Multi-tissue DNA methylation age predictor in mouse.

PubMed

Stubbs, Thomas M; Bonder, Marc Jan; Stark, Anne-Katrien; Krueger, Felix; von Meyenn, Ferdinand; Stegle, Oliver; Reik, Wolf

2017-04-11

DNA methylation changes at a discrete set of sites in the human genome are predictive of chronological and biological age. However, it is not known whether these changes are causative or a consequence of an underlying ageing process. It has also not been shown whether this epigenetic clock is unique to humans or conserved in the more experimentally tractable mouse. We have generated a comprehensive set of genome-scale base-resolution methylation maps from multiple mouse tissues spanning a wide range of ages. Many CpG sites show significant tissue-independent correlations with age which allowed us to develop a multi-tissue predictor of age in the mouse. Our model, which estimates age based on DNA methylation at 329 unique CpG sites, has a median absolute error of 3.33 weeks and has similar properties to the recently described human epigenetic clock. Using publicly available datasets, we find that the mouse clock is accurate enough to measure effects on biological age, including in the context of interventions. While females and males show no significant differences in predicted DNA methylation age, ovariectomy results in significant age acceleration in females. Furthermore, we identify significant differences in age-acceleration dependent on the lipid content of the diet. Here we identify and characterise an epigenetic predictor of age in mice, the mouse epigenetic clock. This clock will be instrumental for understanding the biology of ageing and will allow modulation of its ticking rate and resetting the clock in vivo to study the impact on biological age.

Accelerated telomere shortening and replicative senescence in human fibroblasts overexpressing mutant and wild-type lamin A

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

Huang Shurong; Risques, Rosa Ana; Martin, George M.

2008-01-01

LMNA mutations are responsible for a variety of genetic disorders, including muscular dystrophy, lipodystrophy, and certain progeroid syndromes, notably Hutchinson-Gilford Progeria. Although a number of clinical features of these disorders are suggestive of accelerated aging, it is not known whether cells derived from these patients exhibit cellular phenotypes associated with accelerated aging. We examined a series of isogenic skin fibroblast lines transfected with LMNA constructs bearing known pathogenic point mutations or deletion mutations found in progeroid syndromes. Fibroblasts overexpressing mutant lamin A exhibited accelerated rates of loss of telomeres and shortened replicative lifespans, in addition to abnormal nuclear morphology. Tomore » our surprise, these abnormalities were also observed in lines overexpressing wild-type lamin A. Copy number variants are common in human populations; those involving LMNA, whether arising meiotically or mitotically, might lead to progeroid phenotypes. In an initial pilot study of 23 progeroid cases without detectable WRN or LMNA mutations, however, no cases of altered LMNA copy number were detected. Nevertheless, our findings raise a hypothesis that changes in lamina organization may cause accelerated telomere attrition, with different kinetics for overexpession of wild-type and mutant lamin A, which leads to rapid replicative senescence and progroid phenotypes.« less

Early-life stress and reproductive cost: A two-hit developmental model of accelerated aging?

PubMed

Shalev, Idan; Belsky, Jay

2016-05-01

Two seemingly independent bodies of research suggest a two-hit model of accelerated aging, one highlighting early-life stress and the other reproduction. The first, informed by developmental models of early-life stress, highlights reduced longevity effects of early adversity on telomere erosion, whereas the second, informed by evolutionary theories of aging, highlights such effects with regard to reproductive cost (in females). The fact that both early-life adversity and reproductive effort are associated with shorter telomeres and increased oxidative stress raises the prospect, consistent with life-history theory, that these two theoretical frameworks currently informing much research are tapping into the same evolutionary-developmental process of increased senescence and reduced longevity. Here we propose a mechanistic view of a two-hit model of accelerated aging in human females through (a) early-life adversity and (b) early reproduction, via a process of telomere erosion, while highlighting mediating biological embedding mechanisms that might link these two developmental aging processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Accelerated aging-related transcriptome changes in the female prefrontal cortex

PubMed Central

Yuan, Yuan; Chen, Yi-Ping Phoebe; Boyd-Kirkup, Jerome; Khaitovich, Philipp; Somel, Mehmet

2012-01-01

Human female life expectancy is higher than that of males. Intriguingly, it has been reported that women display faster rates of age-related cognitive decline and a higher prevalence of Alzheimer’s disease (AD). To assess the molecular bases of these contradictory trends, we analyzed differences in expression changes with age between adult males and females, in four brain regions. In the superior frontal gyrus (SFG), a part of the prefrontal cortex, we observed manifest differences between the two sexes in the timing of age-related changes, that is, sexual heterochrony. Intriguingly, age-related expression changes predominantly occurred earlier, or at a faster pace, in females compared to men. These changes included decreased energy production and neural function and up-regulation of the immune response, all major features of brain aging. Furthermore, we found that accelerated expression changes in the female SFG correlated with expression changes observed in AD, as well as stress effects in the frontal cortex. Accelerated aging-related changes in the female SFG transcriptome may provide a link between a higher stress exposure or sensitivity in women and the higher prevalence of AD. PMID:22783978

Circadian disruption induced by light-at-night accelerates aging and promotes tumorigenesis in rats

PubMed Central

Vinogradova, Irina A.; Anisimov, Vladimir N.; Bukalev, Andrey V.; Semenchenko, Anna V.; Zabezhinski, Mark A.

2009-01-01

We evaluated the effect of various light/dark regimens on the survival, life span and tumorigenesis in rats. Two hundred eight male and 203 females LIO rats were subdivided into 4 groups and kept at various light/dark regimens: standard 12:12 light/dark (LD); natural lighting of the North-West of Russia (NL); constant light (LL), and constant darkness (DD) since the age of 25 days until natural death. We found that exposure to NL and LL regimens accelerated development of metabolic syndrome and spontaneous tumorigenesis, shortened life span both in male and females rats as compared to the standard LD regimen. We conclude that circadian disruption induced by light-at-night accelerates aging and promotes tumorigenesis in rats. This observation supports the conclusion of the International Agency Research on Cancer that shift-work that involves circadian disruption is probably carcinogenic to humans. PMID:20157558

Effect of extraoral aging conditions on mechanical properties of maxillofacial silicone elastomer.

PubMed

Hatamleh, Muhanad M; Polyzois, Gregory L; Silikas, Nick; Watts, David C

2011-08-01

The purpose of this study was to investigate the effect of extraoral human and environmental conditions on the mechanical properties (tensile strength and modulus, elongation, tear strength hardness) of maxillofacial silicone elastomer. Specimens were fabricated using TechSil-S25 silicone elastomer (Technovent Ltd, Leeds, UK). Eight groups were prepared (21 specimens in each group; eight tensile, eight tear, five hardness) and conditioned differently as follows (groups 1 through 8): Dry storage for 24 hours; dry storage in dark for 6 months; storage in simulated sebum solution for 6 months; storage in simulated acidic perspiration for 6 months; accelerated artificial daylight aging under controlled moisture for 360 hours; outdoor weathering for 6 months; storage in antimicrobial silicone-cleaning solution for 30 hours; and mixed conditioning of sebum storage and light aging for 360 hours. The conditioning period selected simulated a prosthesis being in service for up to 12 months. Tensile and tear test specimens were fabricated and tested according to the International Standards Organization (ISO) standards no. 37 and 34, respectively. Shore A hardness test specimens were fabricated and tested according to the American Standards for Testing and Materials (ASTM) D 2240. Data were analyzed with one-way ANOVA, Bonferroni, and Dunnett's T3 post hoc tests (p < 0.05). Weibull analysis was also used for tensile strength and tear strength. Statistically significant differences were evident among all properties tested. Mixed conditioning of simulated sebum storage under accelerated artificial daylight aging significantly degraded mechanical properties of the silicone (p < 0.05). Mechanical properties of maxillofacial elastomers are adversely affected by human and environmental factors. Mixed aging of storage in simulated sebum under accelerated daylight aging was the most degrading regime. Accelerated aging of silicone specimens in simulated sebum under artificial daylight for 12 months of simulated clinical service greatly affected functional properties of silicone elastomer; however, in real practice, the effect is modest, since sebum concentration is lower, and daylight is less concentrated. © 2011 by The American College of Prosthodontists.

The neuroregenerative capacity of olfactory stem cells is not limitless: implications for aging.

PubMed

Child, Kevin M; Herrick, Daniel B; Schwob, James E; Holbrook, Eric H; Jang, Woochan

2018-06-22

The olfactory epithelium (OE) of vertebrates is a highly regenerative neuroepithelium, maintained under normal condition by a population of stem and progenitor cells - globose basal cells (GBCs) that also contribute to epithelial reconstitution after injury. However, aging of the OE often leads to neurogenic exhaustion - the disappearance of both GBCs and olfactory sensory neurons (OSNs). Aneuronal tissue may remain as olfactory, with an uninterrupted sheet of apically arrayed microvillar-capped sustentacular cell, or may undergo respiratory metaplasia. We have generated a transgenic mouse model for neurogenic exhaustion using OMP-driven Tet-off regulation of the A subunit of Diphtheria toxin such that the death of mature OSNs is accelerated. As early as 2 months of age the epithelium of transgenic mice, regardless of sex, recapitulates what is seen in the aged OE of humans and rodents. Areas of the epithelium completely lack neurons and GBCs, while the horizontal basal cells, a reserve stem cell population, show no evidence of activation. Surprisingly, other areas that were olfactory undergo respiratory metaplasia. The impact of accelerated neuronal death and reduced innervation on the olfactory bulb (OB) is also examined. Constant neuronal turnover leaves glomeruli shrunken and impacts the dopaminergic interneurons in the periglomerular layer. Moreover, the acceleration of OSN death can be reversed in those areas where some GBCs persist. However, the projection onto the OB recovers incompletely and the reinnervated glomeruli are markedly altered. Thus, the capacity for OE regeneration is tempered when GBCs disappear. SIGNIFICANCE STATEMENT A large percentage of humans lose or suffer a significant decline in olfactory function as they age. Consequently, quality of life suffers, and safety and nutritional status are put at risk. With age, the OE apparently becomes incapable of fully maintaining the neuronal population of the epithelium despite its well-known capacity for recovering from most forms of injury when younger which may contribute to age-related olfactory loss. Efforts to identify the mechanism by which olfactory neurogenesis becomes exhausted with age require a powerful model for accelerating age-related tissue pathology. The current OMP-tTA ; TetO-DTA transgenic mouse model, in which olfactory neurons die when they reach maturity and accelerated death can be aborted to assess the capacity for structural recovery, satisfies that need. Copyright © 2018 the authors.

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

PubMed

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

2011-03-11

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

Effects of Horizontal Acceleration on Human Visual Acuity and Stereopsis

PubMed Central

Horng, Chi-Ting; Hsieh, Yih-Shou; Tsai, Ming-Ling; Chang, Wei-Kang; Yang, Tzu-Hung; Yauan, Chien-Han; Wang, Chih-Hung; Kuo, Wu-Hsien; Wu, Yi-Chang

2015-01-01

The effect of horizontal acceleration on human visual acuity and stereopsis is demonstrated in this study. Twenty participants (mean age 22.6 years) were enrolled in the experiment. Acceleration from two different directions was performed at the Taiwan High-Speed Rail Laboratory. Gx and Gy (< and >0.1 g) were produced on an accelerating platform where the subjects stood. The visual acuity and stereopsis of the right eye were measured before and during the acceleration. Acceleration <0.1 g in the X- or Y-axis did not affect dynamic vision and stereopsis. Vision decreased (mean from 0.02 logMAR to 0.25 logMAR) and stereopsis declined significantly (mean from 40 s to 60.2 s of arc) when Gx > 0.1 g. Visual acuity worsened (mean from 0.02 logMAR to 0.19 logMAR) and poor stereopsis was noted (mean from 40 s to 50.2 s of arc) when Gy > 0.1 g. The effect of acceleration from the X-axis on the visual system was higher than that from the Y-axis. During acceleration, most subjects complained of ocular strain when reading. To our knowledge, this study is the first to report the exact levels of visual function loss during Gx and Gy. PMID:25607601

Developmental profile of slow hand movement oscillation coupling in humans.

PubMed

Deutsch, Katherine M; Stephens, John A; Farmer, Simon F

2011-05-01

In adults, slow hand and finger movements are characterized by 6- to 12-Hz discontinuities visible in the raw records and spectra of motion signals such as acceleration. This pulsitile behavior is correlated with motor unit synchronization at 6-12 Hz as shown by significant coherence at these frequencies between pairs of motor units and between the motor units and the acceleration recorded from the limb part controlled by the muscle, suggesting that it has a central origin. In this study, we examined the correlation between this 6- to 12-Hz pulsatile behavior and muscle activity as a function of childhood development. Sixty-eight participants (ages 4-25 yr) performed static wrist extensions against gravity or slow wrist extension and flexion movements while extensor carpi radialis muscle electromyographic (EMG) and wrist acceleration signals were simultaneously recorded. Coherence between EMG and acceleration within the 6- to 12-Hz frequency band was used as an index of the strength of the relation between central drive and the motor output. The main findings of the study are 1) EMG-acceleration coherence increased with increases in age, with the age differences being greater under movement conditions and the difference between conditions increasing with age; 2) the EMG signal showed increases in normalized power with increases in age under both conditions; and 3) coherence under movement conditions was moderately positively correlated with manual dexterity. These findings indicate that the strength of the 6- to 12-Hz central oscillatory drive to the motor output increases through childhood development and may contribute to age-related improvements in motor skills.

Accelerated protein damage in brains of PIMT+/- mice; a possible model for the variability of cognitive decline in human aging.

PubMed

Qin, Zhenxia; Dimitrijevic, Aleksandra; Aswad, Dana W

2015-02-01

Isoaspartate formation is a common type of protein damage normally kept in check by the repair enzyme protein-L-isoaspartyl methyltransferase (PIMT). Mice with a knockout of the gene (Pcmt1) for this enzyme (KO, -/-) exhibit a pronounced neuropathology with fatal epileptic seizures at 30-60 days. Heterozygous (HZ, +/-) mice have 50% of the PIMT activity found in wild-type (WT, +/+) mice, but appear normal. To see if HZ mice exhibit accelerated aging at the molecular level, we compared brain extracts from HZ and WT mice at 8 months and 2 years with regard to PIMT activity, isoaspartate levels, and activity of an endogenous PIMT substrate, creatine kinase B. PIMT activity declined modestly with age in both genotypes. Isoaspartate was significantly higher in HZ than WT mice at 8 months and more so at 2 years, rising 5× faster in HZ males and 3× faster in females. Creatine kinase activity decreased with age and was always lower in the HZ mice. These findings suggest the individual variation of human PIMT levels may significantly influence the course of age-related central nervous system dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

A drug-induced accelerated senescence (DIAS) is a possibility to study aging in time lapse.

PubMed

Alili, Lirija; Diekmann, Johanna; Giesen, Melanie; Holtkötter, Olaf; Brenneisen, Peter

2014-06-01

Currently, the oxidative stress (or free radical) theory of aging is the most popular explanation of how aging occurs at the molecular level. Accordingly, a stress-induced senescence-like phenotype of human dermal fibroblasts can be induced in vitro by the exposure of human diploid fibroblasts to subcytotoxic concentrations of hydrogen peroxide. However, several biomarkers of replicative senescence e.g. cell cycle arrest and enlarged morphology are abrogated 14 days after treatment, indicating that reactive oxygen species (ROS) rather acts as a trigger for short-term senescence (1-3 days) than being responsible for the maintenance of the senescence-like phenotype. Further, DNA-damaging factors are discussed resulting in a permanent senescent cell type. To induce long-term premature senescence and to understand the molecular alterations occurring during the aging process, we analyzed mitomycin C (MMC) as an alkylating DNA-damaging agent and ROS producer. Human dermal fibroblasts (HDF), used as model for skin aging, were exposed to non-cytotoxic concentrations of MMC and analyzed for potential markers of cellular aging, for example enlarged morphology, activity of senescence-associated-ß-galactosidase, cell cycle arrest, increased ROS production and MMP1-activity, which are well-documented for HDF in replicative senescence. Our data show that mitomycin C treatment results in a drug-induced accelerated senescence (DIAS) with long-term expression of senescence markers, demonstrating that a combination of different susceptibility factors, here ROS and DNA alkylation, are necessary to induce a permanent senescent cell type.

Limitations of predicting in vivo biostability of multiphase polyurethane elastomers using temperature-accelerated degradation testing.

PubMed

Padsalgikar, Ajay; Cosgriff-Hernandez, Elizabeth; Gallagher, Genevieve; Touchet, Tyler; Iacob, Ciprian; Mellin, Lisa; Norlin-Weissenrieder, Anna; Runt, James

2015-01-01

Polyurethane biostability has been the subject of intense research since the failure of polyether polyurethane pacemaker leads in the 1980s. Accelerated in vitro testing has been used to isolate degradation mechanisms and predict clinical performance of biomaterials. However, validation that in vitro methods reproduce in vivo degradation is critical to the selection of appropriate tests. High temperature has been proposed as a method to accelerate degradation. However, correlation of such data to in vivo performance is poor for polyurethanes due to the impact of temperature on microstructure. In this study, we characterize the lack of correlation between hydrolytic degradation predicted using a high temperature aging model of a polydimethylsiloxane-based polyurethane and its in vivo performance. Most notably, the predicted molecular weight and tensile property changes from the accelerated aging study did not correlate with clinical explants subjected to human biological stresses in real time through 5 years. Further, DMTA, ATR-FTIR, and SAXS experiments on samples aged for 2 weeks in PBS indicated greater phase separation in samples aged at 85°C compared to those aged at 37°C and unaged controls. These results confirm that microstructural changes occur at high temperatures that do not occur at in vivo temperatures. In addition, water absorption studies demonstrated that water saturation levels increased significantly with temperature. This study highlights that the multiphase morphology of polyurethane precludes the use of temperature accelerated biodegradation for the prediction of clinical performance and provides critical information in designing appropriate in vitro tests for this class of materials. © 2014 Wiley Periodicals, Inc.

The MiAge Calculator: a DNA methylation-based mitotic age calculator of human tissue types.

PubMed

Youn, Ahrim; Wang, Shuang

2018-01-01

Cell division is important in human aging and cancer. The estimation of the number of cell divisions (mitotic age) of a given tissue type in individuals is of great interest as it allows not only the study of biological aging (using a new molecular aging target) but also the stratification of prospective cancer risk. Here, we introduce the MiAge Calculator, a mitotic age calculator based on a novel statistical framework, the MiAge model. MiAge is designed to quantitatively estimate mitotic age (total number of lifetime cell divisions) of a tissue using the stochastic replication errors accumulated in the epigenetic inheritance process during cell divisions. With the MiAge model, the MiAge Calculator was built using the training data of DNA methylation measures of 4,020 tumor and adjacent normal tissue samples from eight TCGA cancer types and was tested using the testing data of DNA methylation measures of 2,221 tumor and adjacent normal tissue samples of five other TCGA cancer types. We showed that within each of the thirteen cancer types studied, the estimated mitotic age is universally accelerated in tumor tissues compared to adjacent normal tissues. Across the thirteen cancer types, we showed that worse cancer survivals are associated with more accelerated mitotic age in tumor tissues. Importantly, we demonstrated the utility of mitotic age by showing that the integration of mitotic age and clinical information leads to improved survival prediction in six out of the thirteen cancer types studied. The MiAge Calculator is available at http://www.columbia.edu/∼sw2206/softwares.htm .

A Normative Data Study of Isometric Neck Strength in Healthy, Adult, Males Ages 18-35

DTIC Science & Technology

1990-01-01

Jonsson (Ed.), Int’l Series on Biomechanics X-A, 6A, (pp. 29-33). Champaign, IL: Human Kinetics Publishers, Inc. Fess, E. & Moran, C. (1981). Clinical...IL: Human Kinetics Publishers, Inc. Harms-Ringdahl, K, Ekholm, J., Schuldt, K, Nemeth, G., & Arborelius U. P. (1986). Load moments and myoelectric...Champaign, IL: Human Kinetics Publishers. Helleur, C., Gracovetsky, S., & Farfan, H. (1984). Tolerance of the human cervical spine to high acceleration: a

Oxidative stress-induced telomeric erosion as a mechanism underlying airborne particulate matter-related cardiovascular disease

PubMed Central

2012-01-01

Particulate matter (PM) pollution is responsible for hundreds of thousands of deaths worldwide, the majority due to cardiovascular disease (CVD). While many potential pathophysiological mechanisms have been proposed, there is not yet a consensus as to which are most important in causing pollution-related morbidity/mortality. Nor is there consensus regarding which specific types of PM are most likely to affect public health in this regard. One toxicological mechanism linking exposure to airborne PM with CVD outcomes is oxidative stress, a contributor to the development of CVD risk factors including atherosclerosis. Recent work suggests that accelerated shortening of telomeres and, thus, early senescence of cells may be an important pathway by which oxidative stress may accelerate biological aging and the resultant development of age-related morbidity. This pathway may explain a significant proportion of PM-related adverse health outcomes, since shortened telomeres accelerate the progression of many diseases. There is limited but consistent evidence that vehicular emissions produce oxidative stress in humans. Given that oxidative stress is associated with accelerated erosion of telomeres, and that shortened telomeres are linked with acceleration of biological ageing and greater incidence of various age-related pathology, including CVD, it is hypothesized that associations noted between certain pollution types and sources and oxidative stress may reflect a mechanism by which these pollutants result in CVD-related morbidity and mortality, namely accelerated aging via enhanced erosion of telomeres. This paper reviews the literature providing links among oxidative stress, accelerated erosion of telomeres, CVD, and specific sources and types of air pollutants. If certain PM species/sources might be responsible for adverse health outcomes via the proposed mechanism, perhaps the pathway to reducing mortality/morbidity from PM would become clearer. Not only would pollution reduction imperatives be more focused, but interventions which could reduce oxidative stress would become all the more important. PMID:22713210

The menopausal mouse: a new neural paradigm of a distressing human condition.

PubMed

Danilovich, Natalia; Sairam, M Ram; Maysinger, Dusica

2003-08-26

Progressive and long-term sex hormone imbalance in the FSH-R haploinsufficient menopausal mouse leads to degenerative changes in the CNS associated with increased anxiety. The brain region most affected by aging in these mice is the hippocampus. Choline acetyltransferase (ChAT) enzymatic activity and synapsin immunoreactivity are reduced at 20 months of age. Neurons in the dentate gyrus show signs of progressive degenerative changes, hypertrophy and glyosis, and subsequent cell shrinkage and death. These results suggest that the menopausal mouse mimics degenerative changes in the hippocampus of hormonally imbalanced aging humans. We propose using this animal model to test the effectiveness of potential therapeutics in paradigms of accelerated aging.

The Effect of Aircrew Age on +Gz Tolerance as Measured in a Human-Use Centrifuge

DTIC Science & Technology

2000-08-01

acceleration stress (+Gz). This type of acceleration displaces blood in the head to foot direction. As the pressure in the vessels of the lower body... blood in the lower extremities translates into reduced cardiac output provoking the cardiovascular system, mainly by the activation of baroreceptor ...This pressure aids the cardiovascular system to maintain adequate blood flow to the CNS by forcing blood towards the head "counteracting" the effect of

Evaluating the Role of p38 MAPK in the Accelerated Cell Senescence of Werner Syndrome Fibroblasts

PubMed Central

Davis, Terence; Brook, Amy J. C.; Rokicki, Michal J.; Bagley, Mark C.; Kipling, David

2016-01-01

Progeroid syndromes show features of accelerated ageing and are used as models for human ageing, of which Werner syndrome (WS) is one of the most widely studied. WS fibroblasts show accelerated senescence that may result from p38 MAP kinase activation since it is prevented by the p38 inhibitor SB203580. Thus, small molecule inhibition of p38-signalling may be a therapeutic strategy for WS. To develop this approach issues such as the in vivo toxicity and kinase selectivity of existing p38 inhibitors need to be addressed, so as to strengthen the evidence that p38 itself plays a critical role in mediating the effect of SB203580, and to find an inhibitor suitable for in vivo use. In this work we used a panel of different p38 inhibitors selected for: (1) having been used successfully in vivo in either animal models or human clinical trials; (2) different modes of binding to p38; and (3) different off-target kinase specificity profiles, in order to critically address the role of p38 in the premature senescence seen in WS cells. Our findings confirmed the involvement of p38 in accelerated cell senescence and identified p38 inhibitors suitable for in vivo use in WS, with BIRB 796 the most effective. PMID:27136566

Volcano-ice age link discounted

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

Kerr, R.A.

