectively, at the protein level. Correction for this in markedly different disposition of CDF, with the area under the concentration versus time curve and Cmax of intracellular CDF increasing by 365 and 160%, respectively. Finally, using kinetic simulations we show that ABCC2 represents a fragile node within this pathway, with alterations in ABCC2 having the most prominent effects on both the Km and Vmax through the pathway. This is the first demonstration of the utility of modeling approaches to estimate the impact of drug transport processes on chemical disposition. PMID:19022944

Molecular model of the outward facing state of the human P-glycoprotein (ABCB1), and comparison to a model of the human MRP5 (ABCC5)

PubMed Central

Ravna, Aina W; Sylte, Ingebrigt; Sager, Georg

2007-01-01

Background Multidrug resistance is a particular limitation to cancer chemotherapy, antibiotic treatment and HIV medication. The ABC (ATP binding cassette) transporters human P-glycoprotein (ABCB1) and the human MRP5 (ABCC5) are involved in multidrug resistance. Results In order to elucidate structural and molecular concepts of multidrug resistance, we have constructed a molecular model of the ATP-bound outward facing conformation of the human multidrug resistance protein ABCB1 using the Sav1866 crystal structure as a template, and compared the ABCB1 model with a previous ABCC5 model. The electrostatic potential surface (EPS) of the ABCB1 substrate translocation chamber, which transports cationic amphiphilic and lipophilic substrates, was neutral with negative and weakly positive areas. In contrast, EPS of the ABCC5 substrate translocation chamber, which transports organic anions, was generally positive. Positive-negative ratios of amino acids in the TMDs of ABCB1 and ABCC5 were also analyzed, and the positive-negative ratio of charged amino acids was higher in the ABCC5 TMDs than in the ABCB1 TMDs. In the ABCB1 model residues Leu65 (transmembrane helix 1 (TMH1)), Ile306 (TMH5), Ile340 (TMH6) and Phe343 (TMH6) may form a binding site, and this is in accordance with previous site directed mutagenesis studies. Conclusion The Sav1866 X-ray structure may serve as a suitable template for the ABCB1 model, as it did with ABCC5. The EPS in the substrate translocation chambers and the positive-negative ratio of charged amino acids were in accordance with the transport of cationic amphiphilic and lipophilic substrates by ABCB1, and the transport of organic anions by ABCC5. PMID:17803828

Self-esteem development across the life span: a longitudinal study with a large sample from Germany.

PubMed

Orth, Ulrich; Maes, Jürgen; Schmitt, Manfred

2015-02-01

The authors examined the development of self-esteem across the life span. Data came from a German longitudinal study with 3 assessments across 4 years of a sample of 2,509 individuals ages 14 to 89 years. The self-esteem measure used showed strong measurement invariance across assessments and birth cohorts. Latent growth curve analyses indicated that self-esteem follows a quadratic trajectory across the life span, increasing during adolescence, young adulthood, and middle adulthood, reaching a peak at age 60 years, and then declining in old age. No cohort effects on average levels of self-esteem or on the shape of the trajectory were found. Moreover, the trajectory did not differ across gender, level of education, or for individuals who had lived continuously in West versus East Germany (i.e., the 2 parts of Germany that had been separate states from 1949 to 1990). However, the results suggested that employment status, household income, and satisfaction in the domains of work, relationships, and health contribute to a more positive life span trajectory of self-esteem. The findings have significant implications, because they call attention to developmental stages in which individuals may be vulnerable because of low self-esteem (such as adolescence and old age) and to factors that predict successful versus problematic developmental trajectories. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Lifelong alpha-tocopherol supplementation increases the median life span of C57BL/6 mice in the cold but has only minor effects on oxidative damage.

PubMed

Selman, Colin; McLaren, Jane S; Mayer, Claus; Duncan, Jackie S; Collins, Andrew R; Duthie, Garry G; Redman, Paula; Speakman, John R

2008-02-01

The effects of dietary antioxidant supplementation on oxidative stress and life span are confused. We maintained C57BL/6 mice at 7 +/- 2 degrees C and supplemented their diet with alpha-tocopherol from 4 months of age. Supplementation significantly increased (p = 0.042) median life span by 15% (785 days, n = 44) relative to unsupplemented controls (682 days, n = 43) and also increased maximum life span (oldest 10%, p = 0.028). No sex or sex by treatment interaction effects were observed on life span, with treatment having no effect on resting or daily metabolic rate. Lymphocyte and hepatocyte oxidative DNA damage and hepatic lipid peroxidation were unaffected by supplementation, but hepatic oxidative DNA damage increased with age. Using a cDNA macroarray, genes associated with xenobiotic metabolism were significantly upregulated in the livers of female mice at 6 months of age (2 months supplementation). At 22 months of age (18 months supplementation) this response had largely abated, but various genes linked to the p21 signaling pathway were upregulated at this time. We suggest that alpha-tocopherol may initially be metabolized as a xenobiotic, potentially explaining why previous studies observe a life span extension generally when lifelong supplementation is initiated early in life. The absence of any significant effect on oxidative damage suggests that the life span extension observed was not mediated via any antioxidant properties of alpha-tocopherol. We propose that the life span extension observed following alpha-tocopherol supplementation may be mediated via upregulation of cytochrome p450 genes after 2 months of supplementation and/or upregulation of p21 signaling genes after 18 months of supplementation. However, these signaling pathways now require further investigation to establish their exact role in life span extension following alpha-tocopherol supplementation.

NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice.

PubMed

Zhang, Hongbo; Ryu, Dongryeol; Wu, Yibo; Gariani, Karim; Wang, Xu; Luan, Peiling; D'Amico, Davide; Ropelle, Eduardo R; Lutolf, Matthias P; Aebersold, Ruedi; Schoonjans, Kristina; Menzies, Keir J; Auwerx, Johan

2016-06-17

Adult stem cells (SCs) are essential for tissue maintenance and regeneration yet are susceptible to senescence during aging. We demonstrate the importance of the amount of the oxidized form of cellular nicotinamide adenine dinucleotide (NAD(+)) and its effect on mitochondrial activity as a pivotal switch to modulate muscle SC (MuSC) senescence. Treatment with the NAD(+) precursor nicotinamide riboside (NR) induced the mitochondrial unfolded protein response and synthesis of prohibitin proteins, and this rejuvenated MuSCs in aged mice. NR also prevented MuSC senescence in the mdx (C57BL/10ScSn-Dmd(mdx)/J) mouse model of muscular dystrophy. We furthermore demonstrate that NR delays senescence of neural SCs and melanocyte SCs and increases mouse life span. Strategies that conserve cellular NAD(+) may reprogram dysfunctional SCs and improve life span in mammals. Copyright © 2016, American Association for the Advancement of Science.

Selected ABCB1, ABCB4 and ABCC2 polymorphisms do not enhance the risk of drug-induced hepatotoxicity in a Spanish cohort.

PubMed

Ulzurrun, Eugenia; Stephens, Camilla; Ruiz-Cabello, Francisco; Robles-Diaz, Mercedes; Saenz-López, Pablo; Hallal, Hacibe; Soriano, German; Roman, Eva; Fernandez, M Carmen; Lucena, M Isabel; Andrade, Raúl J

2014-01-01

Flawed ABC transporter functions may contribute to increased risk of drug-induced liver injury (DILI). We aimed to analyse the influence of genetic variations in ABC transporters on the risk of DILI development and clinical presentations in a large Spanish DILI cohort. A total of ten polymorphisms in ABCB1 (1236T>C, 2677G>T,A, 3435T>C), ABCB4 (1954A>G) and ABCC2 (-1774G>del, -1549A>G, -24C>T, 1249G>A, 3972C>T and 4544G>A) were genotyped using Taqman 5' allelic discrimination assays or sequencing in 141 Spanish DILI patients and 161 controls. The influence of specific genotypes, alleles and haplotypes on the risk of DILI development and clinical presentations was analysed. None of the individual polymorphisms or haplotypes was found to be associated with DILI development. Carriers homozygous for the ABCC2 -1774del allele were however only found in DILI patients. Hence, this genotype could potentially be associated with increased risk, though its low frequency in our Spanish cohort prevented a final conclusion. Furthermore, carriers homozygous for the ABCC2 -1774G/-1549A/-24T/1249G/3972T/4544G haplotype were found to have a higher propensity for total bilirubin elevations when developing DILI. Our findings do not support a role for the analysed polymorphisms in the ABCB1, ABCB4 and ABCC2 transporter genes in DILI development in Spanish patients. The ABCC2 -1774deldel genotype was however restricted to DILI cases and could potentially contribute to enhanced DILI susceptibility.

Photosynthetic thermotolerance of woody savanna species in China is correlated with leaf life span

PubMed Central

Zhang, Jiao-Lin; Poorter, L.; Hao, Guang-You; Cao, Kun-Fang

2012-01-01

Background and Aims Photosynthetic thermotolerance (PT) is important for plant survival in tropical and sub-tropical savannas. However, little is known about thermotolerance of tropical and sub-tropical wild plants and its association with leaf phenology and persistence. Longer-lived leaves of savanna plants may experience a higher risk of heat stress. Foliar Ca is related to cell integrity of leaves under stresses. In this study it is hypothesized that (1) species with leaf flushing in the hot-dry season have greater PT than those with leaf flushing in the rainy season; and (2) PT correlates positively with leaf life span, leaf mass per unit area (LMA) and foliar Ca concentration ([Ca]) across woody savanna species. Methods The temperature-dependent increase in minimum fluorescence was measured to assess PT, together with leaf dynamics, LMA and [Ca] for a total of 24 woody species differing in leaf flushing time in a valley-type savanna in south-west China. Key Results The PT of the woody savanna species with leaf flushing in the hot-dry season was greater than that of those with leaf flushing in the rainy season. Thermotolerance was positively associated with leaf life span and [Ca] for all species irrespective of the time of flushing. The associations of PT with leaf life span and [Ca] were evolutionarily correlated. Thermotolerance was, however, independent of LMA. Conclusions Chinese savanna woody species are adapted to hot-dry habitats. However, the current maximum leaf temperature during extreme heat stress (44·3 °C) is close to the critical temperature of photosystem II (45·2 °C); future global warming may increase the risk of heat damage to the photosynthetic apparatus of Chinese savanna species. PMID:22875810

Nup100 regulates Saccharomyces cerevisiae replicative life span by mediating the nuclear export of specific tRNAs

PubMed Central

Lord, Christopher L.; Ospovat, Ophir; Wente, Susan R.

2017-01-01

Nuclear pore complexes (NPCs), which are composed of nucleoporins (Nups) and regulate transport between the nucleus and cytoplasm, significantly impact the replicative life span (RLS) of Saccharomyces cerevisiae. We previously reported that deletion of the nonessential gene NUP100 increases RLS, although the molecular basis for this effect was unknown. In this study, we find that nuclear tRNA accumulation contributes to increased longevity in nup100Δ cells. Fluorescence in situ hybridization (FISH) experiments demonstrate that several specific tRNAs accumulate in the nuclei of nup100Δ mutants. Protein levels of the transcription factor Gcn4 are increased when NUP100 is deleted, and GCN4 is required for the elevated life spans of nup100Δ mutants, similar to other previously described tRNA export and ribosomal mutants. Northern blots indicate that tRNA splicing and aminoacylation are not significantly affected in nup100Δ cells, suggesting that Nup100 is largely required for nuclear export of mature, processed tRNAs. Distinct tRNAs accumulate in the nuclei of nup100Δ and msn5Δ mutants, while Los1-GFP nucleocytoplasmic shuttling is unaffected by Nup100. Thus, we conclude that Nup100 regulates tRNA export in a manner distinct from Los1 or Msn5. Together, these experiments reveal a novel Nup100 role in the tRNA life cycle that impacts the S. cerevisiae life span. PMID:27932586

Gains and Losses in Creative Personality as Perceived by Adults across the Life Span

ERIC Educational Resources Information Center

Hui, Anna N. N.; Yeung, Dannii Y.; Sue-Chan, Christina; Chan, Kara; Hui, Desmond C. K.; Cheng, Sheung-Tak

2014-01-01

In this study, we used a life span model to study the subjective perception of creative personality (CP) in emerging, young, middle-aged, and older Hong Kong Chinese adults. We also asked participants to estimate the approximate age by which people develop and lose CP across adulthood. We expected an interesting interplay between internalized age…

Extending the Human Life Span: An Exploratory Study of Pro- and Anti-Longevity Attitudes

ERIC Educational Resources Information Center

Kogan, Nathan; Tucker, Jennifer; Porter, Matthew

2011-01-01

Successful efforts by biologists to substantially increase the life span of non-human animals has raised the possibility of extrapolation to humans, which in turn has given rise to bioethical argumentation, pro and con. The present study converts these arguments into pro- and anti-longevity items on a questionnaire and examines the structure and…

Auditory Environment across the Life Span of Cochlear Implant Users: Insights from Data Logging

ERIC Educational Resources Information Center

Busch, Tobias; Vanpoucke, Filiep; van Wieringen, Astrid

2017-01-01

Purpose: We describe the natural auditory environment of people with cochlear implants (CIs), how it changes across the life span, and how it varies between individuals. Method: We performed a retrospective cross-sectional analysis of Cochlear Nucleus 6 CI sound-processor data logs. The logs were obtained from 1,501 people with CIs (ages 0-96…

Mutational analysis of ABCC8, KCNJ11, GLUD1, HNF4A and GCK genes in 30 Chinese patients with congenital hyperinsulinism.

PubMed

Sang, Yanmei; Xu, Zidi; Liu, Min; Yan, Jie; Wu, Yujun; Zhu, Cheng; Ni, Guichen

2014-01-01

We conducted a cohort study to elucidate the molecular spectrum of congenital hyperinsulinism (CHI) in Chinese pediatric patients. Thirty Chinese children with CHI were chosen as research subjects, 16 of whom were responsive to diazoxide and 13 of whom were not (1 patient was not given the drug for medical reasons). All exons of the adenosine triphosphate (ATP)-sensitive potassium channel (KATP channel) genes KCNJ11 and ABCC8, the hepatocyte nuclear factor 4 α (HNF4A) gene, and the Glucokinase (GCK) gene as well as exons 6 and 7 and 10-12 of the glutamate dehydrogenase 1 (GLUD1) gene were amplified from genomic DNA and directly sequenced. Mutations were identified in 14 of 30 patients (47%): 3 in GLUD1 (10%) and 11 in the KATP channel genes (37%). Six patients had paternally derived monoallelic KATP channel mutations predictive of the focal CHI form. We found a novel de novo ABCC8 mutation, p. C1000*, a novel paternally inherited ABCC8 mutation, D1505H, and a dominantly inherited ABCC8 mutation, R1217K. The GLUD1 activating mutation R269H was found in 2 patients: 1 de novo and the other paternally inherited. A de novo S445L mutation was found in 1 patient. No significant HNF4A or GCK mutations were found. CHI has complex genetic onset mechanisms. Paternally inherited monoallelic mutations of ABCC8 and KCNJ11 are likely the main causes of KATP-CHI in Chinese patients. Glutamate dehydrogenase-CHI is the second most common cause of CHI, while HNF4A and GCK are rare types of CHI in Chinese patients.

Selected ABCB1, ABCB4 and ABCC2 Polymorphisms Do Not Enhance the Risk of Drug-Induced Hepatotoxicity in a Spanish Cohort

PubMed Central

Ulzurrun, Eugenia; Stephens, Camilla; Ruiz-Cabello, Francisco; Robles-Diaz, Mercedes; Saenz-López, Pablo; Hallal, Hacibe; Soriano, German; Roman, Eva; Fernandez, M. Carmen; Lucena, M. Isabel; Andrade, Raúl J.

2014-01-01

Background and Aims Flawed ABC transporter functions may contribute to increased risk of drug-induced liver injury (DILI). We aimed to analyse the influence of genetic variations in ABC transporters on the risk of DILI development and clinical presentations in a large Spanish DILI cohort. Methods A total of ten polymorphisms in ABCB1 (1236T>C, 2677G>T,A, 3435T>C), ABCB4 (1954A>G) and ABCC2 (−1774G>del, −1549A>G, −24C>T, 1249G>A, 3972C>T and 4544G>A) were genotyped using Taqman 5′ allelic discrimination assays or sequencing in 141 Spanish DILI patients and 161 controls. The influence of specific genotypes, alleles and haplotypes on the risk of DILI development and clinical presentations was analysed. Results None of the individual polymorphisms or haplotypes was found to be associated with DILI development. Carriers homozygous for the ABCC2 −1774del allele were however only found in DILI patients. Hence, this genotype could potentially be associated with increased risk, though its low frequency in our Spanish cohort prevented a final conclusion. Furthermore, carriers homozygous for the ABCC2 −1774G/−1549A/−24T/1249G/3972T/4544G haplotype were found to have a higher propensity for total bilirubin elevations when developing DILI. Conclusions Our findings do not support a role for the analysed polymorphisms in the ABCB1, ABCB4 and ABCC2 transporter genes in DILI development in Spanish patients. The ABCC2 −1774deldel genotype was however restricted to DILI cases and could potentially contribute to enhanced DILI susceptibility. PMID:24732756

Developmental change in proactive interference across the life span: evidence from two working memory tasks.

PubMed

Loosli, Sandra V; Rahm, Benjamin; Unterrainer, Josef M; Weiller, Cornelius; Kaller, Christoph P

2014-04-01

Working memory (WM) as the ability to temporarily maintain and manipulate various kinds of information is known to be affected by proactive interference (PI) from previously relevant contents, but studies on developmental changes in the susceptibility to PI are scarce. In the present study, we investigated life span development of item-specific PI. To this end, 92 individuals between the ages of 8 and 74 years completed a recent-probes task and an n-back task that both composed experimental manipulations of PI. Regarding global WM development, young adults had higher WM performance than children and older adults in both tasks. Significant PI × Age interactions revealed that susceptibility to PI changed over the life span in both tasks, whereas the developmental course of PI differed between the tasks: Children committed more PI-related errors than young adults in the recent-probes task but showed marginally less PI in the n-back task. Regarding reaction time costs, children did not differ from adults in the recent-probes task and were less affected than adults in the n-back. Older adults showed more PI-related errors than young adults in both tasks. Therefore, as expected, item-specific PI changed over the life span with the young adults being less susceptible to PI than children and older adults. The diverging developmental effects of PI across both tasks, especially in the children, are supposed to reflect different causes for the difficulties regarding resisting PI in children and older adults. These might concern differently developed underlying cognitive processes such as inhibition or recollection, or different responses to task demands across both tasks. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Relationships of leaf dark respiration to leaf nitrogen, specific leaf area and leaf life-span: a test across biomes and functional groups.

PubMed

Reich, Peter B; Walters, Michael B; Ellsworth, David S; Vose, James M; Volin, John C; Gresham, Charles; Bowman, William D

1998-05-01

Based on prior evidence of coordinated multiple leaf trait scaling, we hypothesized that variation among species in leaf dark respiration rate (R d ) should scale with variation in traits such as leaf nitrogen (N), leaf life-span, specific leaf area (SLA), and net photosynthetic capacity (A max ). However, it is not known whether such scaling, if it exists, is similar among disparate biomes and plant functional types. We tested this idea by examining the interspecific relationships between R d measured at a standard temperature and leaf life-span, N, SLA and A max for 69 species from four functional groups (forbs, broad-leafed trees and shrubs, and needle-leafed conifers) in six biomes traversing the Americas: alpine tundra/subalpine forest, Colorado; cold temperate forest/grassland, Wisconsin; cool temperate forest, North Carolina; desert/shrubland, New Mexico; subtropical forest, South Carolina; and tropical rain forest, Amazonas, Venezuela. Area-based R d was positively related to area-based leaf N within functional groups and for all species pooled, but not when comparing among species within any site. At all sites, mass-based R d (R d-mass ) decreased sharply with increasing leaf life-span and was positively related to SLA and mass-based A max and leaf N (leaf N mass ). These intra-biome relationships were similar in shape and slope among sites, where in each case we compared species belonging to different plant functional groups. Significant R d-mass -N mass relationships were observed in all functional groups (pooled across sites), but the relationships differed, with higher R d at any given leaf N in functional groups (such as forbs) with higher SLA and shorter leaf life-span. Regardless of biome or functional group, R d-mass was well predicted by all combinations of leaf life-span, N mass and/or SLA (r 2 ≥ 0.79, P < 0.0001). At any given SLA, R d-mass rises with increasing N mass and/or decreasing leaf life-span; and at any level of N mass , R d

Association of genetic polymorphisms in SLCO1B3 and ABCC2 with docetaxel-induced leukopenia.

PubMed

Kiyotani, Kazuma; Mushiroda, Taisei; Kubo, Michiaki; Zembutsu, Hitoshi; Sugiyama, Yuichi; Nakamura, Yusuke

2008-05-01

Despite long-term clinical experience with docetaxel, unpredictable severe adverse reactions remain an important determinant for limiting the use of the drug. To identify a genetic factor(s) determining the risk of docetaxel-induced leukopenia/neutropenia, we selected subjects who received docetaxel chemotherapy from samples recruited at BioBank Japan, and conducted a case-control association study. We genotyped 84 patients, 28 patients with grade 3 or 4 leukopenia/neutropenia, and 56 with no toxicity (patients with grade 1 or 2 were excluded), for a total of 79 single nucleotide polymorphisms (SNPs) in seven genes possibly involved in the metabolism or transport of this drug: CYP3A4, CYP3A5, ABCB1, ABCC2, SLCO1B3, NR1I2, and NR1I3. Since one SNP in ABCB1, four SNPs in ABCC2, four SNPs in SLCO1B3, and one SNP in NR1I2 showed a possible association with the grade 3 leukopenia/neutropenia (P-value of <0.05), we further examined these 10 SNPs using 29 additionally obtained patients, 11 patients with grade 3/4 leukopenia/neutropenia, and 18 with no toxicity. The combined analysis indicated a significant association of rs12762549 in ABCC2 (P = 0.00022) and rs11045585 in SLCO1B3 (P = 0.00017) with docetaxel-induced leukopenia/neutropenia. When patients were classified into three groups by the scoring system based on the genotypes of these two SNPs, patients with a score of 1 or 2 were shown to have a significantly higher risk of docetaxel-induced leukopenia/neutropenia as compared to those with a score of 0 (P = 0.0000057; odds ratio [OR], 7.00; 95% CI [confidence interval], 2.95-16.59). This prediction system correctly classified 69.2% of severe leukopenia/neutropenia and 75.7% of non-leukopenia/neutropenia into the respective categories, indicating that SNPs in ABCC2 and SLCO1B3 may predict the risk of leukopenia/neutropenia induced by docetaxel chemotherapy.

Proteotoxicity and the contrasting effects of oxaloacetate and glycerol on Caenorhabditis elegans life span: a role for methylglyoxal?

PubMed

Hipkiss, Alan R

2010-10-01

Because accumulation of altered proteins is the most common biochemical symptom of aging, it is at least possible that such proteotoxicity may cause aging and influence life span. The life span of the nematode worm Caenorhabditis elegans is strongly influenced by changes in the intracellular concentration of methylglyoxal (MG), a putative source of much age-related proteotoxicity and organelle, cellular, and molecular dysfunction. Glycerol has recently been shown to shorten, whereas oxaloacetate has been found to extend, life span in C. elegans. It is suggested here that glycerol and oxaloacetate exert opposing effects on MG formation in C. elegans. It is proposed that, if not secreted by aquaporin, glycerol is converted to glycerol phosphate and then to dihydroxyacetone phosphate (DHAP) via a reaction requiring nicotinamide adenine dinucleotide (NAD(+)). This inhibits operation of the glycerol phosphate cycle in which DHAP is converted into glycerol phosphate, which concomitantly regenerates NAD(+) from NADH, thereby ensuring glycolytic oxidation of glyceraldehyde-3-phosphate (G3P). Because DHAP and G3P spontaneously decompose into MG, and NAD(+) is required for conversion of G3P into phosphoglycerate, the glycerol-induced increased DHAP formation and decreased NAD(+) availability will increase the potential for MG generation. In contrast, oxaloacetate may decrease MG generation by stimulating the operation of the malate-oxaloacetate shuttle, in which oxaloacetate is converted to malate, which regenerates NAD(+) from NADH. By the ensuing G3P oxidation, increased NAD(+) availability will decrease the potential for MG formation. It should be noted that mitochondria are involved in the operation of the above cycle/shuttles and that increased NAD(+) availability also stimulates those sirtuin activities that increase mitogenesis and mitochondrial activity via effects on signal transduction and gene expression, which frequently accompany dietary restriction-induced life

Nup100 regulates Saccharomyces cerevisiae replicative life span by mediating the nuclear export of specific tRNAs.

PubMed

Lord, Christopher L; Ospovat, Ophir; Wente, Susan R

2017-03-01

Nuclear pore complexes (NPCs), which are composed of nucleoporins (Nups) and regulate transport between the nucleus and cytoplasm, significantly impact the replicative life span (RLS) of Saccharomyces cerevisiae We previously reported that deletion of the nonessential gene NUP100 increases RLS, although the molecular basis for this effect was unknown. In this study, we find that nuclear tRNA accumulation contributes to increased longevity in nup100 Δ cells. Fluorescence in situ hybridization (FISH) experiments demonstrate that several specific tRNAs accumulate in the nuclei of nup100 Δ mutants. Protein levels of the transcription factor Gcn4 are increased when NUP100 is deleted, and GCN4 is required for the elevated life spans of nup100 Δ mutants, similar to other previously described tRNA export and ribosomal mutants. Northern blots indicate that tRNA splicing and aminoacylation are not significantly affected in nup100 Δ cells, suggesting that Nup100 is largely required for nuclear export of mature, processed tRNAs. Distinct tRNAs accumulate in the nuclei of nup100 Δ and msn5 Δ mutants, while Los1-GFP nucleocytoplasmic shuttling is unaffected by Nup100. Thus, we conclude that Nup100 regulates tRNA export in a manner distinct from Los1 or Msn5. Together, these experiments reveal a novel Nup100 role in the tRNA life cycle that impacts the S. cerevisiae life span. © 2017 Lord et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Basic traits predict the prevalence of personality disorder across the life span: the example of psychopathy.

PubMed

Vachon, David D; Lynam, Donald R; Widiger, Thomas A; Miller, Joshua D; McCrae, Robert R; Costa, Paul T

2013-05-01

Personality disorders (PDs) may be better understood in terms of dimensions of general personality functioning rather than as discrete categorical conditions. Personality-trait descriptions of PDs are robust across methods and settings, and PD assessments based on trait measures show good construct validity. The study reported here extends research showing that basic traits (e.g., impulsiveness, warmth, straightforwardness, modesty, and deliberation) can re-create the epidemiological characteristics associated with PDs. Specifically, we used normative changes in absolute trait levels to simulate age-related differences in the prevalence of psychopathy in a forensic setting. Results demonstrated that trait information predicts the rate of decline for psychopathy over the life span; discriminates the decline of psychopathy from that of a similar disorder, antisocial PD; and accurately predicts the differential decline of subfactors of psychopathy. These findings suggest that basic traits provide a parsimonious account of PD prevalence across the life span.

Developmental Change in Proactive Interference across the Life Span: Evidence from Two Working Memory Tasks

ERIC Educational Resources Information Center

Loosli, Sandra V.; Rahm, Benjamin; Unterrainer, Josef M.; Weiller, Cornelius; Kaller, Christoph P.

2014-01-01

Working memory (WM) as the ability to temporarily maintain and manipulate various kinds of information is known to be affected by proactive interference (PI) from previously relevant contents, but studies on developmental changes in the susceptibility to PI are scarce. In the present study, we investigated life span development of item-specific…

Stochastic variation in telomere shortening rate causes heterogeneity of human fibroblast replicative life span.

PubMed

Martin-Ruiz, Carmen; Saretzki, Gabriele; Petrie, Joanne; Ladhoff, Juliane; Jeyapalan, Jessie; Wei, Wenyi; Sedivy, John; von Zglinicki, Thomas

2004-04-23

The replicative life span of human fibroblasts is heterogeneous, with a fraction of cells senescing at every population doubling. To find out whether this heterogeneity is due to premature senescence, i.e. driven by a nontelomeric mechanism, fibroblasts with a senescent phenotype were isolated from growing cultures and clones by flow cytometry. These senescent cells had shorter telomeres than their cycling counterparts at all population doubling levels and both in mass cultures and in individual subclones, indicating heterogeneity in the rate of telomere shortening. Ectopic expression of telomerase stabilized telomere length in the majority of cells and rescued them from early senescence, suggesting a causal role of telomere shortening. Under standard cell culture conditions, there was a minor fraction of cells that showed a senescent phenotype and short telomeres despite active telomerase. This fraction increased under chronic mild oxidative stress, which is known to accelerate telomere shortening. It is possible that even high telomerase activity cannot fully compensate for telomere shortening in all cells. The data show that heterogeneity of the human fibroblast replicative life span can be caused by significant stochastic cell-to-cell variation in telomere shortening.

Expert Panel Recommendations on Lower Urinary Tract Health of Women Across Their Life Span

PubMed Central

Losada, Liliana; Amundsen, Cindy L.; Ashton-Miller, James; Chai, Toby; Close, Clare; Damaser, Margot; DiSanto, Michael; Dmochowski, Roger; Fraser, Matthew O.; Kielb, Stephanie J.; Kuchel, George; Mueller, Elizabeth R.; Parker-Autry, Candace; Wolfe, Alan J.

2016-01-01

Abstract Urologic and kidney problems are common in women across their life span and affect their daily life, including physical activity, sexual relations, social life, and future health. Urological health in women is still understudied and the underlying mechanisms of female urological dysfunctions are not fully understood. The Society for Women's Health Research (SWHR®) recognized the need to have a roundtable discussion where researchers and clinicians would define the current state of knowledge, gaps, and recommendations for future research directions to transform women's urological health. This report summarizes the discussions, which focused on epidemiology, clinical presentation, basic science, prevention strategies, and efficacy of current therapies. Experts around the table agreed on a set of research, education, and policy recommendations that have the potential to dramatically increase awareness and improve women's urological health at all stages of life. PMID:27285829

The primacy of primary control is a human universal: a reply to Gould's (1999) critique of the life-span theory of control.

PubMed

Heckhausen, J; Schulz, R

1999-07-01

This reply to S. J. Gould's (1999) critique of J. Heckhausen and R. Schulz's (1995) life-span theory of control addresses four issues: (1) the universal claim that primary control holds functional primacy over secondary control, (2) the status of secondary control as a confederate to primary control, (3) empirical evidence and paradigms for investigating universality and cultural variations, and (4) the capacity of the human control system to manage both gains and losses in control throughout the life span and aging-related decline in particular. Theoretical perspectives and empirical evidence from evolutionary, comparative, developmental, and cultural psychology are presented to support the authors' view that primary control striving holds functional primacy throughout the life span and across cultural and historical settings. Recommendations for empirically investigating the variations in the way primary control striving is expressed in different cultures are outlined.

Telomerase-mediated life-span extension of human primary fibroblasts by human artificial chromosome (HAC) vector

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shitara, Shingo; Kakeda, Minoru; Nagata, Keiko

2008-05-09

Telomerase-mediated life-span extension enables the expansion of normal cells without malignant transformation, and thus has been thought to be useful in cell therapies. Currently, integrating vectors including the retrovirus are used for human telomerase reverse transcriptase (hTERT)-mediated expansion of normal cells; however, the use of these vectors potentially causes unexpected insertional mutagenesis and/or activation of oncogenes. Here, we established normal human fibroblast (hPF) clones retaining non-integrating human artificial chromosome (HAC) vectors harboring the hTERT expression cassette. In hTERT-HAC/hPF clones, we observed the telomerase activity and the suppression of senescent-associated SA-{beta}-galactosidase activity. Furthermore, the hTERT-HAC/hPF clones continued growing beyond 120 daysmore » after cloning, whereas the hPF clones retaining the silent hTERT-HAC senesced within 70 days. Thus, hTERT-HAC-mediated episomal expression of hTERT allows the extension of the life-span of human primary cells, implying that gene delivery by non-integrating HAC vectors can be used to control cellular proliferative capacity of primary cultured cells.« less

Evidence for a relationship between longevity of mammalian species and life spans of normal fibroblasts in vitro and erythrocytes in vivo

PubMed Central

Röhme, Dan

1981-01-01

The replicative life spans of mammalian fibroblasts in vitro were studied in a number of cell cultures representing eight species. Emphasis was placed on determining the population doubling level at which phase III (a period of decrease in the rate of proliferation) and chromosomal alterations occur. All the cell cultures studied went through a growth crisis, a period of apparent growth cessation lasting for at least 2 weeks. In most cultures, the crisis represented the end of their replicative capacities, but in some cultures cell proliferation was resumed after the crisis. A predominantly diploid chromosome constitution (more than 75%) was demonstrated prior to the growth crisis. In cultures in which cell proliferation was resumed after the crisis, a nondiploid constitution prevailed in all cases except the rat (with 90% or more diploid cells all the time). The growth crisis occurred at population doubling levels that were characteristic for the species and was shown to be related to the species' maximal life span by a strict power law, being proportional to the square root of the maximal life span. Based on data in the literature, the same relationship was also valid for the lifespans of circulating mammalian erythrocytes in vivo. These results may indicate the prevalence of a common functional basis regulating the life span of fibroblasts and erythrocytes and thus operating in replicative as well as postmitotic cells in vitro and in vivo. PMID:6946449

Age Differences and Educational Attainment across the Life Span on Three Generations of Wechsler Adult Scales

ERIC Educational Resources Information Center

Kaufman, A. S.; Salthouse, T. A.; Scheiber, C.; Chen, H.

2016-01-01

Patterns of maintenance of ability across the life span have been documented on tests of knowledge ("Gc"), as have patterns of steady decline on measures of reasoning ("Gf/Gv"), working memory ("Gsm"), and speed ("Gs"). Whether these patterns occur at the same rate for adults from different educational…

Age differences in five personality domains across the life span.

PubMed

Allemand, Mathias; Zimprich, Daniel; Hendriks, A A Jolijn

2008-05-01

The present study addresses the issue of age differences in 5 personality domains across the life span in a cross-sectional study. In contrast to most previous studies, the present study follows a methodologically more rigorous approach to warrant that age-related differences in personality structure and mean level can be meaningfully compared. It uses data on 50 items of the Five-Factor Personality Inventory (FFPI) available from a study in a large and representative Dutch sample (N = 2,494; age range: 16 to 91 years) conducted in 1996 for the purpose of establishing norms for the FFPI. After having established strict measurement invariance, tests were made for factor covariances to be equal across age groups, revealing structural continuity of personality. Additionally, factor variances were shown to be equal across age groups. A number of age differences in the mean level of the five personality domains emerged. Specifically, older adults were, on average, more agreeable and, especially, more conscientious than middle-aged and younger adults. Findings from our study suggest that both continuity and change may mark personality over the course of life. (PsycINFO Database Record (c) 2008 APA, all rights reserved).

Urinary elimination of coproporphyrins is dependent on ABCC2 polymorphisms and represents a potential biomarker of MRP2 activity in humans.

PubMed

Benz-de Bretagne, Isabelle; Respaud, Renaud; Vourc'h, Patrick; Halimi, Jean-Michel; Caille, Agnès; Hulot, Jean-Sébastien; Andres, Christian R; Le Guellec, Chantal

2011-01-01

MRP2 encoded by ABCC2 gene is involved in the secretion of numerous drugs and endogenous substrates. Patients with Dubin-Johnson syndrome due to mutation in ABCC2 gene have elevated urinary coproporphyrin ratio (UCP I/(I + III)). Here we investigated whether this ratio could serve as a biomarker of MRP2 function. Phenotype-genotype relationships were studied in 74 healthy subjects by measuring individual UCP I/(I + III) ratio obtained on 24-hour urine and by analyzing five common SNPs in ABCC2 gene. The UCP I/(I + III) ratio varied from 14.7% to 46.0% in our population. Subjects with 3972TT genotype had a higher ratio (P = .04) than those carrying the C allele. This higher UCP I/(I + III) ratio was correlated with a higher level of isomer I excretion. This study provides a proof of concept that UCP I/(I + III) ratio can be used as a biomarker of MRP2 function in clinical studies as it provides quantitative information about the in vivo activity of MRP2 in a given patient.

Urinary Elimination of Coproporphyrins Is Dependent on ABCC2 Polymorphisms and Represents a Potential Biomarker of MRP2 Activity in Humans

PubMed Central

Benz-de Bretagne, Isabelle; Respaud, Renaud; Vourc'h, Patrick; Halimi, Jean-Michel; Caille, Agnès; Hulot, Jean-Sébastien; Andres, Christian R.; Le Guellec, Chantal

2011-01-01

MRP2 encoded by ABCC2 gene is involved in the secretion of numerous drugs and endogenous substrates. Patients with Dubin-Johnson syndrome due to mutation in ABCC2 gene have elevated urinary coproporphyrin ratio (UCP I/(I + III)). Here we investigated whether this ratio could serve as a biomarker of MRP2 function. Phenotype-genotype relationships were studied in 74 healthy subjects by measuring individual UCP I/(I + III) ratio obtained on 24-hour urine and by analyzing five common SNPs in ABCC2 gene. The UCP I/(I + III) ratio varied from 14.7% to 46.0% in our population. Subjects with 3972TT genotype had a higher ratio (P = .04) than those carrying the C allele. This higher UCP I/(I + III) ratio was correlated with a higher level of isomer I excretion. This study provides a proof of concept that UCP I/(I + III) ratio can be used as a biomarker of MRP2 function in clinical studies as it provides quantitative information about the in vivo activity of MRP2 in a given patient. PMID:21541183

Dissociable Changes of Frontal and Parietal Cortices in Inherent Functional Flexibility across the Human Life Span.

PubMed

Yin, Dazhi; Liu, Wenjing; Zeljic, Kristina; Wang, Zhiwei; Lv, Qian; Fan, Mingxia; Cheng, Wenhong; Wang, Zheng

2016-09-28

Extensive evidence suggests that frontoparietal regions can dynamically update their pattern of functional connectivity, supporting cognitive control and adaptive implementation of task demands. However, it is largely unknown whether this flexibly functional reconfiguration is intrinsic and occurs even in the absence of overt tasks. Based on recent advances in dynamics of resting-state functional resonance imaging (fMRI), we propose a probabilistic framework in which dynamic reconfiguration of intrinsic functional connectivity between each brain region and others can be represented as a probability distribution. A complexity measurement (i.e., entropy) was used to quantify functional flexibility, which characterizes heterogeneous connectivity between a particular region and others over time. Following this framework, we identified both functionally flexible and specialized regions over the human life span (112 healthy subjects from 13 to 76 years old). Across brainwide regions, we found regions showing high flexibility mainly in the higher-order association cortex, such as the lateral prefrontal cortex (LPFC), lateral parietal cortex, and lateral temporal lobules. In contrast, visual, auditory, and sensory areas exhibited low flexibility. Furthermore, we observed that flexibility of the right LPFC improved during maturation and reduced due to normal aging, with the opposite occurring for the left lateral parietal cortex. Our findings reveal dissociable changes of frontal and parietal cortices over the life span in terms of inherent functional flexibility. This study not only provides a new framework to quantify the spatiotemporal behavior of spontaneous brain activity, but also sheds light on the organizational principle behind changes in brain function across the human life span. Recent neuroscientific research has demonstrated that the human capability of adaptive task control is primarily the result of the flexible operation of frontal brain networks. However

A cost–benefit analysis of acclimation to low irradiance in tropical rainforest tree seedlings: leaf life span and payback time for leaf deployment

PubMed Central

Coste, Sabrina; Roggy, Jean-Christophe; Schimann, Heidy; Epron, Daniel; Dreyer, Erwin

2011-01-01

The maintenance in the long run of a positive carbon balance under very low irradiance is a prerequisite for survival of tree seedlings below the canopy or in small gaps in a tropical rainforest. To provide a quantitative basis for this assumption, experiments were carried out to determine whether construction cost (CC) and payback time for leaves and support structures, as well as leaf life span (i) differ among species and (ii) display an irradiance-elicited plasticity. Experiments were also conducted to determine whether leaf life span correlates to CC and payback time and is close to the optimal longevity derived from an optimization model. Saplings from 13 tropical tree species were grown under three levels of irradiance. Specific-CC was computed, as well as CC scaled to leaf area at the metamer level. Photosynthesis was recorded over the leaf life span. Payback time was derived from CC and a simple photosynthesis model. Specific-CC displayed only little interspecific variability and irradiance-elicited plasticity, in contrast to CC scaled to leaf area. Leaf life span ranged from 4 months to >26 months among species, and was longest in seedlings grown under lowest irradiance. It was always much longer than payback time, even under the lowest irradiance. Leaves were shed when their photosynthesis had reached very low values, in contrast to what was predicted by an optimality model. The species ranking for the different traits was stable across irradiance treatments. The two pioneer species always displayed the smallest CC, leaf life span, and payback time. All species displayed a similar large irradiance-elicited plasticity. PMID:21511904

Delayed accumulation of intestinal coliform bacteria enhances life span and stress resistance in Caenorhabditis elegans fed respiratory deficient E. coli.

PubMed

Gomez, Fernando; Monsalve, Gabriela C; Tse, Vincent; Saiki, Ryoichi; Weng, Emily; Lee, Laura; Srinivasan, Chandra; Frand, Alison R; Clarke, Catherine F

2012-12-20

Studies with the nematode model Caenorhabditis elegans have identified conserved biochemical pathways that act to modulate life span. Life span can also be influenced by the composition of the intestinal microbiome, and C. elegans life span can be dramatically influenced by its diet of Escherichia coli. Although C. elegans is typically fed the standard OP50 strain of E. coli, nematodes fed E. coli strains rendered respiratory deficient, either due to a lack coenzyme Q or the absence of ATP synthase, show significant life span extension. Here we explore the mechanisms accounting for the enhanced nematode life span in response to these diets. The intestinal load of E. coli was monitored by determination of worm-associated colony forming units (cfu/worm or coliform counts) as a function of age. The presence of GFP-expressing E. coli in the worm intestine was also monitored by fluorescence microscopy. Worms fed the standard OP50 E. coli strain have high cfu and GFP-labeled bacteria in their guts at the L4 larval stage, and show saturated coliform counts by day five of adulthood. In contrast, nematodes fed diets of respiratory deficient E. coli lacking coenzyme Q lived significantly longer and failed to accumulate bacteria within the lumen at early ages. Animals fed bacteria deficient in complex V showed intermediate coliform numbers and were not quite as long-lived. The results indicate that respiratory deficient Q-less E. coli are effectively degraded in the early adult worm, either at the pharynx or within the intestine, and do not accumulate in the intestinal tract until day ten of adulthood. The findings of this study suggest that the nematodes fed the respiratory deficient E. coli diet live longer because the delay in bacterial colonization of the gut subjects the worms to less stress compared to worms fed the OP50 E. coli diet. This work suggests that bacterial respiration can act as a virulence factor, influencing the ability of bacteria to colonize and

The development of memory efficiency and value-directed remembering across the life span: a cross-sectional study of memory and selectivity.

PubMed

Castel, Alan D; Humphreys, Kathryn L; Lee, Steve S; Galván, Adriana; Balota, David A; McCabe, David P

2011-11-01

Although attentional control and memory change considerably across the life span, no research has examined how the ability to strategically remember important information (i.e., value-directed remembering) changes from childhood to old age. The present study examined this in different age groups across the life span (N = 320, 5-96 years old). A selectivity task was used in which participants were asked to study and recall items worth different point values in order to maximize their point score. This procedure allowed for measures of memory quantity/capacity (number of words recalled) and memory efficiency/selectivity (the recall of high-value items relative to low-value items). Age-related differences were found for memory capacity, as young adults recalled more words than the other groups. However, in terms of selectivity, younger and older adults were more selective than adolescents and children. The dissociation between these measures across the life span illustrates important age-related differences in terms of memory capacity and the ability to selectively remember high-value information.

Circadian clocks govern calorie restriction-mediated life span extension through BMAL1- and IGF-1-dependent mechanisms.

PubMed

Patel, Sonal A; Chaudhari, Amol; Gupta, Richa; Velingkaar, Nikkhil; Kondratov, Roman V

2016-04-01

Calorie restriction (CR) increases longevity in many species by unknown mechanisms. The circadian clock was proposed as a potential mediator of CR. Deficiency of the core component of the circadian clock-transcriptional factor BMAL1 (brain and muscle ARNT [aryl hydrocarbon receptor nuclear translocator]-like protein 1)-results in accelerated aging. Here we investigated the role of BMAL1 in mechanisms of CR. The 30% CR diet increased the life span of wild-type (WT) mice by 20% compared to mice on anad libitum(AL) diet but failed to increase life span ofBmal1(-/-)mice. BMAL1 deficiency impaired CR-mediated changes in the plasma levels of IGF-1 and insulin. We detected a statistically significantly reduction of IGF-1 in CRvs.AL by 50 to 70% in WT mice at several daily time points tested, while inBmal1(-/-)the reduction was not significant. Insulin levels in WT were reduced by 5 to 9%, whileBmal1(-/-)induced it by 10 to 35% at all time points tested. CR up-regulated the daily average expression ofBmal1(by 150%) and its downstream target genesPeriods(by 470% forPer1and by 130% forPer2). We propose that BMAL1 is an important mediator of CR, and activation of BMAL1 might link CR mechanisms with biologic clocks.-Patel, S. A., Chaudhari, A., Gupta, R., Velingkaar, N., Kondratov, R. V. Circadian clocks govern calorie restriction-mediated life span extension through BMAL1- and IGF-1-dependent mechanisms. © FASEB.

Ovariectomy shortens the life span of female mice

PubMed Central

Benedusi, Valeria; Martini, Elisa; Kallikourdis, Marinos; Villa, Alessandro; Meda, Clara; Maggi, Adriana

2015-01-01

This study shows that lack of ovarian activity has a negative impact on the life span of female mice. The extent to which this phenomenon could be associated with the anti-inflammatory effect of estrogens was analyzed in metabolic organs and aorta, by quantitative analysis of mRNAs encoding proteins in the inflammatory cascade. We demonstrate that the TNFα, IL-1β, MCP-1, MIP-2 and IL-6 mRNA contents are increased in the liver, adipose tissue and aorta 7 months after ovariectomy (ovx) and this increased basal inflammation is maintained as the mice aged. In contrast, the extent of inflammatory gene expression is directly proportional to age in sham-operated mice. As a consequence, at 22 months, most of the inflammatory parameters examined were higher in the sham-operated group compared with the ovx group. These observations led us to propose that the decreased longevity of ovx mice may be due to an acceleration of the basal state of inflammation in metabolic organs, which is likely driven by the combination of a lack of estrogen-mediated anti-inflammatory activity and the loss of gonadal control of energy metabolism. PMID:25719423

Single amino acid insertions in extracellular loop 2 of Bombyx mori ABCC2 disrupt its receptor function for Bacillus thuringiensis Cry1Ab and Cry1Ac but not Cry1Aa toxins.

PubMed

Tanaka, Shiho; Miyamoto, Kazuhisa; Noda, Hiroaki; Endo, Haruka; Kikuta, Shingo; Sato, Ryoichi

2016-04-01

In a previous report, seven Cry1Ab-resistant strains were identified in the silkworm, Bombyx mori; these strains were shown to have a tyrosine insertion at position 234 in extracellular loop 2 of the ABC transporter C2 (BmABCC2). This insertion was confirmed to destroy the receptor function of BmABCC2 and confer the strains resistance against Cry1Ab and Cry1Ac. However, these strains were susceptible to Cry1Aa. In this report, we examined the mechanisms of the loss of receptor function of the transporter by expressing mutations in Sf9 cells. After replacement of one or two of the five amino acid residues in loop 2 of the susceptible BmABCC2 gene [BmABCC2_S] with alanine, cells still showed susceptibility, retaining the receptor function. Five mutants with single amino acid insertions at position 234 in BmABCC2 were also generated, resulting in loop 2 having six amino acids, which corresponds to replacing the tyrosine insertion in the resistant BmABCC2 gene [BmABCC2_R(+(234)Y)] with another amino acid. All five mutants exhibited loss of function against Cry1Ab and Cry1Ac. These results suggest that the amino acid sequence in loop 2 is less important than the loop size (five vs. six amino acids) or loop structure for Cry1Ab and Cry1Ac activity. Several domain-swapped mutant toxins were then generated among Cry1Aa, Cry1Ab, and Cry1Ac, which are composed of three domains. Swapped mutants containing domain II of Cry1Ab or Cry1Ac did not kill Sf9 cells expressing BmABCC2_R(+(234)Y), suggesting that domain II of the Cry toxin is related to the interaction with the receptor function of BmABCC2. This also suggests that different reactions against Bt-toxins in some B. mori strains, that is, Cry1Ab resistance or Cry1Aa susceptibility, are attributable to structural differences in domain II of Cry1A toxins. Copyright © 2016. Published by Elsevier Inc.

ABCC9 gene polymorphism is associated with hippocampal sclerosis of aging pathology

PubMed Central

Estus, Steven; Abner, Erin L.; Parikh, Ishita; Malik, Manasi; Neltner, Janna H.; Ighodaro, Eseosa; Wang, Wang-Xia; Wilfred, Bernard R.; Wang, Li-San; Kukull, Walter A.; Nandakumar, Kannabiran; Farman, Mark L.; Poon, Wayne W.; Corrada, Maria M.; Kawas, Claudia H.; Cribbs, David H.; Bennett, David A.; Schneider, Julie A.; Larson, Eric B.; Crane, Paul K.; Valladares, Otto; Schmitt, Frederick A.; Kryscio, Richard J.; Jicha, Gregory A.; Smith, Charles D.; Scheff, Stephen W.; Sonnen, Joshua A.; Haines, Jonathan L.; Pericak-Vance, Margaret A.; Mayeux, Richard; Farrer, Lindsay A.; Van Eldik, Linda J.; Horbinski, Craig; Green, Robert C.; Gearing, Marla; Poon, Leonard W.; Kramer, Patricia L.; Woltjer, Randall L.; Montine, Thomas J.; Partch, Amanda B.; Rajic, Alexander J.; Richmire, KatieRose; Monsell, Sarah E.; Schellenberg, Gerard D.

2014-01-01

Hippocampal sclerosis of aging (HS-Aging) is a high-morbidity brain disease in the elderly but risk factors are largely unknown. We report the first genome-wide association study (GWAS) with HS-Aging pathology as an endophenotype. In collaboration with the Alzheimer’s Disease Genetics Consortium, data were analyzed from large autopsy cohorts: (#1) National Alzheimer’s Coordinating Center (NACC); (#2) Rush University Religious Orders Study and Memory and Aging Project; (#3) Group Health Research Institute Adult Changes in Thought study; (#4) University of California at Irvine 90+ Study; and (#5) University of Kentucky Alzheimer’s Disease Center. Altogether, 363 HS-Aging cases and 2,303 controls, all pathologically confirmed, provided statistical power to test for risk alleles with large effect size. A two-tier study design included GWAS from cohorts #1–3 (Stage I) to identify promising SNP candidates, followed by focused evaluation of particular SNPs in cohorts #4–5 (Stage II). Polymorphism in the ATP-binding cassette, sub-family C member 9 (ABCC9) gene, also known as sulfonylurea receptor 2, was associated with HS-Aging pathology. In the meta-analyzed Stage I GWAS, ABCC9 polymorphisms yielded the lowest p values, and factoring in the Stage II results, the meta-analyzed risk SNP (rs704178:G) attained genome-wide statistical significance (p = 1.4 × 10−9), with odds ratio (OR) of 2.13 (recessive mode of inheritance). For SNPs previously linked to hippocampal sclerosis, meta-analyses of Stage I results show OR = 1.16 for rs5848 (GRN) and OR = 1.22 rs1990622 (TMEM106B), with the risk alleles as previously described. Sulfonylureas, a widely prescribed drug class used to treat diabetes, also modify human ABCC9 protein function. A subsample of patients from the NACC database (n = 624) were identified who were older than age 85 at death with known drug history. Controlling for important confounders such as diabetes itself, exposure to a sulfonylurea drug was

[Effect of pineal peptide on parameters of the biological age and life span in mice].

PubMed

Anisimov, V N; Khavinson, V Kh; Zavarzina, N Iu; Zabezhinskiĭ, M A; Zimina, O A; Popovich, I G; Shtylik, A V; Arutiunian, A V; Oparina, T I; Prokopenko, V M

2001-01-01

Female CBA mice were injected with s.c. synthetic tetrapeptide Epithalon from a 6-month age until death. The drug failed to affect the body weight or food consumption, physical activity or behavioural parameters. However, it slowed down the age-related switching off of the estrus function, decreased body temperature, decelerated free redical processes, prolonged the mice life span with an accompanying drop in spontaneous tumour incidence.

Self-Esteem Development across the Life Span: A Longitudinal Study with a Large Sample from Germany

ERIC Educational Resources Information Center

Orth, Ulrich; Maes, Jürgen; Schmitt, Manfred

2015-01-01

The authors examined the development of self-esteem across the life span. Data came from a German longitudinal study with 3 assessments across 4 years of a sample of 2,509 individuals ages 14 to 89 years. The self-esteem measure used showed strong measurement invariance across assessments and birth cohorts. Latent growth curve analyses indicated…

Differential longitudinal changes in cortical thickness, surface area and volume across the adult life span: regions of accelerating and decelerating change.

PubMed

Storsve, Andreas B; Fjell, Anders M; Tamnes, Christian K; Westlye, Lars T; Overbye, Knut; Aasland, Hilde W; Walhovd, Kristine B

2014-06-18

Human cortical thickness and surface area are genetically independent, emerge through different neurobiological events during development, and are sensitive to different clinical conditions. However, the relationship between changes in the two over time is unknown. Additionally, longitudinal studies have almost invariably been restricted to older adults, precluding the delineation of adult life span trajectories of change in cortical structure. In this longitudinal study, we investigated changes in cortical thickness, surface area, and volume after an average interval of 3.6 years in 207 well screened healthy adults aged 23-87 years. We hypothesized that the relationships among metrics are dynamic across the life span, that the primary contributor to cortical volume reductions in aging is cortical thinning, and that magnitude of change varies with age and region. Changes over time were seen in cortical area (mean annual percentage change [APC], -0.19), thickness (APC, -0.35), and volume (APC, -0.51) in most regions. Volume changes were primarily explained by changes in thickness rather than area. A negative relationship between change in thickness and surface area was found across several regions, where more thinning was associated with less decrease in area, and vice versa. Accelerating changes with increasing age was seen in temporal and occipital cortices. In contrast, decelerating changes were seen in prefrontal and anterior cingulate cortices. In conclusion, a dynamic relationship between cortical thickness and surface area changes exists throughout the adult life span. The mixture of accelerating and decelerating changes further demonstrates the importance of studying these metrics across the entire adult life span. Copyright © 2014 the authors 0270-6474/14/348488-11$15.00/0.

Childhood Self-Control and Unemployment Throughout the Life Span

PubMed Central

Delaney, Liam; Egan, Mark; Baumeister, Roy F.

2015-01-01

The capacity for self-control may underlie successful labor-force entry and job retention, particularly in times of economic uncertainty. Analyzing unemployment data from two nationally representative British cohorts (N = 16,780), we found that low self-control in childhood was associated with the emergence and persistence of unemployment across four decades. On average, a 1-SD increase in self-control was associated with a reduction in the probability of unemployment of 1.4 percentage points after adjustment for intelligence, social class, and gender. From labor-market entry to middle age, individuals with low self-control experienced 1.6 times as many months of unemployment as those with high self-control. Analysis of monthly unemployment data before and during the 1980s recession showed that individuals with low self-control experienced the greatest increases in unemployment during the recession. Our results underscore the critical role of self-control in shaping life-span trajectories of occupational success and in affecting how macroeconomic conditions affect unemployment levels in the population. PMID:25870404

Immortalization of Human Fetal Cells: The Life Span of Umbilical Cord Blood-derived Cells Can Be Prolonged without Manipulating p16INK4a/RB Braking PathwayD⃞

PubMed Central

Terai, Masanori; Uyama, Taro; Sugiki, Tadashi; Li, Xiao-Kang; Umezawa, Akihiro; Kiyono, Tohru

2005-01-01

Human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) are expected to serve as an excellent alternative to bone marrow-derived human mesenchymal stem cells. However, it is difficult to study them because of their limited life span. To overcome this problem, we attempted to produce a strain of UCBMSCs with a long life span and to investigate whether the strain could maintain phenotypes in vitro. UCBMSCs were infected with retrovirus carrying the human telomerase reverse transcriptase (hTERT) to prolong their life span. The UCBMSCs underwent 30 population doublings (PDs) and stopped dividing at PD 37. The UCBMSCs newly established with hTERT (UCBTERTs) proliferated for >120 PDs. The p16INK4a/RB braking pathway leading to senescence can be inhibited by introduction of Bmi-1, a polycomb-group gene, and human papillomavirus type 16 E7, but the extension of the life span of the UCBMSCs with hTERT did not require inhibition of the p16INK4a/RB pathway. The characteristics of the UCBTERTs remained unchanged during the prolongation of life span. UCBTERTs provide a powerful model for further study of cellular senescence and for future application to cell-based therapy by using umbilical cord blood cells. PMID:15647378

Dietary consumption of monosodium L-glutamate induces adaptive response and reduction in the life span of Drosophila melanogaster.

PubMed

Abolaji, Amos O; Olaiya, Charles O; Oluwadahunsi, Oluwagbenga J; Farombi, Ebenezer O

2017-04-01

Adaptive response is the ability of an organism to better counterattack stress-induced damage in response to a number of different cytotoxic agents. Monosodium L-glutamate (MSG), the sodium salt of amino acid glutamate, is commonly used as a food additive. We investigated the effects of MSG on the life span and antioxidant response in Drosophila melanogaster (D. melanogaster). Both genders (1 to 3 days old) of flies were fed with diet containing MSG (0.1, 0.5, and 2.5-g/kg diet) for 5 days to assess selected antioxidant and oxidative stress markers, while flies for longevity were fed for lifetime. Thereafter, the longevity assay, hydrogen peroxide (H 2 O 2 ), and reactive oxygen and nitrogen species levels were determined. Also, catalase, glutathione S-transferase and acetylcholinesterase activities, and total thiol content were evaluated in the flies. We found that MSG reduced the life span of the flies by up to 23% after continuous exposure. Also, MSG increased reactive oxygen and nitrogen species and H 2 O 2 generations and total thiol content as well as the activities of catalase and glutathione S-transferase in D. melanogaster (P < .05). In conclusion, consumption of MSG for 5 days by D. melanogaster induced adaptive response, but long-term exposure reduced life span of flies. This study may therefore have public health significance in humans, and thus, moderate consumption of MSG is advocated by the authors. Copyright © 2017 John Wiley & Sons, Ltd.

CTT1 overexpression increases life span of calorie-restricted Saccharomyces cerevisiae deficient in Sod1.

PubMed

Rona, Germana; Herdeiro, Ricardo; Mathias, Cristiane Juliano; Torres, Fernando Araripe; Pereira, Marcos Dias; Eleutherio, Elis

2015-06-01

Studies using different organisms revealed that reducing calorie intake, without malnutrition, known as calorie restriction (CR), increases life span, but its mechanism is still unkown. Using the yeast Saccharomyces cerevisiae as eukaryotic model, we observed that Cu, Zn-superoxide dismutase (Sod1p) is required to increase longevity, as well as to confer protection against lipid and protein oxidation under CR. Old cells of sod1 strain also presented a premature induction of apoptosis. However, when CTT1 (which codes for cytosolic catalase) was overexpressed, sod1 and WT strains showed similar survival rates. Furthermore, CTT1 overexpression decreased lipid peroxidation and delayed the induction of apoptotic process. Superoxide is rapidly converted to hydrogen peroxide by superoxide dismutase, but it also undergoes spontaneous dismutation albeit at a slower rate. However, the quantity of peroxide produced from superoxide in this way is two-fold higher. Peroxide degradation, catalyzed by catalase, is of vital importance, because in the presence of a reducer transition metal peroxide is reduced to the highly reactive hydroxyl radical, which reacts indiscriminately with most cellular constituents. These findings might explain why overexpression of catalase was able to overcome the deficiency of Sod1p, increasing life span in response to CR.

The Life Span Model of Suicide and Its Neurobiological Foundation

PubMed Central

Ludwig, Birgit; Roy, Bhaskar; Wang, Qingzhong; Birur, Badari; Dwivedi, Yogesh

2017-01-01

The very incomprehensibility of the suicidal act has been occupying the minds of researchers and health professionals for a long time. Several theories of suicide have been proposed since the beginning of the past century, and a myriad of neurobiological studies have been conducted over the past two decades in order to elucidate its pathophysiology. Both neurobiology and psychological theories tend to work in parallel lines that need behavioral and empirical data respectively, to confirm their hypotheses. In this review, we are proposing a “Life Span Model of Suicide” with an attempt to integrate the “Stress-Diathesis Model” and the “Interpersonal Model of Suicide” into a neurobiological narrative and support it by providing a thorough compilation of related genetic, epigenetic, and gene expression findings. This proposed model comprises three layers, forming the capability of suicide: genetic factors as the predisposing Diathesis on one side and Stress, characterized by epigenetic marks on the other side, and in between gene expression and gene function which are thought to be influenced by Diathesis and Stress components. The empirical evidence of this model is yet to be confirmed and further research, specifically epigenetic studies in particular, are needed to support the presence of a life-long, evolving capability of suicide and identify its neurobiological correlates. PMID:28261051

daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans.

PubMed

Lin, K; Dorman, J B; Rodan, A; Kenyon, C

1997-11-14

The wild-type Caenorhabditis elegans nematode ages rapidly, undergoing development, senescence, and death in less than 3 weeks. In contrast, mutants with reduced activity of the gene daf-2, a homolog of the insulin and insulin-like growth factor receptors, age more slowly than normal and live more than twice as long. These mutants are active and fully fertile and have normal metabolic rates. The life-span extension caused by daf-2 mutations requires the activity of the gene daf-16. daf-16 appears to play a unique role in life-span regulation and encodes a member of the hepatocyte nuclear factor 3 (HNF-3)/forkhead family of transcriptional regulators. In humans, insulin down-regulates the expression of certain genes by antagonizing the activity of HNF-3, raising the possibility that aspects of this regulatory system have been conserved.

Lung glutathione reductase induction in aging catalase-depleted frogs correlates with early survival throughout the life span.

PubMed

Perez-Campo, R; Lopez-Torres, M; Rojas, C; Cadenas, S; Barja de Quiroga, G

1993-02-01

A comprehensive experimental study on free radical-related parameters was performed in the lung throughout the life span of 220 initially young or old frogs. No age related differences were found transversely or longitudinally for lung superoxide dismutase, catalase, Se-dependent and -independent glutathione peroxidases, glutathione reductase, GSH, GSSG, or GSSG/GSH ratio. Continuous catalase depletion with aminotriazole led to glutathione reductase induction in the lung after 14.5 months of experimentation. This was accompanied by a great increase in survival rate of treated animals in relation to controls (especially in the old group). After 26.5 months of experimentation, glutathione reductase induction was lost and GSSG/GSH values tended to increase. This was followed by a 3-month long period of acute decrease in survival rate of treated animals. It is suggested that a high antioxidant/prooxidant balance is of protective value against causes of early death and can possibly be used in the future (when appropriately controlled) to increase the number of healthy years of the normal life span.

DNA damage leads to progressive replicative decline but extends the life span of long-lived mutant animals.

PubMed

Lans, H; Lindvall, J M; Thijssen, K; Karambelas, A E; Cupac, D; Fensgård, O; Jansen, G; Hoeijmakers, J H J; Nilsen, H; Vermeulen, W

2013-12-01

Human-nucleotide-excision repair (NER) deficiency leads to different developmental and segmental progeroid symptoms of which the pathogenesis is only partially understood. To understand the biological impact of accumulating spontaneous DNA damage, we studied the phenotypic consequences of DNA-repair deficiency in Caenorhabditis elegans. We find that DNA damage accumulation does not decrease the adult life span of post-mitotic tissue. Surprisingly, loss of functional ERCC-1/XPF even further extends the life span of long-lived daf-2 mutants, likely through an adaptive activation of stress signaling. Contrariwise, NER deficiency leads to a striking transgenerational decline in replicative capacity and viability of proliferating cells. DNA damage accumulation induces severe, stochastic impairment of development and growth, which is most pronounced in NER mutants that are also impaired in their response to ionizing radiation and inter-strand crosslinks. These results suggest that multiple DNA-repair pathways can protect against replicative decline and indicate that there might be a direct link between the severity of symptoms and the level of DNA-repair deficiency in patients.

Everyday problem solving across the adult life span: solution diversity and efficacy.

PubMed

Mienaltowski, Andrew

2011-10-01

Everyday problem solving involves examining the solutions that individuals generate when faced with problems that take place in their everyday experiences. Problems can range from medication adherence and meal preparation to disagreeing with a physician over a recommended medical procedure or compromising with extended family members over where to host Thanksgiving dinner. Across the life span, research has demonstrated divergent patterns of change in performance based on the type of everyday problems used as well as based on the way that problem-solving efficacy is operationally defined. Advancing age is associated with worsening performance when tasks involve single-solution or fluency-based definitions of effectiveness. However, when efficacy is defined in terms of the diversity of strategies used, as well as by the social and emotional impact of solution choice on the individual, performance is remarkably stable and sometimes even improves in the latter half of life. This article discusses how both of these approaches to everyday problem solving inform research on the influence that aging has on everyday functioning. © 2011 New York Academy of Sciences.

Aging Theories for Establishing Safe Life Spans of Airborne Critical Structural Components

NASA Technical Reports Server (NTRS)

Ko, William L.

2003-01-01

New aging theories have been developed to establish the safe life span of airborne critical structural components such as B-52B aircraft pylon hooks for carrying air-launch drop-test vehicles. The new aging theories use the equivalent-constant-amplitude loading spectrum to represent the actual random loading spectrum with the same damaging effect. The crack growth due to random loading cycling of the first flight is calculated using the half-cycle theory, and then extrapolated to all the crack growths of the subsequent flights. The predictions of the new aging theories (finite difference aging theory and closed-form aging theory) are compared with the classical flight-test life theory and the previously developed Ko first- and Ko second-order aging theories. The new aging theories predict the number of safe flights as considerably lower than that predicted by the classical aging theory, and slightly lower than those predicted by the Ko first- and Ko second-order aging theories due to the inclusion of all the higher order terms.

Everyday problem solving across the adult life span: solution diversity and efficacy

PubMed Central

Mienaltowski, Andrew

2013-01-01

Everyday problem solving involves examining the solutions that individuals generate when faced with problems that take place in their everyday experiences. Problems can range from medication adherence and meal preparation to disagreeing with a physician over a recommended medical procedure or compromising with extended family members over where to host Thanksgiving dinner. Across the life span, research has demonstrated divergent patterns of change in performance based on the type of everyday problems used as well as based on the way that problem-solving efficacy is operationally defined. Advancing age is associated with worsening performance when tasks involve single-solution or fluency-based definitions of effectiveness. However, when efficacy is defined in terms of the diversity of strategies used, as well as by the social and emotional impact of solution choice on the individual, performance is remarkably stable and sometimes even improves in the latter half of life. This article discusses how both of these approaches to everyday problem solving inform research on the influence that aging has on everyday functioning. PMID:22023569

Dietary resveratrol prevents Alzheimer's markers and increases life span in SAMP8.

PubMed

Porquet, David; Casadesús, Gemma; Bayod, Sergi; Vicente, Alberto; Canudas, Anna M; Vilaplana, Jordi; Pelegrí, Carme; Sanfeliu, Coral; Camins, Antoni; Pallàs, Mercè; del Valle, Jaume

2013-10-01

Resveratrol is a polyphenol that is mainly found in grapes and red wine and has been reported to be a caloric restriction (CR) mimetic driven by Sirtuin 1 (SIRT1) activation. Resveratrol increases metabolic rate, insulin sensitivity, mitochondrial biogenesis and physical endurance, and reduces fat accumulation in mice. In addition, resveratrol may be a powerful agent to prevent age-associated neurodegeneration and to improve cognitive deficits in Alzheimer's disease (AD). Moreover, different findings support the view that longevity in mice could be promoted by CR. In this study, we examined the role of dietary resveratrol in SAMP8 mice, a model of age-related AD. We found that resveratrol supplements increased mean life expectancy and maximal life span in SAMP8 and in their control, the related strain SAMR1. In addition, we examined the resveratrol-mediated neuroprotective effects on several specific hallmarks of AD. We found that long-term dietary resveratrol activates AMPK pathways and pro-survival routes such as SIRT1 in vivo. It also reduces cognitive impairment and has a neuroprotective role, decreasing the amyloid burden and reducing tau hyperphosphorylation.

The specificity of childhood adversities and negative life events across the life span to anxiety and depressive disorders.

PubMed

Spinhoven, Philip; Elzinga, Bernet M; Hovens, Jacqueline G F M; Roelofs, Karin; Zitman, Frans G; van Oppen, Patricia; Penninx, Brenda W J H

2010-10-01

Although several studies have shown that life adversities play an important role in the etiology and maintenance of both depressive and anxiety disorders, little is known about the relative specificity of several types of life adversities to different forms of depressive and anxiety disorder and the concurrent role of neuroticism. Few studies have investigated whether clustering of life adversities or comorbidity of psychiatric disorders critically influence these relationships. Using data from the Netherlands Study of Depression and Anxiety (NESDA), we analyzed the association of childhood adversities and negative life experiences across the lifespan with lifetime DSM-IV-based diagnoses of depression or anxiety among 2288 participants with at least one affective disorder. Controlling for comorbidity and clustering of adversities the association of childhood adversity with affective disorders was greater than that of negative life events across the life span with affective disorders. Among childhood adversities, emotional neglect was specifically associated with depressive disorder, dysthymia, and social phobia. Persons with a history of emotional neglect and sexual abuse were more likely to develop more than one lifetime affective disorder. Neuroticism and current affective disorder did not affect the adversity-disorder relationships found. Using a retrospective study design, causal interpretations of the relationships found are not warranted. Emotional neglect seems to be differentially related to depression, dysthymia and social phobia. This knowledge may help to reduce underestimation of the impact of emotional abuse and lead to better recognition and treatment to prevent long-term disorders. Copyright 2010 Elsevier B.V. All rights reserved.

Neuronal inhibition of the autophagy nucleation complex extends life span in post-reproductive C. elegans

PubMed Central

Byrne, Jonathan; Medina, Rebeca; Kolundžić, Ena; Geisinger, Johannes; Hajduskova, Martina; Tursun, Baris; Richly, Holger

2017-01-01

Autophagy is a ubiquitous catabolic process that causes cellular bulk degradation of cytoplasmic components and is generally associated with positive effects on health and longevity. Inactivation of autophagy has been linked with detrimental effects on cells and organisms. The antagonistic pleiotropy theory postulates that some fitness-promoting genes during youth are harmful during aging. On this basis, we examined genes mediating post-reproductive longevity using an RNAi screen. From this screen, we identified 30 novel regulators of post-reproductive longevity, including pha-4. Through downstream analysis of pha-4, we identified that the inactivation of genes governing the early stages of autophagy up until the stage of vesicle nucleation, such as bec-1, strongly extend both life span and health span. Furthermore, our data demonstrate that the improvements in health and longevity are mediated through the neurons, resulting in reduced neurodegeneration and sarcopenia. We propose that autophagy switches from advantageous to harmful in the context of an age-associated dysfunction. PMID:28882853

Effect of GSTP1 and ABCC2 Polymorphisms on Treatment Response in Patients with Advanced Non-Small Cell Lung Cancer Undergoing Platinum-Based Chemotherapy: A Study in a Chinese Uygur Population.

PubMed

Han, Zhi-Gang; Tao, Jie; Yu, Ting-Ting; Shan, Li

2017-04-26

BACKGROUND Gene polymorphisms are associated with sensitivity to platinum drugs. This study aimed to investigate the polymorphisms of GSTP1 rs1695 locus and ABCC2 rs717620 locus, and the sensitivity of patients with advanced non-small cell lung cancer (NSCLC) to platinum drugs in a Xinjiang Uygur population. MATERIAL AND METHODS The gene polymorphisms of GSTP1 rs1695 and ABCC2 rs717620 of Uygur NSCLC patients were assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The relationship between the prognosis of advanced NSCLC Uygur patients and the gene polymorphisms of GSTP1 rs1695 and ABCC2 rs717620 was analyzed using progression-free survival (PFS) and overall survival (OS) as the major outcome indicators. RESULTS The median PFS of patients with advanced NSCLC was 6.9 months and the OS of Uygur patients with advanced NSCLC was 10.8 months. Kaplan-Meier survival analysis indicated that survival time of patients with GSTP1 AG + GG was significantly longer than in patients with AA gene (P<0.05), and survival time of patients with ABCC2 CT + TT was significantly longer than in patients with the CC gene (P<0.05). CONCLUSIONS Polymorphisms of GSTP1 rs1695 and ABCC2 rs717620 can be used to predict the outcomes of Uygur patients with advanced NSCLC who have received platinum-based chemotherapy. Additionally, this information could be used to guide the individualized treatment of Uygur patients with advanced NSCLC.

Modeling Life-Span Growth Curves of Cognition Using Longitudinal Data with Multiple Samples and Changing Scales of Measurement

ERIC Educational Resources Information Center

McArdle, John J.; Grimm, Kevin J.; Hamagami, Fumiaki; Bowles, Ryan P.; Meredith, William

2009-01-01

The authors use multiple-sample longitudinal data from different test batteries to examine propositions about changes in constructs over the life span. The data come from 3 classic studies on intellectual abilities in which, in combination, 441 persons were repeatedly measured as many as 16 times over 70 years. They measured cognitive constructs…

The structure of late-life depressive symptoms across a 20-year span: a taxometric investigation.

PubMed

Holland, Jason M; Schutte, Kathleen K; Brennan, Penny L; Moos, Rudolf H

2010-03-01

Past studies of the underlying structure of depressive symptoms have yielded mixed results, with some studies supporting a continuous conceptualization and others supporting a categorical one. However, no study has examined this research question with an exclusively older adult sample, despite the potential uniqueness of late-life depressive symptoms. In the present study, the underlying structure of late-life depressive symptoms was examined among a sample of 1,289 individuals across 3 waves of data collection spanning 20 years. The authors employed a taxometric methodology using indicators of depression derived from the Research Diagnostic Criteria (R. L. Spitzer, J. Endicott, & E. Robins, 1978). Maximum eigenvalue analyses and inchworm consistency tests generally supported a categorical conceptualization and identified a group that was primarily characterized by thoughts about death and suicide. However, compared to a categorical depression variable, depressive symptoms treated continuously were generally better predictors of relevant criterion variables. These findings suggest that thoughts of death and suicide may characterize a specific type of late-life depression, yet a continuous conceptualization still typically maximizes the predictive utility of late-life depressive symptoms.

Minocycline, but not ascorbic acid, increases motor activity and extends the life span of Drosophila melanogaster.

PubMed

Mora, Marylhi; Medina-Leendertz, Shirley J; Bonilla, Ernesto; Terán, Raikelin E; Paz, Milagros C; Arcaya, José Luis

2013-06-01

In the present study we compared the effects of minocycline and ascorbic acid in the life span, motor activity and lipid peroxidation of Drosophila melanogaster, in an effort to find a substance capable of providing protection against oxidative stress in aging. In the flies treated with minocycline a very significant increase in the life span (101 +/- 1.33 days) was observed when compared to those treated with ascorbic acid and controls (42.3% and 38.4%, respectively). The motor activity of minocycline treated flies also increased significantly with respect to control and ascorbic acid fed flies, from the 3rd to the 9th week of treatment. With regard to lipid peroxidation, it was found that the levels of malondialdehyde (MDA) in flies treated with minocycline showed no statistical differences to the control on the first day of treatment, but a significantly lower content on the day of 50% survival. In contrast, in flies treated with ascorbic acid significantly elevated levels of MDA compared to control and minocycline treated flies were detected throughout. These results suggest a protective effect of minocycline against oxidative stress and aging in D. melanogaster. An inhibitory effect on reactive oxygen species production may be an important contributing factor.

Life span and structure of ephemeral root modules of different functional groups from a desert system.

PubMed

Liu, Bo; He, Junxia; Zeng, Fanjiang; Lei, Jiaqiang; Arndt, Stefan K

2016-07-01

The terminal branch orders of plant root systems have been proposed as short-lived 'ephemeral' modules specialized for resource absorption. The occurrence of ephemeral root modules has so far only been reported for a temperate tree species and it is unclear if the concept also applies to other woody (shrub, tree) and herb species. Fine roots of 12 perennial dicotyledonous herb, shrub and tree species were monitored for two growing seasons using a branch-order classification, sequential sampling and rhizotrons in the Taklamakan desert. Two root modules existed in all three plant functional groups. Among the first five branch orders, the first two (perennial herbs, shrubs) or three (trees) root orders were ephemeral and had a primary anatomical structure, high nitrogen (N) concentrations, high respiration rates and very short life spans of 1-4 months, whereas the last two branch orders in all functional groups were perennial, with thicker diameters, no or collapsed cortex, distinct secondary growth, low N concentrations, low respiration rates, but much longer life spans. Ephemeral, short-lived root modules and long-lived, persistent root modules seem to be a general feature across many plant functional groups and could represent a basic root system design. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Administration of bone marrow derived mesenchymal stem cells into the liver: potential to rescue pseudoxanthoma elasticum in a mouse model (Abcc6-/-).

PubMed

Jiang, Qiujie; Takahagi, Shunsuke; Uitto, Jouni

2012-01-01

Pseudoxanthoma elasticum (PXE) is a heritable ectopic mineralization disorder caused by loss-of-function mutations in the ABCC6 gene which is primarily expressed in the liver. There is currently no effective treatment for PXE. In this study, we characterized bone marrow derived mesenchymal stem cells (MSCs) and evaluated their ability to contribute to liver regeneration, with the aim to rescue PXE phenotype. The MSCs, isolated from GFP-transgenic mice by magnetic cell sorting, were shown to have high potential for hepatic differentiation, with expression of Abcc6, in culture. These cells were transplanted into the livers of 4-week-old immunodeficient Abcc6⁻/⁻ mice by intrasplenic injection one day after partial hepatectomy, when peak expression of the stromal cell derived factor-1 (SDF-1) in the liver was observed. Fluorescent bioimaging analyses indicated that transplanted MSCs homed into liver between day 1 and 7, and significant numbers of GFP-positive cells were confirmed in the liver by immunofluorescence. Moreover, enhanced engraftment efficiency was observed with MSCs with high expression levels of the chemokine receptor Cxcr4, a receptor for SDF-1. These data suggest that purified MSCs have the capability of differentiating into hepatic lineages relevant to PXE pathogenesis and may contribute to partial correction of the PXE phenotype.

A role for calcium in the regulation of ATP-binding cassette, sub-family C, member 3 (ABCC3) gene expression in a model of epidermal growth factor-mediated breast cancer epithelial-mesenchymal transition.

PubMed

Stewart, Teneale A; Azimi, Iman; Thompson, Erik W; Roberts-Thomson, Sarah J; Monteith, Gregory R

2015-03-13

Epithelial-mesenchymal transition (EMT), a process implicated in cancer metastasis, is associated with the transcriptional regulation of members of the ATP-binding cassette superfamily of efflux pumps, and drug resistance in breast cancer cells. Epidermal growth factor (EGF)-induced EMT in MDA-MB-468 breast cancer cells is calcium signal dependent. In this study induction of EMT was shown to result in the transcriptional up-regulation of ATP-binding cassette, subfamily C, member 3 (ABCC3), a member of the ABC transporter superfamily, which has a recognized role in multidrug resistance. Buffering of cytosolic free calcium inhibited EGF-mediated ABCC3 increases, indicating a calcium-dependent mode of regulation. Silencing of TRPM7 (an ion channel involved in EMT associated vimentin induction) did not inhibit ABCC3 up-regulation. Silencing of the store operated calcium entry (SOCE) pathway components ORAI1 and STIM1 also did not alter ABCC3 induction by EGF. However, the calcium permeable ion channel transient receptor potential cation channel, subfamily C, member 1 (TRPC1) appears to contribute to the regulation of both basal and EGF-induced ABCC3 mRNA. Improved understanding of the relationship between calcium signaling, EMT and the regulation of genes important in therapeutic resistance may help identify novel therapeutic targets for breast cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

ABCB1 and ABCC1-like transporters in immune system cells from sea urchins Echinometra lucunter and Echinus esculentus and oysters Crassostrea gasar and Crassostrea gigas.

PubMed

Marques-Santos, Luis Fernando; Hégaret, Hélène; Lima-Santos, Leonardo; Queiroga, Fernando Ramos; da Silva, Patricia Mirella

2017-11-01

ABC transporters activity and expression have been associated with the multixenobiotic resistance phenotype (MXR). The activity of these proteins leads to a reduction in the intracellular concentration of several xenobiotics, thus reducing their toxicity. However, little attention has been given to the expression of ABC transporters in marine invertebrates and few studies have investigated their role in immune system cells of sea urchins and shellfish bivalves. The aim of the present study was to investigate the activity of the ABC transporters ABCB1 and ABCC1 in immune system cells of sea urchins (coelomocytes) and oysters (hemocytes) from different climatic regions (Brazil and France). Sea urchins and oysters were collected at Paraíba coast; Brazil (Echinometra lucunter and Crassostrea gasar) and Rade of Brest; France (Echinus esculentus and Crassostrea gigas). Coelomocytes and hemocytes were stained with the ABC transporter substrate calcein-AM and dye accumulation analyzed under flow cytometry. Reversin 205 (ABCB1 transporter blocker) and MK571 (ABCC1 transporter blocker) were used as pharmacological tools to investigate ABC transporter activity. A different pattern of calcein accumulation was observed in coelomocytes: phagocytes > colorless spherulocytes > vibrate cells > red spherulocytes. The treatment with MK571 increased calcein fluorescence levels in coelomocytes from both species. However, reversin 205 treatment was not able to increase calcein fluorescence in E. esculentus coelomocytes. These data suggest that ABCC1-like transporter activity is present in both sea urchin species, but ABCB1-like transporter activity might only be present in E. lucunter coelomocytes. The activity of ABCC1-like transporter was observed in all cell types from both bivalve species. However, reversin 205 only increased calcein accumulation in hyalinocytes of the oyster C. gasar, suggesting the absence of ABCB1-like transporter activity in all other cell types

The control processes and subjective well-being of Chinese teachers: evidence of convergence with and divergence from the key propositions of the motivational theory of life-span development

PubMed Central

Wong, Wan-chi; Li, Yin; Sun, Xiaoyan; Xu, Huanu

2014-01-01

An analytical review of the motivational theory of life-span development reveals that this theory has undergone a series of elegant theoretical integrations. Its claim to universality nonetheless brings forth unresolved controversies. With the purpose of scrutinizing the key propositions of this theory, an empirical study was designed to examine the control processes and subjective well-being of Chinese teachers (N = 637). The OPS-Scales (Optimization in Primary and Secondary Control Scales) for the Domain of Teaching were constructed to assess patterns of control processes. Three facets of subjective well-being were investigated with the Positive and Negative Affect Schedule, the Life Satisfaction Scale, and the Subjective Vitality Scale. The results revealed certain aspects of alignment with and certain divergences from the key propositions of the motivational theory of life-span development. Neither “primacy of primary control” nor “primacy of secondary control” was clearly supported. Notably, using different criteria for subjective well-being yielded different subtypes of primary and secondary control as predictors. The hypothesized life-span trajectories of primary and secondary control received limited support. To advance the theory in this area, we recommend incorporating Lakatos' ideas about sophisticated falsification by specifying the hard core of the motivational theory of life-span development and articulating new auxiliary hypotheses. PMID:24904483

Linguistic Evidence for the Failure Mindset as a Predictor of Life Span Longevity.

PubMed

Penzel, Ian B; Persich, Michelle R; Boyd, Ryan L; Robinson, Michael D

2017-06-01

When people think that their efforts will fail to achieve positive outcomes, they sometimes give up their efforts after control, which can have negative health consequences. Problematic orientations of this type, such as pessimism, helplessness, or fatalism, seem likely to be associated with a cognitive mindset marked by higher levels of accessibility for failure words or concepts. Thus, the purpose of the present research was to determine whether there are individual differences in the frequency with which people think about failure, which in turn are likely to impact health across large spans of time. Following self-regulatory theories of health and the learned helplessness tradition, two archival studies (total n = 197) scored texts (books or speeches) for their use of failure words, a category within the Harvard IV dictionary of the General Inquirer. People who used failure words more frequently exhibited shorter subsequent life spans, and this relationship remained significant when controlling for birth year. Furthermore, study 2 implicated behavioral factors. For example, the failure/longevity relationship was numerically stronger among people whose causes of death appeared to be preventable rather than non-preventable. These results significantly extend our knowledge of the personality/longevity relationship while highlighting the value of individual differences in word usage as predictors of health and mortality.