1996-05-10

Speculation that huge volcanic eruptions may have caused an immediate `volcanic winter` that devastated early humans and accelerated a slide into the Ice Age. However, further information from the Greenland ice sheet about the Toba errumption on the island of Sumatra 70,000 years ago, seems to indicate that such volcanic actions wasn`t a major climatic catalyst. This article discusses the evidence and further possibilities.

Aging stem cells. A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging.

PubMed

Zhang, Weiqi; Li, Jingyi; Suzuki, Keiichiro; Qu, Jing; Wang, Ping; Zhou, Junzhi; Liu, Xiaomeng; Ren, Ruotong; Xu, Xiuling; Ocampo, Alejandro; Yuan, Tingting; Yang, Jiping; Li, Ying; Shi, Liang; Guan, Dee; Pan, Huize; Duan, Shunlei; Ding, Zhichao; Li, Mo; Yi, Fei; Bai, Ruijun; Wang, Yayu; Chen, Chang; Yang, Fuquan; Li, Xiaoyu; Wang, Zimei; Aizawa, Emi; Goebl, April; Soligalla, Rupa Devi; Reddy, Pradeep; Esteban, Concepcion Rodriguez; Tang, Fuchou; Liu, Guang-Hui; Belmonte, Juan Carlos Izpisua

2015-06-05

Werner syndrome (WS) is a premature aging disorder caused by WRN protein deficiency. Here, we report on the generation of a human WS model in human embryonic stem cells (ESCs). Differentiation of WRN-null ESCs to mesenchymal stem cells (MSCs) recapitulates features of premature cellular aging, a global loss of H3K9me3, and changes in heterochromatin architecture. We show that WRN associates with heterochromatin proteins SUV39H1 and HP1α and nuclear lamina-heterochromatin anchoring protein LAP2β. Targeted knock-in of catalytically inactive SUV39H1 in wild-type MSCs recapitulates accelerated cellular senescence, resembling WRN-deficient MSCs. Moreover, decrease in WRN and heterochromatin marks are detected in MSCs from older individuals. Our observations uncover a role for WRN in maintaining heterochromatin stability and highlight heterochromatin disorganization as a potential determinant of human aging. Copyright © 2015, American Association for the Advancement of Science.

Obesity and Aging in Humans and Nonhuman Primates: A Mini-Review.

PubMed

Vaughan, Kelli L; Mattison, Julie A

2016-01-01

The prevalence of obesity in the US is increasing exponentially across gender, age and ethnic groups. Obesity and a long-term hypercaloric diet result in what appears to be accelerated aging, often leading to a multi-systemic deterioration known as the metabolic syndrome. Due to their physiological similarity to humans as well as comparable rates of spontaneous obesity and diabetes mellitus, nonhuman primates provide a useful translational model for the human condition. They allow for an in vivo study of disease progression, interaction of comorbidities, and novel interventions. However, defining obesity in aged humans and nonhuman primates is difficult as the physiological changes that occur with aging are not accounted for using our current systems (BMI - body mass index and BCS - body condition score). Nonetheless, nonhuman primate studies have greatly contributed to our understanding of obesity and metabolic dysfunction and should continue to play a large role in translational research. Here, methods for defining obesity and metabolic syndrome in humans and nonhuman primates are described along with the prevalence and effects of these conditions. © 2016 S. Karger AG, Basel.

From Hayflick to Walford: the role of T cell replicative senescence in human aging.

PubMed

Effros, Rita B

2004-06-01

The immunologic theory of aging, proposed more than 40 years ago by Roy Walford, suggests that the normal process of aging in man and in animals is pathogenetically related to faulty immunological processes. Since that time, research on immunological aging has undergone extraordinary expansion, leading to new information in areas spanning from molecular biology and cell signaling to large-scale clinical studies. Investigation in this area has also provided unexpected insights into HIV disease, many aspects of which represent accelerated immunological aging. This article describes the initial insights and vision of Roy Walford into one particular facet of human immunological aging, namely, the potential relevance of the well-studied human fibroblast replicative senescence model, initially developed by Leonard Hayflick, to cells of the immune system. Extensive research on T cell senescence in cell culture has now documented changes in vitro that closely mirror alterations occurring during in vivo aging in humans, underscoring the biological significance of T cell replicative senescence. Moreover, the inclusion of high proportions of putatively senescent T cells in the 'immune risk phenotype' that is associated with early mortality in octogenarians provides initial clinical confirmation of both the immunologic theory of aging and the role of the T cell Hayflick Limit in human aging, two areas of gerontological research pioneered by Roy Walford.

A human factors approach to snowsport safety: Novel research on pediatric participants' behaviors and head injury risk.

PubMed

Dickson, Tracey J; Trathen, Stephen; Waddington, Gordon; Terwiel, F Anne; Baltis, Daniel

2016-03-01

This study applied a human factors approach to snowsport resort systems to contribute to the understanding of the incidence and severity of pediatric snowsport head accelerations. Previous research indicates low magnitude head accelerations are common among snowsport participants. This study adds to the knowledge of snowsport safety by measuring aspects of participants' snowsport behavior and linking this with head acceleration data. School-aged students (n = 107) wore telemetry-fitted helmets and Global Positioning System (GPS) devices during snowsport activity. Data was collected over 159 sessions (total hours 701). Head accelerations recorded by the telemetry units were compared with GPS-generated data. This study found speeds attained normally exceed the testing rating for which helmets are designed; lower rates of head accelerations compared to earlier studies and that when head accelerations did occur they were generally below the threshold for concussions. Pediatric snowsport head accelerations are rare and are generally of low magnitude. Those most at risk of a head acceleration >40 g were male snowboarders. Given the recorded speeds in first time participants, increased targeting of novice snowsport participants to encourage education about the use of protective equipment, including helmets, is warranted. Post event recall was not a good indicator of having experienced a head impact. Consideration should be given to raising the standard design speed testing for snowsport helmet protective devices to reflect actual snowsport behaviors. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Hyper telomere recombination accelerates replicative senescence and may promote premature aging

PubMed Central

Hagelstrom, R. Tanner; Blagoev, Krastan B.; Niedernhofer, Laura J.; Goodwin, Edwin H.; Bailey, Susan M.

2010-01-01

Werner syndrome and Bloom syndrome result from defects in the RecQ helicases Werner (WRN) and Bloom (BLM), respectively, and display premature aging phenotypes. Similarly, XFE progeroid syndrome results from defects in the ERCC1-XPF DNA repair endonuclease. To gain insight into the origin of cellular senescence and human aging, we analyzed the dependence of sister chromatid exchange (SCE) frequencies on location [i.e., genomic (G-SCE) vs. telomeric (T-SCE) DNA] in primary human fibroblasts deficient in WRN, BLM, or ERCC1-XPF. Consistent with our other studies, we found evidence of elevated T-SCE in telomerase-negative but not telomerase-positive backgrounds. In telomerase-negative WRN-deficient cells, T-SCE—but not G-SCE—frequencies were significantly increased compared with controls. In contrast, SCE frequencies were significantly elevated in BLM-deficient cells irrespective of genome location. In ERCC1-XPF-deficient cells, neither T- nor G-SCE frequencies differed from controls. A theoretical model was developed that allowed an in silico investigation into the cellular consequences of increased T-SCE frequency. The model predicts that in cells with increased T-SCE, the onset of replicative senescence is dramatically accelerated even though the average rate of telomere loss has not changed. Premature cellular senescence may act as a powerful tumor-suppressor mechanism in telomerase-deficient cells with mutations that cause T-SCE levels to rise. Furthermore, T-SCE-driven premature cellular senescence may be a factor contributing to accelerated aging in Werner and Bloom syndromes, but not XFE progeroid syndrome. PMID:20798040

In vivo observation of age-related structural changes of dermal collagen in human facial skin using collagen-sensitive second harmonic generation microscope equipped with 1250-nm mode-locked Cr:Forsterite laser

NASA Astrophysics Data System (ADS)

Yasui, Takeshi; Yonetsu, Makoto; Tanaka, Ryosuke; Tanaka, Yuji; Fukushima, Shu-ichiro; Yamashita, Toyonobu; Ogura, Yuki; Hirao, Tetsuji; Murota, Hiroyuki; Araki, Tsutomu

2013-03-01

In vivo visualization of human skin aging is demonstrated using a Cr:Forsterite (Cr:F) laser-based, collagen-sensitive second harmonic generation (SHG) microscope. The deep penetration into human skin, as well as the specific sensitivity to collagen molecules, achieved by this microscope enables us to clearly visualize age-related structural changes of collagen fiber in the reticular dermis. Here we investigated intrinsic aging and/or photoaging in the male facial skin. Young subjects show dense distributions of thin collagen fibers, whereas elderly subjects show coarse distributions of thick collagen fibers. Furthermore, a comparison of SHG images between young and elderly subjects with and without a recent life history of excessive sun exposure show that a combination of photoaging with intrinsic aging significantly accelerates skin aging. We also perform image analysis based on two-dimensional Fourier transformation of the SHG images and extracted an aging parameter for human skin. The in vivo collagen-sensitive SHG microscope will be a powerful tool in fields such as cosmeceutical sciences and anti-aging dermatology.

Molecular Aging of Human Liver: An Epigenetic/Transcriptomic Signature.

PubMed

Bacalini, Maria Giulia; Franceschi, Claudio; Gentilini, Davide; Ravaioli, Francesco; Zhou, Xiaoyuan; Remondini, Daniel; Pirazzini, Chiara; Giuliani, Cristina; Marasco, Elena; Gensous, Noémie; Di Blasio, Anna Maria; Ellis, Ewa; Gramignoli, Roberto; Castellani, Gastone; Capri, Miriam; Strom, Stephen; Nardini, Christine; Cescon, Matteo; Grazi, Gian Luca; Garagnani, Paolo

2018-03-15

The feasibility of liver transplantation from old healthy donors suggests that this organ is able to preserve its functionality during aging. To explore the biological basis of this phenomenon, we characterized the epigenetic profile of liver biopsies collected from 45 healthy liver donors ranging from 13 to 90 years old using the Infinium HumanMethylation450 BeadChip. The analysis indicates that a large remodeling in DNA methylation patterns occurs, with 8823 age-associated differentially methylated CpG probes. Notably, these age-associated changes tended to level off after the age of 60, as confirmed by Horvath's clock. Using stringent selection criteria we further identified a DNA methylation signature of aging liver including 75 genomic regions. We demonstrated that this signature is specific for liver compared to other tissues and that it is able to detect biological age-acceleration effects associated with obesity. Finally we combined DNA methylation measurements with available expression data. Although the intersection between the two omic characterizations was low, both approaches suggested a previously unappreciated role of epithelial-mesenchymal transition and Wnt signaling pathways in the aging of human liver.

The application of artificial intelligent techniques to accelerator operations at McMaster University

NASA Astrophysics Data System (ADS)

Poehlman, W. F. S.; Garland, Wm. J.; Stark, J. W.

1993-06-01

In an era of downsizing and a limited pool of skilled accelerator personnel from which to draw replacements for an aging workforce, the impetus to integrate intelligent computer automation into the accelerator operator's repertoire is strong. However, successful deployment of an "Operator's Companion" is not trivial. Both graphical and human factors need to be recognized as critical areas that require extra care when formulating the Companion. They include interactive graphical user's interface that mimics, for the operator, familiar accelerator controls; knowledge of acquisition phases during development must acknowledge the expert's mental model of machine operation; and automated operations must be seen as improvements to the operator's environment rather than threats of ultimate replacement. Experiences with the PACES Accelerator Operator Companion developed at two sites over the past three years are related and graphical examples are given. The scale of the work involves multi-computer control of various start-up/shutdown and tuning procedures for Model FN and KN Van de Graaff accelerators. The response from licensing agencies has been encouraging.

Induced Accelerated Aging in Induced Pluripotent Stem Cell Lines from Patients with Parkinson’s Disease

DTIC Science & Technology

2014-07-01

after manipulation of the cells prohibited this approach. 2. Differentiation into oligoprecursor cells ( OPCs ) and oligodendrocytes As we have...Jing Bian, PhD and Birgitt Schuele, MD 18 Development of expandable OPCs from human iPSC derived...Neri et al., 2010) + + + + Human iPSC derived OPCs and Oligos (Wang et al., 2013) + + + + mEpsc derived OPCs and Oligos (Najm et al

SAMP8 mice as a neuropathological model of accelerated brain aging and dementia: Toshio Takeda's legacy and future directions.

PubMed

Akiguchi, Ichiro; Pallàs, Mercè; Budka, Herbert; Akiyama, Haruhiko; Ueno, Masaki; Han, Jingxian; Yagi, Hideo; Nishikawa, Tomohumi; Chiba, Yoichi; Sugiyama, Hiroshi; Takahashi, Ryoya; Unno, Keiko; Higuchi, Keiichi; Hosokawa, Masanori

2017-08-01

Senescence accelerated mice P8 (SAMP8) show significant age-related deteriorations in memory and learning ability in accordance with early onset and rapid advancement of senescence. Brains of SAMP8 mice reveal an age-associated increase of PAS-positive granular structures in the hippocampal formation and astrogliosis in the brain stem and hippocampus. A spongy degeneration in the brain stem appears at 1 month of age and reaches a maximum at 4-8 months. In addition, clusters of activated microglia also appear around the vacuoles in the brain stem. β/A4(Aβ) protein-like immunoreactive granular structures are observed in various regions and increase in number markedly with age. Other age-associated histological changes include cortical atrophy, neuronal cell loss in locus coeruleus and lateral tegmental nuclei, intraneuronal accumulation of lipopigments in Purkinje cells and eosinophilic inclusion bodies in thalamic neurons. A blood-brain barrier dysfunction and astrogliosis are also prominent with advancing age in the hippocampus. These changes are generally similar to the pathomorphology of aging human brains and characterized by their association with some specific glioneuronal reactions. As for the hallmarks of Alzheimer brains, tau morphology has not yet been confirmed regardless of the age-related increase in phosphorylated tau in SAMP8 mice brains, but early age-related Aβ deposition in the hippocampus has recently been published. SAMP8 mice are, therefore, not only a senescence-accelerated model but also a promising model for Alzheimer's disease and other cognitive disorders. © 2017 Japanese Society of Neuropathology.

Spaceflight and ageing: reflecting on Caenorhabditis elegans in space.

PubMed

Honda, Yoko; Honda, Shuji; Narici, Marco; Szewczyk, Nathaniel J

2014-01-01

The prospect of space travel continues to capture the imagination. Several competing companies are now promising flights for the general population. Previously, it was recognized that many of the physiological changes that occur with spaceflight are similar to those seen with normal ageing. This led to the notion that spaceflight can be used as a model of accelerated ageing and raised concerns about the safety of individuals engaging in space travel. Paradoxically, however, space travel has been recently shown to be beneficial to some aspects of muscle health in the tiny worm Caenorhabditis elegans. C. elegans is a commonly used laboratory animal for studying ageing. C. elegans displays age-related decline of some biological processes observed in ageing humans, and about 35% of C. elegans' genes have human homologs. Space flown worms were found to have decreased expression of a number of genes that increase lifespan when expressed at lower levels. These changes were accompanied by decreased accumulation of toxic protein aggregates in ageing worms' muscles. Thus, in addition to spaceflight producing physiological changes that are similar to accelerated ageing, it also appears to produce some changes similar to delayed ageing. Here, we put forward the hypothesis that in addition to the previously well-appreciated mechanotransduction changes, neural and endocrine signals are altered in response to spaceflight and that these may have both negative (e.g. less muscle protein) and some positive consequences (e.g. healthier muscles), at least for invertebrates, with respect to health in space. Given that changes in circulating hormones are well documented with age and in astronauts, our view is that further research into the relationship between metabolic control, ageing, and adaptation to the environment should be productive in advancing our understanding of the physiology of both spaceflight and ageing.

Sex, kings and serial killers and other group-selected human traits.

PubMed

Bowles, J T

2000-06-01

(Note: This unorthodox paper contains the first argument for heart disease being a programmed age change and promoted by the dramatic, post age-40 increases in the hormones FSH and hCG seen in some individuals.) A recent issue of Science suggests that the evolutionary purpose of sex is unknown. Surviving to adulthood implies a valuable gene combination which is destroyed by sexual recombination. This should be detrimental to offspring. PROPOSED: Sex is group-selected in prey to allow coalescence of beneficial, and disposal of detrimental, mutations in single individuals enabling rapid adaptation to novel predation. Group selection is a universal force driven by local inter-species (not intra-species) competition. Aging, metabolism, litter size, and fixed body size are directly linked. Sexual recombination and chromosomes destroy gene linkage and exist because mutations are usually detrimental, rarely positive, and occur in linked groups. In unevolving environments, sex is selected against and asexuality emerges. Periodic evolution of novel predators, like man, can explain the 'punctuated equilibria' fossil record. Genes inhibited by methylation or chromatin condensation, expressed at older ages in predation-minimized environments, allow for group selection. Stress increases mutation rates and beneficial mutation likelihood. Females select bigger, brighter, louder, or stronger males that can survive predator attention. Size approximates age and thus predator encounters; male traits represent predation-survival potential. Human male traits include, balding, acne, beard-length, wrinkling, graying, nose/ear growth. Progeria accelerates development of most male traits. Domination of groups by single males allows rapid predation-defense evolution: adolescent males are expelled, brave the wild, and expel another group's male to mate. If expelled and dominant males are culled by predation, males reaching puberty first will reproduce. Hormonal acceleration of puberty accelerates aging/population turnover, induces smaller bodies, larger litters. With a fixed group biomass, more, smaller, stressed individuals with faster aging/turnover, increase beneficial mutation likelihood. 'Kin selection', where dominant families are supported by celibate relatives, allow the best group genes to survive famine. Dominant families gorge while others starve. Equal food sharing results in group extinction leading to group-evolved human traits of social hierarchy, greed, king/queen/God worship. Menstrual hormone cycling parallels aging. FSH and DHT promote ovarian, hair, acne, dental, and arterial follicle development causing ovulation, hair growth, pimples, dental caries, and atherosclerotic soft plaques. Soft plaques contain macrophages and LDL plug; upper plaque layers thin and rupture, releasing LDL plug, causing thrombosis. FSH withdrawal or LH/hCG increases trigger ovulation and thrombosis. Artery narrowing atherosclerotic hard plaques are stress-induced through cortisol-promoted necrotic calcification. LH/hCG-induced apoptosis promotes ovulation and aging-related somatic atrophy. Long-term estradiol stimulates, while progesterone suppresses, gonadotropin levels. Estradiol protects by inhibiting gonadotropin bioactivity and has extracellular antioxidant, but intranuclear free radical, effects. Female X-linked gene mosaicism conserves evolved aging systems. Maternal age factors for chromosomal trisomy suggest menopause prevents human parthenogenesis. Homosexuality and serial killing inhibit genetic contribution by individuals evolutionarily perceived as stressed. Smoking during pregnancy may induce homosexual offspring. Nitric oxide, a free radical, stimulates cGMP, but not cAMP. cGMP likely first evolved as an antioxidant defense to free radicals. Human aging syndromes might reflect human evolution progression. AS#4 affects tissues evolved from plant ancestors, AS#5a - from predators, AS#5b-immune system, and AS#6-sex tissues. (ABSTRACT TRUNCA

Accelerated Changes in Cortical Thickness Measurements with Age in Military Service Members with Traumatic Brain Injury.

PubMed

Savjani, Ricky R; Taylor, Brian A; Acion, Laura; Wilde, Elisabeth A; Jorge, Ricardo E

2017-11-15

Finding objective and quantifiable imaging markers of mild traumatic brain injury (TBI) has proven challenging, especially in the military population. Changes in cortical thickness after injury have been reported in animals and in humans, but it is unclear how these alterations manifest in the chronic phase, and it is difficult to characterize accurately with imaging. We used cortical thickness measures derived from Advanced Normalization Tools (ANTs) to predict a continuous demographic variable: age. We trained four different regression models (linear regression, support vector regression, Gaussian process regression, and random forests) to predict age from healthy control brains from publicly available datasets (n = 762). We then used these models to predict brain age in military Service Members with TBI (n = 92) and military Service Members without TBI (n = 34). Our results show that all four models overpredicted age in Service Members with TBI, and the predicted age difference was significantly greater compared with military controls. These data extend previous civilian findings and show that cortical thickness measures may reveal an association of accelerated changes over time with military TBI.

Expression of CGRP neurotransmitter and vascular genesis marker mRNA is age-dependent in superior cervical ganglia of senescence-accelerated prone mice.

PubMed

Mitsuoka, Kazuyuki; Kikutani, Takeshi; Miwa, Yoko; Sato, Iwao

2018-01-18

Calcitonin gene-related peptide (CGRP) is a neurotransmitter that is released from the superior cervical ganglion (SCG) and causes head and neck pain. The morphological properties of human SCG neurons, including neurotransmitter content, are altered during aging. However, morphological changes in CGRP in the SCG during aging are not known. Therefore, we investigated CGRP and other markers in the SCG during aging in an aging model of senescence-accelerated prone mouse (SAMP8) and senescence-accelerated resistant mice (SAMR1) using real-time RT-PCR mRNA analyses and in situ hybridization. The abundance of neurotransmitter (CGRP, NPY, TRPV1), vascular genesis marker (CD31, LYVE-1), and cytochrome C mRNA differed between 12-week-old and 24-week-old SAMP8 and SAMR1. Abundance of TRPV1, CD31 and cytochrome C mRNAs of SAMP8 decreased between 12- and 24-week-old. The ratio of CGRP mRNA positive cells and CGRP mRNA abundance levels of the SCG of aging mouse such as SAMP8 have already been also higher than that of SAMR1 at 12-week-old. The CGRP positive shrunken ganglion cells was increased from 12- to 24-weeks-old mouse in SAMR1 and SAMP8. The SCG primarily affected the internal and external carotid arteries, larynx thyroid gland, and pharyngeal muscle during aging. Copyright © 2017 Elsevier B.V. All rights reserved.

The senescence accelerated mouse prone 8 (SAMP8): A novel murine model for cardiac aging.

PubMed

Karuppagounder, Vengadeshprabhu; Arumugam, Somasundaram; Babu, Sahana Suresh; Palaniyandi, Suresh S; Watanabe, Kenichi; Cooke, John P; Thandavarayan, Rajarajan A

2017-05-01

Because cardiovascular disease remains the major cause of mortality and morbidity world-wide, there remains a compelling need for new insights and novel therapeutic avenues. In this regard, the senescence-accelerated mouse prone 8 (SAMP8) line is a particularly good model for studying the effects of aging on cardiovascular health. Accumulating evidence suggests that this model may shed light on age-associated cardiac and vascular dysfunction and disease. These animals manifest evidence of inflammation, oxidative stress and adverse cardiac remodeling that may recapitulate processes involved in human disease. Early alterations in oxidative damage promote endoplasmic reticulum stress to trigger apoptosis and cytokine production in this genetically susceptible mouse strain. Conversely, pharmacological treatments that reduce inflammation and oxidative stress improve cardiac function in these animals. Therefore, the SAMP8 mouse model provides an exciting opportunity to expand our knowledge of aging in cardiovascular disease and the potential identification of novel targets of treatment. Herein, we review the previous studies performed in SAMP8 mice that provide insight into age-related cardiovascular alterations. Copyright © 2016 Elsevier B.V. All rights reserved.

Holocene age of the Yuha burial: Direct radiocarbon determinations by accelerator mass spectrometry

USGS Publications Warehouse

Stafford, Thomas W.; Jull, A.J.T.; Zabel, T.H.; Donahue, D.J.; Duhamel, R.C.; Brendel, K.; Haynes, C.V.; Bischoff, J.L.; Payen, L.A.; Taylor, R.E.

1984-01-01

The view that human populations may not have arrived in the Western Hemisphere before about 12,000 radiocarbon yr BP1,2 has been challenged by claims of much greater antiquity for a small number of archaeological sites and human skeleton samples. One such site is the Homo sapiens sapiens cairn burial excavated in 1971 from the Yuha desert, Imperial County, California3-5. Radiocarbon analysis of caliche coating one of the bones of the skeleton yielded a radiocarbon age of 21,500??1,000 yr BP4, while radiocarbon and uranium series analyses of caliche coating a cairn boulder yielded ages of 22,125??400 and 19,000??3,000 yr BP, respectively5. The late Pleistocene age assignment to the Yuha burial has been challenged by comparing the cultural context of the burial with other cairn burials in the same region6, on the basis of the site's geomorphological context and from radiocarbon analyses of soil caliches. 7,8 In rebuttal, arguments in defence of the original age assignment have been presented9,10 as well as an amino acid racemization analysis on the Yuha skeleton indicating an age of 23,600??2,600 yr BP11. The tandem accelerator mass spectrometer at the University of Arizona has now been used to measure the ratio of 14C/13C in several organic and inorganic fractions of post-cranial bone from the Yuha H. sapiens sapiens skeleton. Isotope ratios from six chemical fractions all yielded radiocarbon ages for the skeleton of less than 4,000 yr BP. These results indicate that the Yuha skeleton is of Holocene age, in agreement with the cultural context of the burial, and in disagreement with the previously assigned Pleistocene age of 19,000-23,000 yr. ?? 1984 Nature Publishing Group.