Association of KCNJ11 and ABCC8 genetic polymorphisms with response to repaglinide in Chinese diabetic patients.

PubMed

He, Ya-yi; Zhang, Rong; Shao, Xin-yu; Hu, Cheng; Wang, Cong-rong; Lu, Jun-xi; Bao, Yu-qian; Jia, Wei-ping; Xiang, Kun-san

2008-08-01

The aim of this study was to investigate the association of KCNJ11 E23K and ABCC8 exon16-3T/C with the therapeutic effect of repaglinide in patients with type 2 diabetes. A total of 100 Chinese patients with newly diagnosed type 2 diabetes were treated with repaglinide for 24 weeks. Arginine stimulation tests were performed to evaluate beta cell function. Gene variations were detected with PCR-restriction fragment length polymorphism. Responders were defined by a greater than 25% decrease in fasting plasma glucose or a greater than 20% decrease in hemoglobin A1c (HbA1c) values (or both) after the 24 week repaglinide treatment. Both baseline HbA1c and the decrease of HbA1c were significantly higher in patients with E/K and K/K genotypes of the KCNJ11 E23K variant when compared with E/E homozygotes (P=0.0103 and 0.0221, respectively). The decrease in 2 h postprandial plasma glucose (2hPG) was significantly greater in E/K heterozygotes than E/E homozygotes (P=0.0367). There was a significant difference in the response rate to repaglinide treatment between the E and K alleles (68% vs 82%, P=0.0324). The changes in fasting insulin and the homeostasis model assessment of insulin resistance were significantly greater in patients with ABCC8 exon16-3 C/C versus the T/C and T/T genotypes (P=0.0372 and 0.0274, respectively). The KCNJ11 E23K variant was associated with the therapeutic effect of repaglinide. In addition, The C/C homozygotes of the ABCC8 exon16-3T/C variant responded better to repaglinide in insulin sensitivity than the T/C and T/T genotypes.

Minocycline increases the life span and motor activity and decreases lipid peroxidation in manganese treated Drosophila melanogaster.

PubMed

Bonilla, E; Contreras, R; Medina-Leendertz, S; Mora, M; Villalobos, V; Bravo, Y

2012-03-29

The objective of this study was to investigate the effect of Minocycline in the life span, motor activity, and lipid peroxidation of Drosophila melanogaster treated with manganese. Two days after emerging from the pupa male wild-type D. melanogaster were fed for 13 days with corn media containing 15 mM manganese. Then, they were divided in six groups of 300 flies each: group (a) remained treated with manganese (Mn group); group (b) began treatment with Minocycline (0.05 mM) (Mn-Minocycline group); group (c) received no additional treatment (Mn-no treatment group); group (d) simultaneously fed with manganese and Minocycline (Mn+Minocycline group). Additionally, a control (group e) with no treatment and another group (f) fed only with Minocycline after emerging from the pupa were added. All the manganese treated flies (group a) were dead on the 25th day. The life span in group f (101.66±1.33 days, mean S.E.M.) and of group b (97.00±3.46 days) were similar, but in both cases it was significantly higher than in group e (68.33±1.76 days), group c (67.05±2.30 days) and in those of group d (37.33±0.88). Manganese (groups a and d) decreased motor activity in D. melanogaster. In the Minocycline fed flies (groups b and f) a higher motor activity was detected. In Mn-Minocycline and Mn+Minocycline treated flies a significant decrease of MDA levels was detected when compared to the Minocycline group indicating that Minocycline and Mn appear to have a synergistic effect. In conclusion, Minocycline increased the life span and motor activity and decreased MDA formation of manganese treated D. melanogaster, probably by an inhibition of the production of reactive oxygen species. Manganese also exerted an antioxidant effect as shown by the significant decrease of MDA levels when compared to control flies. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The relationship of polymorphisms in ABCC2 and SLCO1B3 with docetaxel pharmacokinetics and neutropenia: CALGB 60805 (Alliance).

PubMed

Lewis, Lionel D; Miller, Antonius A; Owzar, Kouros; Bies, Robert R; Markova, Svetlana; Jiang, Chen; Kroetz, Deanna L; Egorin, Merrill J; McLeod, Howard L; Ratain, Mark J

2013-01-01

Docetaxel-related neutropenia was associated with polymorphisms in the drug transporters ABCC2 and SLCO1B3 in Japanese cancer patients. We hypothesized that this association is because of reduced docetaxel clearance, associated with polymorphisms in those genes. We studied 64 US cancer patients who received a single cycle of 75 mg/m of docetaxel monotherapy. We found that the ABCC2 polymorphism at rs-12762549 trended to show a relationship with reduced docetaxel clearance (P=0.048), but not with neutropenia. There was no significant association of the SLCO1B3 polymorphisms with docetaxel clearance or neutropenia. We conclude that the relationship between docetaxel-associated neutropenia and polymorphisms in drug transporters identified in Japanese patients was not confirmed in this cohort of US cancer patients. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Hour Glass Half-Full or Half-Empty? Future Time Perspective and Preoccupation with Negative Events Across the Life Span

PubMed Central

Strough, JoNell; de Bruin, Wändi Bruine; Parker, Andrew M.; Lemaster, Philip; Pichayayothin, Nipat; Delaney, Rebecca

2016-01-01

According to socioemotional selectivity theory, older adults' emotional well-being stems from having limited future time perspective that motivates them to maximize well-being in the “here and now.” Presumably, then, older adults' time horizons are associated with emotional competencies that boost positive affect and dampen negative affect, but little research has addressed this. Using a US national adult life-span sample (N= 3,933, 18-93 yrs), we found that a two-factor model of future time perspective (focus on future opportunities; focus on limited time) fit the data better than a one-factor model. Through middle age, people perceived the life-span hourglass as half full—they focused more on future opportunities than limited time. Around age 60, the balance changed to increasingly perceiving the life-span hourglass as half empty—they focused less on future opportunities and more on limited time. This pattern held even after accounting for perceived health, self-reported decision-making ability, and retirement status. At all ages, women's time horizons focused more on future opportunities compared to men's, and men's focused more on limited time. Focusing on future opportunities was associated with reporting less preoccupation with negative events, whereas focusing on limited time was associated with reporting more preoccupation. Older adults reported less preoccupation with negative events and this association was stronger after controlling for their perceptions of limited time and fewer future opportunities, suggesting that other pathways may explain older adults' reports of their ability to disengage from negative events. Insights gained and questions raised by measuring future time perspective as two dimensions are discussed. PMID:27267222

Hour glass half full or half empty? Future time perspective and preoccupation with negative events across the life span.

PubMed

Strough, JoNell; Bruine de Bruin, Wändi; Parker, Andrew M; Lemaster, Philip; Pichayayothin, Nipat; Delaney, Rebecca

2016-09-01

According to socioemotional selectivity theory, older adults' emotional well-being stems from having a limited future time perspective that motivates them to maximize well-being in the "here and now." Presumably, then, older adults' time horizons are associated with emotional competencies that boost positive affect and dampen negative affect, but little research has addressed this. Using a U.S. adult life-span sample (N = 3,933; 18-93 years), we found that a 2-factor model of future time perspective (future opportunities; limited time) fit the data better than a 1-factor model. Through middle age, people perceived the life-span hourglass as half full-they focused more on future opportunities than limited time. Around Age 60, the balance changed to increasingly perceiving the life-span hourglass as half empty-they focused less on future opportunities and more on limited time, even after accounting for perceived health, self-reported decision-making ability, and retirement status. At all ages, women's time horizons focused more on future opportunities compared with men's, and men's focused more on limited time. Focusing on future opportunities was associated with reporting less preoccupation with negative events, whereas focusing on limited time was associated with reporting more preoccupation. Older adults reported less preoccupation with negative events, and this association was stronger after controlling for their perceptions of limited time and fewer future opportunities, suggesting that other pathways may explain older adults' reports of their ability to disengage from negative events. Insights gained and questions raised by measuring future time perspective as 2 dimensions are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

A general benevolence dimension that links neural, psychological, economic, and life-span data on altruistic tendencies.

PubMed

Hubbard, Jason; Harbaugh, William T; Srivastava, Sanjay; Degras, David; Mayr, Ulrich

2016-10-01

[Correction Notice: An Erratum for this article was reported in Vol 145(10) of Journal of Experimental Psychology: General (see record 2016-46925-004). In the article, there was an error in the Task, Stimuli, and Procedures section. In the 1st sentence in the 6th paragraph, “Following the scanning phase, participants completed self-report questionnaires meant to reflected the Prosocial Disposition construct: the agreeableness scale from the Big F, which includes empathic concern and perspective-taking, and a scale of personality descriptive adjectives related to altruistic behavior (Wood, Nye, & Saucier, 2010).” should have read: “Following the scanning phase, participants completed self-report questionnaires that contained scales to reflect the Prosocial Disposition construct: the Big Five Inventory (BFI; John et al., 1991), from which we used the agreeableness scale to measure prosocial disposition; the Interpersonal Reactivity Index (IRI; Davis, 1980), from which we used the empathic concern and perspective-taking scales; and a scale of personality descriptive adjectives related to altruistic behavior (Wood, Nye, & Saucier, 2010).”] Individual and life span differences in charitable giving are an important economic force, yet the underlying motives are not well understood. In an adult, life span sample, we assessed manifestations of prosocial tendencies across 3 different measurement domains: (a) psychological self-report measures, (b) actual giving choices, and (c) fMRI-derived, neural indicators of “pure altruism.” The latter expressed individuals’ activity in neural valuation areas when charities received money compared to when oneself received money and thus reflected an altruistic concern for others. Results based both on structural equation modeling and unit-weighted aggregate scores revealed a strong higher-order General Benevolence dimension that accounted for variability across all measurement domains. The fact that the neural measures

Coping strategies: gender differences and development throughout life span.

PubMed

Meléndez, Juan Carlos; Mayordomo, Teresa; Sancho, Patricia; Tomás, José Manuel

2012-11-01

Development during life-span implies to cope with stressful events, and this coping may be done with several strategies. It could be useful to know if these coping strategies differ as a consequence of personal characteristics. This work uses the Coping with Stress Questionnaire with this aim using a sample of 400 participants. Specifically, the effects of gender and age group (young people, middle age and elderly), as well as its interaction on coping strategies is studied. With regard to age, on one hand, it is hypothesised a decrement in the use of coping strategies centred in problem solving and social support seeking as age increases. On the other hand, the use of emotional coping is hypothesised to increase with age. With respect to gender, it is hypothesised a larger use of emotional coping and social support seeking within women, and a larger use of problem solving within men. A MANOVA found significant effects for the two main effects (gender and age) as well as several interactions. Separate ANOVAs allowed us to test for potential differences in each of the coping strategies measured in the CAE. These results partially supported the hypotheses. Results are discussed in relation to scientific literature on coping, age and gender.

Changes in Acoustic Characteristics of the Voice across the Life Span: Measures from Individuals 4-93 Years of Age

ERIC Educational Resources Information Center

Stathopoulos, Elaine T.; Huber, Jessica E.; Sussman, Joan E.

2011-01-01

Purpose: The purpose of the present investigation was to examine acoustic voice changes across the life span. Previous voice production investigations used small numbers of participants, had limited age ranges, and produced contradictory results. Method: Voice recordings were made from 192 male and female participants 4-93 years of age. Acoustic…

CALHM1 Deletion in Mice Affects Glossopharyngeal Taste Responses, Food Intake, Body Weight, and Life Span

PubMed Central

Schmolling, Jared; Marambaud, Philippe; Rose-Hellekant, Teresa A.

2015-01-01

Stimulation of Type II taste receptor cells (TRCs) with T1R taste receptors causes sweet or umami taste, whereas T2Rs elicit bitter taste. Type II TRCs contain the calcium channel, calcium homeostasis modulator protein 1 (CALHM1), which releases adenosine triphosphate (ATP) transmitter to taste fibers. We have previously demonstrated with chorda tympani nerve recordings and two-bottle preference (TBP) tests that mice with genetically deleted Calhm1 (knockout [KO]) have severely impaired perception of sweet, bitter, and umami compounds, whereas their sour and salty tasting ability is unaltered. Here, we present data from KO mice of effects on glossopharyngeal (NG) nerve responses, TBP, food intake, body weight, and life span. KO mice have no NG response to sweet and a suppressed response to bitter compared with control (wild-type [WT]) mice. KO mice showed some NG response to umami, suggesting that umami taste involves both CALHM1- and non-CALHM1-modulated signals. NG responses to sour and salty were not significantly different between KO and WT mice. Behavioral data conformed in general with the NG data. Adult KO mice consumed less food, weighed significantly less, and lived almost a year longer than WT mice. Taken together, these data demonstrate that sweet taste majorly influences food intake, body weight, and life span. PMID:25855639

Younger and older adults' beliefs about the experience and expression of emotions across the life span.

PubMed

Montepare, Joann M; Dobish, Heidi

2014-11-01

Although theorists acknowledge that beliefs about emotions may play a role in age-related emotion behavior, no research has explored these beliefs. This research examined beliefs about the experience and expression of emotions across the life span, especially across the adult years. Younger and older adults rated the extent to which infants, children, adolescents, young adults, middle-aged adults, and older adults were likely to experience and express a range of emotions. Younger and older adults held similar beliefs about the course of emotions across the life span. Moreover, these beliefs differed across emotion categories. In particular, although older adults were believed to experience and express fewer highly charged, negative emotions, they were expected to be more likely to experience and express positive, low arousal emotions, as well as negative, low arousal emotions. The experience and expression of positive, high arousal emotions were seen as more characteristic of very young age groups as opposed to older age groups. These findings beg questions about if and how beliefs about emotion may affect age-related emotion regulation strategies and other everyday emotion-focused behaviors, as well as social reactions to older adults observed experiencing and expressing particular types of emotions. © The Author 2013. 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.

Relation of behaviour and macrophage function to life span in a murine model of premature immunosenescence.

PubMed

Guayerbas, Noelia; Catalán, Marina; Víctor, Víctor M; Miquel, Jaime; De la Fuente, Mónica

2002-08-21

According to our previous work, mice of the same strain and age show striking inter-individual differences in behaviour when exposed to a T-maze test. Further, the animals exploring the maze slowly (slow mice) or staying at the starting point (freezing behaviour), which show high levels of emotionality/anxiety in other standard behavioural tests, have a less competent immune system (earlier immunosenescence) than those which explore it quickly (fast mice). The present longitudinal study on OF-1 Swiss female mice confirms and extends the above findings. Thus, the animals showing a lower performance in the T-test (slow mice) which is accompanied by a poor neuromuscular coordination in a tightrope test, have a shorter life span than the good performers (fast mice). Moreover, the slow mice have a less competent immune system as regards the following functions of peritoneal macrophages: adherence to substrate, chemotaxis, ingestion of particles and superoxide anion production. This suggests that, at the same chronological age and as regards their immune competence, the slow mice are biologically older than the fast mice. This agrees with current ideas on the close functional relationship between the nervous and the immune system in the physiological adaptation to stress, and supports the concept that an optimum level of performance of these two systems is needed to attain a long life span. Copyright 2002 Elsevier Science B.V.

Loss of Ubp3 increases silencing, decreases unequal recombination in rDNA, and shortens the replicative life span in Saccharomyces cerevisiae.

PubMed

Oling, David; Masoom, Rehan; Kvint, Kristian

2014-06-15

Ubp3 is a conserved ubiquitin protease that acts as an antisilencing factor in MAT and telomeric regions. Here we show that ubp3∆ mutants also display increased silencing in ribosomal DNA (rDNA). Consistent with this, RNA polymerase II occupancy is lower in cells lacking Ubp3 than in wild-type cells in all heterochromatic regions. Moreover, in a ubp3∆ mutant, unequal recombination in rDNA is highly suppressed. We present genetic evidence that this effect on rDNA recombination, but not silencing, is entirely dependent on the silencing factor Sir2. Further, ubp3∆ sir2∆ mutants age prematurely at the same rate as sir2∆ mutants. Thus our data suggest that recombination negatively influences replicative life span more so than silencing. However, in ubp3∆ mutants, recombination is not a prerequisite for aging, since cells lacking Ubp3 have a shorter life span than isogenic wild-type cells. We discuss the data in view of different models on how silencing and unequal recombination affect replicative life span and the role of Ubp3 in these processes. © 2014 Öling et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Auditory Environment Across the Life Span of Cochlear Implant Users: Insights From Data Logging.

PubMed

Busch, Tobias; Vanpoucke, Filiep; van Wieringen, Astrid

2017-05-24

We describe the natural auditory environment of people with cochlear implants (CIs), how it changes across the life span, and how it varies between individuals. We performed a retrospective cross-sectional analysis of Cochlear Nucleus 6 CI sound-processor data logs. The logs were obtained from 1,501 people with CIs (ages 0-96 years). They covered over 2.4 million hr of implant use and indicated how much time the CI users had spent in various acoustical environments. We investigated exposure to spoken language, noise, music, and quiet, and analyzed variation between age groups, users, and countries. CI users spent a substantial part of their daily life in noisy environments. As a consequence, most speech was presented in background noise. We found significant differences between age groups for all auditory scenes. Yet even within the same age group and country, variability between individuals was substantial. Regardless of their age, people with CIs face challenging acoustical environments in their daily life. Our results underline the importance of supporting them with assistive listening technology. Moreover, we found large differences between individuals' auditory diets that might contribute to differences in rehabilitation outcomes. Their causes and effects should be investigated further.

View of central lift span truss web of Tensaw River ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

View of central lift span truss web of Tensaw River Bridge, showing support girders for life house, looking east - Tensaw River Lift Bridge, Spanning Tensaw River at U.S. Highway 90, Mobile, Mobile County, AL

Assimilation of Endogenous Nicotinamide Riboside Is Essential for Calorie Restriction-mediated Life Span Extension in Saccharomyces cerevisiae*

PubMed Central

Lu, Shu-Ping; Kato, Michiko; Lin, Su-Ju

2009-01-01

NAD+ (nicotinamide adenine dinucleotide) is an essential cofactor involved in various biological processes including calorie restriction-mediated life span extension. Administration of nicotinamide riboside (NmR) has been shown to ameliorate deficiencies related to aberrant NAD+ metabolism in both yeast and mammalian cells. However, the biological role of endogenous NmR remains unclear. Here we demonstrate that salvaging endogenous NmR is an integral part of NAD+ metabolism. A balanced NmR salvage cycle is essential for calorie restriction-induced life span extension and stress resistance in yeast. Our results also suggest that partitioning of the pyridine nucleotide flux between the classical salvage cycle and the NmR salvage branch might be modulated by the NAD+-dependent Sir2 deacetylase. Furthermore, two novel deamidation steps leading to nicotinic acid mononucleotide and nicotinic acid riboside production are also uncovered that further underscore the complexity and flexibility of NAD+ metabolism. In addition, utilization of extracellular nicotinamide mononucleotide requires prior conversion to NmR mediated by a periplasmic phosphatase Pho5. Conversion to NmR may thus represent a strategy for the transport and assimilation of large nonpermeable NAD+ precursors. Together, our studies provide a molecular basis for how NAD+ homeostasis factors confer metabolic flexibility. PMID:19416965

Assimilation of endogenous nicotinamide riboside is essential for calorie restriction-mediated life span extension in Saccharomyces cerevisiae.

PubMed

Lu, Shu-Ping; Kato, Michiko; Lin, Su-Ju

2009-06-19

NAD(+) (nicotinamide adenine dinucleotide) is an essential cofactor involved in various biological processes including calorie restriction-mediated life span extension. Administration of nicotinamide riboside (NmR) has been shown to ameliorate deficiencies related to aberrant NAD(+) metabolism in both yeast and mammalian cells. However, the biological role of endogenous NmR remains unclear. Here we demonstrate that salvaging endogenous NmR is an integral part of NAD(+) metabolism. A balanced NmR salvage cycle is essential for calorie restriction-induced life span extension and stress resistance in yeast. Our results also suggest that partitioning of the pyridine nucleotide flux between the classical salvage cycle and the NmR salvage branch might be modulated by the NAD(+)-dependent Sir2 deacetylase. Furthermore, two novel deamidation steps leading to nicotinic acid mononucleotide and nicotinic acid riboside production are also uncovered that further underscore the complexity and flexibility of NAD(+) metabolism. In addition, utilization of extracellular nicotinamide mononucleotide requires prior conversion to NmR mediated by a periplasmic phosphatase Pho5. Conversion to NmR may thus represent a strategy for the transport and assimilation of large nonpermeable NAD(+) precursors. Together, our studies provide a molecular basis for how NAD(+) homeostasis factors confer metabolic flexibility.

Personality, self-rated health, and subjective age in a life-span sample: the moderating role of chronological age.

PubMed

Stephan, Yannick; Demulier, Virginie; Terracciano, Antonio

2012-12-01

The present study tested whether chronological age moderates the association between subjective age and self-rated health and personality in a community-dwelling life-span sample (N = 1,016; age range: 18-91 years). Self-rated health, extraversion, and openness to experience were associated with a younger subjective age at older ages. Conscientious individuals felt more mature early in life. Conscientiousness, neuroticism, and agreeableness were not related to subjective age at older ages. These findings suggest that with aging self-rated health and personality traits are increasingly important for subjective age. 2013 APA, all rights reserved

Genetic manipulation of longevity-related genes as a tool to regulate yeast life span and metabolite production during winemaking.

PubMed

Orozco, Helena; Matallana, Emilia; Aranda, Agustín

2013-01-02

Yeast viability and vitality are essential for different industrial processes where the yeast Saccharomyces cerevisiae is used as a biotechnological tool. Therefore, the decline of yeast biological functions during aging may compromise their successful biotechnological use. Life span is controlled by a variety of molecular mechanisms, many of which are connected to stress tolerance and genomic stability, although the metabolic status of a cell has proven a main factor affecting its longevity. Acetic acid and ethanol accumulation shorten chronological life span (CLS), while glycerol extends it. Different age-related gene classes have been modified by deletion or overexpression to test their role in longevity and metabolism. Overexpression of histone deacetylase SIR2 extends CLS and reduces acetate production, while overexpression of SIR2 homolog HST3 shortens CLS, increases the ethanol level, and reduces acetic acid production. HST3 overexpression also enhances ethanol tolerance. Increasing tolerance to oxidative stress by superoxide dismutase SOD2 overexpression has only a moderate positive effect on CLS. CLS during grape juice fermentation has also been studied for mutants on several mRNA binding proteins that are regulators of gene expression at the posttranscriptional level; we found that NGR1 and UTH4 deletions decrease CLS, while PUF3 and PUB1 deletions increase it. Besides, the pub1Δ mutation increases glycerol production and blocks stress granule formation during grape juice fermentation. Surprisingly, factors relating to apoptosis, such as caspase Yca1 or apoptosis-inducing factor Aif1, play a positive role in yeast longevity during winemaking as their deletions shorten CLS. Manipulation of regulators of gene expression at both transcriptional (i.e., sirtuins) and posttranscriptional (i.e., mRNA binding protein Pub1) levels allows to modulate yeast life span during its biotechnological use. Due to links between aging and metabolism, it also influences the

Comparing the Developmental Genetics of Cognition and Personality over the Life Span.

PubMed

Briley, Daniel A; Tucker-Drob, Elliot M

2017-02-01

Empirical studies of cognitive ability and personality have tended to operate in isolation of one another. We suggest that returning to a unified approach to considering the development of individual differences in both cognition and personality can enrich our understanding of human development. We draw on previous meta-analyses of longitudinal, behavior genetic studies of cognition and personality across the life span, focusing particular attention on age trends in heritability and differential stability. Both cognition and personality are moderately heritable and exhibit large increases in stability with age; however, marked differences are evident. First, the heritability of cognition increases substantially with child age, while the heritability of personality decreases modestly with age. Second, increasing stability of cognition with age is overwhelmingly mediated by genetic factors, whereas increasing stability of personality with age is entirely mediated by environmental factors. Third, the maturational time-course of stability differs: Stability of cognition nears its asymptote by the end of the first decade of life, whereas stability of personality takes three decades to near its asymptote. We discuss how proximal gene-environment dynamics, developmental processes, broad social contexts, and evolutionary pressures may intersect to give rise to these divergent patterns. © 2015 Wiley Periodicals, Inc.

Effects of shortened host life span on the evolution of parasite life history and virulence in a microbial host-parasite system

PubMed Central

Nidelet, Thibault; Koella, Jacob C; Kaltz, Oliver

2009-01-01

Background Ecological factors play an important role in the evolution of parasite exploitation strategies. A common prediction is that, as shorter host life span reduces future opportunities of transmission, parasites compensate with an evolutionary shift towards earlier transmission. They may grow more rapidly within the host, have a shorter latency time and, consequently, be more virulent. Thus, increased extrinsic (i.e., not caused by the parasite) host mortality leads to the evolution of more virulent parasites. To test these predictions, we performed a serial transfer experiment, using the protozoan Paramecium caudatum and its bacterial parasite Holospora undulata. We simulated variation in host life span by killing hosts after 11 (early killing) or 14 (late killing) days post inoculation; after killing, parasite transmission stages were collected and used for a new infection cycle. Results After 13 cycles (≈ 300 generations), parasites from the early-killing treatment were less infectious, but had shorter latency time and higher virulence than those from the late-killing treatment. Overall, shorter latency time was associated with higher parasite loads and thus presumably with more rapid within-host replication. Conclusion The analysis of the means of the two treatments is thus consistent with theory, and suggests that evolution is constrained by trade-offs between virulence, transmission and within-host growth. In contrast, we found little evidence for such trade-offs across parasite selection lines within treatments; thus, to some extent, these traits may evolve independently. This study illustrates how environmental variation (experienced by the host) can lead to the evolution of distinct parasite strategies. PMID:19320981

Life-span socioeconomic trajectory, nativity, and cognitive aging in Mexican Americans: the Sacramento Area Latino Study on Aging.

PubMed

Haan, Mary N; Zeki Al-Hazzouri, Adina; Aiello, Allison E

2011-07-01

Early life circumstances influence health across the life span. Migration and ethnicity may modify the lifetime trajectory of socioeconomic status (SES) and lead to heterogeneity in cognitive aging in later life. We examined the effects of both lifetime socioeconomic trajectory and cumulative disadvantage from childhood through adulthood on late life cognitive performance in a 9-year cohort of 1,789 Mexican Americans aged 60-100 years in 1998-1999. Compared with those with low SES sustained over the life course, we found that those with more advantaged lifetime SES trajectories experienced fewer declines on a test of global cognitive function and a short-term verbal memory test. These associations are larger in first- and second-generation immigrant families. Heterogeneity of cognitive aging among diverse race/ethnic groups may be influenced by intergenerational changes in SES, cultural norms, and behaviors and changes in health related to changes in the social and physical environment.

Life-span Socioeconomic Trajectory, Nativity, and Cognitive Aging in Mexican Americans: The Sacramento Area Latino Study on Aging

PubMed Central

Zeki Al-Hazzouri, Adina; Aiello, Allison E.

2011-01-01

Objectives. Early life circumstances influence health across the life span. Migration and ethnicity may modify the lifetime trajectory of socioeconomic status (SES) and lead to heterogeneity in cognitive aging in later life. Methods. We examined the effects of both lifetime socioeconomic trajectory and cumulative disadvantage from childhood through adulthood on late life cognitive performance in a 9-year cohort of 1,789 Mexican Americans aged 60–100 years in 1998–1999. Results. Compared with those with low SES sustained over the life course, we found that those with more advantaged lifetime SES trajectories experienced fewer declines on a test of global cognitive function and a short-term verbal memory test. These associations are larger in first- and second-generation immigrant families. Discussion. Heterogeneity of cognitive aging among diverse race/ethnic groups may be influenced by intergenerational changes in SES, cultural norms, and behaviors and changes in health related to changes in the social and physical environment. PMID:21743044

[Changes in average life span of monks and nuns in Poland in the years 1950-2000].

PubMed

Jenner, Bartosz

2002-01-01

The aim of the research was to find out if healthy lifestyle influences the longevity. The group of 906 monks and 866 nuns who worked and died in Poland in the years 1950-2000 was regarded as people who conducted a healthy lifestyle. The population of adult Poles was chosen as a control group. As a result of the research it is reported that: 1) since 1950 till middle 1960's people in monasteries lived shorter than adult Poles [in the first ten years of the research the average life span of monks was 2.4 years shorter (t162 = 1.99, p = 0.047) and nuns lived 9 years shorter (t56 = 4.2, p < 0.001)], since the middle of 1970's till the end of 1980's the group in question lived as long as the general population, finally, for the last ten years of the investigated period of time people in monasteries lived longer [monks 2.5 (t219 = 2.5, p < 0.05), nuns 2.9 years longer (t209 = 4.6, p < 0.001)]; 2) since 1950's till 2000 the average life span in the investigated group of both sexes was increasing at the rate of 0.175 (t98 = 3.9, p < 0.001) years per calendar year greater than this value in the general population and there is no reason to assume that there have been differences between sexes; 3) as far as men are concerned, joining a monastery in the case of man enter into the monastery a year earlier prolongs life for about 0.1 year (F1,842 = 3.8, P one side test = 0.026). In case of women this relation was not significant (F1,804 < 0.1). The shorter life of people in monasteries after the second world war might be interpreted as a result of their socio-political situation at that time. In the course of time their standard of living and the access to medical treatment has been improving gradually, so their longevity is increasing faster. In the context of the investigated problem the most important results were obtained from the last ten years. These results indicate that healthy lifestyle prolongs life.

The Verriest Lecture: Short-wave-sensitive cone pathways across the life span

PubMed Central

Werner, John S.

2017-01-01

Structurally and functionally, the short-wave-sensitive (S) cone pathways are thought to decline more rapidly with normal aging than the middle- and long-wave-sensitive cone pathways. This would explain the celebrated results by Verriest and others demonstrating that the largest age-related color discrimination losses occur for stimuli on a tritan axis. Here, we challenge convention, arguing from psychophysical data that selective S-cone pathway losses do not cause declines in color discrimination. We show substantial declines in chromatic detection and discrimination, as well as in temporal and spatial vision tasks, that are mediated by S-cone pathways. These functional losses are not, however, unique to S-cone pathways. Finally, despite reduced photon capture by S cones, their postreceptoral pathways provide robust signals for the visual system to renormalize itself to maintain nearly stable color perception across the life span. PMID:26974914

CALHM1 Deletion in Mice Affects Glossopharyngeal Taste Responses, Food Intake, Body Weight, and Life Span.

PubMed

Hellekant, Göran; Schmolling, Jared; Marambaud, Philippe; Rose-Hellekant, Teresa A

2015-07-01

Stimulation of Type II taste receptor cells (TRCs) with T1R taste receptors causes sweet or umami taste, whereas T2Rs elicit bitter taste. Type II TRCs contain the calcium channel, calcium homeostasis modulator protein 1 (CALHM1), which releases adenosine triphosphate (ATP) transmitter to taste fibers. We have previously demonstrated with chorda tympani nerve recordings and two-bottle preference (TBP) tests that mice with genetically deleted Calhm1 (knockout [KO]) have severely impaired perception of sweet, bitter, and umami compounds, whereas their sour and salty tasting ability is unaltered. Here, we present data from KO mice of effects on glossopharyngeal (NG) nerve responses, TBP, food intake, body weight, and life span. KO mice have no NG response to sweet and a suppressed response to bitter compared with control (wild-type [WT]) mice. KO mice showed some NG response to umami, suggesting that umami taste involves both CALHM1- and non-CALHM1-modulated signals. NG responses to sour and salty were not significantly different between KO and WT mice. Behavioral data conformed in general with the NG data. Adult KO mice consumed less food, weighed significantly less, and lived almost a year longer than WT mice. Taken together, these data demonstrate that sweet taste majorly influences food intake, body weight, and life span. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Invited commentary: missing doses in the life span study of Japanese atomic bomb survivors.

PubMed

Ozasa, K; Grant, E J; Cullings, H M; Shore, R E

2013-03-15

The Life Span Study is a long-term epidemiologic cohort study of survivors of the atomic bombs dropped on Hiroshima and Nagasaki, Japan. In this issue of the Journal, Richardson et al. (Am J Epidemiol. 2013;177(6):562-568) suggest that those who died in the earliest years of follow-up were more likely to have a missing dose of radiation exposure assigned, leading to a bias in the radiation risk estimates. We show that nearly all members of the cohort had shielding information recorded before the beginning of follow-up and that much of the alleged bias that Richardson et al. describe simply reflects the geographic distribution of shielding conditions for which reliable dosimetry was impossible.

Atrx deficiency induces telomere dysfunction, endocrine defects, and reduced life span

PubMed Central

Watson, L. Ashley; Solomon, Lauren A.; Li, Jennifer Ruizhe; Jiang, Yan; Edwards, Matthew; Shin-ya, Kazuo; Beier, Frank; Bérubé, Nathalie G.

2013-01-01

Human ATRX mutations are associated with cognitive deficits, developmental abnormalities, and cancer. We show that the Atrx-null embryonic mouse brain accumulates replicative damage at telomeres and pericentromeric heterochromatin, which is exacerbated by loss of p53 and linked to ATM activation. ATRX-deficient neuroprogenitors exhibited higher incidence of telomere fusions and increased sensitivity to replication stress–inducing drugs. Treatment of Atrx-null neuroprogenitors with the G-quadruplex (G4) ligand telomestatin increased DNA damage, indicating that ATRX likely aids in the replication of telomeric G4-DNA structures. Unexpectedly, mutant mice displayed reduced growth, shortened life span, lordokyphosis, cataracts, heart enlargement, and hypoglycemia, as well as reduction of mineral bone density, trabecular bone content, and subcutaneous fat. We show that a subset of these defects can be attributed to loss of ATRX in the embryonic anterior pituitary that resulted in low circulating levels of thyroxine and IGF-1. Our findings suggest that loss of ATRX increases DNA damage locally in the forebrain and anterior pituitary and causes tissue attrition and other systemic defects similar to those seen in aging. PMID:23563309

Use of a combined effect model approach for discriminating between ABCB1- and ABCC1-type efflux activities in native bivalve gill tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Faria, Melissa; CESAM & Departamento de Biologia, Universidade de Aveiro, 3810-193 Aveiro; Pavlichenko, Vasiliy

Aquatic organisms, such as bivalves, employ ATP binding cassette (ABC) transporters for efflux of potentially toxic chemicals. Anthropogenic water contaminants can, as chemosensitizers, disrupt efflux transporter function enabling other, putatively toxic compounds to enter the organism. Applying rapid amplification of cDNA ends (RACE) PCR we identified complete cDNAs encoding ABCB1- and ABCC1-type transporter homologs from zebra mussel providing the molecular basis for expression of both transporter types in zebra mussel gills. Further, efflux activities of both transporter types in gills were indicated with dye accumulation assays where efflux of the dye calcein-am was sensitive to both ABCB1- (reversin 205, verapamil)more » and ABCC1- (MK571) type specific inhibitors. The assumption that different inhibitors targeted different efflux pump types was confirmed when comparing measured effects of binary inhibitor compound mixtures in dye accumulation assays with predictions from mixture effect models. Effects by the MK571/reversin 205 mixture corresponded better with independent action, whereas reversin 205/verapamil joint effects were better predicted by the concentration addition model indicating different and equal targets, respectively. The binary mixture approach was further applied to identify the efflux pump type targeted by environmentally relevant chemosensitizing compounds. Pentachlorophenol and musk ketone, which were selected after a pre-screen of twelve compounds that previously had been identified as chemosensitizers, showed mixture effects that corresponded better with concentration addition when combined with reversine 205 but with independent action predictions when combined with MK571 indicating targeting of an ABCB1-type efflux pump by these compounds. - Highlights: • Sequences and function of ABC efflux transporters in bivalve gills were explored. • Full length Dreissena polymorpha abcb1 and abcc1 cDNA sequences were identified. • A

VIV analysis of pipelines under complex span conditions

NASA Astrophysics Data System (ADS)

Wang, James; Steven Wang, F.; Duan, Gang; Jukes, Paul

2009-06-01

Spans occur when a pipeline is laid on a rough undulating seabed or when upheaval buckling occurs due to constrained thermal expansion. This not only results in static and dynamic loads on the flowline at span sections, but also generates vortex induced vibration (VIV), which can lead to fatigue issues. The phenomenon, if not predicted and controlled properly, will negatively affect pipeline integrity, leading to expensive remediation and intervention work. Span analysis can be complicated by: long span lengths, a large number of spans caused by a rough seabed, and multi-span interactions. In addition, the complexity can be more onerous and challenging when soil uncertainty, concrete degradation and unknown residual lay tension are considered in the analysis. This paper describes the latest developments and a ‘state-of-the-art’ finite element analysis program that has been developed to simulate the span response of a flowline under complex boundary and loading conditions. Both VIV and direct wave loading are captured in the analysis and the results are sequentially used for the ultimate limit state (ULS) check and fatigue life calculation.

The Structure of Working Memory Abilities across the Adult Life Span

PubMed Central

Hale, Sandra; Rose, Nathan S.; Myerson, Joel; Strube, Michael J; Sommers, Mitchell; Tye-Murray, Nancy; Spehar, Brent

2010-01-01

The present study addresses three questions regarding age differences in working memory: (1) whether performance on complex span tasks decreases as a function of age at a faster rate than performance on simple span tasks; (2) whether spatial working memory decreases at a faster rate than verbal working memory; and (3) whether the structure of working memory abilities is different for different age groups. Adults, ages 20–89 (n=388), performed three simple and three complex verbal span tasks and three simple and three complex spatial memory tasks. Performance on the spatial tasks decreased at faster rates as a function of age than performance on the verbal tasks, but within each domain, performance on complex and simple span tasks decreased at the same rates. Confirmatory factor analyses revealed that domain-differentiated models yielded better fits than models involving domain-general constructs, providing further evidence of the need to distinguish verbal and spatial working memory abilities. Regardless of which domain-differentiated model was examined, and despite the faster rates of decrease in the spatial domain, age group comparisons revealed that the factor structure of working memory abilities was highly similar in younger and older adults and showed no evidence of age-related dedifferentiation. PMID:21299306

Functional characterisation of a SNP in the ABCC11 allele - effects on axillary skin metabolism, odour generation and associated behaviours.

PubMed

Harker, Mark; Carvell, Ann-Marie; Marti, Vernon P J; Riazanskaia, Svetlana; Kelso, Hailey; Taylor, David; Grimshaw, Sally; Arnold, David S; Zillmer, Ruediger; Shaw, Jane; Kirk, Jayne M; Alcasid, Zee M; Gonzales-Tanon, Sheila; Chan, Gertrude P; Rosing, Egge A E; Smith, Adrian M

2014-01-01

A single nucleotide polymorphism (SNP), 538G→A, leading to a G180R substitution in the ABCC11 gene results in reduced concentrations of apocrine derived axillary odour precursors. Determine the axillary odour levels in the SNP ABCC11 genotype variants and to investigate if other parameters associated with odour production are affected. Axillary odour was assessed by subjective quantification and gas chromatography headspace analysis. Metabolite profiles, microbiome diversity and personal hygiene habits were also assessed. Axillary odour in the A/A homozygotes was significantly lower compared to the G/A and G/G genotypes. However, the perception-based measures still detected appreciable levels of axillary odour in the A/A subjects. Metabolomic analysis highlighted significant differences in axillary skin metabolites between A/A subjects compared to those carrying the G allele. These differences resulted in A/A subjects lacking specific volatile odourants in the axillary headspace, but all genotypes produced odoriferous short chain fatty acids. Microbiomic analysis revealed differences in the relative abundance of key bacterial genera associated with odour generation between the different genotypes. Deodorant usage indicated a high level of self awareness of axillary odour levels with A/A individuals less likely to adopt personal hygiene habits designed to eradicate/mask its presence. The SNP in the ABCC11 gene results in lower levels of axillary odour in the A/A homozygotes compared to those carrying the G allele, but A/A subjects still produce noticeable amounts of axillary odour. Differences in axillary skin metabolites, bacterial genera and personal hygiene behaviours also appear to be influenced by this SNP. Copyright © 2013. Published by Elsevier Ireland Ltd.

Altered Lipid Synthesis by Lack of Yeast Pah1 Phosphatidate Phosphatase Reduces Chronological Life Span*

PubMed Central

Park, Yeonhee; Han, Gil-Soo; Mileykovskaya, Eugenia; Garrett, Teresa A.; Carman, George M.

2015-01-01

In Saccharomyces cerevisiae, Pah1 phosphatidate phosphatase, which catalyzes the dephosphorylation of phosphatidate to yield diacylglycerol, plays a crucial role in the synthesis of the storage lipid triacylglycerol. This evolutionarily conserved enzyme also plays a negative regulatory role in controlling de novo membrane phospholipid synthesis through its consumption of phosphatidate. We found that the pah1Δ mutant was defective in the utilization of non-fermentable carbon sources but not in oxidative phosphorylation; the mutant did not exhibit major changes in oxygen consumption rate, mitochondrial membrane potential, F1F0-ATP synthase activity, or gross mitochondrial morphology. The pah1Δ mutant contained an almost normal complement of major mitochondrial phospholipids with some alterations in molecular species. Although oxidative phosphorylation was not compromised in the pah1Δ mutant, the cellular levels of ATP in quiescent cells were reduced by 2-fold, inversely correlating with a 4-fold increase in membrane phospholipids. In addition, the quiescent pah1Δ mutant cells had 3-fold higher levels of mitochondrial superoxide and cellular lipid hydroperoxides, had reduced activities of superoxide dismutase 2 and catalase, and were hypersensitive to hydrogen peroxide. Consequently, the pah1Δ mutant had a shortened chronological life span. In addition, the loss of Tsa1 thioredoxin peroxidase caused a synthetic growth defect with the pah1Δ mutation. The shortened chronological life span of the pah1Δ mutant along with its growth defect on non-fermentable carbon sources and hypersensitivity to hydrogen peroxide was suppressed by the loss of Dgk1 diacylglycerol kinase, indicating that the underpinning of pah1Δ mutant defects was the excess synthesis of membrane phospholipids. PMID:26338708

Stability and change: Stress responses and the shaping of behavioral phenotypes over the life span.

PubMed

Hennessy, Michael B; Kaiser, Sylvia; Tiedtke, Tobias; Sachser, Norbert

2015-01-01

In mammals, maternal signals conveyed via influences on hypothalamic-pituitary-adrenal (HPA) activity may shape behavior of the young to be better adapted for prevailing environmental conditions. However, the mother's influence extends beyond classic stress response systems. In guinea pigs, several hours (h) of separation from the mother activates not only the HPA axis, but also the innate immune system, which effects immediate behavioral change, as well as modifies behavioral responsiveness in the future. Moreover, the presence of the mother potently suppresses the behavioral consequences of this innate immune activation. These findings raise the possibility that long-term adaptive behavioral change can be mediated by the mother's influence on immune-related activity of her pups. Furthermore, the impact of social partners on physiological stress responses and their behavioral outcomes are not limited to the infantile period. A particularly crucial period for social development in male guinea pigs is that surrounding the attainment of sexual maturation. At this time, social interactions with adults can dramatically affect circulating cortisol concentrations and social behavior in ways that appear to prepare the male to best cope in its likely future social environment. Despite such multiple social influences on the behavior of guinea pigs at different ages, inter-individual differences in the magnitude of the cortisol response remain surprisingly stable over most of the life span. Together, it appears that throughout the life span, physiological stress responses may be regulated by social stimuli. These influences are hypothesized to adjust behavior for predicted environmental conditions. In addition, stable individual differences might provide a means of facilitating adaptation to less predictable conditions.

Expressions of ecological identity across the life span of eight environmental exemplars

NASA Astrophysics Data System (ADS)

Seydel, Jennifer

While there is a substantial body of literature looking at various aspects of ecological identity and factors that influence it, there has been less work done on how an individual's ecological identity changes with time. Much of that work is limited to short segments of the life span (e.g. the impact of wilderness experiences). This dissertation attempts to address this perceived gap by investigating how the ecological identity of eight environmental exemplars changed during the course of his or her life. What has emerged from this qualitative grounded theory investigation of the lives and works of Charles Darwin, John Muir, Aldo Leopold, Marjory Stoneman Douglas, Hazel Wolf, Rachel Carson, James Lovelock and E.O. Wilson are five sequential expressions of ecological identity. These 'stages' serve as a framework to explain ecological identity as a developmental process, both fluid and continuous, rather than at) end product. The development of an ecological identity is traced, through the development of five cognitive foundations and their alignment with five emotional foundations that reflect a progression from a sensory interaction and a kinship bond with nature into a deep understanding of the interconnectedness of all aspects of the planet. The findings reveal the evolution of an ecological identity and suggest the importance of looking beyond content knowledge in the nurturing of ecological attitudes, values, and lifestyles.

Childhood Adversity, Self-Esteem, and Diurnal Cortisol Profiles Across the Life Span.

PubMed

Zilioli, Samuele; Slatcher, Richard B; Chi, Peilian; Li, Xiaoming; Zhao, Junfeng; Zhao, Guoxiang

2016-09-01

Childhood adversity is associated with poor health outcomes in adulthood; the hypothalamic-pituitary-adrenal (HPA) axis has been proposed as a crucial biological intermediary of these long-term effects. Here, we tested whether childhood adversity was associated with diurnal cortisol parameters and whether this link was partially explained by self-esteem. In both adults and youths, childhood adversity was associated with lower levels of cortisol at awakening, and this association was partially driven by low self-esteem. Further, we found a significant indirect pathway through which greater adversity during childhood was linked to a flatter cortisol slope via self-esteem. Finally, youths who had a caregiver with high self-esteem experienced a steeper decline in cortisol throughout the day compared with youths whose caregiver reported low self-esteem. We conclude that self-esteem is a plausible psychological mechanism through which childhood adversity may get embedded in the activity of the HPA axis across the life span. © The Author(s) 2016.

Exposure To Harmful Workplace Practices Could Account For Inequality In Life Spans Across Different Demographic Groups.

PubMed

Goh, Joel; Pfeffer, Jeffrey; Zenios, Stefanos

2015-10-01

The existence of important socioeconomic disparities in health and mortality is a well-established fact. Many pathways have been adduced to explain inequality in life spans. In this article we examine one factor that has been somewhat neglected: People with different levels of education get sorted into jobs with different degrees of exposure to workplace attributes that contribute to poor health. We used General Social Survey data to estimate differential exposures to workplace conditions, results from a meta-analysis that estimated the effect of workplace conditions on mortality, and a model that permitted us to estimate the overall effects of workplace practices on health. We conclude that 10-38 percent of the difference in life expectancy across demographic groups can be explained by the different job conditions their members experience. Project HOPE—The People-to-People Health Foundation, Inc.

Pervasive gene expression responses to a fluctuating diet in Drosophila melanogaster: The importance of measuring multiple traits to decouple potential mediators of life span and reproduction.

PubMed

Zandveld, Jelle; van den Heuvel, Joost; Mulder, Maarten; Brakefield, Paul M; Kirkwood, Thomas B L; Shanley, Daryl P; Zwaan, Bas J

2017-11-01

Phenotypic plasticity is an important concept in life-history evolution, and most organisms, including Drosophila melanogaster, show a plastic life-history response to diet. However, little is known about how these life-history responses are mediated. In this study, we compared adult female flies fed an alternating diet (yoyo flies) with flies fed a constant low (CL) or high (CH) diet and tested how whole genome expression was affected by these diet regimes and how the transcriptional responses related to different life-history traits. We showed that flies were able to respond quickly to diet fluctuations throughout life span by drastically changing their transcription. Importantly, by measuring the response of multiple life-history traits we were able to decouple groups of genes associated with life span or reproduction, life-history traits that often covary with a diet change. A coexpression network analysis uncovered which genes underpin the separate and shared regulation of these life-history traits. Our study provides essential insights to help unravel the genetic architecture mediating life-history responses to diet, and it shows that the flies' whole genome transcription response is highly plastic. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

The Tölz Temporal Topography Study: mapping the visual field across the life span. Part II: cognitive factors shaping visual field maps.

PubMed

Poggel, Dorothe A; Treutwein, Bernhard; Calmanti, Claudia; Strasburger, Hans

2012-08-01

Part I described the topography of visual performance over the life span. Performance decline was explained only partly by deterioration of the optical apparatus. Part II therefore examines the influence of higher visual and cognitive functions. Visual field maps for 95 healthy observers of static perimetry, double-pulse resolution (DPR), reaction times, and contrast thresholds, were correlated with measures of visual attention (alertness, divided attention, spatial cueing), visual search, and the size of the attention focus. Correlations with the attentional variables were substantial, particularly for variables of temporal processing. DPR thresholds depended on the size of the attention focus. The extraction of cognitive variables from the correlations between topographical variables and participant age substantially reduced those correlations. There is a systematic top-down influence on the aging of visual functions, particularly of temporal variables, that largely explains performance decline and the change of the topography over the life span.

Mutational disruption of the ABCC2 gene in fall armyworm, Spodoptera frugiperda, confers resistance to the Cry1Fa and Cry1A.105 insecticidal proteins.

PubMed

Flagel, Lex; Lee, Young Wha; Wanjugi, Humphrey; Swarup, Shilpa; Brown, Alana; Wang, Jinling; Kraft, Edward; Greenplate, John; Simmons, Jeni; Adams, Nancy; Wang, Yanfei; Martinelli, Samuel; Haas, Jeffrey A; Gowda, Anilkumar; Head, Graham

2018-05-08

The use of Bt proteins in crops has revolutionized insect pest management by offering effective season-long control. However, field-evolved resistance to Bt proteins threatens their utility and durability. A recent example is field-evolved resistance to Cry1Fa and Cry1A.105 in fall armyworm (Spodoptera frugiperda). This resistance has been detected in Puerto Rico, mainland USA, and Brazil. A S. frugiperda population with suspected resistance to Cry1Fa was sampled from a maize field in Puerto Rico and used to develop a resistant lab colony. The colony demonstrated resistance to Cry1Fa and partial cross-resistance to Cry1A.105 in diet bioassays. Using genetic crosses and proteomics, we show that this resistance is due to loss-of-function mutations in the ABCC2 gene. We characterize two novel mutant alleles from Puerto Rico. We also find that these alleles are absent in a broad screen of partially resistant Brazilian populations. These findings confirm that ABCC2 is a receptor for Cry1Fa and Cry1A.105 in S. frugiperda, and lay the groundwork for genetically enabled resistance management in this species, with the caution that there may be several distinct ABCC2 resistances alleles in nature.

Resting-State Network Topology Differentiates Task Signals across the Adult Life Span.

PubMed

Chan, Micaela Y; Alhazmi, Fahd H; Park, Denise C; Savalia, Neil K; Wig, Gagan S

2017-03-08

Brain network connectivity differs across individuals. For example, older adults exhibit less segregated resting-state subnetworks relative to younger adults (Chan et al., 2014). It has been hypothesized that individual differences in network connectivity impact the recruitment of brain areas during task execution. While recent studies have described the spatial overlap between resting-state functional correlation (RSFC) subnetworks and task-evoked activity, it is unclear whether individual variations in the connectivity pattern of a brain area (topology) relates to its activity during task execution. We report data from 238 cognitively normal participants (humans), sampled across the adult life span (20-89 years), to reveal that RSFC-based network organization systematically relates to the recruitment of brain areas across two functionally distinct tasks (visual and semantic). The functional activity of brain areas (network nodes) were characterized according to their patterns of RSFC: nodes with relatively greater connections to nodes in their own functional system ("non-connector" nodes) exhibited greater activity than nodes with relatively greater connections to nodes in other systems ("connector" nodes). This "activation selectivity" was specific to those brain systems that were central to each of the tasks. Increasing age was accompanied by less differentiated network topology and a corresponding reduction in activation selectivity (or differentiation) across relevant network nodes. The results provide evidence that connectional topology of brain areas quantified at rest relates to the functional activity of those areas during task. Based on these findings, we propose a novel network-based theory for previous reports of the "dedifferentiation" in brain activity observed in aging. SIGNIFICANCE STATEMENT Similar to other real-world networks, the organization of brain networks impacts their function. As brain network connectivity patterns differ across

Bmi-1 extends the life span of normal human oral keratinocytes by inhibiting the TGF-{beta} signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Reuben H., E-mail: rkim@dentistry.ucla.edu; UCLA Dental Research Institute, Los Angeles, CA 90095; UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA 90095

2010-10-01

We previously demonstrated that Bmi-1 extended the in vitro life span of normal human oral keratinocytes (NHOK). We now report that the prolonged life span of NHOK by Bmi-1 is, in part, due to inhibition of the TGF-{beta} signaling pathway. Serial subculture of NHOK resulted in replicative senescence and terminal differentiation and activation of TGF-{beta} signaling pathway. This was accompanied with enhanced intracellular and secreted TGF-{beta}1 levels, phosphorylation of Smad2/3, and increased expression of p15{sup INK4B} and p57{sup KIP2}. An ectopic expression of Bmi-1 in NHOK (HOK/Bmi-1) decreased the level of intracellular and secreted TGF-{beta}1 induced dephosphorylation of Smad2/3, andmore » diminished the level of p15{sup INK4B} and p57{sup KIP2}. Moreover, Bmi-1 expression led to the inhibition of TGF-{beta}-responsive promoter activity in a dose-specific manner. Knockdown of Bmi-1 in rapidly proliferating HOK/Bmi-1 and cancer cells increased the level of phosphorylated Smad2/3, p15{sup INK4B}, and p57{sup KIP2}. In addition, an exposure of senescent NHOK to TGF-{beta} receptor I kinase inhibitor or anti-TGF-{beta} antibody resulted in enhanced replicative potential of cells. Taken together, these data suggest that Bmi-1 suppresses senescence of cells by inhibiting the TGF-{beta} signaling pathway in NHOK.« less

Expectations about Memory Change Across the Life Span Are Impacted By Aging Stereotypes

PubMed Central

Lineweaver, Tara T.; Berger, Andrea K.; Hertzog, Christopher

2008-01-01

This study examined whether expectations about memory change with age vary for different personality types. Four adjectives from each of Hummert’s age-stereotype trait sets were selected to create 11 adjective clusters varying in both valence (positive versus negative) and relevance to memory functioning. Three hundred and seventy three participants in three age groups rated the memory abilities of target adults, defined by the adjective clusters, across the adult life span. Consistent with past studies, participants believed in age-related memory decline. However, participants rated target adults with positive personality traits as having better memory ability and less age-related memory decline than target adults with negative personality traits. This effect was larger when the traits were relevant to memory than when they were not. Finally, older participants were more strongly influenced by both the valence and the relevance of the personality descriptions than younger participants. PMID:19290748

Partial ablation of adult Drosophila insulin-producing neurons modulates glucose homeostasis and extends life span without insulin resistance.

PubMed

Haselton, Aaron; Sharmin, Effat; Schrader, Janel; Sah, Megha; Poon, Peter; Fridell, Yih-Woei C

2010-08-01

In Drosophila melanogaster (D. melanogaster), neurosecretory insulin-like peptide-producing cells (IPCs), analogous to mammalian pancreatic beta cells are involved in glucose homeostasis. Extending those findings, we have developed in the adult fly an oral glucose tolerance test and demonstrated that IPCs indeed are responsible for executing an acute glucose clearance response. To further develop D. melanogaster as a relevant system for studying age-associated metabolic disorders, we set out to determine the impact of adult-specific partial ablation of IPCs (IPC knockdown) on insulin-like peptide (ILP) action, metabolic outcomes and longevity. Interestingly, while IPC knockdown flies are hyperglycemic and glucose intolerant, these flies remain insulin sensitive as measured by peripheral glucose disposal upon insulin injection and serine phosphorylation of a key insulin-signaling molecule, Akt. Significant increases in stored glycogen and triglyceride levels as well as an elevated level of circulating lipid measured in adult IPC knockdown flies suggest profound modulation in energy metabolism. Additional physiological outcomes measured in those flies include increased resistance to starvation and impaired female fecundity. Finally, increased life span and decreased mortality rates measured in IPC knockdown flies demonstrate that it is possible to modulate ILP action in adult flies to achieve life span extension without insulin resistance. Taken together, we have established and validated an invertebrate genetic system to further investigate insulin action, metabolic homeostasis and regulation of aging regulated by adult IPCs.

Single nucleotide polymorphisms of ABCC2 modulate renal secretion of endogenous organic anions.

PubMed

Muhrez, Kienana; Largeau, Bérenger; Emond, Patrick; Montigny, Frédéric; Halimi, Jean-Michel; Trouillas, Patrick; Barin-Le Guellec, Chantal

2017-09-15

The ATP-binding cassette family transporter MRP2 (multidrug resistance-associated protein 2), encoded by the ABCC2 gene, is involved in the renal excretion of numerous xenobiotics and it is likely that it also transports many endogenous molecules arising from not only normal essential metabolic processes but also from environmental toxins or food intake. We used a targeted gas chromatography-mass spectrometry metabolomics analysis to study whether endogenous organic anions are differentially excreted in urines of healthy volunteers according to their genotype for three functional single nucleotide polymorphisms (SNPs) in ABCC2. This was the case for 35 of the 108 metabolites analyzed. Eight of them are most likely substrates of MRP2 since they are the most contributive to the difference between carriers of a decreasing function allele vs those carrying an increasing function one. Seven out of 8 metabolites are fatty acids (dodecanoic acid; 3-hydroxypropanoic acid) or metabolites of polyphenols (caffeine; resorcinol; caffeic acid; 2-(3,4-dihydroxyphenyl) acetic acid; and 4-hydroxyhippuric acid). Most of them were structurally similar to a series of substances previously shown to interact with MRP2 function in vitro. Interestingly, coproporphyrin isomer I, a prototypical substrate of MRP2, also belonged to our final list although it was not significantly discriminant on its own. This suggests that the simultaneous measurement of a set of endogenous metabolites in urine, rather than that of unique metabolites, has the potential to provide a phenotypic measure of MRP2 function in vivo. This would represent an innovative tool to study the variability of the transport activity of MRP2 under a physiological or pathological condition, especially in pharmacokinetic studies of its substrates. Copyright © 2017 Elsevier Inc. All rights reserved.

Age Differentiation within Gray Matter, White Matter, and between Memory and White Matter in an Adult Life Span Cohort.

PubMed

de Mooij, Susanne M M; Henson, Richard N A; Waldorp, Lourens J; Kievit, Rogier A

2018-06-20

It is well established that brain structures and cognitive functions change across the life span. A long-standing hypothesis called "age differentiation" additionally posits that the relations between cognitive functions also change with age. To date, however, evidence for age-related differentiation is mixed, and no study has examined differentiation of the relationship between brain and cognition. Here we use multigroup structural equation models (SEMs) and SEM trees to study differences within and between brain and cognition across the adult life span (18-88 years) in a large ( N > 646, closely matched across sexes), population-derived sample of healthy human adults from the Cambridge Centre for Ageing and Neuroscience (www.cam-can.org). After factor analyses of gray matter volume (from T1- and T2-weighted MRI) and white matter organization (fractional anisotropy from diffusion-weighted MRI), we found evidence for the differentiation of gray and white matter, such that the covariance between brain factors decreased with age. However, we found no evidence for age differentiation among fluid intelligence, language, and memory, suggesting a relatively stable covariance pattern among cognitive factors. Finally, we observed a specific pattern of age differentiation between brain and cognitive factors, such that a white matter factor, which loaded most strongly on the hippocampal cingulum, became less correlated with memory performance in later life. These patterns are compatible with the reorganization of cognitive functions in the face of neural decline, and/or with the emergence of specific subpopulations in old age. SIGNIFICANCE STATEMENT The theory of age differentiation posits age-related changes in the relationships among cognitive domains, either weakening (differentiation) or strengthening (dedifferentiation), but evidence for this hypothesis is mixed. Using age-varying covariance models in a large cross-sectional adult life span sample, we found age

The activity-dependent histone variant H2BE modulates the life span of olfactory neurons

PubMed Central

Santoro, Stephen W; Dulac, Catherine

2012-01-01

We have identified a replication-independent histone variant, Hist2h2be (referred to herein as H2be), which is expressed exclusively by olfactory chemosensory neurons. Levels of H2BE are heterogeneous among olfactory neurons, but stereotyped according to the identity of the co-expressed olfactory receptor (OR). Gain- and loss-of-function experiments demonstrate that changes in H2be expression affect olfactory function and OR representation in the adult olfactory epithelium. We show that H2BE expression is reduced by sensory activity and that it promotes neuronal cell death, such that inactive olfactory neurons display higher levels of the variant and shorter life spans. Post-translational modifications (PTMs) of H2BE differ from those of the canonical H2B, consistent with a role for H2BE in altering transcription. We propose a physiological function for H2be in modulating olfactory neuron population dynamics to adapt the OR repertoire to the environment. DOI: http://dx.doi.org/10.7554/eLife.00070.001 PMID:23240083

Expected value information improves financial risk taking across the adult life span.

PubMed

Samanez-Larkin, Gregory R; Wagner, Anthony D; Knutson, Brian

2011-04-01

When making decisions, individuals must often compensate for cognitive limitations, particularly in the face of advanced age. Recent findings suggest that age-related variability in striatal activity may increase financial risk-taking mistakes in older adults. In two studies, we sought to further characterize neural contributions to optimal financial risk taking and to determine whether decision aids could improve financial risk taking. In Study 1, neuroimaging analyses revealed that individuals whose mesolimbic activation correlated with the expected value estimates of a rational actor made more optimal financial decisions. In Study 2, presentation of expected value information improved decision making in both younger and older adults, but the addition of a distracting secondary task had little impact on decision quality. Remarkably, provision of expected value information improved the performance of older adults to match that of younger adults at baseline. These findings are consistent with the notion that mesolimbic circuits play a critical role in optimal choice, and imply that providing simplified information about expected value may improve financial risk taking across the adult life span.

Biological impact of auditory expertise across the life span: musicians as a model of auditory learning

PubMed Central

Strait, Dana L.; Kraus, Nina

2013-01-01

Experience-dependent characteristics of auditory function, especially with regard to speech-evoked auditory neurophysiology, have garnered increasing attention in recent years. This interest stems from both pragmatic and theoretical concerns as it bears implications for the prevention and remediation of language-based learning impairment in addition to providing insight into mechanisms engendering experience-dependent changes in human sensory function. Musicians provide an attractive model for studying the experience-dependency of auditory processing in humans due to their distinctive neural enhancements compared to nonmusicians. We have only recently begun to address whether these enhancements are observable early in life, during the initial years of music training when the auditory system is under rapid development, as well as later in life, after the onset of the aging process. Here we review neural enhancements in musically trained individuals across the life span in the context of cellular mechanisms that underlie learning, identified in animal models. Musicians’ subcortical physiologic enhancements are interpreted according to a cognitive framework for auditory learning, providing a model by which to study mechanisms of experience-dependent changes in auditory function in humans. PMID:23988583

"A general benevolence dimension that links neural, psychological, economic, and life-span data on altruistic tendencies": Correction to Hubbard et al. (2016).

PubMed

2016-10-01

Reports an error in "A general benevolence dimension that links neural, psychological, economic, and life-span data on altruistic tendencies" by Jason Hubbard, William T. Harbaugh, Sanjay Srivastava, David Degras and Ulrich Mayr ( Journal of Experimental Psychology: General , Advanced Online Publication, Aug 11, 2016, np). In the article, there was an error in the Task, Stimuli, and Procedures section. In the 1st sentence in the 6th paragraph, “Following the scanning phase, participants completed self-report questionnaires meant to reflected the Prosocial Disposition construct: the agreeableness scale from the Big F, which includes empathic concern and perspective-taking, and a scale of personality descriptive adjectives related to altruistic behavior (Wood, Nye, & Saucier, 2010).” should have read: “Following the scanning phase, participants completed self-report questionnaires that contained scales to reflect the Prosocial Disposition construct: the Big Five Inventory (BFI; John et al., 1991), from which we used the agreeableness scale to measure prosocial disposition; the Interpersonal Reactivity Index (IRI; Davis, 1980), from which we used the empathic concern and perspective-taking scales; and a scale of personality descriptive adjectives related to altruistic behavior (Wood, Nye, & Saucier, 2010).” (The following abstract of the original article appeared in record 2016-39037-001.) Individual and life span differences in charitable giving are an important economic force, yet the underlying motives are not well understood. In an adult, life span sample, we assessed manifestations of prosocial tendencies across 3 different measurement domains: (a) psychological self-report measures, (b) actual giving choices, and (c) fMRI-derived, neural indicators of “pure altruism.” The latter expressed individuals’ activity in neural valuation areas when charities received money compared to when oneself received money and thus reflected an altruistic concern for

Health Span-Extending Activity of Human Amniotic Membrane- and Adipose Tissue-Derived Stem Cells in F344 Rats

PubMed Central

Kim, Dajeong; Kyung, Jangbeen; Park, Dongsun; Choi, Ehn-Kyoung; Kim, Kwang Sei; Shin, Kyungha; Lee, Hangyoung; Shin, Il Seob; Kang, Sung Keun

2015-01-01

Aging brings about the progressive decline in cognitive function and physical activity, along with losses of stem cell population and function. Although transplantation of muscle-derived stem/progenitor cells extended the health span and life span of progeria mice, such effects in normal animals were not confirmed. Human amniotic membrane-derived mesenchymal stem cells (AMMSCs) or adipose tissue-derived mesenchymal stem cells (ADMSCs) (1 × 106 cells per rat) were intravenously transplanted to 10-month-old male F344 rats once a month throughout their lives. Transplantation of AMMSCs and ADMSCs improved cognitive and physical functions of naturally aging rats, extending life span by 23.4% and 31.3%, respectively. The stem cell therapy increased the concentration of acetylcholine and recovered neurotrophic factors in the brain and muscles, leading to restoration of microtubule-associated protein 2, cholinergic and dopaminergic nervous systems, microvessels, muscle mass, and antioxidative capacity. The results indicate that repeated transplantation of AMMSCs and ADMSCs elongate both health span and life span, which could be a starting point for antiaging or rejuvenation effects of allogeneic or autologous stem cells with minimum immune rejection. Significance This study demonstrates that repeated treatment with stem cells in normal animals has antiaging potential, extending health span and life span. Because antiaging and prolonged life span are issues currently of interest, these results are significant for readers and investigators. PMID:26315571

Health Span-Extending Activity of Human Amniotic Membrane- and Adipose Tissue-Derived Stem Cells in F344 Rats.

PubMed

Kim, Dajeong; Kyung, Jangbeen; Park, Dongsun; Choi, Ehn-Kyoung; Kim, Kwang Sei; Shin, Kyungha; Lee, Hangyoung; Shin, Il Seob; Kang, Sung Keun; Ra, Jeong Chan; Kim, Yun-Bae

2015-10-01

Aging brings about the progressive decline in cognitive function and physical activity, along with losses of stem cell population and function. Although transplantation of muscle-derived stem/progenitor cells extended the health span and life span of progeria mice, such effects in normal animals were not confirmed. Human amniotic membrane-derived mesenchymal stem cells (AMMSCs) or adipose tissue-derived mesenchymal stem cells (ADMSCs) (1×10(6) cells per rat) were intravenously transplanted to 10-month-old male F344 rats once a month throughout their lives. Transplantation of AMMSCs and ADMSCs improved cognitive and physical functions of naturally aging rats, extending life span by 23.4% and 31.3%, respectively. The stem cell therapy increased the concentration of acetylcholine and recovered neurotrophic factors in the brain and muscles, leading to restoration of microtubule-associated protein 2, cholinergic and dopaminergic nervous systems, microvessels, muscle mass, and antioxidative capacity. The results indicate that repeated transplantation of AMMSCs and ADMSCs elongate both health span and life span, which could be a starting point for antiaging or rejuvenation effects of allogeneic or autologous stem cells with minimum immune rejection. This study demonstrates that repeated treatment with stem cells in normal animals has antiaging potential, extending health span and life span. Because antiaging and prolonged life span are issues currently of interest, these results are significant for readers and investigators. ©AlphaMed Press.

Elevated Dietary Magnesium Prevents Connective Tissue Mineralization in a Mouse Model of Pseudoxanthoma Elasticum (Abcc6−/−)

PubMed Central

LaRusso, Jennifer; Li, Qiaoli; Jiang, Qiujie; Uitto, Jouni

2010-01-01

Pseudoxanthoma elasticum (PXE) is an autosomal recessive multi-system disorder characterized by ectopic connective tissue mineralization, with clinical manifestations primarily in the skin, eyes and the cardiovascular system. There is considerable, both intra-and inter-familial variability in the spectrum of phenotypic presentation. Previous studies have suggested that mineral content of the diet may modify the severity of the clinical phenotype in PXE. In this study, we utilized a targeted mutant mouse (Abcc6−/−) as a model system for PXE. We examined the effects of changes in dietary phosphate and magnesium on the mineralization process using calcification of the connective tissue capsule surrounding the vibrissae as an early phenotypic biomarker. Mice placed on custom-designed diets either high or low in phosphate did not show changes in mineralization, which was similar to that noted in Abcc6−/− mice on control diet. However, mice placed on diet enriched in magnesium (5-fold) showed no evidence of connective tissue mineralization in this mouse model of PXE. The inhibitory capacity of magnesium was confirmed in a cell-based mineralization assay system in vitro. Collectively, our observations suggest that assessment of dietary magnesium in patients with PXE may be warranted. PMID:19122649

A new fluorescent dye accumulation assay for parallel measurements of the ABCG2, ABCB1 and ABCC1 multidrug transporter functions.

PubMed

Szabó, Edit; Türk, Dóra; Telbisz, Ágnes; Kucsma, Nóra; Horváth, Tamás; Szakács, Gergely; Homolya, László; Sarkadi, Balázs; Várady, György

2018-01-01

ABC multidrug transporters are key players in cancer multidrug resistance and in general xenobiotic elimination, thus their functional assays provide important tools for research and diagnostic applications. In this study we have examined the potential interactions of three key human ABC multidrug transporters with PhenGreen diacetate (PGD), a cell permeable fluorescent metal ion indicator. The non-fluorescent, hydrophobic PGD rapidly enters the cells and, after cleavage by cellular esterases, in the absence of quenching metal ions, PhenGreen (PG) becomes highly fluorescent. We found that in cells expressing functional ABCG2, ABCB1, or ABCC1 transporters, cellular PG fluorescence is strongly reduced. This fluorescence signal in the presence of specific transporter inhibitors is increased to the fluorescence levels in the control cells. Thus the PG accumulation assay is a new, unique tool for the parallel determination of the function of the ABCG2, ABCB1, and ABCC1 multidrug transporters. Since PG has very low cellular toxicity, the PG accumulation assay also allows the selection, separation and culturing of selected cell populations expressing either of these transporters.

Families as Life Span Experts

ERIC Educational Resources Information Center

Brendtro, Larry K.; Mitchell, Martin L.

2011-01-01

Professionals dealing with challenging behavior frequently operate detached from the other relationships in the child's life. This narrow approach has been called the unilateral strategy based on the belief that the child's outside world can be ignored and behavior can be changed by administering specific corrective interventions. In contrast,…

Mixed emotions across the adult life span in the United States

PubMed Central

Schneider, Stefan; Stone, Arthur A.

2015-01-01

Mixed emotions involve the co-occurrence of positive and negative affect, such that people feel happy and sad at the same time. The purpose of the present study was to investigate age-related differences in the experience of mixed emotions across the adult life span in two nationally representative samples of U.S. residents. Data collected by the Princeton Affect and Time Survey (PATS, n = 3,948) and by the 2010 Wellbeing Module of the American Time Use Survey (ATUS, n = 12,828) were analyzed. In both surveys, respondents (aged 15 years or older) provided a detailed time diary about the preceding day and rated their happiness and sadness for three of the day's episodes. From these reports, three different indices of mixed emotions were derived. Results indicated small, but robust, increases in mixed emotions with age. Linear age increases were consistently evident in both PATS and ATUS, and replicated across the different indices of mixed emotions. There was no significant evidence for curvilinear age trends in either study. Several sociodemographic factors that could plausibly explain age-differences in mixed emotions (e.g., retirement, disability) did not alter the age-effects. The present study adds to the growing literature documenting vital changes in the complexity of emotional experience over the lifespan. PMID:25894487

S-linolenoyl glutathione intake extends life-span and stress resistance via Sir-2.1 upregulation in Caenorhabditis elegans.

PubMed

Cascella, Roberta; Evangelisti, Elisa; Zampagni, Mariagioia; Becatti, Matteo; D'Adamio, Giampiero; Goti, Andrea; Liguri, Gianfranco; Fiorillo, Claudia; Cecchi, Cristina

2014-08-01

Oxidative stress has a prominent role in life-span regulation of living organisms. One of the endogenous free radical scavenger systems is associated with glutathione (GSH), the most abundant nonprotein thiol in mammalian cells, acting as a major reducing agent and in antioxidant defense by maintaining a tight control over redox status. We have recently designed a series of novel S-acyl-GSH derivatives capable of preventing amyloid oxidative stress and cholinergic dysfunction in Alzheimer disease models, upon an increase in GSH intake. In this study we show that the longevity of the wild-type N2 Caenorhabditis elegans strain was significantly enhanced by dietary supplementation with linolenoyl-SG (lin-SG) thioester with respect to the ethyl ester of GSH, linolenic acid, or vitamin E. RNA interference analysis and activity inhibition assay indicate that life-span extension was mediated by the upregulation of Sir-2.1, a NAD-dependent histone deacetylase ortholog of mammalian SIRT1. In particular, lin-SG-mediated overexpression of Sir-2.1 appears to be related to the Daf-16 (FoxO) pathway. Moreover, the lin-SG derivative protects N2 worms from the paralysis and oxidative stress induced by Aβ/H2O2 exposure. Overall, our findings put forward lin-SG thioester as an antioxidant supplement triggering sirtuin upregulation, thus opening new future perspectives for healthy aging or delayed onset of oxidative-related diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

Lignin composition is related to xylem embolism resistance and leaf life span in trees in a tropical semiarid climate.

PubMed

Lima, Taysla R A; Carvalho, Ellen C D; Martins, Fernando R; Oliveira, Rafael S; Miranda, Rafael S; Müller, Caroline S; Pereira, Luciano; Bittencourt, Paulo R L; Sobczak, Jullyana C M S M; Gomes-Filho, Enéas; Costa, Rafael C; Araújo, Francisca S

2018-05-16

Wood properties influence the leaf life span (LL) of tree crowns. As lignin is an important component of wood and the water transport system, we investigated its relationship with embolism resistance and the LL of several tree species in a seasonally dry tropical ecosystem. We determined total lignin and the monomer contents of guaiacyl (G) and syringyl (S) and related them to wood traits and xylem vulnerability to embolism (Ψ 50 ) for the most common species of the Brazilian semiarid, locally known as Caatinga. Leaf life span was negatively related to Ψ 50 and positively related to S : G, which was negatively related to Ψ 50 . This means that greater S : G increases LL by reducing Ψ 50 . Lignin content was not correlated with any variable. We found two apparently unrelated axes of drought resistance. One axis, associated with lignin monomeric composition, increases LL in the dry season as a result of lower xylem embolism vulnerability. The other, associated with wood density and stem water content, helps leafless trees to withstand drought and allows them to resprout at the end of the dry season. The monomeric composition of lignin (S : G) is therefore an important functional wood attribute affecting several key functional aspects of tropical tree species in a semiarid climate. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

Physical Activity Throughout the Adult Life Span and Domain-Specific Cognitive Function in Old Age: A Systematic Review of Cross-Sectional and Longitudinal Data.

PubMed

Engeroff, Tobias; Ingmann, Tobias; Banzer, Winfried

2018-06-01

A growing body of literature suggests that physical activity might alleviate the age-related neurodegeneration and decline of cognitive function. However, most of this evidence is based on data investigating the association of exercise interventions or current physical activity behavior with cognitive function in elderly subjects. We performed a systematic review and hypothesize that physical activity during the adult life span is connected with maintained domain-specific cognitive functions during late adulthood defined as age 60+ years. We performed a systematic literature search up to November 2017 in PubMed, Web of Science, and Google Scholar without language limitations for studies analyzing the association of leisure physical activity during the adult life span (age 18+ years) and domain-specific cognitive functions in older adults (age 60+ years). The literature review yielded 14,294 articles and after applying inclusion and exclusion criteria, nine cross-sectional and 14 longitudinal studies were included. Moderate- and vigorous-intensity leisure physical activity was associated with global cognitive function and specific cognitive domains including executive functions and memory but not attention or working memory. Most studies assessed mid- to late-adulthood physical activity, thus information concerning the influence of young adult life-span physical activity is currently lacking. Observational evidence that moderate- and vigorous-intensity leisure physical activity is beneficially associated with maintained cognitive functions during old age is accumulating. Further studies are necessary to confirm a causal link by assessing objective physical activity data and the decline of cognitive functions at multiple time points during old age.

Relationships of leaf dark respiration to leaf nitrogen, specific leaf area and leaf life-span: a test across biomes and functional groups

Treesearch

Peter B. Reich; Michael B. Walters; David S. Ellsworth; [and others; [Editor’s note: James M.. Vose is the SRS co-author for this publication.

1998-01-01

Based on prior evidence of coordinated multiple leaf trait scaling, the authors hypothesized that variation among species in leaf dark respiration rate (Rd) should scale with variation in traits such as leaf nitrogen (N), leaf life-span, specific leaf area (SLA), and net photosynthetic capacity (Amax). However, it is not known whether such scaling, if it exists, is...

Effects of hunger state on the brain responses to food cues across the life span.

PubMed

Charbonnier, L; van Meer, F; Johnstone, A M; Crabtree, D; Buosi, W; Manios, Y; Androutsos, O; Giannopoulou, A; Viergever, M A; Smeets, P A M

2018-05-01

The abundant exposure to food cues in our environment is one of the main drivers of overconsumption. Food evaluation is important for the regulation of food intake by the brain and it's interaction with hunger state. Children are especially susceptible to food cues. Understanding the mechanisms behind this regulation in healthy individuals across the life span can help to elucidate the mechanisms underlying overconsumption and aid the development of future obesity prevention strategies. Few functional neuroimaging studies have been done in children and elderly. Furthermore, it is unknown how hunger state affects neural food cue reactivity in these groups, since this has not been examined consistently. We examined the effects of hunger state and age on the brain responses to low- and high calorie foods. On two mornings, 122 participants (17 children; 38 teens; 36 adults; 31 elderly) performed a food image viewing task while being scanned using fMRI, either fasted or sated. Hunger induced greater activation during high versus low calorie food image viewing than satiety in the bilateral dorsomedial (dmPFC) and in the right dorsolateral prefrontal cortex (dlPFC) across all age groups. There was no significant main effect of age group on high versus low calorie food image viewing and no interaction between age group and hunger state. The greater activation of the dlPFC across all age groups during high calorie food image viewing in a fasted state might reflect increased inhibitory control in response to these foods. This may underlie the ability to resist overconsumption of high calorie foods. Furthermore, increased medial prefrontal cortex activation during hunger might reflect increased reward value of high calorie foods, which declines with satiation. Further studies are needed to better understand these results. Notably, overweight and obese individuals should be included to examine whether these responses are altered by weight status across the life span. Copyright

Evaluative ratings and attention across the life span: emotional arousal and gender.

PubMed

Ferrari, Vera; Bruno, Nicola; Chattat, Rabih; Codispoti, Maurizio

2017-04-01

This study was designed to investigate the evolution of emotional processing over the whole adult life span as a function of stimulus arousal and participants' gender. To this end, self-reported affective evaluation and attentional capture prompted by pleasant and unpleasant pictures varying in arousal were measured in a large sample of participants (n = 211) balanced by gender and equally spread across seven decades from 20 to 90 years. Results showed age differences only for affective evaluation of pleasant stimuli, with opposite patterns depending on stimulus arousal. As age increased, low-arousing pleasant cues (e.g. images of babies) were experienced as more pleasant and arousing by both males and females, whereas high-arousing stimuli (e.g. erotic images) were experienced as less pleasant only by females. In contrast, emotional pictures (both pleasant and unpleasant) were effective at capturing attention in a similar way across participants, regardless of age and gender. Taken together, these findings suggest that specific emotional cues prompt different subjective responses across different age groups, while basic mechanisms involved in attentional engagement towards both pleasant and unpleasant stimuli are preserved in healthy ageing.

Resveratrol induces mitochondrial dysfunction and decreases chronological life span of Saccharomyces cerevisiae in a glucose-dependent manner.

PubMed

Ramos-Gomez, Minerva; Olivares-Marin, Ivanna Karina; Canizal-García, Melina; González-Hernández, Juan Carlos; Nava, Gerardo M; Madrigal-Perez, Luis Alberto

2017-06-01

A broad range of health benefits have been attributed to resveratrol (RSV) supplementation in mammalian systems, including the increases in longevity. Nonetheless, despite the growing number of studies performed with RSV, the molecular mechanism by which it acts still remains unknown. Recently, it has been proposed that inhibition of the oxidative phosphorylation activity is the principal mechanism of RSV action. This mechanism suggests that RSV might induce mitochondrial dysfunction resulting in oxidative damage to cells with a concomitant decrease of cell viability and cellular life span. To prove this hypothesis, the chronological life span (CLS) of Saccharomyces cerevisiae was studied as it is accepted as an important model of oxidative damage and aging. In addition, oxygen consumption, mitochondrial membrane potential, and hydrogen peroxide (H 2 O 2 ) release were measured in order to determine the extent of mitochondrial dysfunction. The results demonstrated that the supplementation of S. cerevisiae cultures with 100 μM RSV decreased CLS in a glucose-dependent manner. At high-level glucose, RSV supplementation increased oxygen consumption during the exponential phase yeast cultures, but inhibited it in chronologically aged yeast cultures. However, at low-level glucose, oxygen consumption was inhibited in yeast cultures in the exponential phase as well as in chronologically aged cultures. Furthermore, RSV supplementation promoted the polarization of the mitochondrial membrane in both cultures. Finally, RSV decreased the release of H 2 O 2 with high-level glucose and increased it at low-level glucose. Altogether, this data supports the hypothesis that RSV supplementation decreases CLS as a result of mitochondrial dysfunction and this phenotype occurs in a glucose-dependent manner.

Effects of ABCB1, ABCC2, UGT2B7 and HNF4α genetic polymorphisms on oxcarbazepine concentrations and therapeutic efficacy in patients with epilepsy.

PubMed

Shen, Chunhong; Zhang, Bijun; Liu, Zhirong; Tang, Yelei; Zhang, Yinxi; Wang, Shan; Guo, Yi; Ding, Yao; Wang, Shuang; Ding, Meiping

2017-10-01

The aim of the study is to investigate the effects of ABCB1, ABCC2, UGT2B7 and HNF4α genetic polymorphisms on plasma oxcarbazepine (OXC) concentrations and therapeutic efficacy in Han Chinese patients with epilepsy. We recruited 116 Han Chinese patients with epilepsy who were receiving OXC monotherapy. Blood samples were taken and OXC levels were measured. The polymorphisms of ABCB1 rs1045642, ABCC2 rs2273697, UGT2B7 rs7439366, and HNF4α rs2071197 were determined. The therapeutic efficacy of OXC at the 1-year time-point was assessed. Data analysis was performed using IBM SPSS Statistics 22.0. The genetic polymorphism of ABCB1 rs1045642 was found to be associated with normalized OXC concentration and therapeutic efficacy in patients with epilepsy (P<0.05). As for UGT2B7 rs7439366, the allele polymorphism exhibited a correlation with treatment outcome, but not OXC concentration. The polymorphisms of ABCC2 rs2273697 and HNF4α rs2071197 was not associated with OXC concentrations and therapeutic efficacy. These results suggested that ABCB1 rs1045642 and UGT2B7 rs7439366 may affect OXC pharmacokinetics and therapeutic efficacy in Han Chinese patients with epilepsy. However, further studies in larger populations and other ethnic groups are required. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Chips in black boxes? Convenience life span, parafood, brandwidth, families, and co-creation.