Method for quantifying optical properties of the human lens

DOEpatents

Loree, deceased, Thomas R.; Bigio, Irving J.; Zuclich, Joseph A.; Shimada, Tsutomu; Strobl, Karlheinz

1999-01-01

Method for quantifying optical properties of the human lens. The present invention includes the application of fiberoptic, OMA-based instrumentation as an in vivo diagnostic tool for the human ocular lens. Rapid, noninvasive and comprehensive assessment of the optical characteristics of a lens using very modest levels of exciting light are described. Typically, the backscatter and fluorescence spectra (from about 300- to 900-nm) elicited by each of several exciting wavelengths (from about 300- to 600-nm) are collected within a few seconds. The resulting optical signature of individual lenses is then used to assess the overall optical quality of the lens by comparing the results with a database of similar measurements obtained from a reference set of normal human lenses having various ages. Several metrics have been identified which gauge the optical quality of a given lens relative to the norm for the subject's chronological age. These metrics may also serve to document accelerated optical aging and/or as early indicators of cataract or other disease processes.

Method for quantifying optical properties of the human lens

DOEpatents

Loree, T.R.; Bigio, I.J.; Zuclich, J.A.; Shimada, Tsutomu; Strobl, K.

1999-04-13

A method is disclosed for quantifying optical properties of the human lens. The present invention includes the application of fiberoptic, OMA-based instrumentation as an in vivo diagnostic tool for the human ocular lens. Rapid, noninvasive and comprehensive assessment of the optical characteristics of a lens using very modest levels of exciting light are described. Typically, the backscatter and fluorescence spectra (from about 300- to 900-nm) elicited by each of several exciting wavelengths (from about 300- to 600-nm) are collected within a few seconds. The resulting optical signature of individual lenses is then used to assess the overall optical quality of the lens by comparing the results with a database of similar measurements obtained from a reference set of normal human lenses having various ages. Several metrics have been identified which gauge the optical quality of a given lens relative to the norm for the subject`s chronological age. These metrics may also serve to document accelerated optical aging and/or as early indicators of cataract or other disease processes. 8 figs.

Physiological frailty index (PFI): quantitative in-life estimate of individual biological age in mice.

PubMed

Antoch, Marina P; Wrobel, Michelle; Kuropatwinski, Karen K; Gitlin, Ilya; Leonova, Katerina I; Toshkov, Ilia; Gleiberman, Anatoli S; Hutson, Alan D; Chernova, Olga B; Gudkov, Andrei V

2017-03-19

The development of healthspan-extending pharmaceuticals requires quantitative estimation of age-related progressive physiological decline. In humans, individual health status can be quantitatively assessed by means of a frailty index (FI), a parameter which reflects the scale of accumulation of age-related deficits. However, adaptation of this methodology to animal models is a challenging task since it includes multiple subjective parameters. Here we report a development of a quantitative non-invasive procedure to estimate biological age of an individual animal by creating physiological frailty index (PFI). We demonstrated the dynamics of PFI increase during chronological aging of male and female NIH Swiss mice. We also demonstrated acceleration of growth of PFI in animals placed on a high fat diet, reflecting aging acceleration by obesity and provide a tool for its quantitative assessment. Additionally, we showed that PFI could reveal anti-aging effect of mTOR inhibitor rapatar (bioavailable formulation of rapamycin) prior to registration of its effects on longevity. PFI revealed substantial sex-related differences in normal chronological aging and in the efficacy of detrimental (high fat diet) or beneficial (rapatar) aging modulatory factors. Together, these data introduce PFI as a reliable, non-invasive, quantitative tool suitable for testing potential anti-aging pharmaceuticals in pre-clinical studies.

Neurological Limitations of Aircraft Operations: Human Performance Implications (les Limitations neurologiques des operations aeriennes: les Consequences pour les performances des equipages).

DTIC Science & Technology

1996-04-01

Amniotic fluid Debris?* Young women Long bone fracture Fat * Any age Chronic intravenous drug users Talc* Any age Disseminated intravascular coagulapathy...maximal stress at which bone fracture occurs. This study demonstrated the usefulness of finite Results from centrifuge experiments element analysis for...Vine Street M/S 455 Philadelphia, PA 19102-1192, USA SUMMARY Exposure to Impact Acceleration (15). In these reports, fracture of the bones, dislocation

Maternal sensitivity, infant limbic structure volume and functional connectivity: a preliminary study

PubMed Central

Rifkin-Graboi, A; Kong, L; Sim, L W; Sanmugam, S; Broekman, B F P; Chen, H; Wong, E; Kwek, K; Saw, S-M; Chong, Y-S; Gluckman, P D; Fortier, M V; Pederson, D; Meaney, M J; Qiu, A

2015-01-01

Mechanisms underlying the profound parental effects on cognitive, emotional and social development in humans remain poorly understood. Studies with nonhuman models suggest variations in parental care affect the limbic system, influential to learning, autobiography and emotional regulation. In some research, nonoptimal care relates to decreases in neurogenesis, although other work suggests early-postnatal social adversity accelerates the maturation of limbic structures associated with emotional learning. We explored whether maternal sensitivity predicts human limbic system development and functional connectivity patterns in a small sample of human infants. When infants were 6 months of age, 20 mother–infant dyads attended a laboratory-based observational session and the infants underwent neuroimaging at the same age. After considering age at imaging, household income and postnatal maternal anxiety, regression analyses demonstrated significant indirect associations between maternal sensitivity and bilateral hippocampal volume at six months, with the majority of associations between sensitivity and the amygdala demonstrating similar indirect, but not significant results. Moreover, functional analyses revealed direct associations between maternal sensitivity and connectivity between the hippocampus and areas important for emotional regulation and socio-emotional functioning. Sensitivity additionally predicted indirect associations between limbic structures and regions related to autobiographical memory. Our volumetric results are consistent with research indicating accelerated limbic development in response to early social adversity, and in combination with our functional results, if replicated in a larger sample, may suggest that subtle, but important, variations in maternal care influence neuroanatomical trajectories important to future cognitive and emotional functioning. PMID:26506054

Vitamin C mediates chemical aging of lens crystallins by the Maillard reaction in a humanized mouse model

PubMed Central

Fan, Xingjun; Reneker, Lixing W.; Obrenovich, Mark E.; Strauch, Christopher; Cheng, Rongzhu; Jarvis, Simon M.; Ortwerth, Beryl J.; Monnier, Vincent M.

2006-01-01

Senile cataracts are associated with progressive oxidation, fragmentation, cross-linking, insolubilization, and yellow pigmentation of lens crystallins. We hypothesized that the Maillard reaction, which leads browning and aroma development during the baking of foods, would occur between the lens proteins and the highly reactive oxidation products of vitamin C. To test this hypothesis, we engineered a mouse that selectively overexpresses the human vitamin C transporter SVCT2 in the lens. Consequently, lenticular levels of vitamin C and its oxidation products were 5- to 15-fold elevated, resulting in a highly compressed aging process and accelerated formation of several protein-bound advanced Maillard reaction products identical with those of aging human lens proteins. These data strongly implicate vitamin C in lens crystallin aging and may serve as a model for protein aging in other tissues particularly rich in vitamin C, such as the hippocampal neurons and the adrenal gland. The hSVCT2 mouse is expected to facilitate the search for drugs that inhibit damage by vitamin C oxidation products. PMID:17075057

Age-related changes in endothelial function and blood flow regulation.

PubMed

Toda, Noboru

2012-02-01

Vascular endothelial dysfunction is regarded as a primary phenotypic expression of normal human aging. This senescence-induced disorder is the likely culprit underlying the increased cardiovascular and metabolic disease risks associated with aging. The rate of this age-dependent deterioration is largely influenced by the poor-quality lifestyle choice, such as smoking, sedentary daily life, chronic alcohol ingestion, high salt intake, unbalanced diet, and mental stress; and it is accelerated by cardiovascular and metabolic diseases. Although minimizing these detrimental factors is the best course of action, nonetheless chronological age steadily impairs endothelial function through reduced endothelial nitric oxide synthase (eNOS) expression/action, accelerated nitric oxide (NO) degradation, increased phosphodiesterase activity, inhibition of NOS activity by endogenous NOS inhibitors, increased production of reactive oxygen species, inflammatory reactions, decreased endothelial progenitor cell number and function, and impaired telomerase activity or telomere shortening. Endothelial dysfunction in regional vasculatures results in cerebral hypoperfusion triggering cognitive dysfunction and Alzheimer's disease, coronary artery insufficiency, penile erectile dysfunction, and circulatory failures in other organs and tissues. Possible prophylactic measures to minimize age-related endothelial dysfunction are also summarized in this review. Copyright © 2011 Elsevier Inc. All rights reserved.

The effect of accelerated aging on the wear of UHMWPE.

PubMed

Sakoda, H; Fisher, J; Lu, S; Buchanan, F

2001-01-01

Oxidative degradation of UHMWPE has been found to be a cause of elevated wear rate of the polymer in total joint replacement leading to failure of these devices. In order to evaluate long term stability of polymers, various accelerated aging methods have been developed. In this study, wear rates of shelf aged UHMWPE and "accelerated aged" UHMWPE were compared using a multi-directional pin-on-plate wear test machine in order to evaluate the effect of the accelerated aging on wear. Wear factors of the aged materials were found to depend on their density, which is a measure of oxidation level. Finally, accelerated aging was calibrated against shelf aging in terms of wear rate. Copyright 2001 Kluwer Academic Publishers

A three-dimensional skin equivalent reflecting some aspects of in vivo aged skin.

PubMed

Diekmann, Johanna; Alili, Lirija; Scholz, Okka; Giesen, Melanie; Holtkötter, Olaf; Brenneisen, Peter

2016-01-01

Human skin undergoes morphological, biochemical and functional modifications during the ageing process. This study was designed to produce a 3-dimensional (3D) skin equivalent in vitro reflecting some aspects of in vivo aged skin. Reconstructed skin was generated by co-culturing skin fibroblasts and keratinocytes on a collagen-glycosaminoglycan-chitosan scaffold, and ageing was induced by the exposition of fibroblasts to Mitomycin-C (MMC). Recently published data showed that MMC treatment resulted in a drug-induced accelerated senescence (DIAS) in human dermal fibroblast cultures. Next to established ageing markers, histological changes were analysed in comparison with in vivo aged skin. In aged epidermis, the filaggrin expression is reduced in vivo and in vitro. Furthermore, in dermal tissue, the amount of elastin and collagen is lowered in aged skin in vivo as well as after the treatment of 3D skin equivalents with MMC in vitro. Our results show histological signs and some aspects of ageing in a 3D skin equivalent in vitro, which mimics aged skin in vivo. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Molecular and physiological manifestations and measurement of aging in humans.

PubMed

Khan, Sadiya S; Singer, Benjamin D; Vaughan, Douglas E

2017-08-01

Biological aging is associated with a reduction in the reparative and regenerative potential in tissues and organs. This reduction manifests as a decreased physiological reserve in response to stress (termed homeostenosis) and a time-dependent failure of complex molecular mechanisms that cumulatively create disorder. Aging inevitably occurs with time in all organisms and emerges on a molecular, cellular, organ, and organismal level with genetic, epigenetic, and environmental modulators. Individuals with the same chronological age exhibit differential trajectories of age-related decline, and it follows that we should assess biological age distinctly from chronological age. In this review, we outline mechanisms of aging with attention to well-described molecular and cellular hallmarks and discuss physiological changes of aging at the organ-system level. We suggest methods to measure aging with attention to both molecular biology (e.g., telomere length and epigenetic marks) and physiological function (e.g., lung function and echocardiographic measurements). Finally, we propose a framework to integrate these molecular and physiological data into a composite score that measures biological aging in humans. Understanding the molecular and physiological phenomena that drive the complex and multifactorial processes underlying the variable pace of biological aging in humans will inform how researchers assess and investigate health and disease over the life course. This composite biological age score could be of use to researchers seeking to characterize normal, accelerated, and exceptionally successful aging as well as to assess the effect of interventions aimed at modulating human aging. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

The influences of accelerated aging on mechanical properties of veneering ceramics used for zirconia restorations.

PubMed

Luo, Huinan; Tang, Xuehua; Dong, Zhen; Tang, Hui; Nakamura, Takashi; Yatani, Hirofumi

2016-01-01

This study evaluated the influences of accelerated aging on the mechanical properties of veneering ceramics used for zirconia frameworks. Five different veneering ceramics for zirconia frameworks were used. Twenty specimens were fabricated for each veneering ceramic. All specimens were divided into two groups. One was subjected to accelerated aging and the other was used as a control. Accelerated aging was performed in distilled water for 5 h at 200ºC and 2 atm. The density, open porosity, surface roughness, three-point flexural strength, and Vickers hardness were measured. The results showed that the density, open porosity, and surface roughness of all examined veneering ceramics were changed by the accelerated aging process. Accelerated aging was also found to have a positive effect on strength and a negative effect on the hardness.

Systemic Problems: A perspective on stem cell aging and rejuvenation.

PubMed

Conboy, Irina M; Conboy, Michael J; Rebo, Justin

2015-10-01

This review provides balanced analysis of the advances in systemic regulation of young and old tissue stem cells and suggests strategies for accelerating development of therapies to broadly combat age-related tissue degenerative pathologies. Many highlighted recent reports on systemic tissue rejuvenation combine parabiosis with a "silver bullet" putatively responsible for the positive effects. Attempts to unify these papers reflect the excitement about this experimental approach and add value in reproducing previous work. At the same time, defined molecular approaches, which are "beyond parabiosis" for the rejuvenation of multiple old organs represent progress toward attenuating or even reversing human tissue aging.

Comparison between the weightlessness syndrome and aging

NASA Technical Reports Server (NTRS)

Miquel, J.

1982-01-01

The similarity of detrimental effects of normal aging and of exposure to space weightlessness is discussed. The effects include: the reduction in cardiac output, increase in blood pressure, decrease in respiratory vital capacity, decrease in lean body weight and muscle mass, collagen and fat infiltration of muscle, bone demineralization, and a decrease in urinary excretion of total 17-hydroxicorticosteroids. It is also noted that dispite the accelerated aging of organisms, if animals or human subjects were to spend their entire lives in weightlessness, their lifespans might be significantly increased because of a reduction in metabolic rate. Experimental results are cited.

A human prostatic bacterial isolate alters the prostatic microenvironment and accelerates prostate cancer progression.

PubMed

Simons, Brian W; Durham, Nicholas M; Bruno, Tullia C; Grosso, Joseph F; Schaeffer, Anthony J; Ross, Ashley E; Hurley, Paula J; Berman, David M; Drake, Charles G; Thumbikat, Praveen; Schaeffer, Edward M

2015-02-01

Inflammation is associated with several diseases of the prostate including benign enlargement and cancer, but a causal relationship has not been established. Our objective was to characterize the prostate inflammatory microenvironment after infection with a human prostate-derived bacterial strain and to determine the effect of inflammation on prostate cancer progression. To this end, we mimicked typical human prostate infection with retrograde urethral instillation of CP1, a human prostatic isolate of Escherichia coli. CP1 bacteria were tropic for the accessory sex glands and induced acute inflammation in the prostate and seminal vesicles, with chronic inflammation lasting at least 1 year. Compared to controls, infection induced both acute and chronic inflammation with epithelial hyperplasia, stromal hyperplasia, and inflammatory cell infiltrates. In areas of inflammation, epithelial proliferation and hyperplasia often persist, despite decreased expression of androgen receptor (AR). Inflammatory cells in the prostates of CP1-infected mice were characterized at 8 weeks post-infection by flow cytometry, which showed an increase in macrophages and lymphocytes, particularly Th17 cells. Inflammation was additionally assessed in the context of carcinogenesis. Multiplex cytokine profiles of inflamed prostates showed that distinct inflammatory cytokines were expressed during prostate inflammation and cancer, with a subset of cytokines synergistically increased during concurrent inflammation and cancer. Furthermore, CP1 infection in the Hi-Myc mouse model of prostate cancer accelerated the development of invasive prostate adenocarcinoma, with 70% more mice developing cancer by 4.5 months of age. This study provides direct evidence that prostate inflammation accelerates prostate cancer progression and gives insight into the microenvironment changes induced by inflammation that may accelerate tumour initiation or progression. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Factors affecting perception thresholds of vertical whole-body vibration in recumbent subjects: Gender and age of subjects, and vibration duration

NASA Astrophysics Data System (ADS)

Matsumoto, Y.; Maeda, S.; Iwane, Y.; Iwata, Y.

2011-04-01

Some factors that may affect human perception thresholds of the vertical whole-body vibrations were investigated in two laboratory experiments with recumbent subjects. In the first experiment, the effects of gender and age of subjects on perception were investigated with three groups of 12 subjects, i.e., young males, young females and old males. For continuous sinusoidal vibrations at 2, 4, 8, 16, 31.5 and 63 Hz, there were no significant differences in the perception thresholds between male and female subjects, while the thresholds of young subjects tended to be significantly lower than the thresholds of old subjects. In the second experiment, the effect of vibration duration was investigated by using sinusoidal vibrations, at the same frequencies as above, modulated by the Hanning windows with different lengths (i.e., 0.5, 1.0, 2.0 and 4.0 s) for 12 subjects. It was found that the peak acceleration at the threshold tended to decrease with increasing duration of vibration. The perception thresholds were also evaluated by the running root-mean-square (rms) acceleration and the fourth power acceleration method defined in the current standards. The differences in the threshold of the transient vibrations for different durations were less with the fourth power acceleration method. Additionally, the effect of the integration time on the threshold was investigated for the running rms acceleration and the fourth power acceleration. It was found that the integration time that yielded less differences in the threshold of vibrations for different durations depended on the frequency of vibration.

Color Stability of CAD/CAM Fabricated Inlays after Accelerated Artificial Aging.

PubMed

Karaokutan, Isil; Yilmaz Savas, Tuba; Aykent, Filiz; Ozdere, Eda

2016-08-01

To investigate the influence of accelerated artificial aging on the color stability of three different inlay restorations produced with a CAD/CAM system. Thirty non-carious human mandibular molar teeth were used. The teeth were embedded in autopolymerizing acrylic resin blocks. Standard Class I inlay cavities were prepared, and the teeth were randomly divided into three groups (n = 10) to fabricate inlay restorations: (1) a feldspathic-ceramic group, (2) a resin nano-ceramic group, and (3) a leucite glass-ceramic group. Optical impressions were made with CEREC software, and the restorations were designed and then milled. The inlays were adhesively cemented with a dual-polymerizing resin cement and left in distilled water at room temperature for 1 week. Color measurements were performed with a spectrophotometer before and after accelerated aging in a weathering machine with a total energy of 150 kJ/m(2) . Changes in color (∆E, ∆L, ∆a, ∆b, ∆C) were determined using the CIE L*a*b* system. The results were assessed using a one-way ANOVA and Tukey's HSD test (p = 0.05). The color changes of the materials ranged from 2.1 to 9.29. The highest color change was seen in the resin nano-ceramic material. This change was not clinically acceptable (∆E > 5.5). No significant differences were found in the ∆L and ∆a values of the test groups. Color changes were observed in each evaluated material after accelerated aging. All CAD/CAM inlays became darker in appearance, more saturated, a little reddish, and more yellow. © 2015 by the American College of Prosthodontists.

Aging and fertility patterns in wild chimpanzees provide insights into the evolution of menopause

PubMed Central

Thompson, Melissa Emery; Jones, James H.; Pusey, Anne E.; Brewer-Marsden, Stella; Goodall, Jane; Marsden, David; Matsuzawa, Tetsuro; Nishida, Toshisada; Reynolds, Vernon; Sugiyama, Yukimaru; Wrangham, Richard W.

2008-01-01

Summary Human menopause is remarkable in that reproductive senescence is markedly accelerated relative to somatic aging, leaving an extended post-reproductive period for a large proportion of women [1, 2]. Functional explanations for this are debated [4-11], in part because comparative data from closely-related species are inadequate. Existing studies of chimpanzees are based on very small samples and have not provided clear conclusions about the reproductive function of aging females [12-19]. These studies have not examined whether reproductive senescence in chimpanzees exceeds the pace of general aging, as in humans, or occurs in parallel with declines in overall health, as in many other animals [20, 21]. In order to remedy these problems, we examined fertility and mortality patterns in 6 free-living chimpanzee populations. Chimpanzee and human birth rates show similar patterns of decline beginning in the 4th decade, suggesting that the physiology of reproductive senescence was relatively conserved in human evolution. However, in contrast to humans, chimpanzee fertility declines are consistent with declines in survivorship, and healthy females maintain high birth rates late into life. Thus, in contrast to recent claims [16], we find no evidence that menopause is a typical characteristic of chimpanzee life histories. PMID:18083515

FDA-approved drugs that protect mammalian neurons from glucose toxicity slow aging dependent on cbp and protect against proteotoxicity.

PubMed

Lublin, Alex; Isoda, Fumiko; Patel, Harshil; Yen, Kelvin; Nguyen, Linda; Hajje, Daher; Schwartz, Marc; Mobbs, Charles

2011-01-01

Screening a library of drugs with known safety profiles in humans yielded 30 drugs that reliably protected mammalian neurons against glucose toxicity. Subsequent screening demonstrated that 6 of these 30 drugs increase lifespan in C. elegans: caffeine, ciclopirox olamine, tannic acid, acetaminophen, bacitracin, and baicalein. Every drug significantly reduced the age-dependent acceleration of mortality rate. These protective effects were blocked by RNAi inhibition of cbp-1 in adults only, which also blocks protective effects of dietary restriction. Only 2 drugs, caffeine and tannic acid, exhibited a similar dependency on DAF-16. Caffeine, tannic acid, and bacitracin also reduced pathology in a transgenic model of proteotoxicity associated with Alzheimer's disease. These results further support a key role for glucose toxicity in driving age-related pathologies and for CBP-1 in protection against age-related pathologies. These results also provide novel lead compounds with known safety profiles in human for treatment of age-related diseases, including Alzheimer's disease and diabetic complications.

The high cost of the international aging prisoner crisis: well-being as the common denominator for action.

PubMed

Maschi, Tina; Viola, Deborah; Sun, Fei

2013-08-01

The aging prisoner crisis continues to gain international attention as the high human, social, and economic costs of warehousing older adults with complex physical, mental health, and social care needs in prison continues to rise. According to the United Nations, older adults and the serious and terminally ill are considered special needs populations subject to special international health and social practice and policy considerations. We argue that older adults in prison have unique individual and social developmental needs that result from life course exposure to cumulative risk factors compounded by prison conditions that accelerate their aging. We position these factors in a social context model of human development and well-being and present a review of international human rights guidelines that pertain to promoting health and well-being to those aging in custody. The study concludes with promising practices and recommendations of their potential to reduce the high direct and indirect economic costs associated with mass confinement of older adults, many of whom need specialized long-term care that global correctional systems are inadequately equipped to provide.

Accelerated DNA Methylation Age: Associations with PTSD and Neural Integrity

PubMed Central

Wolf, Erika J.; Logue, Mark W.; Hayes, Jasmeet P.; Sadeh, Naomi; Schichman, Steven A.; Stone, Annjanette; Salat, David H.; Milberg, William; McGlinchey, Regina; Miller, Mark W.

2015-01-01

Background Accumulating evidence suggests that post traumatic stress disorder (PTSD) may accelerate cellular aging and lead to premature morbidity and neurocognitive decline. Methods This study evaluated associations between PTSD and DNA methylation (DNAm) age using recently developed algorithms of cellular age by Horvath (2013) and Hannum et al. (2013). These estimates reflect accelerated aging when they exceed chronological age. We also examined if accelerated cellular age manifested in degraded neural integrity, indexed via diffusion tensor imaging. Results Among 281 male and female veterans of the conflicts in Iraq and Afghanistan, DNAm age was strongly related to chronological age (rs ~.88). Lifetime PTSD severity was associated with Hannum DNAm age estimates residualized for chronological age (β = .13, p= .032). Advanced DNAm age was associated with reduced integrity in the genu of the corpus callosum (β = −.17, p= .009) and indirectly linked to poorer working memory performance via this region (indirect β = − .05, p= .029). Horvath DNAm age estimates were not associated with PTSD or neural integrity. Conclusions Results provide novel support for PTSD-related accelerated aging in DNAm and extend the evidence base of known DNAm age correlates to the domains of neural integrity and cognition. PMID:26447678

Adventures in Space Medicine

NASA Technical Reports Server (NTRS)

Billica, Roger D.