PubMed

Jacobs, Marc

2015-11-01

Any consumer who opens a bag of potato or corn chips (or crisps in the UK) knows there is no time to waste to enjoy or share them. The convenience life span of chips is limited: it is the shelf or storage life and a very limited time once outside the bag. Many technologies converge to generate the desired effect as a black box, not only of the packaging but also of the chips themselves. The concept of paratext can be applied to printed messages on the package, including the brand name and other texts like advertising (epitexts), which can be expanded into the concept of parafood. These concepts help to discuss technological developments and interpret why this has recently become a negotiation zone for co-creation (see the Do us a flavor campaigns). They are symptoms of changing relations between production, research and development, marketing, and consumption. This paper pays special attention to back stories, underdog brand biographies and narratives about origin. The concept of brandwidth is introduced to sensitize about the limits of combining different stories about chips. A recent brand biography, a family history and a cookery book are used to discuss the phenomenon of cooking with Fritos. Together with the concepts of parafood, brandwidth and black boxes, more reflection and dialogue about the role of history and heritage in marketing put new challenging perspectives on the agenda. Copyright © 2015 Elsevier Ltd. All rights reserved.

Differential effects of the extracellular microenvironment on human embryonic stem cell differentiation into keratinocytes and their subsequent replicative life span.

PubMed

Movahednia, Mohammad Mehdi; Kidwai, Fahad Karim; Zou, Yu; Tong, Huei Jinn; Liu, Xiaochen; Islam, Intekhab; Toh, Wei Seong; Raghunath, Michael; Cao, Tong

2015-04-01

Culture microenvironment plays a critical role in the propagation and differentiation of human embryonic stem cells (hESCs) and their differentiated progenies. Although high efficiency of hESC differentiation to keratinocytes (hESC-Kert) has been achieved, little is known regarding the effects of early culture microenvironment and pertinent extracellular matrix (ECM) interactions during epidermal commitment on subsequent proliferative capacity of hESC-Kert. The aim of this study is to evaluate the effects of the different ECM microenvironments during hESC differentiation on subsequent replicative life span of hESC-Kert. In doing so, H1-hESCs were differentiated to keratinocytes (H1-Kert) in two differentiation systems. The first system employed autologous fibroblast feeder support, in which keratinocytes (H1-Kert(ACC)) were derived by coculture of hESCs with hESC-derived fibroblasts (H1-ebFs). The second system employed a novel decellularized matrix from H1-ebFs to create a dermoepidermal junction-like (DEJ) matrix. H1-Kert(AFF) were derived by differentiation of hESCs on the feeder-free system employing the DEJ matrix. Our study indicated that the feeder-free system with the use of DEJ matrix was more efficient in differentiation of hESCs toward epidermal progenitors. However, the feeder-free system was not sufficient to support the subsequent replicative capacity of differentiated keratinocytes. Of note, H1-Kert(AFF) showed limited replicative capacity with reduced telomere length and early cellular senescence. We further showed that the lack of cell-cell interactions during epidermal commitment led to heightened production of TGF-β1 by hESC-Kert during extended culture, which in turn was responsible for resulting in the limited replicative life span with cellular senescence of hESC-Kert derived under the feeder-free culture system. This study highlights for the first time the importance of the culture microenvironment and cell-ECM interactions during

Time scale matters: genetic analysis does not support adaptation-by-time as the mechanism for adaptive seasonal declines in kokanee reproductive life span

PubMed Central

Morbey, Yolanda E; Jensen, Evelyn L; Russello, Michael A

2014-01-01

Seasonal declines of fitness-related traits are often attributed to environmental effects or individual-level decisions about reproductive timing and effort, but genetic variation may also play a role. In populations of Pacific salmon (Oncorhynchus spp.), seasonal declines in reproductive life span have been attributed to adaptation-by-time, in which divergent selection for different traits occurs among reproductively isolated temporal components of a population. We evaluated this hypothesis in kokanee (freshwater obligate Oncorhynchus nerka) by testing for temporal genetic structure in neutral and circadian-linked loci. We detected no genetic differences in presumably neutral loci among kokanee with different arrival and maturation dates within a spawning season. Similarly, we detected no temporal genetic structure in OtsClock1b, Omy1009uw, or OmyFbxw11, candidate loci associated with circadian function. The genetic evidence from this study and others indicates a lack of support for adaptation-by-time as an important evolutionary mechanism underlying seasonal declines in reproductive life span and a need for greater consideration of other mechanisms such as time-dependent, adaptive adjustment of reproductive effort. PMID:25478160

[Genome loses all 5-methylcytosine a life span. How is this connected with accumulation of mutations during aging?].

PubMed

Mazin, A L

1993-01-01

The 5-methylcytosine (5mC) content in liver DNA has been determined for rats of different age. The rate of the 5mC loss from DNA is maximal in pre- and neonatal rats, 1.28% of reduction of the 5mC content per day, then it decreases to 0.33% and becomes minimal and constant in adult rats, 0.028% per day. During pregnancy and the first 15 days of postnatal development rat genome loses 49% of all 5mC. Within the next 45 days 15% of 5mC disappears, and during maximal rat life span, about four years, 39% of the genomic 5mC may be lost. Thus, it has been found for the first time that the animal genome loses practically all 5mC residues during the life span. Analysis of the literature data shows that for embryos the rate of the 5mC loss from DNA proves to be higher than that for adult animals by 96 times for mice, 69-for rats and 28-for cows. The rate of embryonal DNA hypomethylation may be inversely proportional to the pregnancy duration of species. In adult animals the rate inversely correlates with their maximal life span and accounts for the 5mC loss from DNA of a mouse by 0.028%, of a rat by 0.024%, of a hamster by 0.007%, of a cow by 0.004% and of a human being by 0.0005% per day. During the entire ontogenesis, the genome of a mouse loses 93% of all 5mC residues, that of a rat-101% and of a cow-88%. The age-dependent loss of 5mC from DNA is also typical for cell lines aging in vitro. It is constant, as a rule, and correlates with the number of cell population doublings (PD). The removal of all 5mC from DNA corresponds to 70-130 PD for human, 40-60 PD-for hamster and 6 PD- for mouse cells. In immortal lines the level of DNA methylation is stable or grows with age. A possible mechanism of an age-related 5mC loss from DNA is discussed. DNA hypomethylation may result from 5mC deamination directly at the moment of replicative DNA methylation and subsequent reparation of the G.T mispairs which leads to accumulation of the 5mC-->T+C substitutions in the genome with each

Magnesium carbonate-containing phosphate binder prevents connective tissue mineralization in Abcc6(-/-) mice-potential for treatment of pseudoxanthoma elasticum.

PubMed

Li, Qiaoli; Larusso, Jennifer; Grand-Pierre, Alix E; Uitto, Jouni

2009-12-01

Pseudoxanthoma elasticum (PXE) is a heritable disorder characterized by ectopic mineralization of connective tissues primarily in the skin, eyes, and the cardiovascular system. PXE is caused by mutations in the ABCC6 gene. While PXE is associated with considerable morbidity and mortality, there is currently no effective or specific treatment. In this study, we tested oral phosphate binders for treatment of a mouse model of PXE which we have developed by targeted ablation of the corresponding mouse gene (Abcc6(-/-)). This "knock-out" (KO) mouse model recapitulates features of PXE and demonstrates mineralization of a number of tissues, including the connective tissue capsule surrounding vibrissae in the muzzle skin which serves as an early biomarker of the mineralization process. Treatment of these mice with a magnesium carbonate-enriched diet (magnesium concentration being 5-fold higher than in the control diet) completely prevented mineralization of the vibrissae up to 6 months of age, as demonstrated by computerized morphometric analysis of histopathology as well as by calcium and phosphate chemical assays. The magnesium carbonate-enriched diet also prevented the progression of mineralization when the mice were placed on that experimental diet at 3 months of age and followed up to 6 months of age. Treatment with magnesium carbonate was associated with a slight increase in the serum concentration of magnesium, with no effect on serum calcium and phosphorus levels. In contrast, concentration of calcium in the urine was increased over 10-fold while the concentration of phosphorus was markedly decreased, being essentially undetectable after long-term (> 4 month) treatment. No significant changes were noted in the serum parathyroid hormone levels. Computerized axial tomography scan of bones in mice placed on magnesium carbonate-enriched diet showed no differences in the bone density compared to mice on the control diet, and chemical assays showed a small increase in

Dietary intake of Curcuma longa and Emblica officinalis increases life span in Drosophila melanogaster.

PubMed

Rawal, Shilpa; Singh, Pavneet; Gupta, Ayush; Mohanty, Sujata

2014-01-01

Intake of food and nutrition plays a major role in affecting aging process and longevity. However, the precise mechanisms underlying the ageing process are still unclear. To this respect, diet has been considered to be a determinant of ageing process. In order to better illustrate this, we used Drosophila melanogaster as a model and fed them orally with different concentrations of two commonly used Indian medicinal plant products, Curcuma longa (rhizome) and Emblica officinalis (fruit). The results revealed significant increase in life span of Drosophila flies on exposure to both the plant products, more efficiently by C. Longa than by E. officinalis. In order to understand whether the increase in lifespan was due to high-antioxidant properties of these medicinal plants, we performed enzymatic assays to assess the SOD and catalase activities in case of both treated and control Drosophila flies. Interestingly, the results support the free radical theory of aging as both these plant derivatives show high reactive oxygen species (ROS) scavenging activities.

Dietary Intake of Curcuma longa and Emblica officinalis Increases Life Span in Drosophila melanogaster

PubMed Central

Rawal, Shilpa; Singh, Pavneet; Gupta, Ayush; Mohanty, Sujata

2014-01-01

Intake of food and nutrition plays a major role in affecting aging process and longevity. However, the precise mechanisms underlying the ageing process are still unclear. To this respect, diet has been considered to be a determinant of ageing process. In order to better illustrate this, we used Drosophila melanogaster as a model and fed them orally with different concentrations of two commonly used Indian medicinal plant products, Curcuma longa (rhizome) and Emblica officinalis (fruit). The results revealed significant increase in life span of Drosophila flies on exposure to both the plant products, more efficiently by C. Longa than by E. officinalis. In order to understand whether the increase in lifespan was due to high-antioxidant properties of these medicinal plants, we performed enzymatic assays to assess the SOD and catalase activities in case of both treated and control Drosophila flies. Interestingly, the results support the free radical theory of aging as both these plant derivatives show high reactive oxygen species (ROS) scavenging activities. PMID:24967413

[Intention for self-change across the life span: Focusing on concern about self-change].

PubMed

Chishima, Yuta

2016-06-01

The purpose of the present study was to examine intention for self-change across the life span using measures of self-esteem, frequency of self-reflection, and concern about self-change. We hypothesized that: (a) Intention for self-change decreases with age because of increased self-esteem, decreased self-reflection and concern about self-change, and (b) Associations among self-esteem, frequency of self-reflection, and intention for self-change are mediated by concern about self-change. Participants (N = 997; age range, 15 to 69 yrs) completed an internet survey. ANOVA results suggested that intention for self-change, concern about self-change, and frequency of self-reflection decreased with age, and that self-esteem-scores increased with age. Simultaneous analysis of multiple age groups showed that for all groups of low self-esteem and frequent self-reflection promoted intention for self-change and that there were significant mediating effects for concern about self-change. Therefore, these findings supported out research hypotheses.

Protection throughout the life span: the psychoneuroimmunologic impact of Indo-Tibetan meditative and yogic practices.

PubMed

Olivo, Erin L

2009-08-01

The Indo-Tibetan tradition claims that proficiency in the suggested longevity practices of meditation, diet, and physical exercise (yoga), will result in profound anti-aging, stress-mediating and health enhancing effects. Western biomedical research has begun to demonstrate that the psychobiological states induced and cultivated by cognitive behavioral practices which are emblematic of those contained within the Indo-Tibetan tradition (hypnosis, meditation, visualization, systematic relaxation), indeed do have a profound impact on the body's protective and regulatory systems. Although continued study is necessary, much of the early research illuminating the mechanisms responsible for the life-span extending and health-enhancing effects of these cognitive behavioral practices points to the importance of their anti-inflammatory, anti-stress, and antioxidant effects as well as their impact in enhancing the production of endogenous substances that possess general longevity-enhancing, regenerative properties.

Increased span length for the MGS long-span guardrail system.

DOT National Transportation Integrated Search

2014-12-01

Long-span guardrail systems have been recognized as an effective means of shielding low-fill culverts while : minimizing construction efforts and limiting culvert damage and repair. The current MGS long-span design provided the : capability to span u...

View of approach span and movable span, looking southeast from ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

View of approach span and movable span, looking southeast from navy land. Note that navigational channel exists only on north side of movable span. - Naval Supply Annex Stockton, Daggett Road Bridge, Daggett Road traversing Burns Cut Off, Stockton, San Joaquin County, CA

Age Differences in Explicit and Implicit Age Attitudes Across the Life Span.

PubMed

Chopik, William J; Giasson, Hannah L

2017-08-01

Biased judgments about others can operate both within and outside of our conscious awareness. However, little attention has been paid to how implicit and explicit attitudes differ across the life span, particularly with respect to age bias. In the current study, we examined age differences in implicit and explicit attitudes towards older individuals. Participants (N = 704,151) ranging from age 15 to 94 completed the Implicit Association Test and explicit self-report measures of bias against older adults. The associations between age bias and several demographic characteristics (e.g., gender, education) were also examined. A preference for younger people was found among participants of all ages; however, implicit and explicit attitudes showed divergent associations with age. Implicit preference for younger people was highest among older adults; explicit preference for younger people was lowest among older adults. Examining age differences in implicit and explicit attitudes sheds light into the development and complexities of aging perceptions in different age groups. The current study's findings are discussed in the context of applications to and implications of reducing prejudice toward older adults. © 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.

Tracking the trajectory of shame, guilt, and pride across the life span.

PubMed

Orth, Ulrich; Robins, Richard W; Soto, Christopher J

2010-12-01

The authors examined age differences in shame, guilt, and 2 forms of pride (authentic and hubristic) from age 13 years to age 89 years, using cross-sectional data from 2,611 individuals. Shame decreased from adolescence into middle adulthood, reaching a nadir around age 50 years, and then increased in old age. Guilt increased from adolescence into old age, reaching a plateau at about age 70 years. Authentic pride increased from adolescence into old age, whereas hubristic pride decreased from adolescence into middle adulthood, reaching a minimum around age 65 years, and then increased in old age. On average, women reported experiencing more shame and guilt; Blacks reported experiencing less shame and Asians more hubristic pride than other ethnicities. Across the life span, shame and hubristic pride tended to be negatively related to psychological well-being, and shame-free guilt and authentic pride showed positive relations with well-being. Overall, the findings support the maturity principle of personality development and suggest that as people age they become more prone to experiencing psychologically adaptive self-conscious emotions, such as guilt and authentic pride, and less prone to experiencing psychologically maladaptive ones, such as shame and hubristic pride. PsycINFO Database Record (c) 2010 APA, all rights reserved.

Life-span retrieval of public events: Reminiscence bump for high-impact events, recency for others.

PubMed

Tekcan, Ali I; Boduroglu, Aysecan; Mutlutürk, Aysu; Aktan Erciyes, Aslı

2017-10-01

Although substantial evidence exists showing a reliable reminiscence bump for personal events, data regarding retrieval distributions for public events have been equivocal. The primary aim of the present study was to address life-span retrieval distributions of different types of public events in comparison to personal events, and to test whether the existing accounts of the bump can explain the distribution of public events. We asked a large national sample to report the most important, happiest, and saddest personal events and the most important, happiest, saddest, most proud, most fearful, and most shameful public events. We found a robust bump corresponding to the third decade of life for the happiest and the most important positive but not for the saddest and most important negative personal events. For the most important public events, a bump emerged only for the two most frequently mentioned events. Distributions of public events cued with emotions were marked by recency. These results point to potential differences in retrieval of important personal and public events. While the life-script framework well accounts for the findings regarding important personal events, a chronologically retroactive search seem to guide retrieval of public events. Reminiscence bump observed for the two public events suggest that age-at-event affects recall of public events to the degree that the events are high-impact ones that dominate nation's collective memory. Results provide further evidence that the bump is not unitary and points to importance of event type and memory elicitation method with regard to competing explanations of the phenomenon.

Multidrug Resistance Protein 1 (MRP1, ABCC1), a “Multitasking” ATP-binding Cassette (ABC) Transporter*

PubMed Central

Cole, Susan P. C.

2014-01-01

The multidrug resistance protein 1 (MRP1) encoded by ABCC1 was originally discovered as a cause of multidrug resistance in tumor cells. However, it is now clear that MRP1 serves a broader role than simply mediating the ATP-dependent efflux of drugs from cells. The antioxidant GSH and the pro-inflammatory cysteinyl leukotriene C4 have been identified as key physiological organic anions effluxed by MRP1, and an ever growing body of evidence indicates that additional lipid-derived mediators are also substrates of this transporter. As such, MRP1 is a multitasking transporter that likely influences the etiology and progression of a host of human diseases. PMID:25281745

6. VIEW OF APPROACH SPAN AND MAIN SPAN OF THE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

6. VIEW OF APPROACH SPAN AND MAIN SPAN OF THE ACCESS BRIDGE AND INTAKE PIER, LOOKING SOUTHWEST. - Sacramento River Water Treatment Plant Intake Pier & Access Bridge, Spanning Sacramento River approximately 175 feet west of eastern levee on river; roughly .5 mile downstream from confluence of Sacramento & American Rivers, Sacramento, Sacramento County, CA

SPAN: Ocean science

NASA Technical Reports Server (NTRS)

Thomas, Valerie L.; Koblinsky, Chester J.; Webster, Ferris; Zlotnicki, Victor; Green, James L.

1987-01-01

The Space Physics Analysis Network (SPAN) is a multi-mission, correlative data comparison network which links space and Earth science research and data analysis computers. It provides a common working environment for sharing computer resources, sharing computer peripherals, solving proprietary problems, and providing the potential for significant time and cost savings for correlative data analysis. This is one of a series of discipline-specific SPAN documents which are intended to complement the SPAN primer and SPAN Management documents. Their purpose is to provide the discipline scientists with a comprehensive set of documents to assist in the use of SPAN for discipline specific scientific research.

ABCC8 R1420H Loss-of-Function Variant in a Southwest American Indian Community: Association With Increased Birth Weight and Doubled Risk of Type 2 Diabetes.

PubMed

Baier, Leslie J; Muller, Yunhua Li; Remedi, Maria Sara; Traurig, Michael; Piaggi, Paolo; Wiessner, Gregory; Huang, Ke; Stacy, Alyssa; Kobes, Sayuko; Krakoff, Jonathan; Bennett, Peter H; Nelson, Robert G; Knowler, William C; Hanson, Robert L; Nichols, Colin G; Bogardus, Clifton

2015-12-01

Missense variants in KCNJ11 and ABCC8, which encode the KIR6.2 and SUR1 subunits of the β-cell KATP channel, have previously been implicated in type 2 diabetes, neonatal diabetes, and hyperinsulinemic hypoglycemia of infancy (HHI). To determine whether variation in these genes affects risk for type 2 diabetes or increased birth weight as a consequence of fetal hyperinsulinemia in Pima Indians, missense and common noncoding variants were analyzed in individuals living in the Gila River Indian Community. A R1420H variant in SUR1 (ABCC8) was identified in 3.3% of the population (N = 7,710). R1420H carriers had higher mean birth weights and a twofold increased risk for type 2 diabetes with a 7-year earlier onset age despite being leaner than noncarriers. One individual homozygous for R1420H was identified; retrospective review of his medical records was consistent with HHI and a diagnosis of diabetes at age 3.5 years. In vitro studies showed that the R1420H substitution decreases KATP channel activity. Identification of this loss-of-function variant in ABCC8 with a carrier frequency of 3.3% affects clinical care as homozygous inheritance and potential HHI will occur in 1/3,600 births in this American Indian population. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

The nucleus- and endoplasmic reticulum-targeted forms of protein tyrosine phosphatase 61F regulate Drosophila growth, life span, and fecundity.

PubMed

Buszard, Bree J; Johnson, Travis K; Meng, Tzu-Ching; Burke, Richard; Warr, Coral G; Tiganis, Tony

2013-04-01

The protein tyrosine phosphatases (PTPs) T cell PTP (TCPTP) and PTP1B share a high level of catalytic domain sequence and structural similarity yet display distinct differences in substrate recognition and function. Their noncatalytic domains contribute to substrate selectivity and function by regulating TCPTP nucleocytoplasmic shuttling and targeting PTP1B to the endoplasmic reticulum (ER). The Drosophila TCPTP/PTP1B orthologue PTP61F has two variants with identical catalytic domains that are differentially targeted to the ER and nucleus. Here we demonstrate that the PTP61F variants differ in their ability to negatively regulate insulin signaling in vivo, with the nucleus-localized form (PTP61Fn) being more effective than the ER-localized form (PTP61Fm). We report that PTP61Fm is reliant on the adaptor protein Dock to attenuate insulin signaling in vivo. Also, we show that the PTP61F variants differ in their capacities to regulate growth, with PTP61Fn but not PTP61Fm attenuating cellular proliferation. Furthermore, we generate a mutant lacking both PTP61F variants, which displays a reduction in median life span and a decrease in female fecundity, and show that both variants are required to rescue these mutant phenotypes. Our findings define the role of PTP61F in life span and fecundity and reinforce the importance of subcellular localization in mediating PTP function in vivo.

Target organ specific activity of drosophila MRP (ABCC1) moderates developmental toxicity of methylmercury.

PubMed

Prince, Lisa; Korbas, Malgorzata; Davidson, Philip; Broberg, Karin; Rand, Matthew Dearborn

2014-08-01

Methylmercury (MeHg) is a ubiquitous and persistent neurotoxin that poses a risk to human health. Although the mechanisms of MeHg toxicity are not fully understood, factors that contribute to susceptibility are even less well known. Studies of human gene polymorphisms have identified a potential role for the multidrug resistance-like protein (MRP/ABCC) family, ATP-dependent transporters, in MeHg susceptibility. MRP transporters have been shown to be important for MeHg excretion in adult mouse models, but their role in moderating MeHg toxicity during development has not been explored. We therefore investigated effects of manipulating expression levels of MRP using a Drosophila development assay. Drosophila MRP (dMRP) is homologous to human MRP1-4 (ABCC1-4), sharing 50% identity and 67% similarity with MRP1. A greater susceptibility to MeHg is seen in dMRP mutant flies, demonstrated by reduced rates of eclosion on MeHg-containing food. Furthermore, targeted knockdown of dMRP expression using GAL4>UAS RNAi methods demonstrates a tissue-specific function for dMRP in gut, Malpighian tubules, and the nervous system in moderating developmental susceptibility to MeHg. Using X-ray synchrotron fluorescence imaging, these same tissues were also identified as the highest Hg-accumulating tissues in fly larvae. Moreover, higher levels of Hg are seen in dMRP mutant larvae compared with a control strain fed an equivalent dose of MeHg. In sum, these data demonstrate that dMRP expression, both globally and within Hg-targeted organs, has a profound effect on susceptibility to MeHg in developing flies. Our findings point to a potentially novel and specific role for dMRP in neurons in the protection against MeHg. Finally, this experimental system provides a tractable model to evaluate human polymorphic variants of MRP and other gene variants relevant to genetic studies of mercury-exposed populations. © The Author 2014. Published by Oxford University Press on behalf of the Society of

Deferasirox associated with liver failure and death in a sickle cell anemia patient homozygous for the -1774delG polymorphism in the Abcc2 gene.

PubMed

Braga, Caroline C B; Benites, Bruno Deltreggia; de Albuquerque, Dulcineia M; Alvarez, Marisa C; Seva-Pereira, Tiago; Duarte, Bruno K L; Costa, Fernando F; Gilli, Simone C O; Saad, Sara T O

2017-08-01

This manuscript describes the case of a patient with sickle cell anemia who died of fulminant hepatitis after therapy with the iron chelator Deferasirox. The patient was homozygous for the -1774delG polymorphism in the Abcc2 gene, which raises the concern about the use of hepatotoxic drugs in this specific context.

Studying the Motivated Agent Through Time: Personal Goal Development During the Adult Life Span.

PubMed

Dunlop, William L; Bannon, Brittany L; McAdams, Dan P

2017-04-01

This research examined the rank-order and mean-level consistency of personal goals at two periods in the adult life span. Personal goal continuity was considered among a group of young adults (N = 145) who reported their goals three times over a 3-year period and among a group of midlife adults (N = 163) who specified their goals annually over a 4-year period. Goals were coded for a series of motive-based (viz., achievement, affiliation, intimacy, power) and domain-based (viz., finance, generativity, health, travel) categories. In both samples, we noted a moderate degree of rank-order consistency across assessment periods. In addition, the majority of goal categories exhibited a high degree of mean-level consistency. The results of this research suggest that (a) the content of goals exhibits a modest degree of rank-order consistency and a substantial degree of mean-level consistency over time, and (b) considering personality continuity and development as manifest via goals represents a viable strategy for personality psychologists. © 2015 Wiley Periodicals, Inc.

Antioxidant Capacity of “Mexican Arnica” Heterotheca inuloides Cass Natural Products and Some Derivatives: Their Anti-Inflammatory Evaluation and Effect on C. elegans Life Span

PubMed Central

Rodríguez-Chávez, José Luis; Nieto-Camacho, Antonio; Delgado-Lamas, Guillermo

2015-01-01

It has been suggested that the accumulation of biomolecular damage caused by reactive oxygen species (ROS) contributes to aging. The antioxidant activity is related to the ability of certain compounds to protect against the potentially harmful effect of processes or reactions involving ROS. This ability is associated with the termination of free radical propagation in biological systems. From Heterotheca inuloides various compounds which have shown to possess antioxidant capacity and scavenging ROS. The aim of this study was to determine the antioxidant capacity of additional natural components isolated from H. inuloides and some semisynthetic derivatives, their anti-inflammatory activity and the effect on Caenorhabditis elegans nematode life span. Compounds showed ability to inhibit various biological processes such as lipid peroxidation, scavenge nonbiological important oxidants such as 1O2, OH∙, H2O2, and HOCl and scavenge non biological stable free radicals (DPPH). Some cadinane type compounds showed possess antioxidant, ROS scavenging capacity, anti-inflammatory activity, and effect on the C. elegans life span. Flavonoid type compounds increased the life of the nematode and quercetin was identified as the compound with the greatest activity. The modification of chemical structure led to a change in the antioxidant capacity, the anti-inflammatory activity, and the survival of the worm. PMID:25821555

Mice selectively bred for open-field thigmotaxis: life span and stability of the selection trait.

PubMed

Leppänen, Pia K; Ewalds-Kvist, S Béatrice M; Selander, Ritva-Kajsa

2005-04-01

In 2 experiments, the authors examined 69 mice selectively bred for high or low levels of open-field (OF) thigmotactic behavior (high open-field thigmotaxis [HOFT] and low open-field thigmotaxis [LOFT], respectively). They found that the strains differed in defecation during the 60-min exposure to the OF. Furthermore, the strains differed with regard to their life spans: The more thigmotactic HOFT mice lived longer than the LOFT mice. The strains were not differentiated by food intake or excretion. The strain difference in thigmotaxis was not age dependent, and it persisted in the home-cage condition as well. Neither the location (center or wall) of the starting point nor the shape (circular or square) of the OF arena affected the difference in wall-seeking behavior between the two strains. The authors concluded that the difference in thigmotaxis (or emotionality) between the HOFT and LOFT mice is a stable and robust feature of these animals.

General Slowing and Education Mediate Task Switching Performance Across the Life-Span

PubMed Central

Moretti, Luca; Semenza, Carlo; Vallesi, Antonino

2018-01-01

Objective: This study considered the potential role of both protective factors (cognitive reserve, CR) and adverse ones (general slowing) in modulating cognitive flexibility in the adult life-span. Method: Ninety-eight individuals performed a task-switching (TS) paradigm in which we adopted a manipulation concerning the timing between the cue and the target. Working memory demands were minimized by using transparent cues. Additionally, indices of cognitive integrity, depression, processing speed and different CR dimensions were collected and used in linear models accounting for TS performance under the different time constraints. Results: The main results showed similar mixing costs and higher switching costs in older adults, with an overall age-dependent effect of general slowing on these costs. The link between processing speed and TS performance was attenuated when participants had more time to prepare. Among the different CR indices, formal education only was associated with reduced switch costs under time pressure. Discussion: Even though CR is often operationalized as a unitary construct, the present research confirms the benefits of using tools designed to distinguish between different CR dimensions. Furthermore, our results provide empirical support to the assumption that processing speed influence on executive performance depends on time constraints. Finally, it is suggested that whether age differences appear in terms of switch or mixing costs depends on working memory demands (which were low in our tasks with transparent cues). PMID:29780341

Eyewitness identification across the life span: A meta-analysis of age differences.

PubMed

Fitzgerald, Ryan J; Price, Heather L

2015-11-01

Lineup identifications are often a critical component of criminal investigations. Over the past 35 years, researchers have been conducting empirical studies to assess the impact of witness age on identification accuracy. A previous meta-analysis indicated that children are less likely than adults to correctly reject a lineup that does not contain the culprit, but children 5 years and older are as likely as adults to make a correct identification if the culprit is in the lineup (Pozzulo & Lindsay, 1998). We report an updated meta-analysis of age differences in eyewitness identification, summarizing data from 20,244 participants across 91 studies. Contrary to extant reviews, we adopt a life span approach and examine witnesses from early childhood to late adulthood. Children's increased tendency to erroneously select a culprit-absent lineup member was replicated. Children were also less likely than young adults to correctly identify the culprit. Group data from culprit-absent and culprit-present lineups were used to produce signal detection measures, which indicated young adults were better able than children to discriminate between guilty and innocent suspects. A strikingly similar pattern emerged for older adults, who had even stronger deficits in discriminability than children, relative to adults. Although identifications by young adults were the most reliable, identifications by all witnesses had probative value. (c) 2015 APA, all rights reserved).

Novel understanding of ABC transporters ABCB1/MDR/P-glycoprotein, ABCC2/MRP2, and ABCG2/BCRP in colorectal pathophysiology

PubMed Central

Andersen, Vibeke; Svenningsen, Katrine; Knudsen, Lina Almind; Hansen, Axel Kornerup; Holmskov, Uffe; Stensballe, Allan; Vogel, Ulla

2015-01-01

AIM: To evaluate ATP-binding cassette (ABC) transporters in colonic pathophysiology as they had recently been related to colorectal cancer (CRC) development. METHODS: Literature search was conducted on PubMed using combinations of the following terms: ABC transporters, ATP binding cassette transporter proteins, inflammatory bowel disease, ulcerative, colitis, Crohns disease, colorectal cancer, colitis, intestinal inflammation, intestinal carcinogenesis, ABCB1/P-glycoprotein (P-gp/CD243/MDR1), ABCC2/multidrug resistance protein 2 (MRP2) and ABCG2/breast cancer resistance protein (BCRP), Abcb1/Mdr1a, abcc2/Mrp2, abcg2/Bcrp, knock-out mice, tight junction, membrane lipid function. RESULTS: Recently, human studies reported that changes in the levels of ABC transporters were early events in the adenoma-carcinoma sequence leading to CRC. A link between ABCB1, high fat diet and gut microbes in relation to colitis was suggested by the animal studies. The finding that colitis was preceded by altered gut bacterial composition suggests that deletion of Abcb1 leads to fundamental changes of host-microbiota interaction. Also, high fat diet increases the frequency and severity of colitis in specific pathogen-free Abcb1 KO mice. The Abcb1 KO mice might thus serve as a model in which diet/environmental factors and microbes may be controlled and investigated in relation to intestinal inflammation. Potential molecular mechanisms include defective transport of inflammatory mediators and/or phospholipid translocation from one side to the other of the cell membrane lipid bilayer by ABC transporters affecting inflammatory response and/or function of tight junctions, phagocytosis and vesicle trafficking. Also, diet and microbes give rise to molecules which are potential substrates for the ABC transporters and which may additionally affect ABC transporter function through nuclear receptors and transcriptional regulation. Another critical role of ABCB1 was suggested by the finding that

Life Span Studies of ADHD-Conceptual Challenges and Predictors of Persistence and Outcome.

PubMed

Caye, Arthur; Swanson, James; Thapar, Anita; Sibley, Margaret; Arseneault, Louise; Hechtman, Lily; Arnold, L Eugene; Niclasen, Janni; Moffitt, Terrie; Rohde, Luis Augusto

2016-12-01

There is a renewed interest in better conceptualizing trajectories of attention-deficit/hyperactivity disorder (ADHD) from childhood to adulthood, driven by an increased recognition of long-term impairment and potential persistence beyond childhood and adolescence. This review addresses the following major issues relevant to the course of ADHD in light of current evidence from longitudinal studies: (1) conceptual and methodological issues related to measurement of persistence of ADHD, (2) estimates of persistence rate from childhood to adulthood and its predictors, (3) long-term negative outcomes of childhood ADHD and their early predictors, and (4) the recently proposed new adult-onset ADHD. Estimates of persistence vary widely in the literature, and diagnostic criteria, sample characteristics, and information source are the most important factors explaining variability among studies. Evidence indicates that ADHD severity, comorbid conduct disorder and major depressive disorder, and treatment for ADHD are the main predictors of ADHD persistence from childhood to adulthood. Comorbid conduct disorder and ADHD severity in childhood are the most important predictors of adverse outcomes in adulthood among children with ADHD. Three recent population studies suggested the existence of a significant proportion of individuals who report onset of ADHD symptoms and impairments after childhood. Finally, we highlight areas for improvement to increase our understanding of ADHD across the life span.

C-SPAN Networks: Professor's Guide. C-SPAN in the Classroom Series.

ERIC Educational Resources Information Center

C-SPAN, Washington, DC.

This C-SPAN publication is intended to serve as a forum, enabling college-level members of C-SPAN in the classroom program to share ideas regarding programming and classroom academic research. This issue explains the different C-SPAN networks and what their purposes are. The publication contains 12 articles written by professors who use the C-SPAN…

Causes of decreased life expectancy over the life span in bipolar disorder.

PubMed

Kessing, Lars Vedel; Vradi, Eleni; McIntyre, Roger S; Andersen, Per Kragh

2015-07-15

Accelerated aging has been proposed as a mechanism explaining the increased prevalence of comorbid general medical illnesses in bipolar disorder. To test the hypothesis that lost life years due to natural causes starts in early and mid-adulthood, supporting the hypothesis of accelerated aging. Using individual data from nationwide registers of patient with a diagnosis of bipolar disorder we calculated remaining life expectancies before age 90 years for values of age 15, 25, 35…75 years among all individuals alive in year 2000. Further, we estimated the reduction in life expectancy due to natural causes (physical illnesses) and unnatural causes (suicide and accidents) in relation to age. A total of 22,635 patients with bipolar disorder were included in the study in addition to data from the entire Danish general population of 5.4 million people. At age 15 years, remaining life expectancy before age 90 years was decreased 12.7 and 8.9 life years, respectively, for men and women with bipolar disorder. For 15-year old boys with bipolar disorder, natural causes accounted for 58% of all lost life years and for 15-year old girls, natural causes accounted for 67% increasing to 74% and 80% for 45-year old men and women, respectively. Data concern patients who get contact to hospital psychiatry only. Natural causes of death is the most prevalent reason for lost life years already from adolescence and increases substantially during early and mid-adulthood, in this way supporting the hypothesis of accelerated aging. Early intervention in bipolar disorder should not only focus on improving outcome of the bipolar disorder but also on decreasing the risk of comorbid general medical illnesses. Copyright © 2015 Elsevier B.V. All rights reserved.

"Life-span development of visual working memory: When is feature binding difficult?": Correction to Cowan et al. (2006).

PubMed

2016-10-01

Reports an error in "Life-span development of visual working memory: When is feature binding difficult?" by Nelson Cowan, Moshe Naveh-Benjamin, Angela Kilb and J. Scott Saults ( Developmental Psychology , 2006[Nov], Vol 42[6], 1089-1102). In the article, there were two errors in experiment 1a. The mean for color item information in older adults was incorrectly calculated. As a result, Figure 3 shows a mean of over .70. The true mean was .63 ( SEM =.04). This change diminishes the magnitude of the aging deficit for associative information, although this deficit still appears to remain, to a smaller extent. (For a conceptual replication see Peterson & Naveh-Benjamin, 2016). There also was an error in the experimental procedure of Experiment 1a. The older adults in that experiment received only half the number of trials specified in the methods section, and half as much as the other groups. For all groups, when there were 4 or 6 items and the probe was a binding change, the probed location was matched by the same color at 1 other location but, when there were 8 or 10 squares, the probed location was matched by the same color at 1, 2, or 3 other locations. For 8 squares the number of trials was identical for these three trial subtypes whereas, for 10 squares, most of the trials had the same color at just 1 other location. These errors suggest that the experiment should be taken as only preliminary evidence that there is an aging deficit in color-location binding in visual working memory when color and binding trials are mixed in the same trial blocks. (The following abstract of the original article appeared in record 2006-20488-009.) We asked whether the ability to keep in working memory the binding between a visual object and its spatial location changes with development across the life span more than memory for item information. Paired arrays of colored squares were identical or differed in the color of one square, and in the latter case, the changed color was unique

The Prolonged Life-Span of Alveolar Macrophages

PubMed Central

Murphy, Jaime; Summer, Ross; Wilson, Andrew A.; Kotton, Darrell N.; Fine, Alan

2008-01-01

To further examine the half-life of alveolar macrophages, chimeric CD 45.2 mice were generated through bone marrow transplantation of donor CD 45.1 cells. Before administration of donor cells, recipient mice were divided into two cohorts: the first cohort received total body irradiation; the second cohort also received irradiation—however, the thorax, head, and upper extremities were shielded with lead. Flow cytometric analysis was then performed on blood, peritoneal, and bronchoalveolar lavage cells over time to quantify engraftment. The data generated for the unshielded cohort of mice revealed a macrophage half-life of 30 days. In the shielded cohort, however, we found that by 8 months there was negligible replacement of recipient alveolar macrophages by donor cells, despite reconstitution of the blood and peritoneum by donor bone marrow. Consistent with these findings, the mean fluorescent intensity of alveolar macrophages remained stable over a 4-week period after in vivo PKH26 dye loading. Together, these data show that previous alveolar macrophage half-life studies were confounded by the fact that they did not account for the toxic effects of irradiation conditioning regimens, and demonstrate that the bone marrow does not significantly contribute to the alveolar macrophage compartment during steady-state conditions. PMID:18192503

Targeting multidrug resistance protein 1 (MRP1, ABCC1): past, present, and future.

PubMed

Cole, Susan P C

2014-01-01

The human ATP-binding cassette transporter multidrug resistance protein 1 (MRP1), encoded by ABCC1, was initially identified because of its ability to confer multidrug resistance in lung cancer cells. It is now established that MRP1 plays a role in protecting certain tissues from xenobiotic insults and that it mediates the cellular efflux of the proinflammatory cysteinyl leukotriene C4 as well as a vast array of other endo- and xenobiotic organic anions. Many of these are glutathione (GSH) or glucuronide conjugates, the products of Phase II drug metabolism. MRP1 also plays a role in the cellular efflux of the reduced and oxidized forms of GSH and thus contributes to the many physiological and pathophysiological processes influenced by these small peptides, including oxidative stress. In this review, the pharmacological and physiological aspects of MRP1 are considered in the context of the current status and future prospects of pharmacological and genetic modulation of MRP1 activity.

Missing doses in the life span study of Japanese atomic bomb survivors.

PubMed

Richardson, David B; Wing, Steve; Cole, Stephen R

2013-03-15

The Life Span Study of atomic bomb survivors is an important source of risk estimates used to inform radiation protection and compensation. Interviews with survivors in the 1950s and 1960s provided information needed to estimate radiation doses for survivors proximal to ground zero. Because of a lack of interview or the complexity of shielding, doses are missing for 7,058 of the 68,119 proximal survivors. Recent analyses excluded people with missing doses, and despite the protracted collection of interview information necessary to estimate some survivors' doses, defined start of follow-up as October 1, 1950, for everyone. We describe the prevalence of missing doses and its association with mortality, distance from hypocenter, city, age, and sex. Missing doses were more common among Nagasaki residents than among Hiroshima residents (prevalence ratio = 2.05; 95% confidence interval: 1.96, 2.14), among people who were closer to ground zero than among those who were far from it, among people who were younger at enrollment than among those who were older, and among males than among females (prevalence ratio = 1.22; 95% confidence interval: 1.17, 1.28). Missing dose was associated with all-cancer and leukemia mortality, particularly during the first years of follow-up (all-cancer rate ratio = 2.16, 95% confidence interval: 1.51, 3.08; and leukemia rate ratio = 4.28, 95% confidence interval: 1.72, 10.67). Accounting for missing dose and late entry should reduce bias in estimated dose-mortality associations.

Effects of kaolin particle films on the life span of an orb-weaver spider.

PubMed

Benhadi-Marín, Jacinto; Pereira, José Alberto; Santos, Sónia A P

2016-02-01

Araniella cucurbitina (Araneae: Araneidae) is a widespread orb-weaver spider commonly found in agroecosystems. Mineral particle films such as kaolin, due to their protective or anti-feeding action, can represent an alternative to pesticides, especially in organic farming systems, but little is known about its effects on A. cucurbitina. Therefore, we tested the effect of kaolin sprays on the life span of A. cucurbitina under laboratory conditions. Four treatments were tested encompassing different exposure routes. Thus, kaolin sprays were applied on (i) the surface, (ii) the prey (fly), (iii) the spider and (iv) both spider & prey. A control group was tested with water in each treatment. Results showed that sprays of kaolin significantly affected the survival of A. curcubitina when applications were done on the surface and on both spider & prey registering a reduction of 48% and 56%, respectively. Spiders in control obtained higher probability of reaching alive at the end of the assay than those treated with kaolin. Differences observed can be explained by the feeding behavior of the species and may depend on the consumption of the web by the spider and the ratio spider/fly for body size. Copyright © 2015 Elsevier Ltd. All rights reserved.

Association of C49620T ABCC8 polymorphism with anthropometric and metabolic parameters in patients with autosomal dominant polycystic kidney disease: a preliminary study.

PubMed

Pietrzak-Nowacka, Maria; Safranow, Krzysztof; Bińczak-Kuleta, Agnieszka; Rózański, Jacek; Ciechanowski, Kazimierz; Ciechanowicz, Andrzej

2012-01-01

The aim of the study was to evaluate an association between the C49620T ABCC8 gene polymorphism and anthropometric, biochemical parameters, pancreatic β-cell function and insulin sensitivity among autosomal dominant polycystic kidney disease (ADPKD) patients. Forty-nine ADPKD patients (M/F: 19/30) and fifty healthy controls (M/F: 22/28) aged above 18 years, with normal kidney function and no diagnosis of diabetes, were enrolled into the study. The ABCC8 (SUR1) C49620T (IVS15-3C/T, rs1799854) genotypes were determined using a PCR-RFLP technique. In the ADPKD group among TT homozygous patients, total body fat content and percentage of fat in body weight were significantly lower than among C allele carriers (16.1 +/- 7.7 vs 22.9 +/- 7.1kg, p=0.04 and 22.8 +/- 6.5 vs 30.0 +/- 6.1%, p=0.001, respectively) while total body water was higher (58.4 +/- 4.3 vs 53.7 +/- 4.0kg, p=0.003). Among TT homozygous controls higher BMI values and LDL-cholesterol levels were observed if compared to C variant carriers (26.3 +/- 3.9 vs 23.8 +/3.4kg/m2 p=0.04 and 133.1 +/- 27.0 vs 114.3 +/- 35.2mg/dL, p=0.05, respectively), as well as higher area under curve of glucose concentrations (115.9 +/- 23.9 vs 102.7 +/- 25.2 mmol*h/L, p=0.046) during an oral glucose tolerance test. In the ADPKD group and among controls no association between the investigated polymorphism and secretory function of the pancreatic β-cells or insulin sensitivity was found. The C49620T ABCC8 polymorphism is associated with anthropometric risk factors for type 2 diabetes among ADPKD patients, with a protective effect of the TT genotype, but without influence on pancreatic β-cell secretory function or insulin sensitivity.

Childhood self-control and unemployment throughout the life span: evidence from two British cohort studies.

PubMed

Daly, Michael; Delaney, Liam; Egan, Mark; Baumeister, Roy F

2015-06-01

The capacity for self-control may underlie successful labor-force entry and job retention, particularly in times of economic uncertainty. Analyzing unemployment data from two nationally representative British cohorts (N = 16,780), we found that low self-control in childhood was associated with the emergence and persistence of unemployment across four decades. On average, a 1-SD increase in self-control was associated with a reduction in the probability of unemployment of 1.4 percentage points after adjustment for intelligence, social class, and gender. From labor-market entry to middle age, individuals with low self-control experienced 1.6 times as many months of unemployment as those with high self-control. Analysis of monthly unemployment data before and during the 1980s recession showed that individuals with low self-control experienced the greatest increases in unemployment during the recession. Our results underscore the critical role of self-control in shaping life-span trajectories of occupational success and in affecting how macroeconomic conditions affect unemployment levels in the population. © The Author(s) 2015.

Genetic variations and patient-reported quality of life among patients with lung cancer.

PubMed

Sloan, Jeff A; de Andrade, Mariza; Decker, Paul; Wampfler, Jason; Oswold, Curtis; Clark, Matthew; Yang, Ping

2012-05-10

Recent evidence has suggested a relationship between the baseline quality of life (QOL) self-reported by patients with cancer and genetic disposition. We report an analysis exploring relationships among baseline QOL assessments and candidate genetic variations in a large cohort of patients with lung cancer. QOL data were provided by 1,299 patients with non-small-cell lung cancer observed at the Mayo Clinic between 1997 and 2007. Overall QOL and subdomains were assessed by either Lung Cancer Symptom Scale or Linear Analog Self Assessment measures; scores were transformed to a scale of 0 to 10, with higher scores representing better status. Baseline QOL scores assessed within 1 year of diagnosis were dichotomized as clinically deficient (CD) or not. A total of 470 single nucleotide polymorphisms (SNPs) in 56 genes of three biologic pathways were assessed for association with QOL measures. Logistic regression with training/validation samples was used to test the association of SNPs with CD QOL. Six SNPs on four genes were replicated using our split schemes. Three SNPs in the MGMT gene (adjusted analysis, rs3858300; unadjusted analysis, rs10741191 and rs3852507) from DNA repair pathway were associated with overall QOL. Two SNPs (rs2287396 [GSTZ1] and rs9524885 [ABCC4]) from glutathione metabolic pathway were associated with fatigue in unadjusted analysis. In adjusted analysis, two SNPs (rs2756109 [ABCC2] and rs9524885 [ABCC4]) from glutathione metabolic pathway were associated with pain. We identified three SNPs in three glutathione metabolic pathway genes and three SNPs in two DNA repair pathway genes associated with QOL measures in patients with non-small-cell lung cancer.

Life Satisfaction, Self-Esteem, and Subjective Age in Women across the Life Span

ERIC Educational Resources Information Center

Borzumato-Gainey, Christine; Kennedy, Alison; McCabe, Beth; Degges-White, Suzanne

2009-01-01

A study of 320 women, ages 21 to 69, explored the relations among relationship status, subjective age, self-esteem, and life satisfaction. Women in married or partnered relationships had higher levels of life satisfaction than did single women. Women in their 30s and 40s had significantly lower levels of life satisfaction than did other age…

Span of control matters.

PubMed

Cathcart, Deb; Jeska, Susan; Karnas, Joan; Miller, Sue E; Pechacek, Judy; Rheault, Lolita

2004-09-01

Prompted by manager concerns about span of control, a large, integrated health system set out to determine if span of control really mattered. Was there something to it, or was it just an excuse for poor performance? A team of middle managers studied the problem and ultimately demonstrated a strong relationship between span of control and employee engagement. Consequently, it was decided to add 4 management positions to note the effect. One year later, positive changes were observed in employee engagement scores in all 4 areas. This study suggests careful review of manager spans of control to address the untoward effects of large spans of control on employee engagement.

Angiotensin Converting Enzyme (ACE) Inhibitor Extends Caenorhabditis elegans Life Span

PubMed Central

Kumar, Sandeep; Dietrich, Nicholas; Kornfeld, Kerry

2016-01-01

Animal aging is characterized by progressive, degenerative changes in many organ systems. Because age-related degeneration is a major contributor to disability and death in humans, treatments that delay age-related degeneration are desirable. However, no drugs that delay normal human aging are currently available. To identify drugs that delay age-related degeneration, we used the powerful Caenorhabdtitis elegans model system to screen for FDA-approved drugs that can extend the adult lifespan of worms. Here we show that captopril extended mean lifespan. Captopril is an angiotensin-converting enzyme (ACE) inhibitor used to treat high blood pressure in humans. To explore the mechanism of captopril, we analyzed the acn-1 gene that encodes the C. elegans homolog of ACE. Reducing the activity of acn-1 extended the mean life span. Furthermore, reducing the activity of acn-1 delayed age-related degenerative changes and increased stress resistance, indicating that acn-1 influences aging. Captopril could not further extend the lifespan of animals with reduced acn-1, suggesting they function in the same pathway; we propose that captopril inhibits acn-1 to extend lifespan. To define the relationship with previously characterized longevity pathways, we analyzed mutant animals. The lifespan extension caused by reducing the activity of acn-1 was additive with caloric restriction and mitochondrial insufficiency, and did not require sir-2.1, hsf-1 or rict-1, suggesting that acn-1 functions by a distinct mechanism. The interactions with the insulin/IGF-1 pathway were complex, since the lifespan extensions caused by captopril and reducing acn-1 activity were additive with daf-2 and age-1 but required daf-16. Captopril treatment and reducing acn-1 activity caused similar effects in a wide range of genetic backgrounds, consistent with the model that they act by the same mechanism. These results identify a new drug and a new gene that can extend the lifespan of worms and suggest new

Life Span Studies of ADHD—Conceptual Challenges and Predictors of Persistence and Outcome

PubMed Central

Caye, Arthur; Swanson, James; Thapar, Anita; Sibley, Margaret; Arseneault, Louise; Hechtman, Lily; Arnold, L. Eugene; Niclasen, Janni; Moffitt, Terrie

2018-01-01

There is a renewed interest in better conceptualizing trajectories of attention-deficit/hyperactivity disorder (ADHD) from childhood to adulthood, driven by an increased recognition of long-term impairment and potential persistence beyond childhood and adolescence. This review addresses the following major issues relevant to the course of ADHD in light of current evidence from longitudinal studies: (1) conceptual and methodological issues related to measurement of persistence of ADHD, (2) estimates of persistence rate from childhood to adulthood and its predictors, (3) long-term negative outcomes of childhood ADHD and their early predictors, and (4) the recently proposed new adult-onset ADHD. Estimates of persistence vary widely in the literature, and diagnostic criteria, sample characteristics, and information source are the most important factors explaining variability among studies. Evidence indicates that ADHD severity, comorbid conduct disorder and major depressive disorder, and treatment for ADHD are the main predictors of ADHD persistence from childhood to adulthood. Comorbid conduct disorder and ADHD severity in childhood are the most important predictors of adverse outcomes in adulthood among children with ADHD. Three recent population studies suggested the existence of a significant proportion of individuals who report onset of ADHD symptoms and impairments after childhood. Finally, we highlight areas for improvement to increase our understanding of ADHD across the life span. PMID:27783340

Magnesium Carbonate‐Containing Phosphate Binder Prevents Connective Tissue Mineralization in Abcc6 −/− Mice–Potential for Treatment of Pseudoxanthoma Elasticum

PubMed Central

Li, Qiaoli; LaRusso, Jennifer; Grand‐Pierre, Alix E.; Uitto, Jouni

2009-01-01

Abstract Pseudoxanthoma elasticum (PXE) is a heritable disorder characterized by ectopic mineralization of connective tissues primarily in the skin, eyes, and the cardiovascular system. PXE is caused by mutations in the ABCC6 gene. While PXE is associated with considerable morbidity and mortality, there is currently no effective or specific treatment. In this study, we tested oral phosphate binders for treatment of a mouse model of PXE which we have developed by targeted ablation of the corresponding mouse gene (Abcc6 −/−). This “knock‐out” (KO) mouse model recapitulates features of PXE and demonstrates mineralization of a number of tissues, including the connective tissue capsule surrounding vibrissae in the muzzle skin which serves as an early biomarker of the mineralization process. Treatment of these mice with a magnesium carbonate‐enriched diet (magnesium concentration being 5‐fold higher than in the control diet) completely prevented mineralization of the vibrissae up to 6 months of age, as demonstrated by computerized morphometric analysis of histopathology as well as by calcium and phosphate chemical assays. The magnesium carbonate‐enriched diet also prevented the progression of mineralization when the mice were placed on that experimental diet at 3 months of age and followed up to 6 months of age. Treatment with magnesium carbonate was associated with a slight increase in the serum concentration of magnesium, with no effect on serum calcium and phosphorus levels. In contrast, concentration of calcium in the urine was increased over 10‐fold while the concentration of phosphorus was markedly decreased, being essentially undetectable after long‐term (>4 month) treatment. No significant changes were noted in the serum parathyroid hormone levels. Computerized axial tomography scan of bones in mice placed on magnesium carbonate‐enriched diet showed no differences in the bone density compared to mice on the control diet, and chemical assays

The influence of sensorimotor experience on the aesthetic evaluation of dance across the life span.

PubMed

Kirsch, Louise P; Cross, Emily S

2018-01-01

Understanding how action perception, embodiment, and emotion interact is essential for advancing knowledge about how we perceive and interact with each other in a social world. One tool that has proved particularly useful in the past decade for exploring the relationship between perception, action, and affect is dance. Dance is, in its essence, a rich and multisensory art form that can be used to help answer not only basic questions about social cognition but also questions concerning how aging shapes the relationship between action perception, and the role played by affect, emotion, and aesthetics in social perception. In the present study, we used a 1-week physical and visual dance training paradigm to instill varying degrees of sensorimotor experience among non-dancers from three distinct age groups (early adolescents, young adults, and older adults). Our aim was to begin to build an understanding of how aging influences the relationship between action embodiment and affective (or aesthetic) value, at both brain and behavioral levels. On balance, our results point toward a similar positive effect of sensorimotor training on aesthetic evaluations across the life span on a behavioral level, but to rather different neural substrates supporting implicit aesthetic judgment of dance movements at different life stages. Taken together, the present study contributes valuable first insights into the relationship between sensorimotor experience and affective evaluations across ages, and underscores the utility of dance as a stimulus and training intervention for addressing key questions relevant to human neuroscience as well as the arts and humanities. © 2018 Elsevier B.V. All rights reserved.

Age-Related Cognitive Effects of Videogame Playing Across the Adult Life span.

PubMed

Wang, Ping; Zhu, Xing-Ting; Liu, Han-Hui; Zhang, Yi-Wen; Hu, Yang; Li, Hui-Jie; Zuo, Xi-Nian

2017-08-01

Previous studies found positive influences of videogame playing on cognition. However, the age-related and task-related effects of videogame experience across the adult life span are still unknown. The current study aimed to systematically investigate this question. The current study used the cross-sectional approach. A total of 166 participants (84 videogame players [VGPs], 82 nonvideogame players [NVGPs]) at the age of 18-80 in the present study were recruited, including 62 young adults aged from 18 to 34 (35 VGPs, 27 NVGPs), 55 middle-aged adults aged between 35 and 59 (24 VGPs, 31 NVGPs), and 49 older adults aged between 60 and 80 (25 VGPs, 24 NVGPs). 1,2 A series of neuropsychological tests from different cognitive domains, including processing speed, visuospatial, attention, memory, and executive function, were conducted on participants. The age-related effects demonstrated that young and older adults benefited more from videogame experience than middle-aged adults. The task-related effects showed that VGPs benefited more from videogame experience in processing speed and visuospatial processing; next was executive function and attention, while no benefits in memory. The effect sizes suggested that the difference in extent between VGPs and NVGPs in processing speed and visuospatial processing is moderate, in attention and executive function is small, and in memory is negligible. The current findings support the beneficial effects and transfer effects of videogame experience; however, the effects presented age-specific and task-specific characteristics. The results provide useful insights for future videogame intervention studies for healthy adults of different ages.

Missing Doses in the Life Span Study of Japanese Atomic Bomb Survivors

PubMed Central

Richardson, David B.; Wing, Steve; Cole, Stephen R.

2013-01-01

The Life Span Study of atomic bomb survivors is an important source of risk estimates used to inform radiation protection and compensation. Interviews with survivors in the 1950s and 1960s provided information needed to estimate radiation doses for survivors proximal to ground zero. Because of a lack of interview or the complexity of shielding, doses are missing for 7,058 of the 68,119 proximal survivors. Recent analyses excluded people with missing doses, and despite the protracted collection of interview information necessary to estimate some survivors' doses, defined start of follow-up as October 1, 1950, for everyone. We describe the prevalence of missing doses and its association with mortality, distance from hypocenter, city, age, and sex. Missing doses were more common among Nagasaki residents than among Hiroshima residents (prevalence ratio = 2.05; 95% confidence interval: 1.96, 2.14), among people who were closer to ground zero than among those who were far from it, among people who were younger at enrollment than among those who were older, and among males than among females (prevalence ratio = 1.22; 95% confidence interval: 1.17, 1.28). Missing dose was associated with all-cancer and leukemia mortality, particularly during the first years of follow-up (all-cancer rate ratio = 2.16, 95% confidence interval: 1.51, 3.08; and leukemia rate ratio = 4.28, 95% confidence interval: 1.72, 10.67). Accounting for missing dose and late entry should reduce bias in estimated dose-mortality associations. PMID:23429722

Individual Differences in Behavioral and Electrophysiological Measures of Binaural Processing Across the Adult Life Span.

PubMed

Roup, Christina M; Leigh, Elizabeth D

2015-06-01

The purpose of the present study was to examine individual differences in binaural processing across the adult life span. Sixty listeners (aged 23-80 years) with symmetrical hearing were tested. Binaural behavioral processing was measured by the Words-in-Noise Test, the 500-Hz masking level difference, and the Dichotic Digit Test. Electrophysiologic responses were assessed by the auditory middle latency response binaural interaction component. No correlations among binaural measures were found. Age accounted for the greatest amount of variability in speech-in-noise performance. Age was significantly correlated with the Words-in-Noise Test binaural advantage and dichotic ear advantage. Partial correlations, however, revealed that this was an effect of hearing status rather than age per se. Inspection of individual results revealed that 20% of listeners demonstrated reduced binaural performance for at least 2 of the binaural measures. The lack of significant correlations among variables suggests that each is an important measurement of binaural abilities. For some listeners, binaural processing was abnormal, reflecting a binaural processing deficit not identified by monaural audiologic tests. The inclusion of a binaural test battery in the audiologic evaluation is supported given that these listeners may benefit from alternative forms of audiologic rehabilitation.

Replication of KCNJ11 (p.E23K) and ABCC8 (p.S1369A) Association in Russian Diabetes Mellitus 2 Type Cohort and Meta-Analysis

PubMed Central

Sokolova, Ekaterina Alekseevna; Bondar, Irina Arkadievna; Shabelnikova, Olesya Yurievna; Pyankova, Olga Vladimirovna; Filipenko, Maxim Leonidovich

2015-01-01

The genes ABCC8 and KCNJ11 have received intense focus in type 2 diabetes mellitus (T2DM) research over the past two decades. It has been hypothesized that the p.E23K (KCNJ11) mutation in the 11p15.1 region may play an important role in the development of T2DM. In 2009, Hamming et al. found that the p.1369A (ABCC8) variant may be a causal factor in the disease; therefore, in this study we performed a meta-analysis to evaluate the association between these single nucleotide polymorphisms (SNPs), including our original data on the Siberian population (1384 T2DM and 414 controls). We found rs5219 and rs757110 were not associated with T2DM in this population, and that there was linkage disequilibrium in Siberians (D’=0.766, r2= 0.5633). In addition, the haplotype rs757110[T]-rs5219[C] (p.23K/p.S1369) was associated with T2DM (OR = 1.52, 95% CI: 1.04-2.24). We included 44 original studies published by June 2014 in a meta-analysis of the p.E23K association with T2DM. The total OR was 1.14 (95% CI: 1.11-1.17) for p.E23K for a total sample size of 137,298. For p.S1369A, a meta-analysis was conducted on a total of 10 studies with a total sample size of 14,136 and pooled OR of 1.14 [95% CI (1.08-1.19); p = 2 x 10-6]. Our calculations identified causal genetic variation within the ABCC8/KCNJ11 region for T2DM with an OR of approximately 1.15 in Caucasians and Asians. Moreover, the OR value was not dependent on the frequency of p.E23K or p.S1369A in the populations. PMID:25955821

Evolution of the antigen-specific CD8+ TCR repertoire across the life span: evidence for clonal homogenization of the old TCR repertoire.

PubMed

Rudd, Brian D; Venturi, Vanessa; Davenport, Miles P; Nikolich-Zugich, Janko

2011-02-15

Defects in T cell responses against pathogens and reduced diversity of TCRs have been described at both extremes of the life span. Yet, we still lack information on how Ag-specific T cell populations are maintained and/or altered from birth to old age. In this study, for the first time to our knowledge, we provide insight into Ag-specific TCR repertoire changes over the life span at the single-cell level. We have examined the TCR diversity of the primary CD8(+) T cell response to the immunodominant HSV-1 epitope HSV glycoprotein B 495-502 (HSV gB(498-505); SSIEFARL) (gB-8p) in neonatal, adult, and old C57BL/6 mice. The global distinctive features of the gB-8p-specific TCR repertoire were preserved in mice of different ages. However, both old and especially neonatal mice exhibited significant decreases in TCR diversity compared with that of adult mice. Still, although the neonatal Ag-specific repertoire comprised expectedly shorter germline-biased CDR3β lengths, the repertoire was surprisingly complex, and only a minority of responding cells lacked random nucleotide additions. Changes with aging included increased use of the already dominant TCRVβ10 family, a trend for lower content of the TCR containing the germline WG motif in the CDR3, and a remarkable sharing of one dominant clonotype between individual old mice, implying operation of selective mechanisms. Implications for the rational design of vaccines for neonates and the elderly are discussed.

What Were They Thinking? Reducing Sunk-Cost Bias in a Life-Span Sample

PubMed Central

Strough, JoNell; Bruine de Bruin, Wändi; Parker, Andrew M.; Karns, Tara; Lemaster, Philip; Pichayayothin, Nipat; Delaney, Rebecca; Stoiko, Rachel

2016-01-01

We tested interventions to reduce “sunk-cost bias,” the tendency to continue investing in failing plans even when those plans have soured and are no longer rewarding. We showed members of a national U.S. life-span panel a hypothetical scenario about a failing plan that was halfway complete. Participants were randomly assigned to an intervention to focus on how to improve the situation, an intervention to focus on thoughts and feelings, or a no-intervention control group. First, we found that the thoughts and feelings intervention reduced sunk-cost bias in decisions about project completion, as compared to the improvement intervention and the no-intervention control. Second, older age was associated with greater willingness to cancel the failing plan across all three groups. Third, we found that introspection processes helped to explain the effectiveness of the interventions. Specifically, the larger reduction in sunk-cost bias as observed in the thoughts and feelings intervention (vs. the improvement intervention) was associated with suppression of future-oriented thoughts of eventual success, and with suppression of augmentations of the scenario that could make it seem reasonable to continue the plan. Fourth, we found that introspection processes were related to age differences in decisions. Older people were less likely to mention future-oriented thoughts of eventual success associated with greater willingness to continue the failing plan. We discuss factors to consider when designing interventions for reducing sunk-cost bias. PMID:27831712

The EPIYA-ABCC motif pattern in CagA of Helicobacter pylori is associated with peptic ulcer and gastric cancer in Mexican population.

PubMed

Beltrán-Anaya, Fredy Omar; Poblete, Tomás Manuel; Román-Román, Adolfo; Reyes, Salomón; de Sampedro, José; Peralta-Zaragoza, Oscar; Rodríguez, Miguel Ángel; del Moral-Hernández, Oscar; Illades-Aguiar, Berenice; Fernández-Tilapa, Gloria

2014-12-24

Helicobacter pylori chronic infection is associated with chronic gastritis, peptic ulcer, and gastric cancer. Cytotoxin-associated gene A (cagA)-positive H. pylori strains increase the risk of gastric pathology. The carcinogenic potential of CagA is linked to its polymorphic EPIYA motif variants. The goals of this study were to investigate the frequency of cagA-positive Helicobacter pylori in Mexican patients with gastric pathologies and to assess the association of cagA EPIYA motif patterns with peptic ulcer and gastric cancer. A total of 499 patients were studied; of these, 402 had chronic gastritis, 77 had peptic ulcer, and 20 had gastric cancer. H. pylori DNA, cagA, and the EPIYA motifs were detected in total DNA from gastric biopsies by PCR. The type and number of EPIYA segments were determined by the electrophoretic patterns. To confirm the PCR results, 20 amplicons of the cagA 3' variable region were sequenced, and analyzed in silico, and the amino acid sequence was predicted with MEGA software, version 5. The odds ratio (OR) was calculated to determine the associations between the EPIYA motif type and gastric pathology and between the number of EPIYA-C segments and peptic ulcers and gastric cancer. H. pylori DNA was found in 287 (57.5%) of the 499 patients, and 214 (74%) of these patients were cagA-positive. The frequency of cagA-positive H. pylori was 74.6% (164/220) in chronic gastritis patients, 73.6% (39/53) in peptic ulcer patients, and 78.6% (11/14) in gastric cancer patients. The EPIYA-ABC pattern was more frequently observed in chronic gastritis patients (79.3%, 130/164), while the EPIYA-ABCC sequence was more frequently observed in peptic ulcer (64.1%, 25/39) and gastric cancer patients (54.5%, 6/11). However, the risks of peptic ulcer (OR = 7.0, 95% CI = 3.3-15.1; p < 0.001) and gastric cancer (OR = 5.9, 95% CI = 1.5-22.1) were significantly increased in individuals who harbored the EPIYA-ABCC cagA gene pattern. cagA-positive H

SPAN: Astronomy and astrophysics

NASA Technical Reports Server (NTRS)

Thomas, Valerie L.; Green, James L.; Warren, Wayne H., Jr.; Lopez-Swafford, Brian

1987-01-01

The Space Physics Analysis Network (SPAN) is a multi-mission, correlative data comparison network which links science research and data analysis computers in the U.S., Canada, and Europe. The purpose of this document is to provide Astronomy and Astrophysics scientists, currently reachable on SPAN, with basic information and contacts for access to correlative data bases, star catalogs, and other astrophysic facilities accessible over SPAN.

Age-related patterns in social networks among European Americans and African Americans: implications for socioemotional selectivity across the life span.

PubMed

Fung, H H; Carstensen, L L; Lang, F R

2001-01-01

Socioemotional selectivity theory contends that as people become increasingly aware of limitations on future time, they are increasingly motivated to be more selective in their choice of social partners, favoring emotionally meaningful relationships over peripheral ones. The theory hypothesizes that because age is negatively associated with time left in life, the social networks of older people contain fewer peripheral social partners than those of their younger counterparts. This study tested the hypothesis among African Americans and European Americans, two ethnic groups whose social structural resources differ. Findings confirm the hypothesis. Across a wide age range (18 to 94 years old) and among both ethnic groups, older people report as many emotionally close social partners but fewer peripheral social partners in their networks as compared to their younger counterparts. Moreover, a greater percentage of very close social partners in social networks is related to lower levels of happiness among the young age group, but not among the older age groups. Implications of findings for adaptive social functioning across the life span are discussed.

Factor validity and reliability of the aberrant behavior checklist-community (ABC-C) in an Indian population with intellectual disability.

PubMed

Lehotkay, R; Saraswathi Devi, T; Raju, M V R; Bada, P K; Nuti, S; Kempf, N; Carminati, G Galli

2015-03-01

In this study realised in collaboration with the department of psychology and parapsychology of Andhra University, validation of the Aberrant Behavior Checklist-Community (ABC-C) in Telugu, the official language of Andhra Pradesh, one of India's 28 states, was carried out. To assess the factor validity and reliability of this Telugu version, 120 participants with moderate to profound intellectual disability (94 men and 26 women, mean age 25.2, SD 7.1) were rated by the staff of the Lebenshilfe Institution for Mentally Handicapped in Visakhapatnam, Andhra Pradesh, India. Rating data were analysed with a confirmatory factor analysis. The internal consistency was estimated by Cronbach's alpha. To confirm the test-retest reliability, 50 participants were rated twice with an interval of 4 weeks, and 50 were rated by pairs of raters to assess inter-rater reliability. Confirmatory factor analysis revealed that the root mean square error of approximation (RMSEA) was equal to 0.06, the comparative fit index (CFI) was equal to 0.77, and the Tucker Lewis index (TLI) was equal to 0.77, which indicated that the model with five correlated factors had a good fit. Coefficient alpha ranged from 0.85 to 0.92 across the five subscales. Spearman's rank correlation coefficients for inter-rater reliability tests ranged from 0.65 to 0.75, and the correlations for test-retest reliability ranged from 0.58 to 0.76. All reliability coefficients were statistically significant (P < 0.01). The factor validity and reliability of Telugu version of the ABC-C evidenced factor validity and reliability comparable to the original English version and appears to be useful for assessing behaviour disorders in Indian people with intellectual disabilities. © 2014 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Lipopolysaccharide-induced inflammation attenuates taste progenitor cell proliferation and shortens the life span of taste bud cells.

PubMed

Cohn, Zachary J; Kim, Agnes; Huang, Liquan; Brand, Joseph; Wang, Hong

2010-06-10

The mammalian taste bud, a complex collection of taste sensory cells, supporting cells, and immature basal cells, is the structural unit for detecting taste stimuli in the oral cavity. Even though the cells of the taste bud undergo constant turnover, the structural homeostasis of the bud is maintained by balancing cell proliferation and cell death. Compared with nongustatory lingual epithelial cells, taste cells express higher levels of several inflammatory receptors and signalling proteins. Whether inflammation, an underlying condition in some diseases associated with taste disorders, interferes with taste cell renewal and turnover is unknown. Here we report the effects of lipopolysaccharide (LPS)-induced inflammation on taste progenitor cell proliferation and taste bud cell turnover in mouse taste tissues. Intraperitoneal injection of LPS rapidly induced expression of several inflammatory cytokines, including tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and interleukin (IL)-6, in mouse circumvallate and foliate papillae. TNF-alpha and IFN-gamma immunoreactivities were preferentially localized to subsets of cells in taste buds. LPS-induced inflammation significantly reduced the number of 5-bromo-2'-deoxyuridine (BrdU)-labeled newborn taste bud cells 1-3 days after LPS injection, suggesting an inhibition of taste bud cell renewal. BrdU pulse-chase experiments showed that BrdU-labeled taste cells had a shorter average life span in LPS-treated mice than in controls. To investigate whether LPS inhibits taste cell renewal by suppressing taste progenitor cell proliferation, we studied the expression of Ki67, a cell proliferation marker. Quantitative real-time RT-PCR revealed that LPS markedly reduced Ki67 mRNA levels in circumvallate and foliate epithelia. Immunofluorescent staining using anti-Ki67 antibodies showed that LPS decreased the number of Ki67-positive cells in the basal regions surrounding circumvallate taste buds, the niche for taste progenitor

Changing the Culture of Academic Medicine to Eliminate the Gender Leadership Gap: 50/50 by 2020

PubMed Central

Valantine, Hannah; Sandborg, Christy I.

2013-01-01

Central to the daily struggles that successful working women face is the misalignment of the current work culture and the values of the workforce. In addition to contributing to work-life integration conflicts, this disconnect also perpetuates the gender leadership gap. The dearth of women at the highest ranks of academic medicine not only sends a clear message to women that they must choose between career advancement and their personal life but also represents a loss of talent for academic health centers as they fail to recruit and retain the best and the brightest. To close the gender leadership gap and to meet the needs of the next generation of physicians, scientists, and educators, the authors argue that the culture of academic medicine must change to one in which flexibility and work-life integration are core parts of the definition of success. Faculty must see flexibility policies, such as tenure clock extensions and parental leaves, as career advancing rather than career limiting. To achieve these goals, the authors describe the Stanford University School of Medicine Academic Biomedical Career Customization (ABCC) model. The ABCC framework includes individualized career plans, which span a faculty member's career, with options to flex up or down in research, patient care, administration, and teaching, and mentoring discussions, which ensure that faculty take full advantage of the existing policies designed to make career customization possible. The authors argue that with vision, determination, and focus, the academic medicine community can eliminate the gender leadership gap to achieve 50/50 by 2020. PMID:23969359

Balancing Life Roles to Achieve Career Happiness and Life Satisfaction.

ERIC Educational Resources Information Center

Peronne, Kristin Marie

2000-01-01

A study guided by Super's Life Span, Life Space approach included a survey of 119 women and 66 men about sacrifices made in life and work roles to achieve balance and satisfaction. Differences in sacrifices and satisfaction were related to the combination of life roles they occupied. (SK)

Pre-Bombing Population Density in Hiroshima and Nagasaki: Its Measurement and Impact on Radiation Risk Estimates in the Life Span Study of Atomic Bomb Survivors.

PubMed

French, Benjamin; Funamoto, Sachiyo; Sugiyama, Hiromi; Sakata, Ritsu; Cologne, John; Cullings, Harry M; Mabuchi, Kiyohiko; Preston, Dale L

2018-03-29

In the Life Span Study of atomic bomb survivors, differences in urbanicity between high-dose and low-dose survivors could confound the association between radiation dose and adverse outcomes. We obtained data on the pre-bombing population distribution in Hiroshima and Nagasaki, and quantified the impact of adjustment for population density on radiation risk estimates for mortality (1950-2003) and incident solid cancer (1958-2009). Population density ranged from 4,671-14,378 and 5,748-19,149 people/km2 in urban regions of Hiroshima and Nagasaki, respectively. Radiation risk estimates for solid cancer mortality were attenuated by 5.1%, but those for all-cause mortality and incident solid cancer were unchanged. There was no overall association between population density and adverse outcomes, but there was evidence that the association between density and mortality differed by age at exposure. Among survivors 10-14 years old in 1945, there was a positive association between population density and risk of all-cause mortality (relative risk, 1.053 per 5,000 people/km2 increase, 95% confidence interval: 1.027, 1.079) and solid cancer mortality (relative risk, 1.069 per 5,000 people/km2 increase, 95% confidence interval: 1.025, 1.115). Our results suggest that radiation risk estimates from the Life Span Study are not sensitive to unmeasured confounding by urban-rural differences.

Physical independence and mortality at the extreme limit of life span: supercentenarians study in Japan.

PubMed

Arai, Yasumichi; Inagaki, Hiroki; Takayama, Michiyo; Abe, Yukiko; Saito, Yasuhiko; Takebayashi, Toru; Gondo, Yasuyuki; Hirose, Nobuyoshi

2014-04-01

Prevention of disability is a major challenge in aging populations; however, the extent to which physical independence can be maintained toward the limit of human life span remains to be determined. We examined the health and functional status of 642 centenarians: 207 younger centenarians (age: 100-104 years), 351 semi-supercentenarians (age: 105-109 years), and 84 supercentenarians (age: >110 years). All-cause mortality was followed by means of an annual telephone or mailed survey. Age-specific disability patterns revealed that the older the age group, the higher the proportion of those manifesting independence in activities of daily living at any given age of entry. Multiple logistic regression analysis identified male gender and better cognitive function as consistent determinants of physical independence across all age categories. In a longitudinal analysis, better physical function was significantly associated with survival advantage until the age of 110. However, mortality beyond that age was predicted neither by functional status nor biomedical measurements, indicating alternative trajectories of mortality at the highest ages. These findings suggest that maintaining physical independence is a key feature of survival into extreme old age. Future studies illuminating genetic and environmental underpinnings of supercentenarians' phenotypes will provide invaluable opportunities not only to improve preventive strategies but also to test the central hypotheses of human aging.

Connective Tissue Mineralization in Abcc6−/− Mice, a Model for Pseudoxanthoma Elasticum

PubMed Central

Kavukcuoglu, N. Beril; Li, Qiaoli; Pleshko, Nancy; Uitto, Jouni

2012-01-01

Pseudoxanthoma elasticum (PXE) is a heritable multisystem disorder characterized by ectopic mineralization. However, the structure of the mineral deposits, their interactions with the connective tissue matrix, and the details of the progressive maturation of the mineral crystals are currently unknown. In this study, we examined the mineralization processes in Abcc6−/− mice, a model system for PXE, by energy dispersive X-ray, and Fourier transform infrared imaging spectroscopy (FT-IRIS). The results indicated that the principal components of the mineral deposits were calcium and phosphate which co-localized within the histologically demonstrable lesions determined by topographic mapping. The Ca/P ratio increased in samples with progressive mineralization reaching the value comparable to that in endochondral bone. A progressive increase in mineralization was also reflected by increased mineral-to-matrix ratio determined by FT-IRIS. Determination of the mineral phases by FT-IRIS suggested progressive maturation of the mineral deposits from amorphous calcium phosphate to hydroxyapatite. These results provide critical information of the mechanisms of mineralization in PXE, with potential pharmacologic implications. PMID:22421595

The Chinese Herb Jianpijiedu Contributes to the Regulation of OATP1B2 and ABCC2 in a Rat Model of Orthotopic Transplantation Liver Cancer Pretreated with Food Restriction and Diarrhea

PubMed Central

Sun, Baoguo; Chen, Yan; Xiang, Ting; Zhang, Lei; Chen, Zexiong; Zhang, Shijun; Zhou, Houming; Chen, Shuqing

2015-01-01

Traditional Chinese Medicine Jianpijiedu decoction (JPJD) could improve the general status of liver cancer patients in clinics, especially the symptoms of decreased food intake and diarrhea. In this study, our results showed that the survival rate of the liver cancer with food restriction and diarrhea (FRD-LC) rats was lower than the liver cancer (LC) rats, and the tumor volume of the FRD-LC rats was higher than the LC rats. It was also shown that the high dose of JPJD significantly improved the survival rate, weight, and organ weight when compared with FRD-LC-induced rats. Moreover, JPJD administration upregulated the mRNA and protein levels of ABCC2 and downregulated the mRNA and protein levels of OATP1B2 in liver tissues. However, opposite results were observed in the cancer tissues. In conclusion, the study indicated that the Chinese Medicine JPJD could contribute to the rats with liver cancer which were pretreated with food restriction and diarrhea by regulating the expression of ABCC2 and OATP1B2 in liver tissues and cancer tissues. PMID:26665149

Life span prediction from the rate of age-related DNA demethylation in normal and cancer cell lines.

PubMed

Mazin, A L

1995-01-01

A method has been proposed for the Hayflick Limit prediction by the analysis of the 5-methylcytosine content in DNA at earlier and later cell passages. The following facts were used as the basis of the method: (i) the rate of m5C loss from DNA remains approximately constant during cell divisions and it does not depend on the cell donor age; (ii) this rate is inversely proportional to the Hayflick Limit as well as to the life span of cell donor species; (iii) the period corresponded to loss of all m5C residues from the genome coincides with or somewhat exceeds the Hayflick Limit of normal cells. The prognosis of the Hayflick Limit has usually been found in good agreement with the experimental evidences for various human, hamster, and mouse cell lines. The method proposed may be used for early detection of precrisis and cancer cells. The age-related m5C loss may result from accumulation of the m5C-->T+C transitions occurring with DNA methylation in every cell division.

An Integrated Socio-Environmental Model of Health and Well-Being: a Conceptual Framework Exploring the Joint Contribution of Environmental and Social Exposures to Health and Disease Over the Life Span.

PubMed

Olvera Alvarez, Hector A; Appleton, Allison A; Fuller, Christina H; Belcourt, Annie; Kubzansky, Laura D

2018-06-01

Environmental and social determinants of health often co-occur, particularly among socially disadvantaged populations, yet because they are usually studied separately, their joint effects on health are likely underestimated. Building on converging bodies of literature, we delineate a conceptual framework to address these issues. Previous models provided a foundation for study in this area, and generated research pointing to additional important issues. These include a stronger focus on biobehavioral pathways, both positive and adverse health outcomes, and intergenerational effects. To accommodate the expanded set of issues, we put forward the Integrated Socio-Environmental Model of Health and Well-Being (ISEM), which examines how social and environmental factors combine and potentially interact, via multi-factorial pathways, to affect health and well-being over the life span. We then provide applied examples including the study of how food environments affect dietary behavior. The ISEM provides a comprehensive, theoretically informed framework to guide future research on the joint contribution of social and environmental factors to health and well-being across the life span.

C-SPAN Networks: Professors' Guide.

ERIC Educational Resources Information Center

C-SPAN in the Classroom, 1993

1993-01-01

The intention of this guide is to serve as a forum for college faculty members to share ideas and articles about using C-SPAN programming in college classrooms and in academic research. The first article, "C-SPAN as a 'Lecture Launcher'" (Stephen Frantzich) illustrates how well-chosen segments of C-SPAN programming can be used to…

The Household School as Life-Span Learning Center.

ERIC Educational Resources Information Center

Warnat, Winifred I.

A constructive, effective, and realistic national educational policy should be established which takes into account the contributions of the household school to individual learning in areas of life roles, feelings, values formation, and behavior development. The adversary relationship between formal educational institutions and the family will be…

Exploring the dimensionality of digit span.

PubMed

Bowden, Stephen C; Petrauskas, Vilija M; Bardenhagen, Fiona J; Meade, Catherine E; Simpson, Leonie C

2013-04-01

The Digit Span subtest from the Wechsler Scales is used to measure Freedom from Distractibility or Working Memory. Some published research suggests that Digit Span forward should be interpreted differently from Digit Span backward. The present study explored the dimensionality of the Wechsler Memory Scale-III Digit Span (forward and backward) items in a sample of heterogeneous neuroscience patients (n = 267) using confirmatory factor analysis (CFA) for dichotomous items. Results suggested that four correlated factors underlie Digit Span, reflecting easy and hard items in both forward and backward presentation orders. The model for Digit Span was then cross-validated in a seizure disorders sample (n = 223) by replication of the CFA and by examination of measurement invariance. Measurement invariance tests of the precise numerical generalization of trait estimation across groups. Results supported measurement invariance and it was concluded that forward and backward digit span scores should be interpreted as measures of the same cognitive ability.

The influence of the hot water extract from shiitake medicinal mushroom, Lentinus edodes (higher Basidiomycetes) on the food intake, life span, and age-related locomotor activity of Drosophila melanogaster.

PubMed

Matjuskova, Natalya; Azena, Elena; Serstnova, Ksenija; Muiznieks, Indrikis

2014-01-01

Shiitake medicinal mushroom, Lentinus edodes, is among the most widely cultivated edible mushrooms in the world and is a well-studied source of nutrients and biologically active compounds. We have studied the influence of the dietary supplement of the polysaccharides containing a hot water extract of the mushroom L. edodes on the fruit fly Drosophila melanogaster in terms of food intake, body weight, life span, and age-related locomotor activity. L. edodes extract, when added to the D. melanogaster feeding substrate at a 0.003-0.030% concentration (calculated for the dry weight of the polysaccharide fraction) did not influence food intake or body weight of the flies. It increased the life span and locomotor activities of male flies but was associated with early mortality and decreased locomotor activity of female flies. We conclude that the observed anti-aging effects of L. edodes extracts in the male D. melanogaster are not the result of dietary restriction. We propose that D. melanogaster is a suitable model organism for researching the molecular basis of the anti-aging effect of the shiitake mushroom extracts and sex linkage of these effects.

Sex Role Orientation Across the Adult Life Span.

ERIC Educational Resources Information Center

Zaks, Peggy M.; And Others

It was hypothesized that four different "life lines" would affect sex role orientations, specifically intimacy, parenting, grandparenting, and work. Subjects were 74 men and 43 women, white, upper middle class with a mean education level of 14 years. Each participant completed a demographic questionnaire, the Bem Sex Role Inventory, a…

Meaning and Purpose in Life across the Life Span: A Cross-Sectional Multivariate Analysis.

ERIC Educational Resources Information Center

Reker, Gary T.; And Others

This paper explores the developmental changes in meaning and purpose across the life course. Thirty males and females at the developmental stages of young adulthood (16-29 years), early middle-age (30-49 years), late middle-age (50-64 years), young-old (65-74 years) and old-old (75+ years) completed the Reker and Peacock (1981) Life Attitude…

Phytoseiid mites in protected crops: the effect of humidity and food availability on egg hatch and adult life span of Iphiseius degenerans, Neoseiulus cucumeris, N. californicus and Phytoseiulus persimilis (Acari: Phytoseiidae).