1999-01-01

Human space flight experience has demonstrated a variety of hazards and risks to health and performance. In developing ways to help respond to these issues, the field of space medicine has developed a comprehensive program of space flight health risk management that has resulted in positive contributions to medicine and society in general. Examples include accelerated focus on critical health issues such as aging and osteoporosis, and development of new technologies such as non-invasive diagnostic testing for diabetics. The role of health care professionals in human space exploration represents a fulfillment of new adventures and expanding frontiers.

Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice

PubMed Central

Safdar, Adeel; Bourgeois, Jacqueline M.; Ogborn, Daniel I.; Little, Jonathan P.; Hettinga, Bart P.; Akhtar, Mahmood; Thompson, James E.; Melov, Simon; Mocellin, Nicholas J.; Kujoth, Gregory C.; Prolla, Tomas A.; Tarnopolsky, Mark A.

2011-01-01

A causal role for mitochondrial DNA (mtDNA) mutagenesis in mammalian aging is supported by recent studies demonstrating that the mtDNA mutator mouse, harboring a defect in the proofreading-exonuclease activity of mitochondrial polymerase gamma, exhibits accelerated aging phenotypes characteristic of human aging, systemic mitochondrial dysfunction, multisystem pathology, and reduced lifespan. Epidemiologic studies in humans have demonstrated that endurance training reduces the risk of chronic diseases and extends life expectancy. Whether endurance exercise can attenuate the cumulative systemic decline observed in aging remains elusive. Here we show that 5 mo of endurance exercise induced systemic mitochondrial biogenesis, prevented mtDNA depletion and mutations, increased mitochondrial oxidative capacity and respiratory chain assembly, restored mitochondrial morphology, and blunted pathological levels of apoptosis in multiple tissues of mtDNA mutator mice. These adaptations conferred complete phenotypic protection, reduced multisystem pathology, and prevented premature mortality in these mice. The systemic mitochondrial rejuvenation through endurance exercise promises to be an effective therapeutic approach to mitigating mitochondrial dysfunction in aging and related comorbidities. PMID:21368114

Anti-aging and aging factors in life. The role of free radicals

NASA Astrophysics Data System (ADS)

Getoff, Nikola

2007-10-01

The present review deals with some factors determining the anti-aging as well as the aging process. In order to get a deeper insight in the subject matter, firstly some less known spectroscopic and kinetic data of antioxidant vitamins (C, E, β-carotene) acting as anti-aging factors by electron transfer are briefly discussed. The generation of oxygen transients (OH, ROO rad , 1O 2, ozone radicals, etc.) by sunlight, ultrasonic and microwave radiation are causing "oxygen stress" and contribute to early ageing is also reviewed. Particular attention is paid to external environmental aging factors. Their action is based on the incorporation of various pollutants contained in water and air in the human organism. In this respect the polycyclic aromatic hydrocarbons (PAHs) play an essential role by initiating DNA-mutation, leading to an accelerate aging, carcinogenesis and diseases.

Growth factors, nutrient signaling, and cardiovascular aging

PubMed Central

Fontana, Luigi; Vinciguerra, Manlio; Longo, Valter D.

2012-01-01

Growth factors regulated by specific macronutrients have been shown to promote aging and accelerate mortality in the great majority of the organisms studied. In particular, the enzymes activated by growth hormone (GH), insulin and insulin-like growth factor 1 (IGF-I) in mammals and their orthologs in simple model organisms represent perhaps the best-understood proteins involved in the aging process. Dietary restriction (DR), which reduces the level of IGF-I and of other growth factors, has been associated with protection from diabetes, cancer, and cardiovascular diseases and deficiencies in GH signaling and IGF-I are strongly associated with protection from cancer and diabetes in both mice and humans, but their role in cardiac function and cardiovascular diseases is controversial. Here we review the link between growth factors, cardiac function and heart disease with focus on the cardioprotective and sensitizing effect of growth factors in both model organisms and humans. PMID:22499903

Growth factors, nutrient signaling, and cardiovascular aging.

PubMed

Fontana, Luigi; Vinciguerra, Manlio; Longo, Valter D

2012-04-13

Growth factors regulated by specific macronutrients have been shown to promote aging and accelerate mortality in the majority of the organisms studied. In particular, the enzymes activated by growth hormone, insulin, and insulin-like growth factor-1 in mammals and their orthologs in simple model organisms represent perhaps the best-understood proteins involved in the aging process. Dietary restriction, which reduces the level of insulin-like growth factor-1 and of other growth factors, has been associated with protection from diabetes, cancer, and cardiovascular diseases, and deficiencies in growth hormone signaling and insulin-like growth factor-1 are strongly associated with protection from cancer and diabetes in both mice and humans; however, their role in cardiac function and cardiovascular diseases is controversial. Here, we review the link between growth factors, cardiac function, and heart disease with focus on the cardioprotective and sensitizing effect of growth factors in both model organisms and humans.

DNA methylation-based measures of biological age: meta-analysis predicting time to death.

PubMed

Chen, Brian H; Marioni, Riccardo E; Colicino, Elena; Peters, Marjolein J; Ward-Caviness, Cavin K; Tsai, Pei-Chien; Roetker, Nicholas S; Just, Allan C; Demerath, Ellen W; Guan, Weihua; Bressler, Jan; Fornage, Myriam; Studenski, Stephanie; Vandiver, Amy R; Moore, Ann Zenobia; Tanaka, Toshiko; Kiel, Douglas P; Liang, Liming; Vokonas, Pantel; Schwartz, Joel; Lunetta, Kathryn L; Murabito, Joanne M; Bandinelli, Stefania; Hernandez, Dena G; Melzer, David; Nalls, Michael; Pilling, Luke C; Price, Timothy R; Singleton, Andrew B; Gieger, Christian; Holle, Rolf; Kretschmer, Anja; Kronenberg, Florian; Kunze, Sonja; Linseisen, Jakob; Meisinger, Christine; Rathmann, Wolfgang; Waldenberger, Melanie; Visscher, Peter M; Shah, Sonia; Wray, Naomi R; McRae, Allan F; Franco, Oscar H; Hofman, Albert; Uitterlinden, André G; Absher, Devin; Assimes, Themistocles; Levine, Morgan E; Lu, Ake T; Tsao, Philip S; Hou, Lifang; Manson, JoAnn E; Carty, Cara L; LaCroix, Andrea Z; Reiner, Alexander P; Spector, Tim D; Feinberg, Andrew P; Levy, Daniel; Baccarelli, Andrea; van Meurs, Joyce; Bell, Jordana T; Peters, Annette; Deary, Ian J; Pankow, James S; Ferrucci, Luigi; Horvath, Steve

2016-09-28

Estimates of biological age based on DNA methylation patterns, often referred to as "epigenetic age", "DNAm age", have been shown to be robust biomarkers of age in humans. We previously demonstrated that independent of chronological age, epigenetic age assessed in blood predicted all-cause mortality in four human cohorts. Here, we expanded our original observation to 13 different cohorts for a total sample size of 13,089 individuals, including three racial/ethnic groups. In addition, we examined whether incorporating information on blood cell composition into the epigenetic age metrics improves their predictive power for mortality. All considered measures of epigenetic age acceleration were predictive of mortality (p≤8.2x10 -9 ) , independent of chronological age, even after adjusting for additional risk factors (p<5.4x10 -4 ) , and within the racial/ethnic groups that we examined (non-Hispanic whites, Hispanics, African Americans). Epigenetic age estimates that incorporated information on blood cell composition led to the smallest p-values for time to death (p=7.5x10 -43 ). Overall, this study a) strengthens the evidence that epigenetic age predicts all-cause mortality above and beyond chronological age and traditional risk factors, and b) demonstrates that epigenetic age estimates that incorporate information on blood cell counts lead to highly significant associations with all-cause mortality.

Accelerated and accentuated neurocognitive aging in HIV infection.

PubMed

Sheppard, David P; Iudicello, Jennifer E; Morgan, Erin E; Kamat, Rujvi; Clark, Lindsay R; Avci, Gunes; Bondi, Mark W; Woods, Steven Paul

2017-06-01

There is debate as to whether the neurocognitive changes associated with HIV infection represent an acceleration of the typical aging process or more simply reflect a greater accentuated risk for age-related declines. We aimed to determine whether accelerated neurocognitive aging is observable in a sample of older HIV-infected individuals compared to age-matched seronegatives and older old (i.e., aged ≥65) seronegative adults. Participants in a cross-sectional design included 48 HIV-seronegative (O-) and 40 HIV-positive (O+) participants between the ages of 50-65 (mean ages = 55 and 56, respectively) and 40 HIV-seronegative participants aged ≥65 (OO-; mean age = 74) who were comparable for other demographics. All participants were administered a brief neurocognitive battery of attention, episodic memory, speeded executive functions, and confrontation naming (i.e., Boston Naming Test). The O+ group performed more poorly than the O- group (i.e., accentuated aging), but not differently from the OO- on digit span and initial recall of a supraspan word list, consistent with an accelerating aging profile. However, the O+ group's performance was comparable to the O- group on all other neurocognitive tests (ps > 0.05). These data partially support a model of accelerated neurocognitive aging in HIV infection, which was observed in the domain of auditory verbal attention, but not in the areas of memory, language, or speeded executive functions. Future studies should examine whether HIV-infected adults over 65 evidence accelerated aging in downstream neurocognitive domains and subsequent everyday functioning outcomes.

Traumatic stress and accelerated DNA methylation age: A meta-analysis.

PubMed

Wolf, Erika J; Maniates, Hannah; Nugent, Nicole; Maihofer, Adam X; Armstrong, Don; Ratanatharathorn, Andrew; Ashley-Koch, Allison E; Garrett, Melanie; Kimbrel, Nathan A; Lori, Adriana; Va Mid-Atlantic Mirecc Workgroup; Aiello, Allison E; Baker, Dewleen G; Beckham, Jean C; Boks, Marco P; Galea, Sandro; Geuze, Elbert; Hauser, Michael A; Kessler, Ronald C; Koenen, Karestan C; Miller, Mark W; Ressler, Kerry J; Risbrough, Victoria; Rutten, Bart P F; Stein, Murray B; Ursano, Robert J; Vermetten, Eric; Vinkers, Christiaan H; Uddin, Monica; Smith, Alicia K; Nievergelt, Caroline M; Logue, Mark W

2018-06-01

Recent studies examining the association between posttraumatic stress disorder (PTSD) and accelerated aging, as defined by DNA methylation-based estimates of cellular age that exceed chronological age, have yielded mixed results. We conducted a meta-analysis of trauma exposure and PTSD diagnosis and symptom severity in association with accelerated DNA methylation age using data from 9 cohorts contributing to the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (combined N = 2186). Associations between demographic and cellular variables and accelerated DNA methylation age were also examined, as was the moderating influence of demographic variables. Meta-analysis of regression coefficients from contributing cohorts revealed that childhood trauma exposure (when measured with the Childhood Trauma Questionnaire) and lifetime PTSD severity evidenced significant, albeit small, meta-analytic associations with accelerated DNA methylation age (ps = 0.028 and 0.016, respectively). Sex, CD4T cell proportions, and natural killer cell proportions were also significantly associated with accelerated DNA methylation age (all ps < 0.02). PTSD diagnosis and lifetime trauma exposure were not associated with advanced DNA methylation age. There was no evidence of moderation of the trauma or PTSD variables by demographic factors. Results suggest that traumatic stress is associated with advanced epigenetic age and raise the possibility that cells integral to immune system maintenance and responsivity play a role in this. This study highlights the need for additional research into the biological mechanisms linking traumatic stress to accelerated DNA methylation age and the importance of furthering our understanding of the neurobiological and health consequences of PTSD. Published by Elsevier Ltd.

Homo sapiens-Specific Binding Site Variants within Brain Exclusive Enhancers Are Subject to Accelerated Divergence across Human Population.

PubMed

Zehra, Rabail; Abbasi, Amir Ali

2018-03-01

Empirical assessments of human accelerated noncoding DNA frgaments have delineated presence of many cis-regulatory elements. Enhancers make up an important category of such accelerated cis-regulatory elements that efficiently control the spatiotemporal expression of many developmental genes. Establishing plausible reasons for accelerated enhancer sequence divergence in Homo sapiens has been termed significant in various previously published studies. This acceleration by including closely related primates and archaic human data has the potential to open up evolutionary avenues for deducing present-day brain structure. This study relied on empirically confirmed brain exclusive enhancers to avoid any misjudgments about their regulatory status and categorized among them a subset of enhancers with an exceptionally accelerated rate of lineage specific divergence in humans. In this assorted set, 13 distinct transcription factor binding sites were located that possessed unique existence in humans. Three of 13 such sites belonging to transcription factors SOX2, RUNX1/3, and FOS/JUND possessed single nucleotide variants that made them unique to H. sapiens upon comparisons with Neandertal and Denisovan orthologous sequences. These variants modifying the binding sites in modern human lineage were further substantiated as single nucleotide polymorphisms via exploiting 1000 Genomes Project Phase3 data. Long range haplotype based tests laid out evidence of positive selection to be governing in African population on two of the modern human motif modifying alleles with strongest results for SOX2 binding site. In sum, our study acknowledges acceleration in noncoding regulatory landscape of the genome and highlights functional parts within it to have undergone accelerated divergence in present-day human population.

Menopause increases the iron storage protein ferritin in skin.

PubMed

Pelle, Edward; Jian, Jinlong; Zhang, Qi; Muizzuddin, Neelam; Yang, Qing; Dai, Jisen; Maes, Daniel; Pernodet, Nadine; Yarosh, Daniel B; Frenkel, Krystyna; Huang, Xi

2013-01-01

Menstruation and desquamation are important routes for humans to excrete iron. Because menstruation is no longer available in postmenopausal women, in the present study, we examined whether iron accumulates more in postmenopausal skin than in premenopausal skin. Skin biopsy samples were obtained from six pre- and six postmenopausal Caucasian women. Iron levels in the form of ferritin were 42% higher, but vascular endothelial growth factor and total antioxidant capacity were 45% and 34% lower in postmenopausal skin (58.8 ± 1.3 years old) than in premenopausal skin (41.6 ± 1.7 years old), respectively. Moreover, in vitro cultured normal human epidermal keratinocytes had surprisingly high levels of ferritin when compared to immortalized human breast epithelial MCF-10A cells or human liver HepG2 cancer cells. Our results indicate that skin is a cellular repository of iron and that menopause increases iron in skin and, thus, may contribute to the manifestation of accelerated skin aging and photo aging after menopause.

Estrogens and aging skin.

PubMed

Thornton, M Julie

2013-04-01

Estrogen deficiency following menopause results in atrophic skin changes and acceleration of skin aging. Estrogens significantly modulate skin physiology, targeting keratinocytes, fibroblasts, melanocytes, hair follicles and sebaceous glands, and improve angiogenesis, wound healing and immune responses. Estrogen insufficiency decreases defense against oxidative stress; skin becomes thinner with less collagen, decreased elasticity, increased wrinkling, increased dryness and reduced vascularity. Its protective function becomes compromised and aging is associated with impaired wound healing, hair loss, pigmentary changes and skin cancer.   Skin aging can be significantly delayed by the administration of estrogen. This paper reviews estrogen effects on human skin and the mechanisms by which estrogens can alleviate the changes due to aging. The relevance of estrogen replacement, selective estrogen receptor modulators (SERMs) and phytoestrogens as therapies for diminishing skin aging is highlighted. Understanding estrogen signaling in skin will provide a basis for interventions in aging pathologies.

[The use of biological age on mental work capacity model in accelerated aging assessment of professional lorry-drivers].

PubMed

Bashkireva, A S

2012-01-01

The studies of biological age, aging rate, mental work capacity in professional drivers were conducted. The examination revealed peculiarities of system organization of functions determining the mental work capacity levels. Dynamics of the aging process of professional driver's organism in relation with calendar age and driving experience were shown using the biological age model. The results point at the premature decrease of the mental work capacity in professional drivers. It was proved, that premature age-related changes of physiologic and psychophysiologic indices in drivers are just "risk indicators", while long driving experience is a real risk factor, accelerating the aging process. The "risk group" with manifestations of accelerating aging was observed in 40-49-year old drivers with 15-19 years of professional experience. The expediency of using the following methods for the age rate estimation according to biologic age indices and necessity of prophylactic measures for premature and accelerated aging prevention among working population was demonstrated.

Alzheimer’s disease is not “brain aging”: neuropathological, genetic, and epidemiological human studies

PubMed Central

Head, Elizabeth; Schmitt, Frederick A.; Davis, Paulina R.; Neltner, Janna H.; Jicha, Gregory A.; Abner, Erin L.; Smith, Charles D.; Van Eldik, Linda J.; Kryscio, Richard J.; Scheff, Stephen W.

2011-01-01

Human studies are reviewed concerning whether “aging”-related mechanisms contribute to Alzheimer’s disease (AD) pathogenesis. AD is defined by specific neuropathology: neuritic amyloid plaques and neocortical neurofibrillary tangles. AD pathology is driven by genetic factors related not to aging per se, but instead to the amyloid precursor protein (APP). In contrast to genes involved in APP-related mechanisms, there is no firm connection between genes implicated in human “accelerated aging” diseases (progerias) and AD. The epidemiology of AD in advanced age is highly relevant but deceptively challenging to address given the low autopsy rates in most countries. In extreme old age, brain diseases other than AD approximate AD prevalence while the impact of AD pathology appears to peak by age 95 and decline thereafter. Many distinct brain diseases other than AD afflict older human brains and contribute to cognitive impairment. Additional prevalent pathologies include cerebrovascular disease and hippocampal sclerosis, both high-morbidity brain diseases that appear to peak in incidence later than AD chronologically. Because of these common brain diseases of extreme old age, the epidemiology differs between clinical “dementia” and the subset of dementia cases with AD pathology. Additional aging-associated mechanisms for cognitive decline such as diabetes and synapse loss have been linked to AD and these hypotheses are discussed. Criteria are proposed to define an “aging-linked” disease, and AD fails all of these criteria. In conclusion, it may be most fruitful to focus attention on specific pathways involved in AD rather than attributing it to an inevitable consequence of aging. PMID:21516511

Menopause accelerates biological aging

PubMed Central

Levine, Morgan E.; Lu, Ake T.; Chen, Brian H.; Hernandez, Dena G.; Singleton, Andrew B.; Ferrucci, Luigi; Bandinelli, Stefania; Salfati, Elias; Manson, JoAnn E.; Quach, Austin; Kusters, Cynthia D. J.; Kuh, Diana; Wong, Andrew; Teschendorff, Andrew E.; Widschwendter, Martin; Ritz, Beate R.; Absher, Devin; Assimes, Themistocles L.; Horvath, Steve

2016-01-01

Although epigenetic processes have been linked to aging and disease in other systems, it is not yet known whether they relate to reproductive aging. Recently, we developed a highly accurate epigenetic biomarker of age (known as the “epigenetic clock”), which is based on DNA methylation levels. Here we carry out an epigenetic clock analysis of blood, saliva, and buccal epithelium using data from four large studies: the Women's Health Initiative (n = 1,864); Invecchiare nel Chianti (n = 200); Parkinson's disease, Environment, and Genes (n = 256); and the United Kingdom Medical Research Council National Survey of Health and Development (n = 790). We find that increased epigenetic age acceleration in blood is significantly associated with earlier menopause (P = 0.00091), bilateral oophorectomy (P = 0.0018), and a longer time since menopause (P = 0.017). Conversely, epigenetic age acceleration in buccal epithelium and saliva do not relate to age at menopause; however, a higher epigenetic age in saliva is exhibited in women who undergo bilateral oophorectomy (P = 0.0079), while a lower epigenetic age in buccal epithelium was found for women who underwent menopausal hormone therapy (P = 0.00078). Using genetic data, we find evidence of coheritability between age at menopause and epigenetic age acceleration in blood. Using Mendelian randomization analysis, we find that two SNPs that are highly associated with age at menopause exhibit a significant association with epigenetic age acceleration. Overall, our Mendelian randomization approach and other lines of evidence suggest that menopause accelerates epigenetic aging of blood, but mechanistic studies will be needed to dissect cause-and-effect relationships further. PMID:27457926

Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice.

PubMed

Vermeij, W P; Dollé, M E T; Reiling, E; Jaarsma, D; Payan-Gomez, C; Bombardieri, C R; Wu, H; Roks, A J M; Botter, S M; van der Eerden, B C; Youssef, S A; Kuiper, R V; Nagarajah, B; van Oostrom, C T; Brandt, R M C; Barnhoorn, S; Imholz, S; Pennings, J L A; de Bruin, A; Gyenis, Á; Pothof, J; Vijg, J; van Steeg, H; Hoeijmakers, J H J

2016-09-15

Mice deficient in the DNA excision-repair gene Ercc1 (Ercc1 ∆/- ) show numerous accelerated ageing features that limit their lifespan to 4-6 months. They also exhibit a 'survival response', which suppresses growth and enhances cellular maintenance. Such a response resembles the anti-ageing response induced by dietary restriction (also known as caloric restriction). Here we report that a dietary restriction of 30% tripled the median and maximal remaining lifespans of these progeroid mice, strongly retarding numerous aspects of accelerated ageing. Mice undergoing dietary restriction retained 50% more neurons and maintained full motor function far beyond the lifespan of mice fed ad libitum. Other DNA-repair-deficient, progeroid Xpg -/- (also known as Ercc5 -/- ) mice, a model of Cockayne syndrome, responded similarly. The dietary restriction response in Ercc1 ∆/- mice closely resembled the effects of dietary restriction in wild-type animals. Notably, liver tissue from Ercc1 ∆/- mice fed ad libitum showed preferential extinction of the expression of long genes, a phenomenon we also observed in several tissues ageing normally. This is consistent with the accumulation of stochastic, transcription-blocking lesions that affect long genes more than short ones. Dietary restriction largely prevented this declining transcriptional output and reduced the number of γH2AX DNA damage foci, indicating that dietary restriction preserves genome function by alleviating DNA damage. Our findings establish the Ercc1 ∆/- mouse as a powerful model organism for health-sustaining interventions, reveal potential for reducing endogenous DNA damage, facilitate a better understanding of the molecular mechanism of dietary restriction and suggest a role for counterintuitive dietary-restriction-like therapy for human progeroid genome instability syndromes and possibly neurodegeneration in general.

Testing the hypothesis of accelerated cerebral white matter aging in schizophrenia and major depression.

PubMed

Kochunov, Peter; Glahn, David C; Rowland, Laura M; Olvera, Rene L; Winkler, Anderson; Yang, Yi-Hong; Sampath, Hemalatha; Carpenter, Will T; Duggirala, Ravindranath; Curran, Joanne; Blangero, John; Hong, L Elliot

2013-03-01

Elevated rate of aging-related biological and functional decline, termed "accelerated aging," is reported in patients with schizophrenia (SCZ) and major depressive disorder (MDD). We used diffusion tensor imaging derived fractional anisotropy (FA) as a biomarker of aging-related decline in white matter (WM) integrity to test the hypotheses of accelerated aging in SCZ and MDD. The SCZ cohort comprised 58 SCZ patients and 60 controls (aged 20-60 years). The MDD cohort comprised 136 MDD patients and 351 controls (aged 20-79 years). The main outcome measures were the diagnosis-by-age interaction on whole-brain-averaged WM FA values and FA values from 12 major WM tracts. Diagnosis-by-age interaction for the whole-brain average FA was significant for the SCZ (p = .04) but not the MDD (p = .80) cohort. Diagnosis-by-age interaction was nominally significant (p<.05) for five WM tracts for SCZ and for none of the tracts in the MDD cohort. Tract-specific heterochronicity of the onset of age-related decline in SCZ demonstrated strong negative correlations with the age-of-peak myelination and the rates of age-related decline obtained from normative sample (r =-.61 and-.80, p<.05, respectively). No such trends existed for MDD cohort. Cerebral WM showed accelerated aging in SCZ but not in MDD, suggesting some difference in the pathophysiology underlying their WM aging changes. Tract-specific heterochronicity of WM development modulated presentation of accelerated aging in SCZ: WM tracts that matured later in life appeared more sensitive to the pathophysiology of SCZ and demonstrated more susceptibility to disorder-related accelerated decline in FA values with age. This trend was not observed in MDD cohort. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Testing the hypothesis of accelerated cerebral white matter aging in schizophrenia and major depression

PubMed Central

Kochunov, P.; Glahn, D.C.; Rowland, L.M.; Olvera, R.L.; Winkler, A; Yang, Y.H.; Sampath, H.; Carpenter, W.T.; Dugarrila, R.; Curran, J.; Blangero, J.; Hong, L.E.

2012-01-01

Introduction Elevated rate of aging-related biological and functional decline, termed accelerated aging, is reported in patients with schizophrenia (SCZ) and major depressive disorder (MDD). We used diffusion tensor imaging (DTI) derived fractional anisotropy (FA) as biomarkers of aging-related decline in white matter (WM) integrity to test the hypotheses of accelerated aging in SCZ and MDD. Methods The SCZ cohort was composed of 58/60 SCZ patients/controls (age=20–60years). MDD cohort was composed of 136/351 MDD patients/controls (age=20–79years). Main outcome measures were the diagnosis-by-age interaction on whole-brain-averaged WM FA values and FA values from twelve major WM tracts. Results Diagnosis-by-age interaction for the whole-brain average FA was significant for the SCZ (p=0.04) but not in MDD cohort (p=0.80). Diagnosis-by-age interaction was nominally significant (p<0.05) for five WM tracts for SCZ and for none of the tracts in the MDD cohort. Tract-specific heterochronicity of the onset of age-related decline in SCZ demonstrated strong negative correlations with the age-of- peak myelination and the rates of age-related decline obtained from normative sample (r=−0.61 and −0.80, p<0.05, respectively). No such trends existed for MDD cohort. Conclusion Cerebral WM showed accelerated aging in SCZ but not in MDD, suggesting some difference in the pathophysiology underlying their WM aging changes. Tract-specific heterochronicity of WM development modulated presentation of accelerated aging in SCZ: white matter tracts that matured later in life appeared more sensitive to the pathophysiology of SCZ and demonstrated more susceptibility to disorder-related accelerated decline in FA values with age. This trend was not observed in MDD cohort. PMID:23200529

Evidence of Highly Conserved β-Crystallin Disulfidome that Can be Mimicked by In Vitro Oxidation in Age-related Human Cataract and Glutathione Depleted Mouse Lens*

PubMed Central

Fan, Xingjun; Zhou, Sheng; Wang, Benlian; Hom, Grant; Guo, Minfei; Li, Binbin; Yang, Jing; Vaysburg, Dennis; Monnier, Vincent M

2015-01-01

Low glutathione levels are associated with crystallin oxidation in age-related nuclear cataract. To understand the role of cysteine residue oxidation, we used the novel approach of comparing human cataracts with glutathione-depleted LEGSKO mouse lenses for intra- versus intermolecular disulfide crosslinks using 2D-PAGE and proteomics, and then systematically identified in vivo and in vitro all disulfide forming sites using ICAT labeling method coupled with proteomics. Crystallins rich in intramolecular disulfides were abundant at young age in human and WT mouse lens but shifted to multimeric intermolecular disulfides at older age. The shift was ∼4x accelerated in LEGSKO lens. Most cysteine disulfides in β-crystallins (except βA4 in human) were highly conserved in mouse and human and could be generated by oxidation with H2O2, whereas γ-crystallin oxidation selectively affected γC23/42/79/80/154, γD42/33, and γS83/115/130 in human cataracts, and γB79/80/110, γD19/109, γF19/79, γE19, γS83/130, and γN26/128 in mouse. Analysis based on available crystal structure suggests that conformational changes are needed to expose Cys42, Cys79/80, Cys154 in γC; Cys42, Cys33 in γD, and Cys83, Cys115, and Cys130 in γS. In conclusion, the β-crystallin disulfidome is highly conserved in age-related nuclear cataract and LEGSKO mouse, and reproducible by in vitro oxidation, whereas some of the disulfide formation sites in γ-crystallins necessitate prior conformational changes. Overall, the LEGSKO mouse model is closely reminiscent of age-related nuclear cataract. PMID:26453637

Accelerated cellular senescence in degenerate intervertebral discs: a possible role in the pathogenesis of intervertebral disc degeneration

PubMed Central

Le Maitre, Christine Lyn; Freemont, Anthony John; Hoyland, Judith Alison

2007-01-01

Current evidence implicates intervertebral disc degeneration as a major cause of low back pain, although its pathogenesis is poorly understood. Numerous characteristic features of disc degeneration mimic those seen during ageing but appear to occur at an accelerated rate. We hypothesised that this is due to accelerated cellular senescence, which causes fundamental changes in the ability of disc cells to maintain the intervertebral disc (IVD) matrix, thus leading to IVD degeneration. Cells isolated from non-degenerate and degenerate human tissue were assessed for mean telomere length, senescence-associated β-galactosidase (SA-β-gal), and replicative potential. Expression of P16INK4A (increased in cellular senescence) was also investigated in IVD tissue by means of immunohistochemistry. RNA from tissue and cultured cells was used for real-time polymerase chain reaction analysis for matrix metalloproteinase-13, ADAMTS 5 (a disintegrin and metalloprotease with thrombospondin motifs 5), and P16INK4A. Mean telomere length decreased with age in cells from non-degenerate tissue and also decreased with progressive stages of degeneration. In non-degenerate discs, there was an age-related increase in cellular expression of P16INK4A. Cells from degenerate discs (even from young patients) exhibited increased expression of P16INK4A, increased SA-β-gal staining, and a decrease in replicative potential. Importantly, there was a positive correlation between P16INK4A and matrix-degrading enzyme gene expression. Our findings indicate that disc cell senescence occurs in vivo and is accelerated in IVD degeneration. Furthermore, the senescent phenotype is associated with increased catabolism, implicating cellular senescence in the pathogenesis of IVD degeneration. PMID:17498290

A Direct Role of Collagen Glycation in Bone Fracture

PubMed Central

Poundarik, Atharva A.; Wu, Ping-Cheng; Evis, Zafer; Sroga, Grazyna E.; Ural, Ani; Rubin, Mishaela; Vashishth, Deepak

2015-01-01

Non-enzymatic glycation (NEG) is an age-related process accelerated by diseases like diabetes, and causes the accumulation of advanced glycation end-products (AGEs). NEG-mediated modification of bone’s organic matrix, principally collagen type-I, has been implicated in impairing skeletal physiology and mechanics. Here, we present evidence, from in vitro and in vivo models, and establish a causal relationship between collagen glycation and alterations in bone fracture at multiple length scales. Through atomic force spectroscopy, we established that NEG impairs collagen’s ability to dissipate energy. Mechanical testing of in vitro glycated human bone specimen revealed that AGE accumulation due to NEG dramatically reduces the capacity of organic and mineralized matrix to creep and caused bone to fracture under impact at low levels of strain (3000–5000 μstrain) typically associated with fall. Fracture mechanics tests of NEG modified human cortical bone of varying ages, and their age-matched controls revealed that NEG disrupted microcracking based toughening mechanisms and reduced bone propagation and initiation fracture toughness across all age groups. A comprehensive mechanistic model, based on experimental and modeling data, was developed to explain how NEG and AGEs are causal to, and predictive of bone fragility. Furthermore, fracture mechanics and indentation testing on diabetic mice bones revealed that diabetes mediated NEG severely disrupts bone matrix quality in vivo. Finally, we show that AGEs are predictive of bone quality in aging humans and have diagnostic applications in fracture risk. PMID:26530231

Late Pleistocene age and archaeological context for the hominin calvaria from GvJm-22 (Lukenya Hill, Kenya)

PubMed Central

Tryon, Christian A.; Crevecoeur, Isabelle; Faith, J. Tyler; Ekshtain, Ravid; Nivens, Joelle; Patterson, David; Mbua, Emma N.; Spoor, Fred

2015-01-01

Kenya National Museums Lukenya Hill Hominid 1 (KNM-LH 1) is a Homo sapiens partial calvaria from site GvJm-22 at Lukenya Hill, Kenya, associated with Later Stone Age (LSA) archaeological deposits. KNM-LH 1 is securely dated to the Late Pleistocene, and samples a time and region important for understanding the origins of modern human diversity. A revised chronology based on 26 accelerator mass spectrometry radiocarbon dates on ostrich eggshells indicates an age range of 23,576–22,887 y B.P. for KNM-LH 1, confirming prior attribution to the Last Glacial Maximum. Additional dates extend the maximum age for archaeological deposits at GvJm-22 to >46,000 y B.P. (>46 kya). These dates are consistent with new analyses identifying both Middle Stone Age and LSA lithic technologies at the site, making GvJm-22 a rare eastern African record of major human behavioral shifts during the Late Pleistocene. Comparative morphometric analyses of the KNM-LH 1 cranium document the temporal and spatial complexity of early modern human morphological variability. Features of cranial shape distinguish KNM-LH 1 and other Middle and Late Pleistocene African fossils from crania of recent Africans and samples from Holocene LSA and European Upper Paleolithic sites. PMID:25730861

Cloud-based Monte Carlo modelling of BSSRDF for the rendering of human skin appearance (Conference Presentation)

NASA Astrophysics Data System (ADS)

Doronin, Alexander; Rushmeier, Holly E.; Meglinski, Igor; Bykov, Alexander V.

2016-03-01

We present a new Monte Carlo based approach for the modelling of Bidirectional Scattering-Surface Reflectance Distribution Function (BSSRDF) for accurate rendering of human skin appearance. The variations of both skin tissues structure and the major chromophores are taken into account correspondingly to the different ethnic and age groups. The computational solution utilizes HTML5, accelerated by the graphics processing units (GPUs), and therefore is convenient for the practical use at the most of modern computer-based devices and operating systems. The results of imitation of human skin reflectance spectra, corresponding skin colours and examples of 3D faces rendering are presented and compared with the results of phantom studies.

Accelerated epigenetic aging in Werner syndrome.

PubMed

Maierhofer, Anna; Flunkert, Julia; Oshima, Junko; Martin, George M; Haaf, Thomas; Horvath, Steve

2017-04-01

Individuals suffering from Werner syndrome (WS) exhibit many clinical signs of accelerated aging. While the underlying constitutional mutation leads to accelerated rates of DNA damage, it is not yet known whether WS is also associated with an increased epigenetic age according to a DNA methylation based biomarker of aging (the "Epigenetic Clock"). Using whole blood methylation data from 18 WS cases and 18 age matched controls, we find that WS is associated with increased extrinsic epigenetic age acceleration (p=0.0072) and intrinsic epigenetic age acceleration (p=0.04), the latter of which is independent of age-related changes in the composition of peripheral blood cells. A multivariate model analysis reveals that WS is associated with an increase in DNA methylation age (on average 6.4 years, p=0.011) even after adjusting for chronological age, gender, and blood cell counts. Further, WS might be associated with a reduction in naïve CD8+ T cells (p=0.025) according to imputed measures of blood cell counts. Overall, this study shows that WS is associated with an increased epigenetic age of blood cells which is independent of changes in blood cell composition. The extent to which this alteration is a cause or effect of WS disease phenotypes remains unknown.

Effect of accelerated aging on the cross-link density of medical grade silicones.

PubMed

Mahomed, Aziza; Pormehr, Negin Bagheri

2016-11-25

Four specimens of Nagor silicone of different hardness (soft, medium and hard) were swollen, until they reached equilibrium (i.e. constant mass) in five liquids at 25°C, before and after accelerated aging. For the specimens swollen before accelerated aging, the greatest swelling was obtained in methyl cyclohexane, while for the specimens swollen after accelerated aging, the greatest swelling was obtained in cyclohexane. The cross-link density, υ, was also calculated from the swelling measurements for all the specimens, before and after accelerated aging, using the Flory-Rehner equation. The softer silicones, which swelled the most, had lower υ values than harder silicones. The amount of swelling (measured in terms of ϕ) and υ varied significantly (p<0.05) in some cases, between the different silicone hardness and between different liquids. Furthermore, the cross-link density, υ, significantly (p<0.05) increased after accelerated aging in most liquids.Note: ϕ is defined as the volume fraction of polymer in its equilibrium swollen state. A probability value of statistical significance of 0.05 or 5% was selected, hence if a p value of less than 0.05 was obtained, the null hypothesis was rejected (i.e. significant if p<0.05).

Shortened estrous cycle length, increased FSH levels, FSH variance, oocyte spindle aberrations, and early declining fertility in aging senescence-accelerated mouse prone-8 (SAMP8) mice: concomitant characteristics of human midlife female reproductive aging.

PubMed

Bernstein, Lori R; Mackenzie, Amelia C L; Kraemer, Duane C; Morley, John E; Farr, Susan; Chaffin, Charles L; Merchenthaler, István

2014-06-01

Women experience a series of specific transitions in their reproductive function with age. Shortening of the menstrual cycle begins in the mid to late 30s and is regarded as the first sign of reproductive aging. Other early changes include elevation and increased variance of serum FSH levels, increased incidences of oocyte spindle aberrations and aneuploidy, and declining fertility. The goal of this study was to investigate whether the mouse strain senescence-accelerated mouse-prone-8 (SAMP8) is a suitable model for the study of these midlife reproductive aging characteristics. Midlife SAMP8 mice aged 6.5-7.85 months (midlife SAMP8) exhibited shortened estrous cycles compared with SAMP8 mice aged 2-3 months (young SAMP8, P = .0040). Midlife SAMP8 mice had high FSH levels compared with young SAMP8 mice, and mice with a single day of high FSH exhibited statistically elevated FSH throughout the cycle, ranging from 1.8- to 3.6-fold elevation on the days of proestrus, estrus, metestrus, and diestrus (P < .05). Midlife SAMP8 mice displayed more variance in FSH than young SAMP8 mice (P = .01). Midlife SAMP8 ovulated fewer oocytes (P = .0155). SAMP8 oocytes stained with fluorescently labeled antitubulin antibodies and scored in fluorescence microscopy exhibited increased incidence of meiotic spindle aberrations with age, from 2/126 (1.59%) in young SAMP8 to 38/139 (27.3%) in midlife SAMP8 (17.2-fold increase, P < .0001). Finally, SAMP8 exhibited declining fertility from 8.9 pups/litter in young SAMP8 to 3.5 pups/litter in midlife SAMP8 mice (P < .0001). The age at which these changes occur is younger than for most mouse strains, and their simultaneous occurrence within a single strain has not been described previously. We propose that SAMP8 mice are a model of midlife human female reproductive aging.

A roadmap for the genetic analysis of renal aging

PubMed Central

Noordmans, Gerda A; Hillebrands, Jan-Luuk; van Goor, Harry; Korstanje, Ron

2015-01-01

Several studies show evidence for the genetic basis of renal disease, which renders some individuals more prone than others to accelerated renal aging. Studying the genetics of renal aging can help us to identify genes involved in this process and to unravel the underlying pathways. First, this opinion article will give an overview of the phenotypes that can be observed in age-related kidney disease. Accurate phenotyping is essential in performing genetic analysis. For kidney aging, this could include both functional and structural changes. Subsequently, this article reviews the studies that report on candidate genes associated with renal aging in humans and mice. Several loci or candidate genes have been found associated with kidney disease, but identification of the specific genetic variants involved has proven to be difficult. CUBN, UMOD, and SHROOM3 were identified by human GWAS as being associated with albuminuria, kidney function, and chronic kidney disease (CKD). These are promising examples of genes that could be involved in renal aging, and were further mechanistically evaluated in animal models. Eventually, we will provide approaches for performing genetic analysis. We should leverage the power of mouse models, as testing in humans is limited. Mouse and other animal models can be used to explain the underlying biological mechanisms of genes and loci identified by human GWAS. Furthermore, mouse models can be used to identify genetic variants associated with age-associated histological changes, of which Far2, Wisp2, and Esrrg are examples. A new outbred mouse population with high genetic diversity will facilitate the identification of genes associated with renal aging by enabling high-resolution genetic mapping while also allowing the control of environmental factors, and by enabling access to renal tissues at specific time points for histology, proteomics, and gene expression. PMID:26219736

Accelerated Aging with Electrical Overstress and Prognostics for Power MOSFETs

NASA Technical Reports Server (NTRS)

Saha, Sankalita; Celaya, Jose Ramon; Vashchenko, Vladislav; Mahiuddin, Shompa; Goebel, Kai F.

2011-01-01

Power electronics play an increasingly important role in energy applications as part of their power converter circuits. Understanding the behavior of these devices, especially their failure modes as they age with nominal usage or sudden fault development is critical in ensuring efficiency. In this paper, a prognostics based health management of power MOSFETs undergoing accelerated aging through electrical overstress at the gate area is presented. Details of the accelerated aging methodology, modeling of the degradation process of the device and prognostics algorithm for prediction of the future state of health of the device are presented. Experiments with multiple devices demonstrate the performance of the model and the prognostics algorithm as well as the scope of application. Index Terms Power MOSFET, accelerated aging, prognostics

Explosive and pyrotechnic aging demonstration

NASA Technical Reports Server (NTRS)

Rouch, L. L., Jr.; Maycock, J. N.

1976-01-01

The survivability was experimentally verified of fine selected explosive and pyrotechnic propellant materials when subjected to sterilization, and prolonged exposure to space environments. This verification included thermal characterization, sterilization heat cycling, sublimation measurements, isothermal decomposition measurements, and accelerated aging at a preselected elevated temperature. Temperatures chosen for sublimation and isothermal decomposition measurements were those in which the decomposition processess occurring would be the same as those taking place in real-time aging. The elevated temperature selected (84 C) for accelerated aging was based upon the parameters calculated from the kinetic data obtained in the isothermal measurement tests and was such that one month of accelerated aging in the laboratory approximated one year of real-time aging at 66 C. Results indicate that HNS-IIA, pure PbN6, KDNBF, and Zr/KC10 are capable of withstanding sterilization. The accelerated aging tests indicated that unsterilized HNS-IIA and Zr/KC104 can withstand the 10 year, elevated temperature exposure, pure PbN6 and KDNBF exhibit small weight losses (less than 2 percent) and B/KC104 exhibits significant changes in its thermal characteristics. Accelerated aging tests after sterilization indicated that only HNS-IIA exhibited high stability.

A longitudinal study of DNA methylation as a potential mediator of age-related diabetes risk.

PubMed

Grant, Crystal D; Jafari, Nadereh; Hou, Lifang; Li, Yun; Stewart, James D; Zhang, Guosheng; Lamichhane, Archana; Manson, JoAnn E; Baccarelli, Andrea A; Whitsel, Eric A; Conneely, Karen N

2017-12-01

DNA methylation (DNAm) has been found to show robust and widespread age-related changes across the genome. DNAm profiles from whole blood can be used to predict human aging rates with great accuracy. We sought to test whether DNAm-based predictions of age are related to phenotypes associated with type 2 diabetes (T2D), with the goal of identifying risk factors potentially mediated by DNAm. Our participants were 43 women enrolled in the Women's Health Initiative. We obtained methylation data via the Illumina 450K Methylation array on whole blood samples from participants at three timepoints, covering on average 16 years per participant. We employed the method and software of Horvath, which uses DNAm at 353 CpGs to form a DNAm-based estimate of chronological age. We then calculated the epigenetic age acceleration, or Δ age , at each timepoint. We fit linear mixed models to characterize how Δ age contributed to a longitudinal model of aging and diabetes-related phenotypes and risk factors. For most participants, Δ age remained constant, indicating that age acceleration is generally stable over time. We found that Δ age associated with body mass index (p = 0.0012), waist circumference (p = 0.033), and fasting glucose (p = 0.0073), with the relationship with BMI maintaining significance after correction for multiple testing. Replication in a larger cohort of 157 WHI participants spanning 3 years was unsuccessful, possibly due to the shorter time frame covered. Our results suggest that DNAm has the potential to act as a mediator between aging and diabetes-related phenotypes, or alternatively, may serve as a biomarker of these phenotypes.

Modulation of telomere binding proteins: a future area of research for skin protection and anti-aging target.

PubMed

Imbert, Isabelle; Botto, Jean-Marie; Farra, Claude D; Domloge, Nouha

2012-06-01

Telomere shortening is considered as one of the main characteristics of cellular aging by limiting cellular division. Besides the fundamental advances through the discoveries of telomere and telomerase, which were recognized by a Nobel Prize, telomere protection remains an essential area of research. Recently, it was evidenced that studying the cross-talks between the proteins associated with telomere should provide a better understanding of the mechanistic basis for telomere-associated aging phenotypes. In this review, we discuss the current knowledge on telomere shortening, telomerase activity, and the essential role of telomere binding proteins in telomere stabilization and telomere-end protection. This review highlights the capacity of telomere binding proteins to limit cellular senescence and to maintain skin tissue homeostasis, which is of key importance to reduce accelerated tissue aging. Future studies addressing telomere protection and limitation of DNA damage response in human skin should include investigations on telomere binding proteins. As little is known about the expression of telomere binding proteins in human skin and modulation of their expression with aging, it remains an interesting field of skin research and a key area for future skin protection and anti-aging developments. © 2012 Wiley Periodicals, Inc.

In situ longitudinal pre-stretch in the human femoropopliteal artery.

PubMed

Kamenskiy, Alexey; Seas, Andreas; Bowen, Grant; Deegan, Paul; Desyatova, Anastasia; Bohlim, Nick; Poulson, William; MacTaggart, Jason

2016-03-01

In situ longitudinal (axial) pre-stretch (LPS) plays a fundamental role in the mechanics of the femoropopliteal artery (FPA). It conserves energy during pulsation and prevents buckling of the artery during limb movement. We investigated how LPS is affected by demographics and risk factors, and how these patient characteristics associate with the structural and physiologic features of the FPA. LPS was measured in n=148 fresh human FPAs (14-80 years old). Mechanical properties were characterized with biaxial extension and histopathological characteristics were quantified with Verhoeff-Van Gieson Staining. Constitutive modeling was used to calculate physiological stresses and stretches which were then analyzed in the context of demographics, risk factors and structural characteristics. Age had the strongest negative effect (r=-0.812, p<0.01) on LPS and could alone explain 66% of LPS variability. Male gender, higher body mass index, hypertension, diabetes, coronary artery disease, dyslipidemia and tobacco use had negative effects on LPS, but only the effect of tobacco was not associated with aging. FPAs with less pre-stretch had thicker medial layers, but thinner intramural elastic fibers with less dense and more fragmented external elastic laminae. Elastin degradation was associated with decreased physiological tethering force and longitudinal stress, while circumferential stress remained constant. FPA wall pathology was negatively associated with LPS (r=-0.553, p<0.01), but the effect was due primarily to aging. LPS in the FPA may serve as an energy reserve for adaptive remodeling. Reduction of LPS due to degradation and fragmentation of intramural longitudinal elastin during aging can be accelerated in tobacco users. This work studies in situ longitudinal pre-stretch (LPS) in the human femoropopliteal artery. LPS has a fundamental role in arterial mechanics, but is rather poorly studied due to lack of direct in vivo measurement method. We have investigated LPS in the n=148 human femoropopliteal arteries in the context of subject demographics and risk factors, and structural and physiologic characteristics of the artery. Our results demonstrate that LPS reduces with age due to degradation and fragmentation of intramural elastin. LPS may serve as an energy reserve for adaptive remodeling, and reduction of LPS can be accelerated in tobacco users. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

DNA methylation age is not accelerated in brain or blood of subjects with schizophrenia.

PubMed

McKinney, Brandon C; Lin, Huang; Ding, Ying; Lewis, David A; Sweet, Robert A

2017-10-05

Individuals with schizophrenia (SZ) exhibit multiple premature age-related phenotypes and die ~20years prematurely. The accelerated aging hypothesis of SZ has been advanced to explain these observations, it posits that SZ-associated factors accelerate the progressive biological changes associated with normal aging. Testing the hypothesis has been limited by the absence of robust, meaningful, and multi-tissue measures of biological age. Recently, a method was described in which DNA methylation (DNAm) levels at 353 genomic sites are used to produce "DNAm age", an estimate of biological age with advantages over existing measures. We used this method and 3 publicly-available DNAm datasets, 1 from brain and 2 from blood, to test the hypothesis. The brain dataset was composed of data from the dorsolateral prefrontal cortex of 232 non-psychiatric control (NPC) and 195 SZ subjects. Blood dataset #1 was composed of data from whole blood of 304 NPC and 332 SZ subjects, and blood dataset #2 was composed of data from whole blood of 405 NPC and 260 SZ subjects. DNAm age and chronological age correlated strongly (r=0.92-0.95, p<0.0001) in both NPC and SZ subjects in all 3 datasets. DNAm age acceleration did not differ between NPC and SZ subjects in the brain dataset (t=0.52, p=0.60), blood dataset #1 (t=1.51, p=0.13), or blood dataset #2 (t=0.93, p=0.35). Consistent with our previous findings from a smaller study of postmortem brains, our findings suggest there is no acceleration of brain or blood aging in SZ and, thus, do not support the accelerated aging hypothesis of SZ. Copyright © 2017 Elsevier B.V. All rights reserved.