PubMed

De Courcy Williams, Michael E; Kravar-Garde, Lidija; Fenlon, John S; Sunderland, Keith D

2004-01-01

The effect of relative humidity on egg hatch success for Iphiseius degenerans, Neoseiulus californicus and N. cucumeris was described by a binomial model with a parallel slope. The shape of the response differed for Phytoseiulus persimilis and a model with separate parameters gave a significantly better fit. Fitted response curves showed that I. degenerans, N. cucumeris, N. californicus and P. persimilis were ranked by decreasing tolerance to low humidity, with egg mortalities of < 0.5, 3, 12 and 16% respectively at 75-80% RH at 20 degrees C. Egg stage duration for I. degenerans and N. cucumeris was unaffected over the range 60-82% RH. For N. californicus and P. persimilis egg duration was significantly longer at 60 and 70% than for either 82 or 90% RH. No effect of relative humidity was found on the mean life span of adult females when food was available continuously to the mites. N. californicus lived significantly longer (58 days after the first egg was laid) than the other species. No significant difference was observed in mean life span between adult females of I. degenerans and N. cucumeris (25 and 28 days respectively). The mean life span of adult female P. persimilis (19 days) was significantly shorter than the other species. In the absence of both food and water, the survival of adult female mites was reduced to 2-4 days. Survival time was at least doubled when free water was available in the absence of food. Mean survival of adult female mites with water but without food was 10 days for N. cucumeris, 18 days for N. californicus, 6 days for P. persimilis and 4 days for I. degenerans. Survival of adult female N. cucumeris and N. californicus was increased significantly, to 20 and 22 days respectively, when fungal hyphae were present along with water but in the absence of other food.

All about Animal Life Cycles. Animal Life for Children. [Videotape].

ERIC Educational Resources Information Center

2000

While watching the development from tadpole to frog, caterpillar to butterfly, and pup to wolf, children learn about the life cycles of animals, the different stages of development, and the average life spans of a variety of creatures. This videotape correlates to the following National Science Education Standards for Life Science: characteristics…

Implications of Extreme Life Span in Clonal Organisms: Millenary Clones in Meadows of the Threatened Seagrass Posidonia oceanica

PubMed Central

Arnaud-Haond, Sophie; Duarte, Carlos M.; Diaz-Almela, Elena; Marbà, Núria; Sintes, Tomas; Serrão, Ester A.

2012-01-01

The maximum size and age that clonal organisms can reach remains poorly known, although we do know that the largest natural clones can extend over hundreds or thousands of metres and potentially live for centuries. We made a review of findings to date, which reveal that the maximum clone age and size estimates reported in the literature are typically limited by the scale of sampling, and may grossly underestimate the maximum age and size of clonal organisms. A case study presented here shows the occurrence of clones of slow-growing marine angiosperm Posidonia oceanica at spatial scales ranging from metres to hundreds of kilometres, using microsatellites on 1544 sampling units from a total of 40 locations across the Mediterranean Sea. This analysis revealed the presence, with a prevalence of 3.5 to 8.9%, of very large clones spreading over one to several (up to 15) kilometres at the different locations. Using estimates from field studies and models of the clonal growth of P. oceanica, we estimated these large clones to be hundreds to thousands of years old, suggesting the evolution of general purpose genotypes with large phenotypic plasticity in this species. These results, obtained combining genetics, demography and model-based calculations, question present knowledge and understanding of the spreading capacity and life span of plant clones. These findings call for further research on these life history traits associated with clonality, considering their possible ecological and evolutionary implications. PMID:22312426

Ageless and Timeless: Perspectives on Giftedness across the Life Span

ERIC Educational Resources Information Center

Fiedler, Ellen D.

2016-01-01

Annemarie Roeper's timeless perspectives were demonstrated throughout her long and productive life. Her prolific writings and speeches continue to influence our understanding of giftedness at all ages and stages of life, and the time I spent with her had a profound and meaningful effect on my work. Annemarie incorporated her inner view of…

Life and Self Meaning: The Process of Their Creation.

ERIC Educational Resources Information Center

Weenolsen, Patricia

Research has not addressed issues of life meaning in a life-span developmental framework. The Loss and Transcendence paradigm was developed as a humanistic-existential approach to life-span development which has as its central theme the concept that individuals are in a continuous process of creating their lives and their selves. To explore loss…

Full Scale Span Load Distribution on a Tapered Wing with Split Flaps of Various Spans

NASA Technical Reports Server (NTRS)

Parsons, John F; Silverstein, Abe

1937-01-01

Pressure-distribution tests were conducted in the full-scale wind tunnel on a 2:1 tapered U.S.A. 45 airfoil equipped with 20 percent chord split trailing-edge flaps of various spans. A special installation was employed in the tests utilizing a half-span airfoil mounted vertically above a reflection plane. The airfoil has a constant chord center section and rounded tips and is tapered in thickness from 18 percent c at the root to 9 percent c at the tip. The aerodynamic characteristics, given by the usual dimension less coefficients, are presented graphically as functions of flap span and angle of attack as well as by semispan load diagrams. The results indicate, in general, that only a relatively small increase in the normal-force coefficient is to be expected by extending the flap span of an airfoil-flap combination, similar to the one tested, beyond 70 percent of the wing span.

Reading Ability and Memory Span: Long-Term Memory Contributions to Span for Good and Poor Readers.

ERIC Educational Resources Information Center

McDougall, Sine J. P.; Donohoe, Rachael

2002-01-01

Investigates the extent to which differences in memory span for good and poor readers can be explained by differences in a long-term memory component to span as well as by differences in short-term memory processes. Discusses the nature of the interrelationships between memory span, reading and measures of phonological awareness. (SG)

Multimodal neuroimaging of male and female brain structure in health and disease across the life span

PubMed Central

Thompson, Paul M.

2016-01-01

Sex differences in brain development and aging are important to identify, as they may help to understand risk factors and outcomes in brain disorders that are more prevalent in one sex compared with the other. Brain imaging techniques have advanced rapidly in recent years, yielding detailed structural and functional maps of the living brain. Even so, studies are often limited in sample size, and inconsistent findings emerge, one example being varying findings regarding sex differences in the size of the corpus callosum. More recently, large‐scale neuroimaging consortia such as the Enhancing Neuro Imaging Genetics through Meta Analysis Consortium have formed, pooling together expertise, data, and resources from hundreds of institutions around the world to ensure adequate power and reproducibility. These initiatives are helping us to better understand how brain structure is affected by development, disease, and potential modulators of these effects, including sex. This review highlights some established and disputed sex differences in brain structure across the life span, as well as pitfalls related to interpreting sex differences in health and disease. We also describe sex‐related findings from the ENIGMA consortium, and ongoing efforts to better understand sex differences in brain circuitry. © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc. PMID:27870421

Effect of rosmarinic acid in motor dysfunction and life span in a mouse model of familial amyotrophic lateral sclerosis.

PubMed

Shimojo, Yosuke; Kosaka, Kunio; Noda, Yoshihiro; Shimizu, Takahiko; Shirasawa, Takuji

2010-03-01

Amyotrophic lateral sclerosis (ALS) is a late-onset progressive neurodegenerative disease affecting motor neurons. About 2% of patients with the disease are associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). The purpose of this study is to assess the effect of rosemary extract and its major constituents, rosmarinic acid (RA) and carnosic acid (CA), in human SOD1 G93A transgenic mice, which are well-established mouse models for ALS. The present study demonstrates that intraperitoneal administration of rosemary extract or RA from the presymptomatic stage significantly delayed motor dysfunction in paw grip endurance tests, attenuated the degeneration of motor neurons, and extended the life span of ALS model mice. In addition, RA administration significantly improved the clinical score and suppressed body weight loss compared with a vehicle-treated group. In conclusion, this study provides the first report that rosemary extract and, especially, RA have preventive effects in the mouse model of ALS.

Low-speed aerodynamic performance of an aspect-ratio-10 supercritical-wing transport model equipped with a full-span slat and part-span and full-span double-slotted flaps

NASA Technical Reports Server (NTRS)

Morgan, H. L., Jr.

1981-01-01

An investigation was conducted in the Langley 4 by 7 Meter Tunnel to determine the static longitudinal and lateral directional aerodynamic characteristics of an advanced aspect ratio 10 supercritical wing transport model equipped with a full span leading edge slat as well as part span and full span trailing edge flaps. This wide body transport model was also equipped with spoiler and aileron roll control surfaces, flow through nacelles, landing gear, and movable horizontal tails. Six basic wing configurations were tested: (1) cruise (slats and flaps nested), (2) climb (slats deflected and flaps nested), (3) part span flap, (4) full span flap, (5) full span flap with low speed ailerons, and (6) full span flap with high speed ailerons. Each of the four flapped wing configurations was tested with leading edge slat and trailing edge flaps deflected to settings representative of both take off and landing conditions. Tests were conducted at free stream conditions corresponding to Reynolds number of 0.97 to 1.63 x 10 to the 6th power and corresponding Mach numbers of 0.12 to 0.20, through an angle of attack range of 4 to 24, and a sideslip angle range of -10 deg to 5 deg. The part and full span wing configurations were also tested in ground proximity.

An overview of a multifactor-system theory of personality and individual differences: III. Life span development and the heredity-environment issue.

PubMed

Powell, A; Royce, J R

1981-12-01

In Part III of this three-part series on multifactor-system theory, multivariate, life-span development is approached from the standpoint of a quantitative and qualitative analysis of the ontogenesis of factors in each of the six systems. The pattern of quantitative development (described via the Gompertz equation and three developmental parameters) involves growth, stability, and decline, and qualitative development involves changes in the organization of factors (e.g., factor differentiation and convergence). Hereditary and environmental sources of variation are analyzed via the factor gene model and the concept of heredity-dominant factors, and the factor-learning model and environment-dominant factors. It is hypothesized that the sensory and motor systems are heredity dominant, that the style and value systems are environment dominant, and that the cognitive and affective systems are partially heredity dominant.

Effect of DHEAS on skeletal muscle over the life span: the InCHIANTI study.

PubMed

Valenti, Giorgio; Denti, Licia; Maggio, Marcello; Ceda, GianPaolo; Volpato, Stefano; Bandinelli, Stefania; Ceresini, Graziano; Cappola, Anne; Guralnik, Jack M; Ferrucci, Luigi

2004-05-01

It has been suggested that the reduced production of dehydroepiandrosterone sulfate (DHEAS) may be partially responsible for the decline of muscle strength and mass that often occurs with aging. However, this hypothesis has been only tested in small series of normal volunteers, with little consideration for potential confounders. Using data from a representative sample of 558 men (20-95 years) we tested the hypothesis that circulating DHEAS is independently associated with muscle strength and mass. Data are from InCHIANTI, an epidemiological study conducted in the Chianti geographic area (Tuscany, Italy). DHEAS serum levels were related to lower extremity muscle strength assessed by hand-held dynamometry and calf muscle area estimated from quantitative computerized tomography. Confounders included age, anthropometrics, physical activity, smoking, energy and alcohol intake, albumin, lipids, interleukin-6, comorbidity, depressive symptoms, and disability in activities of daily living. In fully adjusted models predicting lower extremity muscle strength and calf muscle area, we found significant age*log DHEAS interactions, suggesting that the relationship between DHEAS levels and muscle parameters differs across the life span. In age-stratified models adjusted for confounders, serum DHEAS was an independent predictor of muscle strength (p <.02) and mass (p <.01), but only for men between 60 and 79 years of age. After adjusting these models for serum-free or bioavailable testosterone, results were unchanged. In men aged 60-79 years, circulating DHEAS is an independent correlate of muscle strength and calf muscle area. The possible causal role of declining DHEAS in age-related sarcopenia should be further explored in longitudinal studies.

Attachment and the processing of social information across the life span: theory and evidence.

PubMed

Dykas, Matthew J; Cassidy, Jude

2011-01-01

Researchers have used J. Bowlby's (1969/1982, 1973, 1980, 1988) attachment theory frequently as a basis for examining whether experiences in close personal relationships relate to the processing of social information across childhood, adolescence, and adulthood. We present an integrative life-span-encompassing theoretical model to explain the patterns of results that have emerged from these studies. The central proposition is that individuals who possess secure experience-based internal working models of attachment will process--in a relatively open manner--a broad range of positive and negative attachment-relevant social information. Moreover, secure individuals will draw on their positive attachment-related knowledge to process this information in a positively biased schematic way. In contrast, individuals who possess insecure internal working models of attachment will process attachment-relevant social information in one of two ways, depending on whether the information could cause the individual psychological pain. If processing the information is likely to lead to psychological pain, insecure individuals will defensively exclude this information from further processing. If, however, the information is unlikely to lead to psychological pain, then insecure individuals will process this information in a negatively biased schematic fashion that is congruent with their negative attachment-related experiences. In a comprehensive literature review, we describe studies that illustrate these patterns of attachment-related information processing from childhood to adulthood. This review focuses on studies that have examined specific components (e.g., attention and memory) and broader aspects (e.g., attributions) of social information processing. We also provide general conclusions and suggestions for future research.

Spermatozoid life-span of two brown seaweeds, Saccharina japonica and Undaria pinnatifida, as measured by fertilization efficiency

NASA Astrophysics Data System (ADS)

Li, Jing; Pang, Shaojun; Liu, Feng; Shan, Tifeng; Gao, Suqin

2013-07-01

During sexual reproduction of seaweeds, spermatozoid (sperm) discharge is triggered by chemical messengers (pheromones) released by the female gametes. The chemotactic ability of the sperm ensures fertilization success. Using unialgal male and female gametophyte material under designated standard gametogenesis testing (SGT) conditions, the potential life-span of the sperm of two seaweeds, Saccharina japonica and Undaria pinnatifida, was assessed by their ability to fertilize eggs. Results show that within 20-30 min after being discharged, sperm of both species could complete fertilization without an apparent decline in fertilization rate. Although fertilization rate 60-120 min after sperm discharge dropped significantly in both species, some sperm were viable enough to fertilize the eggs. In S. japonica, at 12°C, some sperm were able to fertilize eggs up to 12 h after discharge. In both species, egg discharge rates (EDR) in the male and female mixed positive controls were significantly higher than those of all the sperm-testing groups. Doubling the seeded male gametophytes of S. japonica in the SGT tests significantly increased the EDR, further confirming the effect of the presence of the male on the female in terms of facilitating egg discharge from oogonia.

A unifying perspective on personality pathology across the life span: Developmental considerations for the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders

PubMed Central

TACKETT, JENNIFER L.; BALSIS, STEVE; OLTMANNS, THOMAS F.; KRUEGER, ROBERT F.

2010-01-01

Proposed changes in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) include replacing current personality disorder (PD) categories on Axis II with a taxonomy of dimensional maladaptive personality traits. Most of the work on dimensional models of personality pathology, and on personality disorders per se, has been conducted on young and middle-aged adult populations. Numerous questions remain regarding the applicability and limitations of applying various PD models to early and later life. In the present paper, we provide an overview of such dimensional models and review current proposals for conceptualizing PDs in DSM-V. Next, we extensively review existing evidence on the development, measurement, and manifestation of personality pathology in early and later life focusing on those issues deemed most relevant for informing DSM-V. Finally, we present overall conclusions regarding the need to incorporate developmental issues in conceptualizing PDs in DSM-V and highlight the advantages of a dimensional model in unifying PD perspectives across the life span. PMID:19583880

Age differences in big five behavior averages and variabilities across the adult life span: moving beyond retrospective, global summary accounts of personality.

PubMed

Noftle, Erik E; Fleeson, William

2010-03-01

In 3 intensive cross-sectional studies, age differences in behavior averages and variabilities were examined. Three questions were posed: Does variability differ among age groups? Does the sizable variability in young adulthood persist throughout the life span? Do past conclusions about trait development, based on trait questionnaires, hold up when actual behavior is examined? Three groups participated: young adults (18-23 years), middle-aged adults (35-55 years), and older adults (65-81 years). In 2 experience-sampling studies, participants reported their current behavior multiple times per day for 1- or 2-week spans. In a 3rd study, participants interacted in standardized laboratory activities on 8 occasions. First, results revealed a sizable amount of intraindividual variability in behavior for all adult groups, with average within-person standard deviations ranging from about half a point to well over 1 point on 6-point scales. Second, older adults were most variable in Openness, whereas young adults were most variable in Agreeableness and Emotional Stability. Third, most specific patterns of maturation-related age differences in actual behavior were more greatly pronounced and differently patterned than those revealed by the trait questionnaire method. When participants interacted in standardized situations, personality differences between young adults and middle-aged adults were larger, and older adults exhibited a more positive personality profile than they exhibited in their everyday lives.

What Prolongs a Butterfly's Life?: Trade-Offs between Dormancy, Fecundity and Body Size

PubMed Central

Haeler, Elena; Fiedler, Konrad; Grill, Andrea

2014-01-01

In butterflies, life span often increases only at the expense of fecundity. Prolonged life span, on the other hand, provides more opportunities for oviposition. Here, we studied the association between life span and summer dormancy in two closely related species of Palearctic Meadow Brown butterflies, the endemic Maniola nurag and the widespread M. jurtina, from two climatic provenances, a Mediterranean and a Central European site, and tested the relationships between longevity, body size and fecundity. We experimentally induced summer dormancy and hence prolonged the butterflies’ life in order to study the effects of such a prolonged life. We were able to modulate longevity only in Mediterranean females by rearing them under summer photoperiodic conditions (light 16 h : dark 8 h), thereby more than doubling their natural life span, to up to 246 days. Central European individuals kept their natural average live span under all treatments, as did Mediterranean individuals under autumn treatment (light 11: dark 13). Body size only had a significant effect in the smaller species, M. nurag, where it affected the duration of dormancy and lifetime fecundity. In the larger species, M. jurtina, a prolonged adult life span did, surprisingly, not convey any fecundity loss. In M. nurag, which generally deposited fewer eggs, extended life had a fecundity cost. We conclude that Mediterranen M. jurtina butterflies have an extraordinary plasticity in aging which allows them to extend life span in response to adverse environmental conditions and relieve the time limitation on egg-laying while maintaining egg production at equal levels. PMID:25390334

Incremental Revisions across the Life Span of Ophthalmic Devices after Initial Food and Drug Administration Premarket Approval, 1979-2015.

PubMed

Gopal, Anand D; Rathi, Vinay K; Teng, Christopher C; Del Priore, Lucian; Ross, Joseph S

2017-08-01

To characterize the frequency, nature, and regulatory mechanisms by which ophthalmic devices are iteratively modified after initial Food and Drug Administration (FDA) Premarket Approval (PMA). Retrospective cross-sectional analysis using publicly available FDA data. Ophthalmic devices initially approved via the FDA's PMA pathway between January 1, 1979 and December 31, 2015. We used the FDA's PMA Database to identify and characterize initial approvals and subsequent postmarket modifications to Class III ophthalmic devices. The FDA Recalls Database was used to identify associated safety events. Median iterated life span (timespan across which modifications occurred after initial PMA) and median number of supplements approved per device, by device type, and overall, stratified by regulatory pathway and modification type. Between 1979 and 2015, the FDA approved 168 original ophthalmic devices via the PMA pathway and 2813 subsequent modifications. More than one third (n = 64; 38%) of original approvals were intraocular lenses. Overall, devices underwent a median of 11 postmarket modifications (interquartile range [IQR], 3-24.8) across a median 10.0-year iterated life span (IQR, 4.1-16.7). The majority of devices (n = 144; 86%) underwent more than 1 postapproval modification, including more than 1 design modification (n = 84; 50%). The median number of changes altering device design or labeling was 3.5 (IQR, 1-9). Although manufacturing alterations (n = 834 of 2813; 30%) were the most frequent type of revision, changes involving device design (n = 667; 24%) and labeling (n = 417; 15%) were common. Recalled devices underwent more frequent postapproval modifications per year (median, 1.4; IQR, 0.7-2.3; mean, 1.5; 95% confidence interval, 1.1-1.9) in the period preceding recall than did nonrecalled devices (median, 0.5; IQR, 0.2-1.1; mean, 0.8; 95% confidence interval, 0.7-1.0) across their market approval period (P < 0.001). Most ophthalmic devices approved via the

Investigation of a free-tip rotor configuration for research on spanwise life distributions and wake velocity surveys of a semi-span wing with a discontinuous twist

NASA Technical Reports Server (NTRS)

Fortin, Paul; Kumagai, Hiroyuki

1989-01-01

A wind tunnel test was conducted in the NASA Ames 7 x 10 Foot Wind Tunnel to investigate the lift distribution on a semi-span wing with a discontinuous change in spanwise twist. The semi-span wing had a tip with an adjustable pitch angle independent on the inboard section pitch angle simulating the free-tip rotor blade when its free-tip is at a deflected position. The spanwise lift distribution over the wing and the tip were measured and three component velocity surveys behind the wing were obtained with a three dimensional laser Doppler velocimeter (LV) with the wing at one angle of attack and the tip deflected at different pitch angles. A six component internal strain gage balance was also used to measure total forces and moments on the tip. The three dimensional lift was computed from the two dimensional life distributions obtained from the LV and from the strain gage balance. The results from both experimental methods are shown to be in agreement with predictions made by a steady, three dimensional panel code, VSAERO.

Node degree distribution in spanning trees

NASA Astrophysics Data System (ADS)

Pozrikidis, C.

2016-03-01

A method is presented for computing the number of spanning trees involving one link or a specified group of links, and excluding another link or a specified group of links, in a network described by a simple graph in terms of derivatives of the spanning-tree generating function defined with respect to the eigenvalues of the Kirchhoff (weighted Laplacian) matrix. The method is applied to deduce the node degree distribution in a complete or randomized set of spanning trees of an arbitrary network. An important feature of the proposed method is that the explicit construction of spanning trees is not required. It is shown that the node degree distribution in the spanning trees of the complete network is described by the binomial distribution. Numerical results are presented for the node degree distribution in square, triangular, and honeycomb lattices.

Akt2 ablation prolongs life span and improves myocardial contractile function with adaptive cardiac remodeling: role of Sirt1-mediated autophagy regulation.

PubMed

Ren, Jun; Yang, Lifang; Zhu, Li; Xu, Xihui; Ceylan, Asli F; Guo, Wei; Yang, Jian; Zhang, Yingmei

2017-10-01

Aging is accompanied with unfavorable geometric and functional changes in the heart involving dysregulation of Akt and autophagy. This study examined the impact of Akt2 ablation on life span and cardiac aging as well as the mechanisms involved with a focus on autophagy and mitochondrial integrity. Cardiac geometry, contractile, and intracellular Ca 2+ properties were evaluated using echocardiography, IonOptix ® edge-detection and fura-2 techniques. Levels of Sirt1, mitochondrial integrity, autophagy, and mitophagy markers were evaluated using Western blot. Our results revealed that Akt2 ablation prolonged life span (by 9.1%) and alleviated aging (24 months)-induced unfavorable changes in myocardial function and intracellular Ca 2+ handling (SERCA2a oxidation) albeit with more pronounced cardiac hypertrophy (58.1%, 47.8%, and 14.5% rises in heart weight, wall thickness, and cardiomyocyte cross-sectional area). Aging downregulated levels of Sirt1, increased phosphorylation of Akt, and the nuclear transcriptional factor Foxo1, as well as facilitated acetylation of Foxo1, the effects of which (except Sirt1 and Foxo1 acetylation) were significantly attenuated or negated by Akt2 ablation. Advanced aging disturbed autophagy, mitophagy, and mitochondrial integrity as evidenced by increased p62, decreased levels of beclin-1, Atg7, LC3B, BNIP3, PTEN-induced putative kinase 1 (PINK1), Parkin, UCP-2, PGC-1α, and aconitase activity, the effects of which were reversed by Akt2 ablation. Aging-induced cardiomyocyte contractile dysfunction and loss of mitophagy were improved by rapamycin and the Sirt1 activator SRT1720. Activation of Akt using insulin or Parkin deficiency prevented SRT1720-induced beneficial effects against aging. In conclusion, our data indicate that Akt2 ablation protects against cardiac aging through restored Foxo1-related autophagy and mitochondrial integrity. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Metric half-span model support system

NASA Technical Reports Server (NTRS)

Jackson, C. M., Jr.; Dollyhigh, S. M.; Shaw, D. S. (Inventor)

1982-01-01

A model support system used to support a model in a wind tunnel test section is described. The model comprises a metric, or measured, half-span supported by a nonmetric, or nonmeasured half-span which is connected to a sting support. Moments and forces acting on the metric half-span are measured without interference from the support system during a wind tunnel test.

Multimodal neuroimaging of male and female brain structure in health and disease across the life span.

PubMed

Jahanshad, Neda; Thompson, Paul M

2017-01-02

Sex differences in brain development and aging are important to identify, as they may help to understand risk factors and outcomes in brain disorders that are more prevalent in one sex compared with the other. Brain imaging techniques have advanced rapidly in recent years, yielding detailed structural and functional maps of the living brain. Even so, studies are often limited in sample size, and inconsistent findings emerge, one example being varying findings regarding sex differences in the size of the corpus callosum. More recently, large-scale neuroimaging consortia such as the Enhancing Neuro Imaging Genetics through Meta Analysis Consortium have formed, pooling together expertise, data, and resources from hundreds of institutions around the world to ensure adequate power and reproducibility. These initiatives are helping us to better understand how brain structure is affected by development, disease, and potential modulators of these effects, including sex. This review highlights some established and disputed sex differences in brain structure across the life span, as well as pitfalls related to interpreting sex differences in health and disease. We also describe sex-related findings from the ENIGMA consortium, and ongoing efforts to better understand sex differences in brain circuitry. © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc. © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.

Social network changes and life events across the life span: a meta-analysis.

PubMed

Wrzus, Cornelia; Hänel, Martha; Wagner, Jenny; Neyer, Franz J

2013-01-01

For researchers and practitioners interested in social relationships, the question remains as to how large social networks typically are, and how their size and composition change across adulthood. On the basis of predictions of socioemotional selectivity theory and social convoy theory, we conducted a meta-analysis on age-related social network changes and the effects of life events on social networks using 277 studies with 177,635 participants from adolescence to old age. Cross-sectional as well as longitudinal studies consistently showed that (a) the global social network increased up until young adulthood and then decreased steadily, (b) both the personal network and the friendship network decreased throughout adulthood, (c) the family network was stable in size from adolescence to old age, and (d) other networks with coworkers or neighbors were important only in specific age ranges. Studies focusing on life events that occur at specific ages, such as transition to parenthood, job entry, or widowhood, demonstrated network changes similar to such age-related network changes. Moderator analyses detected that the type of network assessment affected the reported size of global, personal, and family networks. Period effects on network sizes occurred for personal and friendship networks, which have decreased in size over the last 35 years. Together the findings are consistent with the view that a portion of normative, age-related social network changes are due to normative, age-related life events. We discuss how these patterns of normative social network development inform research in social, evolutionary, cultural, and personality psychology. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

Character strengths and well-being across the life span: data from a representative sample of German-speaking adults living in Switzerland

PubMed Central

Martínez-Martí, María L.; Ruch, Willibald

2014-01-01

Character strengths are positive, morally valued traits of personality. This study aims at assessing the relationship between character strengths and subjective well-being (i.e., life satisfaction, positive and negative affect) in a representative sample of German-speaking adults living in Switzerland (N = 945). We further test whether this relationship is consistent at different stages in life. Results showed that hope, zest, love, social intelligence and perseverance yielded the highest positive correlations with life satisfaction. Hope, zest, humor, gratitude and love presented the highest positive correlations with positive affect. Hope, humor, zest, honesty, and open-mindedness had the highest negative correlations with negative affect. When examining the relationship between strengths and well-being across age groups, in general, hope, zest and humor consistently yielded the highest correlations with well-being. Additionally, in the 27–36 years group, strengths that promote commitment and affiliation (i.e., kindness and honesty) were among the first five positions in the ranking of the relationship between strengths and well-being. In the 37–46 years group, in addition to hope, zest and humor, strengths that promote the maintenance of areas such as family and work (i.e., love, leadership) were among the first five positions in the ranking. Finally, in the 47–57 years group, in addition to hope, zest and humor, strengths that facilitate integration and a vital involvement with the environment (i.e., gratitude, love of learning) were among the first five positions in the ranking. This study partially supports previous findings with less representative samples on the association between character strengths and well-being, and sheds light on the relative importance of some strengths over others for well-being across the life span. PMID:25408678

Sodium Intake of Special Populations in the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) Study

PubMed Central

Cotugna, Nancy; Fanelli-Kuczmarksi, Marie; Clymer, Julie; Hotchkiss, Lawrence; Zonderman, Alan B.; Evans, Michele K.

2013-01-01

Objective The sodium intake of participants of the Healthy Aging in Neighborhoods of Diversity across the Life Span study who were in three of the special population groups identified by the Dietary Guidelines for Americans, 2010 (those with hypertension, African Americans, and those ≥51 years) was analyzed to determine if they met sodium recommendations. Methods The sample included 2152 African American and White subjects, aged 30-64 years. Major dietary sources of sodium for each group were determined from two 24-hour dietary recalls, and dietary intakes were compared with sodium recommendations. Dietary potassium was also evaluated. Results The intakes of the groups studied exceeded 1500 mg sodium while their potassium intakes were lower than the Adequate Intake of 4700 mg. The major contributors of sodium included “cold cuts, sausage, and franks,” “protein foods”, and yeast breads. Conclusions Excessive sodium intake characterized the diet of an urban, socioeconomically diverse population who are hypertensive or at risk for having hypertension. These findings have implications for health professionals and the food industry. PMID:23769900

Effects of Grape Skin Extract on Age-Related Mitochondrial Dysfunction, Memory and Life Span in C57BL/6J Mice.

PubMed

Asseburg, Heike; Schäfer, Carmina; Müller, Madeleine; Hagl, Stephanie; Pohland, Maximilian; Berressem, Dirk; Borchiellini, Marta; Plank, Christina; Eckert, Gunter P

2016-09-01

Dementia contributes substantially to the burden of disability experienced at old age, and mitochondrial dysfunction (MD) was identified as common final pathway in brain aging and Alzheimer's disease. Due to its early appearance, MD is a promising target for nutritional prevention strategies and polyphenols as potential neurohormetic inducers may be strong neuroprotective candidates. This study aimed to investigate the effects of a polyphenol-rich grape skin extract (PGE) on age-related dysfunctions of brain mitochondria, memory, life span and potential hormetic pathways in C57BL/6J mice. PGE was administered at a dose of 200 mg/kg body weight/d in a 3-week short-term, 6-month long-term and life-long study. MD in the brains of aged mice (19-22 months old) compared to young mice (3 months old) was demonstrated by lower ATP levels and by impaired mitochondrial respiratory complex activity (except for mice treated with antioxidant-depleted food pellets). Long-term PGE feeding partly enhanced brain mitochondrial respiration with only minor beneficial effect on brain ATP levels and memory of aged mice. Life-long PGE feeding led to a transient but significant shift of survival curve toward higher survival rates but without effect on the overall survival. The moderate effects of PGE were associated with elevated SIRT1 but not SIRT3 mRNA expressions in brain and liver tissue. The beneficial effects of the grape extract may have been influenced by the profile of bioavailable polyphenols and the starting point of interventions.

Language decline across the life span: findings from the Nun Study.

PubMed

Kemper, S; Greiner, L H; Marquis, J G; Prenovost, K; Mitzner, T L

2001-06-01

The present study examines language samples from the Nun Study. Measures of grammatical complexity and idea density were obtained from autobiographies written over a 60-year span. Participants who had met criteria for dementia were contrasted with those who did not. Grammatical complexity initially averaged 4.78 (on a 0-to-7-point scale) for participants who did not meet criteria for dementia and declined .04 units per year; grammatical complexity for participants who met criteria for dementia initially averaged 3.86 and declined .03 units per year. Idea density averaged 5.35 propositions per 10 words initially for participants who did not meet criteria for dementia and declined an average of .03 units per year, whereas idea density averaged 4.34 propositions per 10 words initially for participants who met criteria for dementia and declined .02 units per year. Adult experiences, in general, did not moderate these declines.

A stockpile of ova in the grass frog Rana temporaria is established once for the life span. Do ovaries in amphibians and in mammals follow the same evolutionary strategy?

PubMed

Ogielska, Maria; Kotusz, Agnieszka; Augustyńska, Renata; Ihnatowicz, Jerzy; Paśko, Łukasz

2013-04-01

Most anuran amphibians produce high numbers of eggs during several consecutive breeding seasons. The question is still open whether oocytes are formed anew as a result of oogonial proliferation after each spawning or the definitive pool of oocytes is established during the juvenile period and is sufficient for the whole reproductive life span of a female. Our quantitative studies show that primary oogonia in adult female frogs can proliferate, but they fail to differentiate further and do not enter meiosis, and thereby there is no supplementation of new generations of oocytes after each spawning. Ovaries of one-year-old grass frogs contain (median) 53,447 diplotene oocytes, in two-years-old frogs this number decreased to 33,583 and eventually reached 25,679 in virgin mature females. More than 50% decrease in the total oocyte number was accompanied by massive degeneration (atresia) of oocytes. The final number of oocytes in a female forms a stock for 11-12 breeding seasons and exceeds the number of eggs produced during the potential reproductive life span of this species. The phylogenetic context of oocyte recruitment modes in the major clades of vertebrates is discussed in respect to their ability to replenish the stock (a renewable stock in ovaries named "open" vs. a non-renewable stock in ovaries named "closed"). Copyright © 2013 Wiley Periodicals, Inc.

Age Differences in Memory Span

ERIC Educational Resources Information Center

Chi, Michelene T. H.

1977-01-01

Three experiments were conducted to determine processes underlying age differences in the level of recall in a memory-span task. Five-year-olds recalled fewer items than adults in memory-span tasks involving both familiar and unfamiliar faces, even though the use of rehearsal and recoding strategies was minimized for adults. (MS)

Effects of salinity on egg and fecal pellet production, development and survival, adult sex ratio and total life span in the calanoid copepod, Acartia tonsa: a laboratory study

NASA Astrophysics Data System (ADS)

Shayegan, Majid; Esmaeili Fereidouni, Abolghasem; Agh, Naser; Jani Khalili, Khosrow

2016-07-01

The effects of salinity on the copepod, Acartia tonsa in terms of daily egg production rate (EPR), hatching success, fecal pellet production rate (FPR), naupliar development time and survival, sex ratio, and total life span were determined in laboratory conditions through three experiments. In experiment 1, EPR, hatching success, and FPR of individual females were monitored at salinities of 13, 20, 35 and 45 during short-periods (seven consecutive days). Results show EPR was affected by salinity with the highest outputs recorded at 20 and 35, respectively, which were considerably higher than those at 13 and 45. Mean FPR was also higher in 35 and 20. In experiment 2, the same parameters were evaluated over total life span of females (long-term study). The best EPR and FPR were observed in 35, which was statistically higher than at 13 and 20. In experiment 3, survival rates of early nauplii until adult stage were lowest at a salinity of 13. The development time increased with increasing of salinity. Female percentage clearly decreased with increasing salinity. Higher female percentages (56.7% and 52.2%, respectively) were significantly observed at two salinities of 13 and 20 compared to that at 35 (25%). Total longevity of females was not affected by salinity increment. Based on our results, for mass culture we recommend that a salinity of 35 be adopted due to higher reproductive performances, better feeding, and faster development of A. tonsa.

Changes in gas exchange characteristics during the life span of giant sequoia: implications for response to current and future concentrations of atmospheric ozone.

PubMed

Grulke, N. E.; Miller, P. R.

1994-01-01

Native stands of giant sequoia (Sequoiadendron giganteum Bucholz) are being exposed to relatively high concentrations of atmospheric ozone produced in urban and agricultural areas upwind. The expected change in environmental conditions over the next 100 years is likely to be unprecedented in the life span (about 2,500 years) of giant sequoia. We determined changes in physiological responses of three age classes of giant sequoia (current-year, 12-, and 125-year-old) to differing concentrations of ozone, and assessed age-related differences in sensitivity to pollutants by examining physiological changes (gas exchange, water use efficiency) across the life span of giant sequoia (current-year, 2-, 5-, 20-, 125-, and > 2,000-year-old trees). The CO(2) exchange rate (CER) was greater in current-year (12.1 micro mol CO(2) m(-2) s(-1)) and 2-year-old seedlings (4.8 micro mol CO(2) m(-2) s(-1)) than in all older trees (3.0 micro mol CO(2) m(-2) s(-1), averaged across the four older age classes). Dark respiration was highest for current-year seedlings (-6.5 +/- 0.7 micro mol CO(2) m(-2) s(-1)) and was increased twofold in symptomatic individuals exposed to elevated ozone concentrations. Stomatal conductance (g(s)) was greater in current-year (355 mmol H(2)O m(-2) s(-1)) and 2-year-old seedlings (200 mmol H(2)O m(-2) s(-1)) than in all older trees (50 mmol H(2)O m(-2) s(-1)), indicating that the ozone concentration in substomatal cavities is higher in young seedlings than in trees. Significant changes in water use efficiency, as indicated by C(i)/C(a), occurred in trees between ages 5 and 20 years. We conclude that giant sequoias seedlings are sensitive to atmospheric ozone until they are about 5 years old. Low conductance, high water use efficiency, and compact mesophyll all contribute to a natural ozone tolerance, or defense, or both, in foliage of older trees.

Improving Memory Span in Children with Down Syndrome

ERIC Educational Resources Information Center

Conners, F. A.; Rosenquist, C. J.; Arnett, L.; Moore, M. S.; Hume, L. E.

2008-01-01

Background: Down syndrome (DS) is characterized by impaired memory span, particularly auditory verbal memory span. Memory span is linked developmentally to several language capabilities, and may be a basic capacity that enables language learning. If children with DS had better memory span, they might benefit more from language intervention. The…

Linking crowding, visual span, and reading.

PubMed

He, Yingchen; Legge, Gordon E

2017-09-01

The visual span is hypothesized to be a sensory bottleneck on reading speed with crowding thought to be the major sensory factor limiting the size of the visual span. This proposed linkage between crowding, visual span, and reading speed is challenged by the finding that training to read crowded letters reduced crowding but did not improve reading speed (Chung, 2007). Here, we examined two properties of letter-recognition training that may influence the transfer to improved reading: the spatial arrangement of training stimuli and the presence of flankers. Three groups of nine young adults were trained with different configurations of letter stimuli at 10° in the lower visual field: a flanked-local group (flanked letters localized at one position), a flanked-distributed group (flanked letters distributed across different horizontal locations), and an isolated-distributed group (isolated and distributed letters). We found that distributed training, but not the presence of flankers, appears to be necessary for the training benefit to transfer to increased reading speed. Localized training may have biased attention to one specific, small area in the visual field, thereby failing to improve reading. We conclude that the visual span represents a sensory bottleneck on reading, but there may also be an attentional bottleneck. Reducing the impact of crowding can enlarge the visual span and can potentially facilitate reading, but not when adverse attentional bias is present. Our results clarify the association between crowding, visual span, and reading.

Linking crowding, visual span, and reading

PubMed Central

He, Yingchen; Legge, Gordon E.

2017-01-01

The visual span is hypothesized to be a sensory bottleneck on reading speed with crowding thought to be the major sensory factor limiting the size of the visual span. This proposed linkage between crowding, visual span, and reading speed is challenged by the finding that training to read crowded letters reduced crowding but did not improve reading speed (Chung, 2007). Here, we examined two properties of letter-recognition training that may influence the transfer to improved reading: the spatial arrangement of training stimuli and the presence of flankers. Three groups of nine young adults were trained with different configurations of letter stimuli at 10° in the lower visual field: a flanked-local group (flanked letters localized at one position), a flanked-distributed group (flanked letters distributed across different horizontal locations), and an isolated-distributed group (isolated and distributed letters). We found that distributed training, but not the presence of flankers, appears to be necessary for the training benefit to transfer to increased reading speed. Localized training may have biased attention to one specific, small area in the visual field, thereby failing to improve reading. We conclude that the visual span represents a sensory bottleneck on reading, but there may also be an attentional bottleneck. Reducing the impact of crowding can enlarge the visual span and can potentially facilitate reading, but not when adverse attentional bias is present. Our results clarify the association between crowding, visual span, and reading. PMID:28973564

Detection and functional characterization of Pgp1 (ABCB1) and MRP3 (ABCC3) efflux transporters in the PLHC-1 fish hepatoma cell line.

PubMed

Zaja, Roko; Klobucar, Roberta Sauerborn; Smital, Tvrtko

2007-03-30

The PLHC-1 hepatoma cell line derived from topminnow (Poeciliopsis lucida) is one of the most frequently used fish cell lines in aquatic ecotoxicology. These cells have been well characterized regarding the presence of phase I and phase II enzymes involved in the metabolism of xenobiotics. However, the presence of the ABC transport proteins possibly involved in the MultiXenobiotic Resistance (MXR) mechanism as phase III of cellular detoxification has never been described in the PLHC-1 cells. The main goal of this study was the detection and functional characterization of toxicologically relevant xenobiotic efflux transporters from ABCB and ABCC subfamily in the PLHC-1 cells. Using specific primer pairs two PCR products 1769 and 1023bp in length were successfully cloned and sequenced. Subsequent multiple alignment and phylogenetic analysis showed that these sequences share a high degree of homology with the P-glycoprotein (Pgp1; ABCB1) and the MRP3 (ABCC3). Functional experiments with fluorescent model substrates and specific inhibitors were used to verify that transport activities of Pgp- and MRP-related proteins are indeed present in PLHC-1 cells. Accumulation or efflux/retention rates of rhodamine 123, calcein-AM or monochlorbimane were time- and concentration-dependent. Cyclosporine A, MK571, verapamil, reversine 205, indomethacine and probenecid were used as specific inhibitors of Pgp1 and/or MRPs transport activities, resulting in a dose dependent inhibition of related transport activities in PLHC-1 cells. Similar to mammalian systems, the obtained IC(50) values were in the lower micromolar range. Taken together these data demonstrate that: (1) the PLHC-1 cells do express a functional MXR mechanism mediated by toxicologically relevant ABC efflux transporters; and (2) the presence of all three critical phases of cellular detoxification additionally affirms the PLHC-1 cells as a reliable in vitro model in aquatic toxicology.