Earliest evidence of modern human life history in North African early Homo sapiens.

PubMed

Smith, Tanya M; Tafforeau, Paul; Reid, Donald J; Grün, Rainer; Eggins, Stephen; Boutakiout, Mohamed; Hublin, Jean-Jacques

2007-04-10

Recent developmental studies demonstrate that early fossil hominins possessed shorter growth periods than living humans, implying disparate life histories. Analyses of incremental features in teeth provide an accurate means of assessing the age at death of developing dentitions, facilitating direct comparisons with fossil and modern humans. It is currently unknown when and where the prolonged modern human developmental condition originated. Here, an application of x-ray synchrotron microtomography reveals that an early Homo sapiens juvenile from Morocco dated at 160,000 years before present displays an equivalent degree of tooth development to modern European children at the same age. Crown formation times in the juvenile's macrodont dentition are higher than modern human mean values, whereas root development is accelerated relative to modern humans but is less than living apes and some fossil hominins. The juvenile from Jebel Irhoud is currently the oldest-known member of Homo with a developmental pattern (degree of eruption, developmental stage, and crown formation time) that is more similar to modern H. sapiens than to earlier members of Homo. This study also underscores the continuing importance of North Africa for understanding the origins of human anatomical and behavioral modernity. Corresponding biological and cultural changes may have appeared relatively late in the course of human evolution.

DNA methylation-based measures of biological age: meta-analysis predicting time to death

PubMed Central

Chen, Brian H.; Marioni, Riccardo E.; Colicino, Elena; Peters, Marjolein J.; Ward-Caviness, Cavin K.; Tsai, Pei-Chien; Roetker, Nicholas S.; Just, Allan C.; Demerath, Ellen W.; Guan, Weihua; Bressler, Jan; Fornage, Myriam; Studenski, Stephanie; Vandiver, Amy R.; Moore, Ann Zenobia; Tanaka, Toshiko; Kiel, Douglas P.; Liang, Liming; Vokonas, Pantel; Schwartz, Joel; Lunetta, Kathryn L.; Murabito, Joanne M.; Bandinelli, Stefania; Hernandez, Dena G.; Melzer, David; Nalls, Michael; Pilling, Luke C.; Price, Timothy R.; Singleton, Andrew B.; Gieger, Christian; Holle, Rolf; Kretschmer, Anja; Kronenberg, Florian; Kunze, Sonja; Linseisen, Jakob; Meisinger, Christine; Rathmann, Wolfgang; Waldenberger, Melanie; Visscher, Peter M.; Shah, Sonia; Wray, Naomi R.; McRae, Allan F.; Franco, Oscar H.; Hofman, Albert; Uitterlinden, André G.; Absher, Devin; Assimes, Themistocles; Levine, Morgan E.; Lu, Ake T.; Tsao, Philip S.; Hou, Lifang; Manson, JoAnn E.; Carty, Cara L.; LaCroix, Andrea Z.; Reiner, Alexander P.; Spector, Tim D.; Feinberg, Andrew P.; Levy, Daniel; Baccarelli, Andrea; van Meurs, Joyce; Bell, Jordana T.; Peters, Annette; Deary, Ian J.; Pankow, James S.; Ferrucci, Luigi; Horvath, Steve

2016-01-01

Estimates of biological age based on DNA methylation patterns, often referred to as “epigenetic age”, “DNAm age”, have been shown to be robust biomarkers of age in humans. We previously demonstrated that independent of chronological age, epigenetic age assessed in blood predicted all-cause mortality in four human cohorts. Here, we expanded our original observation to 13 different cohorts for a total sample size of 13,089 individuals, including three racial/ethnic groups. In addition, we examined whether incorporating information on blood cell composition into the epigenetic age metrics improves their predictive power for mortality. All considered measures of epigenetic age acceleration were predictive of mortality (p≤8.2×10−9), independent of chronological age, even after adjusting for additional risk factors (p<5.4×10−4), and within the racial/ethnic groups that we examined (non-Hispanic whites, Hispanics, African Americans). Epigenetic age estimates that incorporated information on blood cell composition led to the smallest p-values for time to death (p=7.5×10−43). Overall, this study a) strengthens the evidence that epigenetic age predicts all-cause mortality above and beyond chronological age and traditional risk factors, and b) demonstrates that epigenetic age estimates that incorporate information on blood cell counts lead to highly significant associations with all-cause mortality. PMID:27690265

The path from mitochondrial ROS to aging runs through the mitochondrial permeability transition pore.

PubMed

Rottenberg, Hagai; Hoek, Jan B

2017-10-01

Excessive production of mitochondrial reactive oxygen species (mROS) is strongly associated with mitochondrial and cellular oxidative damage, aging, and degenerative diseases. However, mROS also induces pathways of protection of mitochondria that slow aging, inhibit cell death, and increase lifespan. Recent studies show that the activation of the mitochondrial permeability transition pore (mPTP), which is triggered by mROS and mitochondrial calcium overloading, is enhanced in aged animals and humans and in aging-related degenerative diseases. mPTP opening initiates further production and release of mROS that damage both mitochondrial and nuclear DNA, proteins, and phospholipids, and also releases matrix NAD that is hydrolyzed in the intermembrane space, thus contributing to the depletion of cellular NAD that accelerates aging. Oxidative damage to calcium transporters leads to calcium overload and more frequent opening of mPTP. Because aging enhances the opening of the mPTP and mPTP opening accelerates aging, we suggest that mPTP opening drives the progression of aging. Activation of the mPTP is regulated, directly and indirectly, not only by the mitochondrial protection pathways that are induced by mROS, but also by pro-apoptotic signals that are induced by DNA damage. We suggest that the integration of these contrasting signals by the mPTP largely determines the rate of cell aging and the initiation of cell death, and thus animal lifespan. The suggestion that the control of mPTP activation is critical for the progression of aging can explain the conflicting and confusing evidence regarding the beneficial and deleterious effects of mROS on health and lifespan. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Establishing the Biodynamics Data Resource (BDR): Human Volunteer Impact Acceleration Research Data in the BDR

DTIC Science & Technology

2009-10-01

accelerations (+Z) were applied to HRVs in the supine position to mimic the acceleration of an ejection seat , while runs simulating aircraft crashes were...Naval Biodynamics Laboratory, 1985). The vertical testing provided a more authentic ejection seat simulation than was achievable using axial...impact acceleration exposures with hundreds of human research volunteers. The resulting volumes of kinematic and physiological data serve as a

Genome-Wide Identification of Regulatory Sequences Undergoing Accelerated Evolution in the Human Genome

PubMed Central

Dong, Xinran; Wang, Xiao; Zhang, Feng; Tian, Weidong

2016-01-01

Accelerated evolution of regulatory sequence can alter the expression pattern of target genes, and cause phenotypic changes. In this study, we used DNase I hypersensitive sites (DHSs) to annotate putative regulatory sequences in the human genome, and conducted a genome-wide analysis of the effects of accelerated evolution on regulatory sequences. Working under the assumption that local ancient repeat elements of DHSs are under neutral evolution, we discovered that ∼0.44% of DHSs are under accelerated evolution (ace-DHSs). We found that ace-DHSs tend to be more active than background DHSs, and are strongly associated with epigenetic marks of active transcription. The target genes of ace-DHSs are significantly enriched in neuron-related functions, and their expression levels are positively selected in the human brain. Thus, these lines of evidences strongly suggest that accelerated evolution on regulatory sequences plays important role in the evolution of human-specific phenotypes. PMID:27401230

Major Depressive Disorder and Measures of Cellular Aging: An Integrative Review

PubMed Central

Kinser, Patricia Anne; Lyon, Debra E.

2013-01-01

Major depressive disorder (MDD) affects millions of individuals and causes significant suffering worldwide. It has been speculated that MDD is associated with accelerated aging-related biological and functional decline. To examine the accelerated aging hypothesis, one of the biomarkers under study is leukocyte telomeres, and specifically the measure of telomere length and telomerase activity. This review integrates findings from eleven human studies which evaluated telomere length and telomerase activity, in order to synthesize the state of the current science and to inform the development of new knowledge and enhance nursing research of depression using appropriate biobehavioral measures. Although preliminary, the findings from this integrated review suggest that there is evidence to support a conceptualization of depression as a stress-related condition in which telomeres shorten over time in relation to cumulative exposure to the chronic stress of depression. For the purposes of testing in future nursing research, visual representations of the theoretical connection between stress vulnerabilities, depression, and health outcomes and key moderators and mediators involved in this conceptualization are provided. The findings from this review and the conceptual framework provided may be a useful step towards advancing therapeutic nursing interventions for this debilitating chronic condition. PMID:23691300

Correlation between mechanical and chemical degradation after outdoor and accelerated laboratory aging for multilayer photovoltaic backsheets

NASA Astrophysics Data System (ADS)

Lin, Chiao-Chi; Lyu, Yadong; Yu, Li-Chieh; Gu, Xiaohong

2016-09-01

Channel cracking fragmentation testing and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy were utilized to study mechanical and chemical degradation of a multilayered backsheet after outdoor and accelerated laboratory aging. A model sample of commercial PPE backsheet, namely polyethylene terephthalate/polyethylene terephthalate/ethylene vinyl acetate (PET/PET/EVA) was investigated. Outdoor aging was performed in Gaithersburg, Maryland, USA for up to 510 days, and complementary accelerated laboratory aging was conducted on the NIST (National Institute of Standards and Technology) SPHERE (Simulated Photodegradation via High Energy Radiant Exposure). Fracture energy, mode I stress intensity factor and film strength were analyzed using an analytical model based on channel cracking fragmentation testing results. The correlation between mechanical and chemical degradation was discussed for both outdoor and accelerated laboratory aging. The results of this work provide preliminary understanding on failure mechanism of backsheets after weathering, laying the groundwork for linking outdoor and indoor accelerated laboratory testing for multilayer photovoltaic backsheets.

Short Stature, Accelerated Bone Maturation, and Early Growth Cessation Due to Heterozygous Aggrecan Mutations

PubMed Central

Nilsson, Ola; Guo, Michael H.; Dunbar, Nancy; Popovic, Jadranka; Flynn, Daniel; Jacobsen, Christina; Lui, Julian C.; Hirschhorn, Joel N.; Baron, Jeffrey

2014-01-01

Context: Many children with idiopathic short stature have a delayed bone age. Idiopathic short stature with advanced bone age is far less common. Objective: The aim was to identify underlying genetic causes of short stature with advanced bone age. Setting and Design: We used whole-exome sequencing to study three families with autosomal-dominant short stature, advanced bone age, and premature growth cessation. Results: Affected individuals presented with short stature [adult heights −2.3 to −4.2 standard deviation scores (SDS)] with histories of early growth cessation or childhood short stature (height SDS −1.9 to −3.5 SDS), advancement of bone age, and normal endocrine evaluations. Whole-exome sequencing identified novel heterozygous variants in ACAN, which encodes aggrecan, a proteoglycan in the extracellular matrix of growth plate and other cartilaginous tissues. The variants were present in all affected, but in no unaffected, family members. In Family 1, a novel frameshift mutation in exon 3 (c.272delA) was identified, which is predicted to cause early truncation of the aggrecan protein. In Family 2, a base-pair substitution was found in a highly conserved location within a splice donor site (c.2026+1G>A), which is also likely to alter the amino acid sequence of a large portion of the protein. In Family 3, a missense variant (c.7064T>C) in exon 14 affects a highly conserved residue (L2355P) and is strongly predicted to perturb protein function. Conclusions: Our study demonstrates that heterozygous mutations in ACAN can cause a mild skeletal dysplasia, which presents clinically as short stature with advanced bone age. The accelerating effect on skeletal maturation has not previously been noted in the few prior reports of human ACAN mutations. Our findings thus expand the spectrum of ACAN defects and provide a new molecular genetic etiology for the unusual child who presents with short stature and accelerated skeletal maturation. PMID:24762113

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

PubMed Central

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

2016-01-01

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

Effect of accelerated aging on the viscoelastic properties of a medical grade silicone.

PubMed

Mahomed, Aziza; Hukins, David W L; Kukureka, Stephen N

2015-01-01

The viscoelastic properties of cylinders (diameter 5 mm, height 2.2 ± 0.2 mm) of Nagor silicone elastomer of medium hardness, were investigated before and after the specimens had undergone accelerated aging in saline solution at 70°C for 38, 76 and 114 days (to simulate aging at 37°C, for 1, 2 and 3 years, respectively). All sets of specimens were immersed in physiological saline solution at 37°C during testing and the properties were measured using dynamic mechanical analysis (DMA). A sinusoidal cyclic compression of 40 N ± 5 N was applied over a frequency range, f, of 0.02-25 Hz. Values of the storage, E', and loss, E″, moduli were found to depend on f; the dependence of E' or E″ on the logarithm (base 10) of f was represented by a second-order polynomial. After accelerated aging, the E' and E″ values did not increase significantly (p<0.05). Furthermore, scanning electron microscopy (SEM) showed that accelerated aging did not affect the surface morphology of silicone. Attenuated total reflectance Fourier transform infra-red spectroscopy (ATR-FTIR) showed that accelerated aging had a negligible effect on the surface chemical structures of the material. Differential scanning calorimetry (DSC) showed no changes to the bulk properties of silicone, following accelerated aging.

Challenges of accelerated aging techniques for elastomer lifetime predictions

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

Gillen, Kenneth T.; Bernstein, R.; Celina, M.

Elastomers are often degraded when exposed to air or high humidity for extended times (years to decades). Lifetime estimates normally involve extrapolating accelerated aging results made at higher than ambient environments. Several potential problems associated with such studies are reviewed, and experimental and theoretical methods to address them are provided. The importance of verifying time–temperature superposition of degradation data is emphasized as evidence that the overall nature of the degradation process remains unchanged versus acceleration temperature. The confounding effects that occur when diffusion-limited oxidation (DLO) contributes under accelerated conditions are described, and it is shown that the DLO magnitude canmore » be modeled by measurements or estimates of the oxygen permeability coefficient (P Ox) and oxygen consumption rate (Φ). P Ox and Φ measurements can be influenced by DLO, and it is demonstrated how confident values can be derived. In addition, several experimental profiling techniques that screen for DLO effects are discussed. Values of Φ taken from high temperature to temperatures approaching ambient can be used to more confidently extrapolate accelerated aging results for air-aged materials, and many studies now show that Arrhenius extrapolations bend to lower activation energies as aging temperatures are lowered. Furthermore, best approaches for accelerated aging extrapolations of humidity-exposed materials are also offered.« less

Challenges of accelerated aging techniques for elastomer lifetime predictions

DOE PAGES

Gillen, Kenneth T.; Bernstein, R.; Celina, M.

2015-03-01

Elastomers are often degraded when exposed to air or high humidity for extended times (years to decades). Lifetime estimates normally involve extrapolating accelerated aging results made at higher than ambient environments. Several potential problems associated with such studies are reviewed, and experimental and theoretical methods to address them are provided. The importance of verifying time–temperature superposition of degradation data is emphasized as evidence that the overall nature of the degradation process remains unchanged versus acceleration temperature. The confounding effects that occur when diffusion-limited oxidation (DLO) contributes under accelerated conditions are described, and it is shown that the DLO magnitude canmore » be modeled by measurements or estimates of the oxygen permeability coefficient (P Ox) and oxygen consumption rate (Φ). P Ox and Φ measurements can be influenced by DLO, and it is demonstrated how confident values can be derived. In addition, several experimental profiling techniques that screen for DLO effects are discussed. Values of Φ taken from high temperature to temperatures approaching ambient can be used to more confidently extrapolate accelerated aging results for air-aged materials, and many studies now show that Arrhenius extrapolations bend to lower activation energies as aging temperatures are lowered. Furthermore, best approaches for accelerated aging extrapolations of humidity-exposed materials are also offered.« less

Age-related increase in Wnt inhibitor causes a senescence-like phenotype in human cardiac stem cells

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

Nakamura, Tamami; Hosoyama, Tohru; Regenerative Medicine Institute, Yamaguchi University Graduate School of Medicine

Aging of cardiac stem/progenitor cells (CSCs) impairs heart regeneration and leads to unsatisfactory outcomes of cell-based therapies. As the precise mechanisms underlying CSC aging remain unclear, the use of therapeutic strategies for elderly patients with heart failure is severely delayed. In this study, we used human cardiosphere-derived cells (CDCs), a subtype of CSC found in the postnatal heart, to identify secreted factor(s) associated with CSC aging. Human CDCs were isolated from heart failure patients of various ages (2–83 years old). Gene expression of key soluble factors was compared between CDCs derived from young and elderly patients. Among these factors, SFRP1,more » a gene encoding a Wnt antagonist, was significantly up-regulated in CDCs from elderly patients (≥65 years old). sFRP1 levels was increased significantly also in CDCs, whose senescent phenotype was induced by anti-cancer drug treatment. These results suggest the participation of sFRP1 in CSC aging. We show that the administration of recombinant sFRP1 induced cellular senescence in CDCs derived from young patients, as indicated by increased levels of markers such as p16, and a senescence-associated secretory phenotype. In addition, co-administration of recombinant sFRP1 could abrogate the accelerated CDC proliferation induced by Wnt3A. Taken together, our results suggest that canonical Wnt signaling and its antagonist, sFRP1, regulate proliferation of human CSCs. Furthermore, excess sFRP1 in elderly patients causes CSC aging. - Highlights: • Wnt signaling regulates proliferation of human cardiac stem cells. • Expression of sFRP1, which is a Wnt antagonist, is up-regulated in elderly patients with heart failure. • Expression of sFRP1 is increased in anti-cancer drug-induced senescent human cardiac stem cells. • sFRP1 causes cellular senescence of young patients-derived cardiac stem cells.« less

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.

Accelerating cocaine metabolism as an approach to the treatment of cocaine abuse and toxicity

PubMed Central

Schindler, Charles W; Goldberg, Steven R

2012-01-01

One pharmacokinetic approach to the treatment of cocaine abuse and toxicity involves the development of compounds that can be safely administered to humans and that accelerate the metabolism of cocaine to inactive components. Catalytic antibodies have been developed and shown to accelerate cocaine metabolism, but their catalytic efficiency for cocaine is relatively low. Mutations of human butyrylcholinesterase and a bacterial cocaine esterase found in the soil of coca plants have also been developed. These compounds accelerate cocaine metabolism and antagonize the behavioral and toxic effects of cocaine in animal models. Of these two approaches, the human butyrylcholinesterase mutants show the most immediate promise as they would not be expected to evoke an immune response in humans. PMID:22300096

Data Mining of Historical Human Data to Assess the Risk of Injury due to Dynamic Loads

NASA Technical Reports Server (NTRS)

Wells, Jesica; Somers, Jeffrey T.; Newby, N.; Gernhardt, Michael

2014-01-01

The NASA Occupant Protection Group is charged with ensuring crewmembers are protected during all dynamic phases of spaceflight. Previous work with outside experts has led to the development of a definition of acceptable risk (DAR) for space capsule vehicles. The DAR defines allowable probability rates for various categories of injuries. An important question is how to validate these probabilities for a given vehicle. One approach is to impact test human volunteers under projected nominal landing loads. The main drawback is the large number of subject tests required to attain a reasonable level of confidence that the injury probability rates would meet those outlined in the DAR. An alternative is to mine existing databases containing human responses to impact. Testing an anthropomorphic test device (ATD) at the same human-exposure levels could yield a range of ATD responses that would meet DAR. As one aspect of future vehicle validation, the ATD could be tested in the vehicle's seat and suit configuration at nominal landing loads and compared with the ATD responses supported by the human data set. This approach could reduce the number of human-volunteer tests NASA would need to conduct to validate that a vehicle meets occupant protection standards. METHODS: The U.S. Air Force has recorded hundreds of human responses to frontal, lateral, and spinal impacts at many acceleration levels and pulse durations. All of this data are stored on the Collaborative Biomechanics Data Network (CBDN), which is maintained by the Wright Patterson Air Force Base (WPAFB). The test device for human occupant restraint (THOR) ATD was impact tested on WPAFB's horizontal impulse accelerator (HIA) matching human-volunteer exposures on the HIA to 5 frontal and 3 spinal loading conditions. No human injuries occurred as a result of these impact conditions. Peak THOR response variables for neck axial tension and compression, and thoracic-spine axial compression were collected. Maximal chest deflection was determined from motion capture video of the impact test. HIC- 15 and BRIC were calculated from head acceleration responses. Given the number of human subjects for each test condition a confidence interval of injury probability will be obtained. RESULTS: Results will be discussed in terms of injury-risk probability estimates based on the human data set evaluated. Also, gaps in the data set will be identified. These gaps could be one of two types. One is areas where additional THOR testing would increase the comparable human data set, thereby improving confidence in the injury probability rate. The other is where additional human testing would assist in obtaining information on other acceleration levels or directions. DISCUSSION: The historical human data showed validity of the THOR ATD for supplemental testing. The historical human data are limited in scope, however. Further data are needed to characterize the effects of sex, age, anthropometry, and deconditioning due to spaceflight on risk of injury

Association of hormonal responses and performance of student pilots during acceleration training on the human centrifuge

NASA Astrophysics Data System (ADS)

Wirth, D.; Rohleder, N.; Welsch, H.

2005-08-01

Prediction of student pilots' +Gz tolerance by stress hormone levels would be a useful tool in aviation medicine. The aim of the present study was to analyze the relationship between neuroendocrine parameters with performance during acceleration training on the human centrifuge (HC).We investigated 21 student pilots during self-controlled acceleration training on the HC. Adrenocorticotropic hormone (ACTH), cortisol, epinephrine, and norepinephrine were measured after individual training sessions and at rest. Performance was defined by several characteristics including maximum tolerated acceleration. ACTH and cortisol, were significantly higher 20 minutes after acceleration training compared to the resting condition. Subjects tolerated a maximal acceleration of +6.69 Gz. HPA hormone levels and responses were associated with maximum tolerated acceleration +Gz. These findings support the expectation that acceleration- induced increases in stress hormones may enable the organism to tolerate a higher acceleration and could therefore be used as predictors for acceleration tolerance.

Senescent intervertebral disc cells exhibit perturbed matrix homeostasis phenotype.

PubMed

Ngo, Kevin; Patil, Prashanti; McGowan, Sara J; Niedernhofer, Laura J; Robbins, Paul D; Kang, James; Sowa, Gwendolyn; Vo, Nam

2017-09-01

Aging greatly increases the risk for intervertebral disc degeneration (IDD) as a result of proteoglycan loss due to reduced synthesis and enhanced degradation of the disc matrix proteoglycan (PG). How disc matrix PG homeostasis becomes perturbed with age is not known. The goal of this study is to determine whether cellular senescence is a source of this perturbation. We demonstrated that disc cellular senescence is dramatically increased in the DNA repair-deficient Ercc1 -/Δ mouse model of human progeria. In these accelerated aging mice, increased disc cellular senescence is closely associated with the rapid loss of disc PG. We also directly examine PG homeostasis in oxidative damage-induced senescent human cells using an in vitro cell culture model system. Senescence of human disc cells treated with hydrogen peroxide was confirmed by growth arrest, senescence-associated β-galactosidase activity, γH2AX foci, and acquisition of senescence-associated secretory phenotype. Senescent human disc cells also exhibited perturbed matrix PG homeostasis as evidenced by their decreased capacity to synthesize new matrix PG and enhanced degradation of aggrecan, a major matrix PG. of the disc. Our in vivo and in vitro findings altogether suggest that disc cellular senescence is an important driver of PG matrix homeostatic perturbation and PG loss. Published by Elsevier B.V.

Comparison of cable ageing

NASA Astrophysics Data System (ADS)

Plaček, Vít; Kohout, Tomáš

2010-03-01

Two cable types, which currently are used in nuclear power plants (NPP) and which are composed by jacket/insulation materials, i.e. PVC/PVC and PVC/PE, were exposed to accelerated ageing conditions, in order to simulate their behavior after 10 years in service. The cables were aged under two different test conditions: With relatively high accelerating ageing speed:Radiation ageing was carried out at room temperature at a dose rate of 2900 Gy/h, followed by thermal ageing at 100 °C. This accelerated ageing condition was fairly fast, but still in compliance with the standards. With moderate ageing speed:The radiation and thermal ageing was performed simultaneously (superimposed) at a dose rate of 2.7-3.7Gy/h and a temperature of 68-70 °C. Such a test condition seems to be very close to the radiation and temperature impact onto the cables in the real NPP service. Finally, mechanical properties were measured to characterize the ageing status of the cables. The purpose of this study was to compare degradation effects, derived from both ageing methods, and to demonstrate that results obtained from high values of accelerating parameters and from fast ageing simulation can be very different from reality. The observed results corroborated this assumption.