Study of Semi-Span Model Testing Techniques

NASA Technical Reports Server (NTRS)

Gatlin, Gregory M.; McGhee, Robert J.

1996-01-01

An investigation has been conducted in the NASA Langley 14- by 22-Foot Subsonic Tunnel in order to further the development of semi-span testing capabilities. A twin engine, energy efficient transport (EET) model with a four-element wing in a takeoff configuration was used for this investigation. Initially a full span configuration was tested and force and moment data, wing and fuselage surface pressure data, and fuselage boundary layer measurements were obtained as a baseline data set. The semi-span configurations were then mounted on the wind tunnel floor, and the effects of fuselage standoff height and shape as well as the effects of the tunnel floor boundary layer height were investigated. The effectiveness of tangential blowing at the standoff/floor juncture as an active boundary-layer control technique was also studied. Results indicate that the semi-span configuration was more sensitive to variations in standoff height than to variations in floor boundary layer height. A standoff height equivalent to 30 percent of the fuselage radius resulted in better correlation with full span data than no standoff or the larger standoff configurations investigated. Undercut standoff leading edges or the use of tangential blowing in the standoff/ floor juncture improved correlation of semi-span data with full span data in the region of maximum lift coefficient.

Metal-based superoxide dismutase and catalase mimics reduce oxidative stress biomarkers and extend life span of Saccharomyces cerevisiae.

PubMed

Ribeiro, Thales de P; Fonseca, Fernanda L; de Carvalho, Mariana D C; Godinho, Rodrigo M da C; de Almeida, Fernando Pereira; Saint'Pierre, Tatiana D; Rey, Nicolás A; Fernandes, Christiane; Horn, Adolfo; Pereira, Marcos D

2017-01-15

Aging is a natural process characterized by several biological changes. In this context, oxidative stress appears as a key factor that leads cells and organisms to severe dysfunctions and diseases. To cope with reactive oxygen species and oxidative-related damage, there has been increased use of superoxide dismutase (SOD)/catalase (CAT) biomimetic compounds. Recently, we have shown that three metal-based compounds {[Fe(HPClNOL)Cl 2 ]NO 3 , [Cu(HPClNOL)(CH 3 CN)](ClO 4 ) 2 and Mn(HPClNOL)(Cl) 2 }, harboring in vitro SOD and/or CAT activities, were critical for protection of yeast cells against oxidative stress. In this work, treating Saccharomyces cerevisiae with these SOD/CAT mimics (25.0 µM/1 h), we highlight the pivotal role of these compounds to extend the life span of yeast during chronological aging. Evaluating lipid and protein oxidation of aged cells, it becomes evident that these mimics extend the life expectancy of yeast mainly due to the reduction in oxidative stress biomarkers. In addition, the treatment of yeast cells with these mimics regulated the amounts of lipid droplet occurrence, consistent with the requirement and protection of lipids for cell integrity during aging. Concerning SOD/CAT mimics uptake, using inductively coupled plasma mass spectrometry, we add new evidence that these complexes, besides being bioabsorbed by S. cerevisiae cells, can also affect metal homeostasis. Finally, our work presents a new application for these SOD/CAT mimics, which demonstrate a great potential to be employed as antiaging agents. Taken together, these promising results prompt future studies concerning the relevance of administration of these molecules against the emerging aging-related diseases such as Parkinson's, Alzheimer's and Huntington's. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

The concept of homology as a basis for evaluating developmental mechanisms: exploring selective attention across the life-span.

PubMed

Lickliter, Robert; Bahrick, Lorraine E

2013-01-01

Research with human infants as well as non-human animal embryos and infants has consistently demonstrated the benefits of intersensory redundancy for perceptual learning and memory for redundantly specified information during early development. Studies of infant affect discrimination, face discrimination, numerical discrimination, sequence detection, abstract rule learning, and word comprehension and segmentation have all shown that intersensory redundancy promotes earlier detection of these properties when compared to unimodal exposure to the same properties. Here we explore the idea that such intersensory facilitation is evident across the life-span and that this continuity is an example of a developmental behavioral homology. We present evidence that intersensory facilitation is most apparent during early phases of learning for a variety of tasks, regardless of developmental level, including domains that are novel or tasks that require discrimination of fine detail or speeded responses. Under these conditions, infants, children, and adults all show intersensory facilitation, suggesting a developmental homology. We discuss the challenge and propose strategies for establishing appropriate guidelines for identifying developmental behavioral homologies. We conclude that evaluating the extent to which continuities observed across development are homologous can contribute to a better understanding of the processes of development. Copyright © 2012 Wiley Periodicals, Inc.

Targeted disruption of Pten in ovarian granulosa cells enhances ovulation and extends the life span of luteal cells.

PubMed

Fan, Heng-Yu; Liu, Zhilin; Cahill, Nicola; Richards, JoAnne S

2008-09-01

FSH activates the phosphatidylinositol-3 kinase (PI3K)/acute transforming retrovirus thymoma protein kinase pathway and thereby enhances granulosa cell differentiation in culture. To identify the physiological role of the PI3K pathway in vivo we disrupted the PI3K suppressor, Pten, in developing ovarian follicles. To selectively disrupt Pten expression in granulosa cells, Ptenfl/fl mice were mated with transgenic mice expressing cAMP response element recombinase driven by Cyp19 promoter (Cyp19-Cre). The resultant Pten mutant mice were fertile, ovulated more oocytes, and produced moderately more pups than control mice. These physiological differences in the Pten mutant mice were associated with hyperactivation of the PI3K/acute transforming retrovirus thymoma protein kinase pathway, decreased susceptibility to apoptosis, and increased proliferation of mutant granulosa cells. Strikingly, corpora lutea of the Pten mutant mice persisted longer than those of control mice. Although the follicular and luteal cell steroidogenesis in Ptenfl/fl;Cyp19-Cre mice was similar to controls, viable nonsteroidogenic luteal cells escaped structural luteolysis. These findings provide the novel evidence that Pten impacts the survival/life span of granulosa/luteal cells and that its loss not only results in the facilitated ovulation but also in the persistence of nonsteroidogenic luteal structures in the adult mouse ovary.

Trajectories of maternal depressive symptoms over her child's life span: Relation to adrenocortical, cardiovascular, and emotional functioning in children

PubMed Central

Gump, Brooks B.; Reihman, Jacki; Stewart, Paul; Lonky, ED; Darvill, Tom; Granger, Douglas A.; Matthews, Karen A.

2015-01-01

Maternal depression has a number of adverse effects on children. In the present study, maternal depressive symptoms were assessed (using the Center for Epidemiological Studies Depression Scale) when their child was 3 months, 6 months, 1 year, 2 years, 4.25 years, 6 years, 7 years, 8 years, and 10 years of age. At 9.5 years of age, children's (94 females, 82 males) depressive symptoms as well as cardiovascular and cortisol levels during baseline and two psychologically stressful tasks were measured. Using multilevel modeling, maternal depressive symptom trajectories were considered in relation to their child's adrenocortical and cardiovascular responses to acute stress. Our goal was to determine maternal depressive symptom trajectories for children with elevated cardiovascular and cortisol reactivity to acute stress and elevated depressive symptoms. In general, those mothers with chronically elevated depressive symptoms over their child's life span had children with lower initial cortisol, higher cardiac output and stroke volume in response to acute stress, lower vascular resistance during acute stress tasks, and significantly more depressive symptoms at 9.5 years of age. These results are discussed in the context of established associations among hypothalamic–pituitary–adrenal axis dysregulation, depression, and cardiovascular disease. PMID:19144231

Understanding Aggressive Behavior Across the Life Span

PubMed Central

Liu, Jianghong; Lewis, Gary; Evans, Lois

2012-01-01

Aggressive behavior is the observable manifestation of aggression and is often associated with developmental transitions and a range of medical and psychiatric diagnoses across the lifespan. As healthcare professionals involved in the medical and psychosocial care of patients from birth through death, nurses frequently encounter—and may serve as—both victims and perpetrators of aggressive behavior in the workplace. While the nursing literature has continually reported research on prevention and treatment approaches, less emphasis has been given to understanding the etiology, including contextual precipitants of aggressive behavior. This paper provides a brief review of the biological, social, and environmental risk factors that purportedly give rise to aggressive behavior. Further, many researchers have focused specifically on aggressive behavior in adolescence and adulthood. Less attention has been given to understanding the etiology of such behavior in young children and older adults. This paper emphasizes the unique risk factors for aggressive behavior across the developmental spectrum, including childhood, adolescence, adulthood, and late life. Appreciation of the risk factors of aggressive behavior, and, in particular, how they relate to age-specific manifestations, can aid nurses in better design and implementation of prevention and treatment programs. PMID:22471771

Semi-span model testing in the National Transonic Facility

NASA Technical Reports Server (NTRS)

Chokani, Ndaona; Milholen, William E., II

1993-01-01

A semi-span testing technique has been proposed for the NASA Langley Research Center's National Transonic Facility (NTF). Semi-span testing has several advantages including (1) larger model size, giving increased Reynolds number capability; (2) improved model fidelity, allowing ease of flap and slat positioning which ultimately improves data quality; and (3) reduced construction costs compared with a full-span model. In addition, the increased model size inherently allows for increased model strength, reducing aeroelastic effects at the high dynamic pressure levels necessary to simulate flight Reynolds numbers. The Energy Efficient Transport (EET) full-span model has been modified to become the EET semi-span model. The full-span EET model was tested extensively at both NASA LRC and NASA Ames Research Center. The available full-span data will be useful in validating the semi-span test strategy in the NTF. In spite of the advantages discussed above, the use of a semi-span model does introduce additional challenges which must be addressed in the testing procedure. To minimize the influence of the sidewall boundary layer on the flow over the semi-span model, the model must be off-set from the sidewall. The objective is to remove the semi-span model from the sidewall boundary layer by use of a stand-off geometry. When this is done however, the symmetry along the centerline of the full-span model is lost when the semi-span model is mounted on the wind tunnel sidewall. In addition, the large semi-span model will impose a significant pressure loading on the sidewall boundary layer, which may cause separation. Even under flow conditions where the sidewall boundary layer remains attached, the sidewall boundary layer may adversely effect the flow over the semi-span model. Also, the increased model size and sidewall mounting requires a modified wall correction strategy. With these issues in mind, the semi-span model has been well instrumented with surface pressure taps to

Development of Semi-Span Model Test Techniques

NASA Technical Reports Server (NTRS)

Pulnam, L. Elwood (Technical Monitor); Milholen, William E., II; Chokani, Ndaona; McGhee, Robert J.

1996-01-01

A computational investigation was performed to support the development of a semi-span model test capability in the NASA Langley Research Center's National Transonic Facility. This capability is desirable for the testing of advanced subsonic transport aircraft at full-scale Reynolds numbers. A state-of-the-art three-dimensional Navier-Stokes solver was used to examine methods to improve the flow over a semi-span configuration. First, a parametric study is conducted to examine the influence of the stand-off height on the flow over the semi-span model. It is found that decreasing the stand-off height, below the maximum fuselage radius, improves the aerodynamic characteristics of the semi-span model. Next, active sidewall boundary layer control techniques are examined. Juncture region blowing jets, upstream tangential blowing, and sidewall suction are found to improve the flow over the aft portion of the semi-span model. Both upstream blowing and suction are found to reduce the sidewall boundary layer separation. The resulting near surface streamline patterns are improved, and found to be quite similar to the full-span results. Both techniques however adversely affect the pitching moment coefficient.

Dependence of deodorant usage on ABCC11 genotype: scope for personalized genetics in personal hygiene.

PubMed

Rodriguez, Santiago; Steer, Colin D; Farrow, Alexandra; Golding, Jean; Day, Ian N M

2013-07-01

Earwax type and axillary odor are genetically determined by rs17822931, a single-nucleotide polymorphism (SNP) located in the ABCC11 gene. The literature has been concerned with the Mendelian trait of earwax, although axillary odor is also Mendelian. Ethnic diversity in rs17822931 exists, with higher frequency of allele A in east Asians. Influence on deodorant usage has not been investigated. In this work, we present a detailed analysis of the rs17822931 effect on deodorant usage in a large (N∼17,000 individuals) population cohort (the Avon Longitudinal Study of Parents and Children (ALSPAC)). We found strong evidence (P=3.7 × 10(-20)) indicating differential deodorant usage according to the rs17822931 genotype. AA homozygotes were almost 5-fold overrepresented in categories of never using deodorant or using it infrequently. However, 77.8% of white European genotypically nonodorous individuals still used deodorant, and 4.7% genotypically odorous individuals did not. We provide evidence of a behavioral effect associated with rs17822931. This effect has a biological basis that can result in a change in the family's environment if an aerosol deodorant is used. It also indicates potential cost saving to the nonodorous and scope for personalized genetics usage in personal hygiene choices, with consequent reduction of inappropriate chemical exposures for some.

Auditory Brainstem Response (ABR) Abnormalities across the Life Span of Rats Prenatally Exposed to Alcohol

PubMed Central

Church, Michael W.; Hotra, John W.; Holmes, Pamela A.; Anumba, Jennifer I.; Jackson, Desmond A.; Adams, Brittany R.

2011-01-01

Background Fetal Alcohol Syndrome is a leading cause of neurodevelopmental impairments (NDI) in developed countries. Sensory deficits can play a major role in NDI, yet few studies have investigated the effects of prenatal alcohol exposure on sensory function. In addition, there is a paucity of information on the life-long effects of prenatal alcohol exposure. Thus, we sought to investigate the effects of prenatal alcohol exposure on auditory function across the life span in an animal model. Based on prior findings with prenatal alcohol exposure and other forms of adverse prenatal environments, we hypothesized that animals prenatally exposed to alcohol would show an age-dependent pattern of (A) hearing and neurological abnormalities as post-weanling pups, (B) a substantial dissipation of such abnormalities in young adulthood, and (C) a resurgence of such abnormalities in middle-aged adulthood. Method Pregnant rats were randomly assigned to an untreated control (CON), a pair-fed control (PFC) or an alcohol treated group (ALC). The ALC dams were gavaged with 6 mg/kg alcohol daily from gestation day (GD) 6 to 21. The PFC dams were gavaged daily from GD6-21 with an isocaloric and isovolumetric water-based solution of Maltose-Dextrins and pair-fed to the ALC dams. The CON dams were the untreated group to which the ALC and CON groups were compared. Hearing and neurological functions in the offspring were assessed with the Auditory Brainstem Response (ABR) at the postnatal ages of 22, 220 and 520 days of age. Results & Conclusions In accord with our hypothesis, ABR abnormalities were first observed in the post-weanling pups, largely dissipated in young adulthood, and then resurged in middle-aged adulthood. This age-related pattern suggests that the ALC pups had a developmental delay that dissipated in young adulthood and an enhanced age-related deterioration that occurred in middle-aged adulthood. Such a pattern is consistent with the fetal programming hypothesis of adult

Reconstructing life history of hominids and humans.

PubMed

Crews, Douglas E; Gerber, Linda M

2003-06-01

Aspects of life history, such as processes and timing of development, age at maturation, and life span are consistently associated with one another across the animal kingdom. Species that develop rapidly tend to mature and reproduce early, have many offspring, and exhibit shorter life spans (r-selection) than those that develop slowly, have extended periods of premature growth, mature later in life, reproduce later and less frequently, have few offspring and/or single births, and exhibit extended life spans (K-selection). In general, primates are among the most K-selected of species. A suite of highly derived life history traits characterizes humans. Among these are physically immature neonates, slowed somatic development both in utero and post-natally, late attainment of reproductive maturity and first birth, and extended post-mature survival. Exactly when, why, and through what types of evolutionary interactions this suite arose is currently the subject of much conjecture and debate. Humankind's biocultural adaptations have helped to structure human life history evolution in unique ways not seen in other animal species. Among all species, life history traits may respond rapidly to alterations in selective pressures through hormonal processes. Selective pressures on life history likely varied widely among hominids and humans over their evolutionary history. This suggests that current patterns of human growth, development, maturation, reproduction, and post-mature survival may be of recent genesis, rather then long-standing adaptations. Thus, life history patterns observed among contemporary human and chimpanzee populations may provide little insight to those that existed earlier in hominid/human evolution.

Social relationships and physiological determinants of longevity across the human life span

PubMed Central

Yang, Yang Claire; Boen, Courtney; Gerken, Karen; Li, Ting; Schorpp, Kristen; Harris, Kathleen Mullan

2016-01-01

Two decades of research indicate causal associations between social relationships and mortality, but important questions remain as to how social relationships affect health, when effects emerge, and how long they last. Drawing on data from four nationally representative longitudinal samples of the US population, we implemented an innovative life course design to assess the prospective association of both structural and functional dimensions of social relationships (social integration, social support, and social strain) with objectively measured biomarkers of physical health (C-reactive protein, systolic and diastolic blood pressure, waist circumference, and body mass index) within each life stage, including adolescence and young, middle, and late adulthood, and compare such associations across life stages. We found that a higher degree of social integration was associated with lower risk of physiological dysregulation in a dose–response manner in both early and later life. Conversely, lack of social connections was associated with vastly elevated risk in specific life stages. For example, social isolation increased the risk of inflammation by the same magnitude as physical inactivity in adolescence, and the effect of social isolation on hypertension exceeded that of clinical risk factors such as diabetes in old age. Analyses of multiple dimensions of social relationships within multiple samples across the life course produced consistent and robust associations with health. Physiological impacts of structural and functional dimensions of social relationships emerge uniquely in adolescence and midlife and persist into old age. PMID:26729882

Social relationships and physiological determinants of longevity across the human life span.

PubMed

Yang, Yang Claire; Boen, Courtney; Gerken, Karen; Li, Ting; Schorpp, Kristen; Harris, Kathleen Mullan

2016-01-19

Two decades of research indicate causal associations between social relationships and mortality, but important questions remain as to how social relationships affect health, when effects emerge, and how long they last. Drawing on data from four nationally representative longitudinal samples of the US population, we implemented an innovative life course design to assess the prospective association of both structural and functional dimensions of social relationships (social integration, social support, and social strain) with objectively measured biomarkers of physical health (C-reactive protein, systolic and diastolic blood pressure, waist circumference, and body mass index) within each life stage, including adolescence and young, middle, and late adulthood, and compare such associations across life stages. We found that a higher degree of social integration was associated with lower risk of physiological dysregulation in a dose-response manner in both early and later life. Conversely, lack of social connections was associated with vastly elevated risk in specific life stages. For example, social isolation increased the risk of inflammation by the same magnitude as physical inactivity in adolescence, and the effect of social isolation on hypertension exceeded that of clinical risk factors such as diabetes in old age. Analyses of multiple dimensions of social relationships within multiple samples across the life course produced consistent and robust associations with health. Physiological impacts of structural and functional dimensions of social relationships emerge uniquely in adolescence and midlife and persist into old age.

Increased production of mitochondrial reactive oxygen species and reduced adult life span in an insecticide-resistant strain of Anopheles gambiae

PubMed Central

Otali, Dennis; Novak, Robert J.; Wan, Wen; Bu, Su; Moellering, Douglas R.; De Luca, Maria

2014-01-01

Control of the malaria vector An. gambiae is still largely obtained through chemical intervention using pyrethroids, such as permethrin. However, strains of An. gambiae that are resistant to the toxic effects of pyrethroids have become widespread in several endemic areas over the last decade. The objective of this study was to assess differences in five life-history traits (larval developmental time and the body weight, fecundity, hatch rate, and longevity of adult females) and energy metabolism between a strain of An. gambiae that is resistant to permethrin (RSP), due to knockdown resistance and enhanced metabolic detoxification, and a permethrin susceptible strain reared under laboratory conditions. We also quantified the expression levels of five antioxidant enzyme genes: GSTe3, CAT, GPXH1, SOD1, and SOD2. We found that the RSP strain had a longer developmental time than the susceptible strain. Additionally, RSP adult females had higher wet body weight and increased water and glycogen levels. Compared to permethrin susceptible females, RSP females displayed reduced metabolic rate and mitochondrial coupling efficiency and higher mitochondrial ROS production. Furthermore, despite higher levels of GSTe3 and CAT transcripts, RSP females had a shorter adult life span than susceptible females. Collectively, these results suggest that permethrin resistance alleles might affect energy metabolism, oxidative stress, and adult survival of An. gambiae. However, because the strains used in this study differ in their genetic backgrounds, the results need to be interpreted with caution and replicated in other strains in order to have significant implications for malaria transmission and vector control. PMID:24555527

Type 2 Diabetes–Associated Missense Polymorphisms KCNJ11 E23K and ABCC8 A1369S Influence Progression to Diabetes and Response to Interventions in the Diabetes Prevention Program

PubMed Central

Florez, Jose C.; Jablonski, Kathleen A.; Kahn, Steven E.; Franks, Paul W.; Dabelea, Dana; Hamman, Richard F.; Knowler, William C.; Nathan, David M.; Altshuler, David

2008-01-01

The common polymorphisms KCNJ11 E23K and ABCC8 A1369S have been consistently associated with type 2 diabetes. We examined whether these variants are also associated with progression from impaired glucose tolerance (IGT) to diabetes and responses to preventive interventions in the Diabetes Prevention Program. We genotyped both variants in 3,534 participants and performed Cox regression analysis using genotype, intervention, and their interactions as predictors of diabetes incidence over ~3 years. We also assessed the effect of genotype on insulin secretion and insulin sensitivity at 1 year. As previously shown in other studies, lysine carriers at KCNJ11 E23K had reduced insulin secretion at baseline; however, they were less likely to develop diabetes than E/E homozygotes. Lysine carriers were less protected by 1-year metformin treatment than E/E homozygotes (P < 0.02). Results for ABCC8 A1369S were essentially identical to those for KCNJ11 E23K. We conclude that the lysine variant in KCNJ11 E23K leads to diminished insulin secretion in individuals with IGT. Given our contrasting results compared with case-control analyses, we hypothesize that its effect on diabetes risk may occur before the IGT-to-diabetes transition. We further hypothesize that the diabetes-preventive effect of metformin may interact with the impact of these variants on insulin regulation. Diabetes 56: 531–536, 2007 PMID:17259403

Relating Life-Span Research to the Development of Gifted and Talented Children. Abstracts of Selected Papers [from] The Annual Esther Katz Rosen Symposium on the Psychological Development of Gifted Children (3rd, Lawrence, Kansas, February 19-20, 1993).

ERIC Educational Resources Information Center

Kansas Univ., Lawrence.

This monograph presents abstracts of 29 papers that relate life-span research to the development of gifted and talented children. Sample topics include: attitudes about rural schools and programs for the gifted; social competence, self-esteem, and parent-child time and interaction in an advantaged subculture; helping families of gifted children…

Span graphics display utilities handbook, first edition

NASA Technical Reports Server (NTRS)

Gallagher, D. L.; Green, J. L.; Newman, R.

1985-01-01

The Space Physics Analysis Network (SPAN) is a computer network connecting scientific institutions throughout the United States. This network provides an avenue for timely, correlative research between investigators, in a multidisciplinary approach to space physics studies. An objective in the development of SPAN is to make available direct and simplified procedures that scientists can use, without specialized training, to exchange information over the network. Information exchanges include raw and processes data, analysis programs, correspondence, documents, and graphite images. This handbook details procedures that can be used to exchange graphic images over SPAN. The intent is to periodically update this handbook to reflect the constantly changing facilities available on SPAN. The utilities described within reflect an earnest attempt to provide useful descriptions of working utilities that can be used to transfer graphic images across the network. Whether graphic images are representative of satellite servations or theoretical modeling and whether graphics images are of device dependent or independent type, the SPAN graphics display utilities handbook will be the users guide to graphic image exchange.

Computational analysis of semi-span model test techniques

NASA Technical Reports Server (NTRS)

Milholen, William E., II; Chokani, Ndaona

1996-01-01

A computational investigation was conducted to support the development of a semi-span model test capability in the NASA LaRC's National Transonic Facility. This capability is required for the testing of high-lift systems at flight Reynolds numbers. A three-dimensional Navier-Stokes solver was used to compute the low-speed flow over both a full-span configuration and a semi-span configuration. The computational results were found to be in good agreement with the experimental data. The computational results indicate that the stand-off height has a strong influence on the flow over a semi-span model. The semi-span model adequately replicates the aerodynamic characteristics of the full-span configuration when a small stand-off height, approximately twice the tunnel empty sidewall boundary layer displacement thickness, is used. Several active sidewall boundary layer control techniques were examined including: upstream blowing, local jet blowing, and sidewall suction. Both upstream tangential blowing, and sidewall suction were found to minimize the separation of the sidewall boundary layer ahead of the semi-span model. The required mass flow rates are found to be practicable for testing in the NTF. For the configuration examined, the active sidewall boundary layer control techniques were found to be necessary only near the maximum lift conditions.

Developmental Changes in the Visual Span for Reading

PubMed Central

Kwon, MiYoung; Legge, Gordon E.; Dubbels, Brock R.

2007-01-01

The visual span for reading refers to the range of letters, formatted as in text, that can be recognized reliably without moving the eyes. It is likely that the size of the visual span is determined primarily by characteristics of early visual processing. It has been hypothesized that the size of the visual span imposes a fundamental limit on reading speed (Legge, Mansfield, & Chung, 2001). The goal of the present study was to investigate developmental changes in the size of the visual span in school-age children, and the potential impact of these changes on children’s reading speed. The study design included groups of 10 children in 3rd, 5th, and 7th grade, and 10 adults. Visual span profiles were measured by asking participants to recognize letters in trigrams (random strings of three letters) flashed for 100 ms at varying letter positions left and right of the fixation point. Two print sizes (0.25° and 1.0°) were used. Over a block of trials, a profile was built up showing letter recognition accuracy (% correct) versus letter position. The area under this profile was defined to be the size of the visual span. Reading speed was measured in two ways: with Rapid Serial Visual Presentation (RSVP) and with short blocks of text (termed Flashcard presentation). Consistent with our prediction, we found that the size of the visual span increased linearly with grade level and it was significantly correlated with reading speed for both presentation methods. Regression analysis using the size of the visual span as a predictor indicated that 34% to 52% of variability in reading speeds can be accounted for by the size of the visual span. These findings are consistent with a significant role of early visual processing in the development of reading skills. PMID:17845810

General closeup view of the swing span bridge in the ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

General close-up view of the swing span bridge in the close position, looking upriver. The pivot/center pier is positioned in the center of Tennessee River. Note: Each arm of the continuous swing span acts as simple spans. The total span over four (4) supports is partially continuous-- the middle panel at the center pier is continuous for bending moments, but discontinuous for shears. - Bridgeport Swing Span Bridge, Spanning Tennessee River, Bridgeport, Jackson County, AL

Clinical and molecular characterisation of 300 patients with congenital hyperinsulinism

PubMed Central

Kapoor, Ritika R; Flanagan, Sarah E; Arya, Ved Bhushan; Shield, Julian P; Ellard, Sian; Hussain, Khalid

2013-01-01

Background Congenital hyperinsulinism (CHI) is a clinically heterogeneous condition. Mutations in eight genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A and HNF1A) are known to cause CHI. Aim To characterise the clinical and molecular aspects of a large cohort of patients with CHI. Methodology Three hundred patients were recruited and clinical information was collected before genotyping. ABCC8 and KCNJ11 genes were analysed in all patients. Mutations in GLUD1, HADH, GCK and HNF4A genes were sought in patients with diazoxide-responsive CHI with hyperammonaemia (GLUD1), raised 3-hydroxybutyrylcarnitine and/or consanguinity (HADH), positive family history (GCK) or when CHI was diagnosed within the first week of life (HNF4A). Results Mutations were identified in 136/300 patients (45.3%). Mutations in ABCC8/KCNJ11 were the commonest genetic cause identified (n=109, 36.3%). Among diazoxide-unresponsive patients (n=105), mutations in ABCC8/KCNJ11 were identified in 92 (87.6%) patients, of whom 63 patients had recessively inherited mutations while four patients had dominantly inherited mutations. A paternal mutation in the ABCC8/KCNJ11 genes was identified in 23 diazoxide-unresponsive patients, of whom six had diffuse disease. Among the diazoxide-responsive patients (n=183), mutations were identified in 41 patients (22.4%). These include mutations in ABCC8/KCNJ11 (n=15), HNF4A (n=7), GLUD1 (n=16) and HADH (n=3). Conclusions A genetic diagnosis was made for 45.3% of patients in this large series. Mutations in the ABCC8 gene were the commonest identifiable cause. The vast majority of patients with diazoxide-responsive CHI (77.6%) had no identifiable mutations, suggesting other genetic and/or environmental mechanisms. PMID:23345197

Integrating Varieties of Life Course Concepts

PubMed Central

2012-01-01

A body of work referred to as the “life course” framework (also known as “life course theory,” the “life course paradigm,” and the “life course perspective”) has been increasingly used to motivate and justify the examination of the relationships among variables in social and behavioral science, particularly in the study of population health and aging. Yet, there is very little agreement on what some of these concepts mean, and there is hardly any agreement on what the “life course” is. This article focuses on the different ways in which the concept of “life course” is used in the contemporary study of aging and human development, particularly with regard to health and well-being. Clarification is given for how “life course” is distinguished from “life span” and “life cycle,” among other “life” words. This work reviews the conceptual literature on the life course, beginning with its formative years in the 1960s and 1970s, through to the present time. Detailed research of several literatures across disciplines revealed five different uses of the term “life course”: (a) life course as time or age, (b) life course as life stages, (c) life course as events, transitions, and trajectories, (d) life course as life-span human development, and (e) life course as early life influences (and their cumulation) on later adult outcomes. To the extent the concept of life course has a multiplicity of meanings that are at variance with one another, this is problematic, as communication is thereby hindered. On the other hand, to the extent the concept of life course involves a rich tapestry of different emphases, this is a good thing, and the diversity of meanings should be retained. This paper proposes a conceptual integration based in part on Riley’s age stratification model that resolves the various meanings of life course into one general framework. Coupled with a demographic conceptualization of the life course, this framework embeds

Malingering in Toxic Exposure. Classification Accuracy of Reliable Digit Span and WAIS-III Digit Span Scaled Scores

ERIC Educational Resources Information Center

Greve, Kevin W.; Springer, Steven; Bianchini, Kevin J.; Black, F. William; Heinly, Matthew T.; Love, Jeffrey M.; Swift, Douglas A.; Ciota, Megan A.

2007-01-01

This study examined the sensitivity and false-positive error rate of reliable digit span (RDS) and the WAIS-III Digit Span (DS) scaled score in persons alleging toxic exposure and determined whether error rates differed from published rates in traumatic brain injury (TBI) and chronic pain (CP). Data were obtained from the files of 123 persons…

Dependence of Deodorant Usage on ABCC11 Genotype: Scope for Personalized Genetics in Personal Hygiene

PubMed Central

Rodriguez, Santiago; Steer, Colin D; Farrow, Alexandra; Golding, Jean; Day, Ian N M

2013-01-01

Earwax type and axillary odor are genetically determined by rs17822931, a single-nucleotide polymorphism (SNP) located in the ABCC11 gene. The literature has been concerned with the Mendelian trait of earwax, although axillary odor is also Mendelian. Ethnic diversity in rs17822931 exists, with higher frequency of allele A in east Asians. Influence on deodorant usage has not been investigated. In this work, we present a detailed analysis of the rs17822931 effect on deodorant usage in a large (N∼17,000 individuals) population cohort (the Avon Longitudinal Study of Parents and Children (ALSPAC)). We found strong evidence (P=3.7 × 10−20) indicating differential deodorant usage according to the rs17822931 genotype. AA homozygotes were almost 5-fold overrepresented in categories of never using deodorant or using it infrequently. However, 77.8% of white European genotypically nonodorous individuals still used deodorant, and 4.7% genotypically odorous individuals did not. We provide evidence of a behavioral effect associated with rs17822931. This effect has a biological basis that can result in a change in the family's environment if an aerosol deodorant is used. It also indicates potential cost saving to the nonodorous and scope for personalized genetics usage in personal hygiene choices, with consequent reduction of inappropriate chemical exposures for some. PMID:23325016

Span efficiency of wings with leading edge protuberances

NASA Astrophysics Data System (ADS)

Custodio, Derrick; Henoch, Charles; Johari, Hamid

2013-11-01

Past work has shown that sinusoidal leading edge protuberances resembling those found on humpback whale flippers alter the lift and drag coefficients of full- and finite-span foils and wings depending on the angle of attack and leading edge geometry. Although the load characteristics of protuberance modified finite-span wings have been reported for flipper-like geometries at higher Reynolds numbers and for rectangular planforms at lower Reynolds numbers, the effects of leading edge geometry on the span efficiency, which is indicative of the deviation of the spanwise lift distribution from elliptical and the viscous effects, for a range of planforms and Reynolds numbers have not been addressed. The lift and drag coefficients of 7 rectangular, 2 swept, and 2 flipper-like planform models with aspect ratios of 4.3, 4.0, and 8.86, respectively, were used to compute the span efficiency at Reynolds numbers ranging from 0.9 to 4.5 × 105. The span efficiency, based on the data at lower angles of attack, of modified wings was compared with the unmodified models. For the cases considered, the span efficiencies of the leading edge modified models were less than those of the equivalent unmodified models. The dependence of span efficiency on the leading edge geometry, planform, and Reynolds number will be presented. Supported by the ONR-ULI program.

Comparison of wing-span averaging effects on lift, rolling moment, and bending moment for two span load distributions and for two turbulence representations

NASA Technical Reports Server (NTRS)

Lichtenstein, J. H.

1978-01-01

An analytical method of computing the averaging effect of wing-span size on the loading of a wing induced by random turbulence was adapted for use on a digital electronic computer. The turbulence input was assumed to have a Dryden power spectral density. The computations were made for lift, rolling moment, and bending moment for two span load distributions, rectangular and elliptic. Data are presented to show the wing-span averaging effect for wing-span ratios encompassing current airplane sizes. The rectangular wing-span loading showed a slightly greater averaging effect than did the elliptic loading. In the frequency range most bothersome to airplane passengers, the wing-span averaging effect can reduce the normal lift load, and thus the acceleration, by about 7 percent for a typical medium-sized transport. Some calculations were made to evaluate the effect of using a Von Karman turbulence representation. These results showed that using the Von Karman representation generally resulted in a span averaging effect about 3 percent larger.

Activation of the AMPK/Sirt1 pathway by a leucine-metformin combination increases insulin sensitivity in skeletal muscle, and stimulates glucose and lipid metabolism and increases life span in Caenorhabditis elegans.

PubMed

Banerjee, Jheelam; Bruckbauer, Antje; Zemel, Michael B

2016-11-01

We have previously shown leucine (Leu) to activate Sirt1 by lowering its K M for NAD + , thereby amplifying the effects of other sirtuin activators and improving insulin sensitivity. Metformin (Met) converges on this pathway both indirectly (via AMPK) and by direct activation of Sirt1, and we recently found Leu to synergize with Met to improve insulin sensitivity and glycemic control while achieving ~80% dose-reduction in diet-induced obese mice. Accordingly, we sought here to define the mechanism of this interaction. Muscle cells C2C12 and liver cells HepG2 were used to test the effect of Met-Leu on Sirt1 activation. Caenorhabditis elegans was used for glucose utilization and life span studies. Leu (0.5mmol/L)+Met (50-100μmol/L) synergistically activated Sirt1 (p<0.001) at low (≤100μmol/L) NAD + levels while Met exerted no independent effect. This was associated with an increase in AMPK and ACC, phosphorylation, and increased fatty acid oxidation, which was prevented by AMPK or Sirt inhibition or silencing. Met-Leu also increased P-IRS1/IRS1 and P-AKT/AKT and in insulin-independent glucose disposal in myotubes (~50%, p<0.002) evident within 30 min as well as a 60% reduction in insulin EC 50 . In addition, in HepG2 liver cells nuclear CREB regulated transcription coactivator 2 (CRTC2) protein expression and phosphorylation of glycogen synthase was decreased, while glycogen synthase kinase phosphorylation was increased indicating decreased gluconeogenesis and glycogen synthesis. We utilized C. elegans to assess the metabolic consequences of this interaction. Exposure to high glucose impaired glucose utilization and shortened life span by ~25%, while addition of Leu+Met to high glucose worms increased median and maximal life span by 29 and 15%, respectively (p=0.023), restored normal glucose utilization and increased fat oxidation ~two-fold (p<0.005), while metformin exerted no independent effect at any concentration (0.1-0.5mmol/L). Thus, Leu and Met synergize

Electrode spanning with partial tripolar stimulation mode in cochlear implants.

PubMed

Wu, Ching-Chih; Luo, Xin

2014-12-01

The perceptual effects of electrode spanning (i.e., the use of nonadjacent return electrodes) in partial tripolar (pTP) mode were tested on a main electrode EL8 in five cochlear implant (CI) users. Current focusing was controlled by σ (the ratio of current returned within the cochlea), and current steering was controlled by α (the ratio of current returned to the basal electrode). Experiment 1 tested whether asymmetric spanning with α = 0.5 can create additional channels around standard pTP stimuli. It was found that in general, apical spanning (i.e., returning current to EL6 rather than EL7) elicited a pitch between those of standard pTP stimuli on main electrodes EL8 and EL9, while basal spanning (i.e., returning current to EL10 rather than EL9) elicited a pitch between those of standard pTP stimuli on main electrodes EL7 and EL8. The pitch increase caused by apical spanning was more salient than the pitch decrease caused by basal spanning. To replace the standard pTP channel on the main electrode EL8 when EL7 or EL9 is defective, experiment 2 tested asymmetrically spanned pTP stimuli with various α, and experiment 3 tested symmetrically spanned pTP stimuli with various σ. The results showed that pitch increased with decreasing α in asymmetric spanning, or with increasing σ in symmetric spanning. Apical spanning with α around 0.69 and basal spanning with α around 0.38 may both elicit a similar pitch as the standard pTP stimulus. With the same σ, the symmetrically spanned pTP stimulus was higher in pitch than the standard pTP stimulus. A smaller σ was thus required for symmetric spanning to match the pitch of the standard pTP stimulus. In summary, electrode spanning is an effective field-shaping technique that is useful for adding spectral channels and handling defective electrodes with CIs.

Enumeration of spanning trees in planar unclustered networks

NASA Astrophysics Data System (ADS)

Xiao, Yuzhi; Zhao, Haixing; Hu, Guona; Ma, Xiujuan

2014-07-01

Among a variety of subgraphs, spanning trees are one of the most important and fundamental categories. They are relevant to diverse aspects of networks, including reliability, transport, self-organized criticality, loop-erased random walks and so on. In this paper, we introduce a family of modular, self-similar planar networks with zero clustering. Relevant properties of this family are comparable to those networks associated with technological systems having low clustering, like power grids, some electronic circuits, the Internet and some biological systems. So, it is very significant to research on spanning trees of planar networks. However, for a large network, evaluating the relevant determinant is intractable. In this paper, we propose a fairly generic linear algorithm for counting the number of spanning trees of a planar network. Using the algorithm, we derive analytically the exact numbers of spanning trees in planar networks. Our result shows that the computational complexity is O(t) , which is better than that of the matrix tree theorem with O(m2t2) , where t is the number of steps and m is the girth of the planar network. We also obtain the entropy for the spanning trees of a given planar network. We find that the entropy of spanning trees in the studied network is small, which is in sharp contrast to the previous result for planar networks with the same average degree. We also determine an upper bound and a lower bound for the numbers of spanning trees in the family of planar networks by the algorithm. As another application of the algorithm, we give a formula for the number of spanning trees in an outerplanar network with small-world features.

Developmental dyslexia: the visual attention span deficit hypothesis.

PubMed

Bosse, Marie-Line; Tainturier, Marie Josèphe; Valdois, Sylviane

2007-08-01

The visual attention (VA) span is defined as the amount of distinct visual elements which can be processed in parallel in a multi-element array. Both recent empirical data and theoretical accounts suggest that a VA span deficit might contribute to developmental dyslexia, independently of a phonological disorder. In this study, this hypothesis was assessed in two large samples of French and British dyslexic children whose performance was compared to that of chronological-age matched control children. Results of the French study show that the VA span capacities account for a substantial amount of unique variance in reading, as do phonological skills. The British study replicates this finding and further reveals that the contribution of the VA span to reading performance remains even after controlling IQ, verbal fluency, vocabulary and single letter identification skills, in addition to phoneme awareness. In both studies, most dyslexic children exhibit a selective phonological or VA span disorder. Overall, these findings support a multi-factorial view of developmental dyslexia. In many cases, developmental reading disorders do not seem to be due to phonological disorders. We propose that a VA span deficit is a likely alternative underlying cognitive deficit in dyslexia.

Introduction to the Space Physics Analysis Network (SPAN)

NASA Technical Reports Server (NTRS)

Green, J. L. (Editor); Peters, D. J. (Editor)

1985-01-01

The Space Physics Analysis Network or SPAN is emerging as a viable method for solving an immediate communication problem for the space scientist. SPAN provides low-rate communication capability with co-investigators and colleagues, and access to space science data bases and computational facilities. The SPAN utilizes up-to-date hardware and software for computer-to-computer communications allowing binary file transfer and remote log-on capability to over 25 nationwide space science computer systems. SPAN is not discipline or mission dependent with participation from scientists in such fields as magnetospheric, ionospheric, planetary, and solar physics. Basic information on the network and its use are provided. It is anticipated that SPAN will grow rapidly over the next few years, not only from the standpoint of more network nodes, but as scientists become more proficient in the use of telescience, more capability will be needed to satisfy the demands.

9. VIEW SHOWING JUNCTION OF CONCRETE EAST APPROACH SPAN WITH ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

9. VIEW SHOWING JUNCTION OF CONCRETE EAST APPROACH SPAN WITH STEEL SPAN, LOOKING NORTH. NOTE ROCKING CAST STEEL SHOE ATTACHED TO PIER TO ALLOW FOR EXPANSION OF STEEL SPAN - Jensen Bridge, Spanning Green River at Town of Jensen, Jensen, Uintah County, UT

C-SPAN in the High School Classroom: A Guide for Educators.

ERIC Educational Resources Information Center

C-SPAN, Washington, DC.

Intended for middle and high school educators, the publication provides information about the C-SPAN networks and facilitates the use of the network's programming as a teaching resource. The section on the C-SPAN cable networks contains information on C-SPAN, C-SPAN 2, C-SPAN Audio 1, and C-SPAN Audio 2, regularly scheduled programs, ways to…