[Effect of Earth magnetic field on circadian rhythm of total antioxidant capacity of human saliva in the North].

PubMed

Borisenkov, M F

2007-01-01

In the inhabitants of the North during increase of geomagnetic activity and during magnetic calm the decrease of amplitude of circadian rhythm of total antioxidant capacity of saliva is observed. The most favorable conditions to display the circadian rhythm are observed at Kp from 0,5 up to 2. The long residing in the North is connected to influence of irregularly varying geomagnetic activity causing disturbance of function of circadian and antioxidant systems that, probably, is one of the reasons of acceleration of process of aging at northerner and of higher risk of occurrence in them the age associated diseases.

Brain-Derived Neurotrophic Factor Expression in Individuals With Schizophrenia and Healthy Aging: Testing the Accelerated Aging Hypothesis of Schizophrenia.

PubMed

Islam, Farhana; Mulsant, Benoit H; Voineskos, Aristotle N; Rajji, Tarek K

2017-07-01

Schizophrenia has been hypothesized to be a syndrome of accelerated aging. Brain plasticity is vulnerable to the normal aging process and affected in schizophrenia: brain-derived neurotrophic factor (BDNF) is an important neuroplasticity molecule. The present review explores the accelerated aging hypothesis of schizophrenia by comparing changes in BDNF expression in schizophrenia with aging-associated changes. Individuals with schizophrenia show patterns of increased overall mortality, metabolic abnormalities, and cognitive decline normally observed later in life in the healthy population. An overall decrease is observed in BDNF expression in schizophrenia compared to healthy controls and in older individuals compared to a younger cohort. There is a marked decrease in BDNF levels in the frontal regions and in the periphery among older individuals and those with schizophrenia; however, data for BDNF expression in the occipital, parietal, and temporal cortices and the hippocampus is inconclusive. Accelerated aging hypothesis is supported based on frontal regions and peripheral studies; however, further studies are needed in other brain regions.

Human RecQL4 helicase plays multifaceted roles in the genomic stability of normal and cancer cells.

PubMed

Mo, Dongliang; Zhao, Yongliang; Balajee, Adayabalam S

2018-01-28

Human RecQ helicases that share homology with E. coli RecQ helicase play critical roles in diverse biological activities such as DNA replication, transcription, recombination and repair. Mutations in three of the five human RecQ helicases (RecQ1, WRN, BLM, RecQL4 and RecQ5) result in autosomal recessive syndromes characterized by accelerated aging symptoms and cancer incidence. Mutational inactivation of Werner (WRN) and Bloom (BLM) genes results in Werner syndrome (WS) and Bloom syndrome (BS) respectively. However, mutations in RecQL4 result in three human disorders: (I) Rothmund-Thomson syndrome (RTS), (II) RAPADILINO and (III) Baller-Gerold syndrome (BGS). Cells from WS, BS and RTS are characterized by a unique chromosomal anomaly indicating that each of the RecQ helicases performs specialized function(s) in a non-redundant manner. Elucidating the biological functions of RecQ helicases will enable us to understand not only the aging process but also to determine the cause for age-associated human diseases. Recent biochemical and molecular studies have given new insights into the multifaceted roles of RecQL4 that range from genomic stability to carcinogenesis and beyond. This review summarizes some of the existing and emerging knowledge on diverse biological functions of RecQL4 and its significance as a potential molecular target for cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Accelerated aging, natural aging, and small punch testing of gamma-air sterilized polycarbonate urethane acetabular components.

PubMed

Kurtz, S M; Siskey, R; Reitman, M

2010-05-01

The objectives of this study were three-fold: (1) to determine the applicability of the small punch test to characterize Bionate 80A polycarbonate urethane (PCU) acetabular implants; (2) to evaluate the susceptibility of PCU acetabular implants to exhibit degradation of mechanical behavior following gamma irradiation in air and accelerated aging; and (3) to compare the oxidation of gamma-air sterilized PCU following accelerated aging and 5 years of natural shelf aging. In addition to attenuated total reflectance-Fourier transform infrared spectroscopy, we also adapted a miniature specimen mechanical test, the small punch test, for the deformable PCU cups. Accelerated aging was performed using ASTM F2003, a standard test that represents a severe oxidative challenge. The results of this study suggest that the small punch test is sufficiently sensitive and reproducible to discriminate slight differences in the large-deformation mechanical behavior of Bionate 80A following accelerated aging. The gamma-air sterilized PCU had a reduction of 9% in ultimate load after aging. Five years of shelf aging had little effect on the mechanical properties of the PCU. Overall, our findings suggest that the Bionate 80A material has greater oxidative stability than ultra-high molecular weight polyethylene following gamma irradiation in air and exposure to a severe oxidative challenge. (c) 2010 Wiley Periodicals, Inc.

Human Disc Nucleus Properties and Vertebral Endplate Permeability

PubMed Central

Rodriguez, Azucena G.; Slichter, Chloe K.; Acosta, Frank L.; Rodriguez-Soto, Ana E.; Burghardt, Andrew J.; Majumdar, Sharmila; Lotz, Jeffrey C.

2010-01-01

Study of human cadaveric discs quantifying endplate permeability and porosity and correlating these with measures of disc quality: cell density, proteoglycan content, and overall degeneration. Permeability and porosity increased with age and were not correlated with cell density or overall degeneration, suggesting that endplate calcification may not accelerate disc degeneration. Study Design Experimental quantification of relationships between vertebral endplate morphology, permeability, disc cell density, glycosaminoglycan content and degeneration in samples harvested from human cadaveric spines. Objective To test the hypothesis that variation in endplate permeability and porosity contribute to changes in intervertebral disc cell density and overall degeneration. Summary of Background Data Cells within the intervertebral disc are dependent on diffusive exchange with capillaries in the adjacent vertebral bone. Previous findings suggest that blocked routes of transport negatively affect disc quality, yet there are no quantitative relationships between human vertebral endplate permeability, porosity, cell density and disc degeneration. Such relationships would be valuable for clarifying degeneration risk factors, and patient features that may impede efforts at disc tissue engineering. Methods Fifty-one motion segments were harvested from 13 frozen cadaveric human lumbar spines (32 to 85 years) and classified for degeneration using the MRI-based Pfirrmann scale. A cylindrical core was harvested from the center of each motion segment that included vertebral bony and cartilage endplates along with adjacent nucleus tissue. The endplate mobility, a type of permeability, was measured directly using a custom-made permeameter before and after the cartilage endplate was removed. Cell density within the nucleus tissue was estimated using the picogreen method while the nuclear GAG content was quantified using the DMMB technique. Specimens were imaged at 8 μm resolution using microCT, bony porosity was calculated. Analysis of variance, linear regression, and multiple comparison tests were used to analyze the data. Results Nucleus cell density increased as the disc height decreased (R2=0.13; p=0.01) but was not related to subchondral bone porosity (p>0.5), total mobility (p>0.4) or age (p>0.2). When controlling for disc height however, a significant, negative effect of age on cell density was observed (p=0.03). In addition to this, GAG content decreased with age non-linearly (R2=0.83, p<0.0001) and a cell function measurement, GAGs/cell decreased with degeneration (R2=0.24; p<0.0001). Total mobility (R2=0.14; p<0.01) and porosity (R2=0.1, p<0.01) had a positive correlation with age. Conclusion Although cell density increased with degeneration, cell function indicated that GAGs/cell decreased. Since permeability and porosity increase with age and degeneration, this implies that cell dysfunction, rather than physical barriers to transport, accelerate disc disease. PMID:21240044

Accelerated Aging Experiments for Prognostics of Damage Growth in Composite Materials

DTIC Science & Technology

2011-09-01

possible resource to collect such data is an accelerated aging platform. To that end this paper describes a fatigue cycling experiment with the goal to...possible resource to collect such data is an accelerated aging platform. To that end this paper describes a fatigue cycling experiment with the goal to...suffer from two damage types: matrix micro-cracks and inter- laminar delamination. When subject to fatigue loading matrix micro-cracks develop in the

Accelerated aging: prediction of chemical stability of pharmaceuticals.

PubMed

Waterman, Kenneth C; Adami, Roger C

2005-04-11

Methods of rapidly and accurately assessing the chemical stability of pharmaceutical dosage forms are reviewed with respect to the major degradation mechanisms generally observed in pharmaceutical development. Methods are discussed, with the appropriate caveats, for accelerated aging of liquid and solid dosage forms, including small and large molecule active pharmaceutical ingredients. In particular, this review covers general thermal methods, as well as accelerated aging methods appropriate to oxidation, hydrolysis, reaction with reactive excipient impurities, photolysis and protein denaturation.

[Characteristics of the sympathoadrenal system response to psychoemotional stress under hypoxic conditions in aged people with physiological and accelerated aging of the respiratory system].

PubMed

Asanov, E O; Os'mak, Ie D; Kuz'mins'ka, L A

2013-01-01

The peculiarities of the response of the sympathoadrenal system to psychoemotional and hypoxic stress in healthy young people and in aged people with physiological and accelerated aging of respiratory system were studied. It was shown that in aging a more pronounced response of the sympathoadrenal system to psychoemotional stress. At the same time, elderly people with different types of aging of the respiratory system did not demonstrate a difference in the response of the sympathoadrenal system to psychoemotional stress. Unlike in young people, in aged people, combination of psychoemotional and hypoxic stresses resulted in further activation of the sympathoadrenal system. The reaction of the sympathoadrenal system was more expressed in elderly people with accelerated ageing of the respiratory system.

SoM: a smart sensor for human activity monitoring and assisted healthy ageing.

PubMed

Naranjo-Hernández, David; Roa, Laura M; Reina-Tosina, Javier; Estudillo-Valderrama, Miguel Ángel

2012-11-01

This paper presents the hardware and software design and implementation of a low-cost, wearable, and unobstructive intelligent accelerometer sensor for the monitoring of human physical activities. In order to promote healthy lifestyles to elders for an active, independent, and healthy ageing, as well as for the early detection of psychomotor abnormalities, the activity monitoring is performed in a holistic manner in the same device through different approaches: 1) a classification of the level of activity that allows to establish patterns of behavior; 2) a daily activity living classifier that is able to distinguish activities such as climbing or descending stairs using a simple method to decouple the gravitational acceleration components of the motion components; and 3) an estimation of metabolic expenditure independent of the activity performed and the anthropometric characteristics of the user. Experimental results have demonstrated the feasibility of the prototype and the proposed algorithms.

Biochemical Reversal of Aging

NASA Astrophysics Data System (ADS)

Ely, John T. A.

2006-03-01

We cite our progress on biochemical reversal of aging. However, it may be circa 2 years before we have necessary substances at low cost. Meanwhile, without them, a number of measures can be adopted providing marked improvement for the problems of aging in modern societies. For example, enzymes are needed to excrete toxins that accelerate aging; Hg is the ultimate toxin that disables all enzymes (including those needed to excrete Hg itself). Low Hg level in the urine, due to loss of excretory ability, causes the diagnosis of Hg toxicity to almost always be missed. Hg sources must be removed from the body! Another example is excess sugar; hyperglycemia decreases intracellular ascorbic acid (AA) by competitively inhibiting the insulin- mediated active transport of AA into cells. Thus, immunity is impaired by low leucocyte AA. AA is needed for new proteins in aging tissues. Humans must supplement AA; their need same as in AA-synthesizing mammals.

Protective actions of melatonin and growth hormone on the aged cardiovascular system.

PubMed

Paredes, Sergio D; Forman, Katherine A; García, Cruz; Vara, Elena; Escames, Germaine; Tresguerres, Jesús A F

2014-05-01

Epidemiological studies indicate that certain aspects of lifestyle and genetics act as risk factors for a variety of cardiovascular disorders, including coronary disease, hypertension, heart failure and stroke. Aging, however, appears to be the major contributor for morbidity and mortality of the impaired cardiovascular system. Growth hormone (GH) and melatonin seem to prevent cardiac aging, as they contribute to the recovery of several physiological parameters affected by age. These hormones exhibit antioxidant properties and decrease oxidative stress and apoptosis. This paper summarizes a set of studies related to the potential role that therapy with GH and melatonin may play in the protection of the altered cardiac function due to aging, with a focus on experiments performed in our laboratory using the senescence-accelerated mouse as an aging model. In general, we observed significantly increased inflammation, oxidative stress and apoptosis markers in hearts from senescence-accelerated prone 10-month-old animals compared to 2-month-old controls, while anti-inflammatory and antiapoptotic markers as well as endothelial nitric oxide synthase were decreased. Senescence-accelerated resistant animals showed no significant changes with age. GH or melatonin treatment prevented the age-dependent cardiac alterations observed in the senescence-accelerated prone group. Combined administration of GH plus melatonin reduced the age-related changes in senescence-accelerated prone hearts in an additive fashion that was different to that displayed when administered alone. GH and melatonin may be potential agents for counteracting oxidative stress, apoptosis and inflammation in the aging heart.

Genome-Wide Identification of Regulatory Sequences Undergoing Accelerated Evolution in the Human Genome.

PubMed

Dong, Xinran; Wang, Xiao; Zhang, Feng; Tian, Weidong

2016-10-01

Accelerated evolution of regulatory sequence can alter the expression pattern of target genes, and cause phenotypic changes. In this study, we used DNase I hypersensitive sites (DHSs) to annotate putative regulatory sequences in the human genome, and conducted a genome-wide analysis of the effects of accelerated evolution on regulatory sequences. Working under the assumption that local ancient repeat elements of DHSs are under neutral evolution, we discovered that ∼0.44% of DHSs are under accelerated evolution (ace-DHSs). We found that ace-DHSs tend to be more active than background DHSs, and are strongly associated with epigenetic marks of active transcription. The target genes of ace-DHSs are significantly enriched in neuron-related functions, and their expression levels are positively selected in the human brain. Thus, these lines of evidences strongly suggest that accelerated evolution on regulatory sequences plays important role in the evolution of human-specific phenotypes. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

BrainAGE score indicates accelerated brain aging in schizophrenia, but not bipolar disorder.

PubMed

Nenadić, Igor; Dietzek, Maren; Langbein, Kerstin; Sauer, Heinrich; Gaser, Christian

2017-08-30

BrainAGE (brain age gap estimation) is a novel morphometric parameter providing a univariate score derived from multivariate voxel-wise analyses. It uses a machine learning approach and can be used to analyse deviation from physiological developmental or aging-related trajectories. Using structural MRI data and BrainAGE quantification of acceleration or deceleration of in individual aging, we analysed data from 45 schizophrenia patients, 22 bipolar I disorder patients (mostly with previous psychotic symptoms / episodes), and 70 healthy controls. We found significantly higher BrainAGE scores in schizophrenia, but not bipolar disorder patients. Our findings indicate significantly accelerated brain structural aging in schizophrenia. This suggests, that despite the conceptualisation of schizophrenia as a neurodevelopmental disorder, there might be an additional progressive pathogenic component. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Family-centered prevention ameliorates the longitudinal association between risky family processes and epigenetic aging.

PubMed

Brody, Gene H; Yu, Tianyi; Chen, Edith; Beach, Steven R H; Miller, Gregory E

2016-05-01

Research has suggested that 'risky' family processes have unforeseen negative consequences for health later in life. The purpose of this study was to further understanding of risky family environments and development of health vulnerabilities by (a) examining the likelihood that elevated levels of parental depressive symptoms when children are age 11 forecast accelerated epigenetic aging 9 years later at age 20; (b) determining whether participation in an efficacious family-centered prevention program focused on enhancing supportive parenting and strengthening family relationships will ameliorate this association; and (c) testing a moderation-mediation hypothesis that prevention-induced reductions in harsh parenting across adolescence will account for prevention effects in reducing accelerated epigenetic aging. In the rural southeastern United States, parents and 11-year-old children from 399 families participated in the Strong African American Families (SAAF) program or a control condition. Parents reported their own depressive symptoms when their children were 11, and both youths and parents reported youth exposure to harsh parenting at ages 11 and 16. Blood was drawn from youths at age 20 to measure accelerated epigenetic aging using a marker derived from the DNA methylation of cells. Elevated parental depressive symptoms forecast accelerated epigenetic aging among youths in the control condition, but not among SAAF participants. Moderated-mediation analyses confirmed that reductions in harsh parenting accounted for SAAF's protective effects on epigenetic aging. Subsequent exploratory analyses indicated that accelerated epigenetic aging forecast emotional distress among young adults in the control condition but not among those who participated in SAAF. This study is unique in using a randomized prevention trial to test hypotheses about the ways risky family processes contribute to accelerated epigenetic aging. The results suggest that developmentally appropriate family-centered interventions designed to enhance parenting and strengthen families can buffer the biological residue of life in a risky family. © 2015 Association for Child and Adolescent Mental Health.

Nuclear lamina defects cause ATM-dependent NF-κB activation and link accelerated aging to a systemic inflammatory response.

PubMed

Osorio, Fernando G; Bárcena, Clea; Soria-Valles, Clara; Ramsay, Andrew J; de Carlos, Félix; Cobo, Juan; Fueyo, Antonio; Freije, José M P; López-Otín, Carlos

2012-10-15

Alterations in the architecture and dynamics of the nuclear lamina have a causal role in normal and accelerated aging through both cell-autonomous and systemic mechanisms. However, the precise nature of the molecular cues involved in this process remains incompletely defined. Here we report that the accumulation of prelamin A isoforms at the nuclear lamina triggers an ATM- and NEMO-dependent signaling pathway that leads to NF-κB activation and secretion of high levels of proinflammatory cytokines in two different mouse models of accelerated aging (Zmpste24(-/-) and Lmna(G609G/G609G) mice). Causal involvement of NF-κB in accelerated aging was demonstrated by the fact that both genetic and pharmacological inhibition of NF-κB signaling prevents age-associated features in these animal models, significantly extending their longevity. Our findings provide in vivo proof of principle for the feasibility of pharmacological modulation of the NF-κB pathway to slow down the progression of physiological and pathological aging.

Reaction time in pilots during intervals of high sustained g.

PubMed

Truszczynski, Olaf; Lewkowicz, Rafal; Wojtkowiak, Mieczyslaw; Biernacki, Marcin P

2014-11-01

An important problem for pilots is visual disturbances occurring under +Gz acceleration. Assessment of the degree of intensification of these disturbances is generally accepted as the acceleration tolerance level (ATL) criterion determined in human centrifuges. The aim of this research was to evaluate the visual-motor responses of pilots during rapidly increasing acceleration contained in cyclic intervals of +6 Gz to the maximum ATL. The study involved 40 male pilots ages 32-41 yr. The task was a quick and faultless response to the light stimuli presented on a light bar during exposure to acceleration until reaching the ATL. Simple response time (SRT) measurements were performed using a visual-motor analysis system throughout the exposures which allowed assessment of a pilot's ATL. There were 29 pilots who tolerated the initial phase of interval acceleration and achieved +6 Gz, completing the test at ATL. Relative to the control measurements, the obtained results indicate a significant effect of the applied acceleration on response time. SRT during +6 Gz exposure was not significantly longer compared with the reaction time between each of the intervals. SRT and erroneous reactions indicated no statistically significant differences between the "lower" and "higher" ATL groups. SRT measurements over the +6-Gz exposure intervals did not vary between "lower" and "higher" ATL groups and, therefore, are not useful in predicting pilot performance. The gradual exposure to the maximum value of +6 Gz with exposure to the first three intervals on the +6-Gz plateau effectively differentiated pilots.

Curcumin prevents mitochondrial dysfunction in the brain of the senescence-accelerated mouse-prone 8.

PubMed

Eckert, Gunter P; Schiborr, Christina; Hagl, Stephanie; Abdel-Kader, Reham; Müller, Walter E; Rimbach, Gerald; Frank, Jan

2013-04-01

The aging brain suffers mitochondrial dysfunction and a reduced availability of energy in the form of ATP, which in turn may cause or promote the decline in cognitive, sensory, and motor function observed with advancing age. There is a need for animal models that display some of the pathological features of human brain aging in order to study their prevention by e.g. dietary factors. We thus investigated the suitability of the fast-aging senescence-accelerated mouse-prone 8 (SAMP8) strain and its normally aging control senescence-accelerated mouse-resistant 1 (SAMR1) as a model for the age-dependent changes in mitochondrial function in the brain. To this end, 2-months old male SAMR1 (n=10) and SAMP8 mice (n=7) were fed a Western type diet (control groups) for 5months and one group of SAMP8 mice (n=6) was fed an identical diet fortified with 500mg curcumin per kg. Dissociated brain cells and brain tissue homogenates were analyzed for malondialdehyde, heme oxygenase-1 mRNA, mitochondrial membrane potential (MMP), ATP concentrations, protein levels of mitochondrial marker proteins for mitochondrial membranes (TIMM, TOMM), the mitochondrial permeability transition pore (ANT1, VDAC1, TSPO), respiration complexes, and fission and fusion (Fis, Opa1, Mfn1, Drp1). Dissociated brain cells isolated from SAMP8 mice showed significantly reduced MMP and ATP levels, probably due to significantly diminished complex V protein expression, and increased expression of TSPO. Fission and fusion marker proteins indicate enhanced mitochondrial fission in brains of SAMP8 mice. Treatment of SAMP8 mice with curcumin improved MMP and ATP and restored mitochondrial fusion, probably by up-regulating nuclear factor PGC1α protein expression. In conclusion, SAMP8 compared to SAMR1 mice are a suitable model to study age-dependent changes in mitochondrial function and curcumin emerges as a promising nutraceutical for the prevention of neurodegenerative diseases that are accompanied or caused by mitochondrial dysfunction. Copyright © 2013 Elsevier Ltd. All rights reserved.

Longevity factor klotho and chronic psychological stress

PubMed Central

Prather, A A; Epel, E S; Arenander, J; Broestl, L; Garay, B I; Wang, D; Dubal, D B

2015-01-01

Chronic psychological stress is associated with accelerated aging and premature morbidity and mortality; however, the biology linking chronic psychological stress and its maladaptive effects remains largely unknown. Klotho is a pleiotropic hormone that regulates the aging process and promotes better brain and body health. Whether klotho is linked to psychosocial stress or its negative impact in humans has not been investigated. To address this gap, we recruited 178 healthy women who were either chronically high-stress maternal caregivers for a child with autism spectrum disorder (n=90) or low-stress control mothers of a typically developing child (n=88). We found that women under high chronic stress displayed significantly lower levels of the longevity hormone klotho compared with low-stress controls (t(176)=2.92, P=0.004; d=0.44), and the decrease among those under high stress was age-dependent. In addition, high-stress caregivers who reported more depressive symptoms displayed even lower klotho levels compared with low-stress participants. These findings provide the first evidence that klotho levels are sensitive to psychosocial stressors and raise the possibility that klotho may serve as a novel biological link connecting stress, depression and risk for accelerated disease development. Furthermore, these findings have important implications for understanding the plasticity of the aging process and may represent a therapeutic target for mitigating the deleterious effects of chronic psychological stress on health and well-being. PMID:26080320

Long-term exposure to air pollution is associated with biological aging.

PubMed

Ward-Caviness, Cavin K; Nwanaji-Enwerem, Jamaji C; Wolf, Kathrin; Wahl, Simone; Colicino, Elena; Trevisi, Letizia; Kloog, Itai; Just, Allan C; Vokonas, Pantel; Cyrys, Josef; Gieger, Christian; Schwartz, Joel; Baccarelli, Andrea A; Schneider, Alexandra; Peters, Annette

2016-11-15

Long-term exposure to air pollution is associated with age-related diseases. We explored the association between accelerated biological aging and air pollution, a potential mechanism linking air pollution and health. We estimated long-term exposure to PM10, PM2.5, PM2.5 absorbance/black carbon (BC), and NOx via land-use regression models in individuals from the KORA F4 cohort. Accelerated biological aging was assessed using telomere length (TeloAA) and three epigenetic measures: DNA methylation age acceleration (DNAmAA), extrinsic epigenetic age acceleration (correlated with immune cell counts, EEAA), and intrinsic epigenetic age acceleration (independent of immune cell counts, IEAA). We also investigated sex-specific associations between air pollution and biological aging, given the published association between sex and aging measures. In KORA an interquartile range (0.97 µg/m3) increase in PM2.5 was associated with a 0.33 y increase in EEAA (CI = 0.01, 0.64; P = 0.04). BC and NOx (indicators or traffic exposure) were associated with DNAmAA and IEAA in women, while TeloAA was inversely associated with BC in men. We replicated this inverse BC-TeloAA association in the Normative Aging Study, a male cohort based in the USA. A multiple phenotype analysis in KORA F4 combining all aging measures showed that BC and PM10 were broadly associated with biological aging in men. Thus, we conclude that long-term exposure to air pollution is associated with biological aging measures, potentially in a sex-specific manner. However, many of the associations were relatively weak and further replication of overall and sex-specific associations is warranted.

Long-term exposure to air pollution is associated with biological aging

PubMed Central

Ward-Caviness, Cavin K.; Nwanaji-Enwerem, Jamaji C.; Wolf, Kathrin; Wahl, Simone; Colicino, Elena; Trevisi, Letizia; Kloog, Itai; Just, Allan C.; Vokonas, Pantel; Cyrys, Josef; Gieger, Christian; Schwartz, Joel; Baccarelli, Andrea A.; Schneider, Alexandra; Peters, Annette

2016-01-01

Long-term exposure to air pollution is associated with age-related diseases. We explored the association between accelerated biological aging and air pollution, a potential mechanism linking air pollution and health. We estimated long-term exposure to PM10, PM2.5, PM2.5 absorbance/black carbon (BC), and NOx via land-use regression models in individuals from the KORA F4 cohort. Accelerated biological aging was assessed using telomere length (TeloAA) and three epigenetic measures: DNA methylation age acceleration (DNAmAA), extrinsic epigenetic age acceleration (correlated with immune cell counts, EEAA), and intrinsic epigenetic age acceleration (independent of immune cell counts, IEAA). We also investigated sex-specific associations between air pollution and biological aging, given the published association between sex and aging measures. In KORA an interquartile range (0.97 μg/m3) increase in PM2.5 was associated with a 0.33 y increase in EEAA (CI = 0.01, 0.64; P = 0.04). BC and NOx (indicators or traffic exposure) were associated with DNAmAA and IEAA in women, while TeloAA was inversely associated with BC in men. We replicated this inverse BC-TeloAA association in the Normative Aging Study, a male cohort based in the USA. A multiple phenotype analysis in KORA F4 combining all aging measures showed that BC and PM10 were broadly associated with biological aging in men. Thus, we conclude that long-term exposure to air pollution is associated with biological aging measures, potentially in a sex-specific manner. However, many of the associations were relatively weak and further replication of overall and sex-specific associations is warranted. PMID:27793020

How Well Does the Latest Anthropomorphic Test Device Mimic Human Impact Responses?

NASA Technical Reports Server (NTRS)

Newby, N.; Somers, J. T.; Caldwell, E.; Gernhardt, M.

2014-01-01

One of the goals of the NASA Occupant Protection Group is to understand the human tolerance to dynamic loading. This knowledge has to come through indirect approaches such as existing human response databases, anthropometric test devices (ATD), animal testing, post-mortem human subjects, and models. This study investigated the biofidelity of the National Highway Traffic Safety Administration's ATD named the THOR (test device for human occupant restraint). If THOR responds comparably to humans, then it could potentially be used as a human surrogate to help validate space vehicle requirements for occupant protection. The THOR responses to frontal and spinal impacts (ranging from 8 to 12 G with rise times of 40, 70, and 100 ms) were measured and compared to human volunteer responses (95 trials in frontal and 58 in spinal) previously collected by the U. S. Air Force on the same horizontal impact accelerator. The impact acceleration profiles tested are within the expected range of multi-purpose crew vehicle (MPCV) landing dynamics. A correlation score was calculated for each THOR to human comparison using CORA (CORrelation and Analysis) software. A two-parameter beta distribution model fit was obtained for each dependent variable using maximum likelihood estimation. For frontal impacts, the THOR head x-acceleration peak response correlated with the human response at 8 and 10-G 100 ms but not 10-G 70 ms. The phase lagged the human response. Head z-acceleration was not correlated. Chest x-acceleration was in phase, had a higher peak response, and was well correlated with lighter subjects (Cora = 0.8 for 46 kg vs. Cora = 0.4 for 126 kg). Head x-displacement had a leading phase. Several subjects responded with the same peak displacement but the mean of the group was lower. The shoulder x-displacement was in phase but had higher peaks than the human response. For spinal impacts, the THOR head x-acceleration was not well correlated. Head and chest z-acceleration was in phase but had a higher peak response. Chest z-acceleration was highly correlated with heavier subjects at lower G pulses (Cora = 0.86 for 125 kg at 8 G). The human response was variable in shoulder z-displacement but the THOR was in phase and was comparable to the mean peak response. Head xand z-displacement was in phase but had higher peaks. Seat pan forces were well correlated, were in phase, but had a larger peak response than most subjects. The THOR does not respond to frontal and spinal impacts exactly the same way that a human does. Some responses are well matched and others are not. Understanding the strengths and weaknesses of this ATD is an important first step in determining its usefulness in occupant protection at NASA

Accelerated White Matter Aging in Schizophrenia: Role of White Matter Blood Perfusion

PubMed Central

Chiappelli, Joshua; McMahon, Robert; Muellerklein, Florian; Wijtenburg, S. Andrea; White, Michael G.; Rowland, Laura M.; Hong, L. Elliot

2014-01-01

Elevated rate of age-related decline in white matter integrity, indexed by fractional anisotropy (FA) from diffusion tensor imaging, was reported in patients with schizophrenia. Its etiology is unknown. We hypothesized that a decline of blood perfusion to the white matter may underlie the accelerated age-related reduction in FA in schizophrenia. Resting white matter perfusion and FA were collected using pseudo-continuous arterial spin labeling and high-angular-resolution diffusion tensor imaging, respectively, in 50 schizophrenia patients and 70 controls (age=18-63 years). Main outcome measures were the diagnosis-by-age interaction on whole-brain white matter perfusion, and FA. Significant age-related decline in brain white matter perfusion and FA were present in both groups. Age-by-diagnosis interaction was significant for FA (p<0.001) but not white matter perfusion. Age-by-diagnosis interaction for FA values remained significant even after accounting for age-related decline in perfusion. Therefore, we replicated the finding of an increased rate of age-related white matter FA decline in schizophrenia, and observed a significant age-related decline in white matter blood perfusion, although the latter did not contribute to the accelerated age-related decline in FA. The results suggest that factors other than reduced perfusion account for the accelerated age-related decline in white matter integrity in schizophrenia. PMID:24680326

Repeated superovulation increases the risk of osteoporosis and cardiovascular diseases by accelerating ovarian aging in mice.

PubMed

Zhang, Jinjin; Lai, Zhiwen; Shi, Liangyan; Tian, Yong; Luo, Aiyue; Xu, Zheyuan; Ma, Xiangyi; Wang, Shixuan

2018-05-22

Superovulation procedures and assisted reproductive technologies have been widely used to treat couples who have infertility problems. Although generally safe, the superovulation procedures are associated with a series of complications, such as ovarian hyper-stimulation syndrome, thromboembolism, and adnexal torsion. The role of long-term repeated superovulation in ovarian aging and especially in associated disorders such as osteoporosis and cardiovascular diseases is still unclear. In this study, we sought to determine if repeated superovulation by ten cycles of treatment with pregnant mare serum gonadotropin/human chorionic gonadotropin could affect ovarian reserve, ovarian function, bone density and heart function. Ovarian reserve and function were reflected by the size of the primordial follicle pool, anti-Mullerian hormone expressions, hormone levels and fertility status. Furthermore, we examined bone density and heart function by microCT and cardiovascular ultrasonography, respectively. After repeated superovulation, the size of the primordial follicle pool and the expression of anti-mullerian hormone decreased, along with the concentrations of estrogen and progesterone. Mice exposed to repeated superovulation showed an obvious decrease in fertility and fecundity. Furthermore, both bone density and heart ejection fraction significantly decreased. These results suggest that repeated superovulation may increase the risk of osteoporosis and cardiovascular diseases by accelerating ovarian aging.

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

PubMed Central

Ames, Bruce N.

2006-01-01

Inadequate dietary intakes of vitamins and minerals are widespread, most likely due to excessive consumption of energy-rich, micronutrient-poor, refined food. Inadequate intakes may result in chronic metabolic disruption, including mitochondrial decay. Deficiencies in many micronutrients cause DNA damage, such as chromosome breaks, in cultured human cells or in vivo. Some of these deficiencies also cause mitochondrial decay with oxidant leakage and cellular aging and are associated with late onset diseases such as cancer. I propose DNA damage and late onset disease are consequences of a triage allocation response to micronutrient scarcity. Episodic shortages of micronutrients were common during evolution. Natural selection favors short-term survival at the expense of long-term health. I hypothesize that short-term survival was achieved by allocating scarce micronutrients by triage, in part through an adjustment of the binding affinity of proteins for required micronutrients. If this hypothesis is correct, micronutrient deficiencies that trigger the triage response would accelerate cancer, aging, and neural decay but would leave critical metabolic functions, such as ATP production, intact. Evidence that micronutrient malnutrition increases late onset diseases, such as cancer, is discussed. A multivitamin-mineral supplement is one low-cost way to ensure intake of the Recommended Dietary Allowance of micronutrients throughout life. PMID:17101959

[PSYCHO PHYSIOLOGICAL MARKERS OF ACCELERATED AGING AMONG THOSE WORKING WITH OCCUPATIONAL HAZARDS].

PubMed

Bashkireva, A S; Kachan, Ye Yu; Kulapina, M E

2015-01-01

Using comparative analysis of two occupational groups we assessed the significance of psycho physiological markers of short-term memory accelerated aging in order to reveal how the age-related changes and working process affect mental work capacity. We revealed peculiarities of systemic structure of functions which determine mental work capacity depending on the age and length of service in lorry drivers. It was proved that age and long driving experience affect mnestic functions which show up quantitative and qualitative changes such as reduced volume of memorized information, longer time needed to memorize it, and tendency to diminished accuracy of memorization. We also proved that premature age-related changes of psycho physiological indices in drivers are the "risk indicators", while long driving experience is a real risk factor contributing to the acceleration of aging.

US Particle Accelerators at Age 50.

ERIC Educational Resources Information Center

Wilson, R. R.

1981-01-01

Reviews the development of accelerators over the past 50 years. Topics include: types of accelerators, including cyclotrons; sociology of accelerators (motivation, financing, construction, and use); impact of war; national laboratories; funding; applications; future projects; foreign projects; and international collaborations. (JN)

Experimental investigation of biodynamic human body models subjected to whole-body vibration during a vehicle ride.

PubMed

Taskin, Yener; Hacioglu, Yuksel; Ortes, Faruk; Karabulut, Derya; Arslan, Yunus Ziya

2018-02-06

In this study, responses of biodynamic human body models to whole-body vibration during a vehicle ride were investigated. Accelerations were acquired from three different body parts, such as the head, upper torso and lower torso, of 10 seated passengers during a car ride while two different road conditions were considered. The same multipurpose vehicle was used during all experiments. Additionally, by two widely used biodynamic models in the literature, a set of simulations were run to obtain theoretical accelerations of the models and were compared with those obtained experimentally. To sustain a quantified comparison between experimental and theoretical approaches, the root mean square acceleration and acceleration spectral density were calculated. Time and frequency responses of the models demonstrated that neither of the models showed the best prediction performance of the human body behaviour in all cases, indicating that further models are required for better prediction of the human body responses.

Longitudinal study of surrogate aging measures during human immunodeficiency virus seroconversion.

PubMed

Leung, Janice M; Fishbane, Nick; Jones, Meaghan; Morin, Alexander; Xu, Stella; Liu, Joseph Cy; MacIsaac, Julie; Milloy, M-J; Hayashi, Kanna; Montaner, Julio; Horvath, Steve; Kobor, Michael; Sin, Don D; Harrigan, P Richard; Man, S F Paul

2017-02-23

Persons living with human immunodeficiency virus (HIV) harbor an increased risk of age-related conditions. We measured changes in telomere length and DNA methylation in the peripheral blood of 31 intravenous drug users, who were followed longitudinally with blood samples pre-HIV (T1), immediately post-HIV (T2; 1.9±1 year from T1), and at a later follow-up time (T3; 2.2±1 year from T2). Absolute telomere length measurements were performed using polymerase chain reaction methods. Methylation profiles were obtained using the Illumina Human Methylation450 platform. Methylation aging was assessed using the Horvath method. Telomere length significantly decreased between T1 and T2 (227±46 at T1 vs. 201±48 kbp/genome at T2, p=0.045), while no differences were observed between T2 and T3 (201±48 at T2 vs. 186±27 kbp/genome at T3, p=0.244). Methylation aging as measured by the age acceleration residual increased over the time course of HIV infection (p=0.035). CpG sites corresponding to PCBP2 and CSRNP1 were differentially methylated between T1 and T2 at a q-value <0.05. Telomere shortening and methylation changes can therefore be observed in the short-term period immediately following HIV seroconversion. Further studies to confirm these results in larger sample sizes and to compare these results to non-HIV and non-injection drug users are warranted.

Persistent viral infections and immune aging.

PubMed

Brunner, Stefan; Herndler-Brandstetter, Dietmar; Weinberger, Birgit; Grubeck-Loebenstein, Beatrix

2011-07-01

Immunosenescence comprises a set of dynamic changes occurring to both, the innate as well as the adaptive immune system that accompany human aging and result in complex manifestations of still poorly defined deficiencies in the elderly population. One of the most prominent alterations during aging is the continuous involution of the thymus gland which is almost complete by the age of 50. Consequently, the output of naïve T cells is greatly diminished in elderly individuals which puts pressure on homeostatic forces to maintain a steady T cell pool for most of adulthood. In a great proportion of the human population, this fragile balance is challenged by persistent viral infections, especially Cytomegalovirus (CMV), that oblige certain T cell clones to monoclonally expand repeatedly over a lifetime which then occupy space within the T cell pool. Eventually, these inflated memory T cell clones become exhausted and their extensive accumulation accelerates the age-dependent decline of the diversity of the T cell pool. As a consequence, infectious diseases are more frequent and severe in elderly persons and immunological protection following vaccination is reduced. This review therefore aims to shed light on how various types of persistent viral infections, especially CMV, influence the aging of the immune system and highlight potential measures to prevent the age-related decline in immune function. Copyright © 2010 Elsevier B.V. All rights reserved.

Nuclear lamina defects cause ATM-dependent NF-κB activation and link accelerated aging to a systemic inflammatory response

PubMed Central

Osorio, Fernando G.; Bárcena, Clea; Soria-Valles, Clara; Ramsay, Andrew J.; de Carlos, Félix; Cobo, Juan; Fueyo, Antonio; Freije, José M.P.; López-Otín, Carlos

2012-01-01

Alterations in the architecture and dynamics of the nuclear lamina have a causal role in normal and accelerated aging through both cell-autonomous and systemic mechanisms. However, the precise nature of the molecular cues involved in this process remains incompletely defined. Here we report that the accumulation of prelamin A isoforms at the nuclear lamina triggers an ATM- and NEMO-dependent signaling pathway that leads to NF-κB activation and secretion of high levels of proinflammatory cytokines in two different mouse models of accelerated aging (Zmpste24−/− and LmnaG609G/G609G mice). Causal involvement of NF-κB in accelerated aging was demonstrated by the fact that both genetic and pharmacological inhibition of NF-κB signaling prevents age-associated features in these animal models, significantly extending their longevity. Our findings provide in vivo proof of principle for the feasibility of pharmacological modulation of the NF-κB pathway to slow down the progression of physiological and pathological aging. PMID:23019125

Lifetime stress accelerates epigenetic aging in an urban, African American cohort: relevance of glucocorticoid signaling.

PubMed

Zannas, Anthony S; Arloth, Janine; Carrillo-Roa, Tania; Iurato, Stella; Röh, Simone; Ressler, Kerry J; Nemeroff, Charles B; Smith, Alicia K; Bradley, Bekh; Heim, Christine; Menke, Andreas; Lange, Jennifer F; Brückl, Tanja; Ising, Marcus; Wray, Naomi R; Erhardt, Angelika; Binder, Elisabeth B; Mehta, Divya

2015-12-17

Chronic psychological stress is associated with accelerated aging and increased risk for aging-related diseases, but the underlying molecular mechanisms are unclear. We examined the effect of lifetime stressors on a DNA methylation-based age predictor, epigenetic clock. After controlling for blood cell-type composition and lifestyle parameters, cumulative lifetime stress, but not childhood maltreatment or current stress alone, predicted accelerated epigenetic aging in an urban, African American cohort (n = 392). This effect was primarily driven by personal life stressors, was more pronounced with advancing age, and was blunted in individuals with higher childhood abuse exposure. Hypothesizing that these epigenetic effects could be mediated by glucocorticoid signaling, we found that a high number (n = 85) of epigenetic clock CpG sites were located within glucocorticoid response elements. We further examined the functional effects of glucocorticoids on epigenetic clock CpGs in an independent sample with genome-wide DNA methylation (n = 124) and gene expression data (n = 297) before and after exposure to the glucocorticoid receptor agonist dexamethasone. Dexamethasone induced dynamic changes in methylation in 31.2 % (110/353) of these CpGs and transcription in 81.7 % (139/170) of genes neighboring epigenetic clock CpGs. Disease enrichment analysis of these dexamethasone-regulated genes showed enriched association for aging-related diseases, including coronary artery disease, arteriosclerosis, and leukemias. Cumulative lifetime stress may accelerate epigenetic aging, an effect that could be driven by glucocorticoid-induced epigenetic changes. These findings contribute to our understanding of mechanisms linking chronic stress with accelerated aging and heightened disease risk.

Accelerated aging of concrete : a literature review

DOT National Transportation Integrated Search

2002-02-01

This report provides a review of the literature on accelerated aging of concrete. It was undertaken, as part of a research project : on predicting the long-term environmental performance of Portland cement concrete (PCC) pavements containing coal fly...

AGE/RAGE-Induced EMP Release via the NOX-Derived ROS Pathway

PubMed Central

Chen, Ying-Hua; Chen, Zhang-Wei; Li, Hong-Mei

2018-01-01

Objective Diabetes is associated with accelerated formation of advanced glycation end products (AGEs) that are extensively found in circulating endothelial microparticles (EMPs). This study aimed to investigate whether AGEs have a direct effect on EMP formation and the possible underlying mechanism. Methods In vitro, cultured human umbilical vein endothelial cells (HUVECs) were incubated with AGEs (200 and 400 μg/ml) for 24 hours with or without pretreatment with anti-RAGE antibody, NOX inhibitor, or ROS scavenger. The number of CD31-positive EMPs was assessed by flow cytometry. Results The number of EMPs was significantly increased in HUVECs stimulated by AGEs in a dose-dependent manner. In addition, receptors for AGEs (RAGE), NAD(P)H oxidase (NOX), and reactive oxygen species (ROS) were increased by AGEs as compared to the control group. These changes could be reversed when HUVECs were pretreated with anti-RAGE antibody. Moreover, inhibition of NOX as well as antioxidant treatment reduced the release of EMPs induced by AGEs. Conclusion Our study suggested that AGEs increased EMP generation, which was mediated by RAGE signaling through NOX-derived ROS. PMID:29744367

AGE/RAGE-Induced EMP Release via the NOX-Derived ROS Pathway.

PubMed

Chen, Ying-Hua; Chen, Zhang-Wei; Li, Hong-Mei; Yan, Xin-Feng; Feng, Bo

2018-01-01

Diabetes is associated with accelerated formation of advanced glycation end products (AGEs) that are extensively found in circulating endothelial microparticles (EMPs). This study aimed to investigate whether AGEs have a direct effect on EMP formation and the possible underlying mechanism. In vitro, cultured human umbilical vein endothelial cells (HUVECs) were incubated with AGEs (200 and 400  μ g/ml) for 24 hours with or without pretreatment with anti-RAGE antibody, NOX inhibitor, or ROS scavenger. The number of CD31-positive EMPs was assessed by flow cytometry. The number of EMPs was significantly increased in HUVECs stimulated by AGEs in a dose-dependent manner. In addition, receptors for AGEs (RAGE), NAD(P)H oxidase (NOX), and reactive oxygen species (ROS) were increased by AGEs as compared to the control group. These changes could be reversed when HUVECs were pretreated with anti-RAGE antibody. Moreover, inhibition of NOX as well as antioxidant treatment reduced the release of EMPs induced by AGEs. Our study suggested that AGEs increased EMP generation, which was mediated by RAGE signaling through NOX-derived ROS.

Declining performance of master athletes: silhouettes of the trajectory of healthy human ageing?

PubMed

Lazarus, Norman R; Harridge, Stephen D R

2017-05-01

Analysis of world record performances by master athletes suggests an essentially linear decline with age until around the eighth decade after which performance decline accelerates. Because these records are obtained from highly trained individuals they can be viewed as being reflective of the diminution of integrative physiological prowess that occurs solely as a result of ageing, unaffected by the confounding effects of inactivity. It can also be argued that these performance profiles mirror and provide an insight into the trajectory of the physiology of the human ageing process. Here we propose a set point theory that hypothesises that a given threshold of physical activity is needed to age optimally and to maximise the 'healthspan'. Exercising at levels below the set point will result in ageing being contaminated by the unpredictable and pathological effects of inactivity. Exercise above this threshold stimulates adaptations towards maximising athletic performance, but is unlikely to have further beneficial effects on health. Thus the decades-long, controlled diminution in athletic performance, should not be seen as a disease process. The ageing process is separate from, and independent of, exercise-mediated processes that maintain or adapt physiological function. Whether an understanding of these mechanisms will also help uncover mechanisms underpinning the ageing process itself is open to question. However, any model which does not take into account the effects of activity will not adequately describe the inherent ageing process. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Simultaneous Thermal and Gamma Radiation Aging of Cable Polymers

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

Fifield, Leonard S.; Liu, Shuaishuai; Bowler, Nicola

Polymers used in nuclear power plant electrical cable systems experience aging and degradation over time due to environmental stress including heat and gamma irradiation. Prediction of long-term cable performance has been based on results of short-term accelerated laboratory aging studies, but questions remain regarding the correlation of accelerated aging to long-term, in-plant aging. This work seeks to increase understanding of the combined effects of heat and radiation on cable polymer material aging toward addressing these questions.

How Well Does the Latest Anthropomorphic Test Device Mimic Human Impact Responses?

NASA Technical Reports Server (NTRS)

Newby, Nate; Somers, Jeff; Caldewll, Erin; Gernhardt, Michael

2014-01-01

One of the goals of the NASA Occupant Protection Group is to understand the human tolerance to dynamic loading. This knowledge has to come through indirect approaches such as existing human response databases, anthropometric test devices (ATD), animal testing, post-­-mortem human subjects, and models. This study investigated the biofidelity of the National Highway Traffic Safety Administration's ATD named the THOR (test device for human occupant restraint). If THOR responds comparably to humans, then it could potentially be used as a human surrogate to help validate space vehicle requirements for occupant protection. The THOR responses to frontal and spinal impacts (ranging from 8 to 12 G with rise times of 40, 70, and 100 ms) were measured and compared to human volunteer responses (95 trials in frontal and 58 in spinal) previously collected by the U. S. Air Force on the same horizontal impact accelerator. The impact acceleration profiles tested are within the expected range of multi-­-purpose crew vehicle (MPCV) landing dynamics. A correlation score was calculated for each THOR to human comparison using CORA (CORrelation and Analysis) software. A two-­-parameter beta distribution model fit was obtained for each dependent variable using maximum likelihood estimation. For frontal impacts, the THOR head x-­-acceleration peak response correlated with the human response at 8 and 10-­-G 100 ms but not 10-­-G 70 ms. The phase lagged the human response. Head z-­-acceleration was not correlated. Chest x-­-acceleration was in phase, had a higher peak response, and was well correlated with lighter subjects (Cora = 0.8 for 46 kg vs. Cora = 0.4 for 126 kg). Head x-­-displacement had a leading phase. Several subjects responded with the same peak displacement but the mean of the group was lower. The shoulder x-­-displacement was in phase but had higher peaks than the human response. For spinal impacts, the THOR head x-­-acceleration was not well correlated. Head and chest z-­-acceleration was in phase but had a higher peak response. Chest z-­-acceleration was highly correlated with heavier subjects at lower G pulses (Cora = 0.86 for 125 kg at 8 G). The human response was variable in shoulder z-­-displacement but the THOR was in phase and was comparable to the mean peak response. Head x-­- and z-­-displacement was in phase but had higher peaks. Seat pan forces were well correlated, were in phase, but had a larger peak response than most subjects. The THOR does not respond to frontal and spinal impacts exactly the same way that a human does. Some responses are well matched and others are not. Understanding the strengths and weaknesses of this ATD is an important first step in determining its usefulness in occupant protection at NASA

Overview of Light-Ion Beam Therapy

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

Chu, William T.

2006-03-16

In 1930, Ernest Orlando Lawrence at the University of California at Berkeley invented the cyclotron. One of his students, M. Stanley Livingston, constructed a 13-cm diameter model that had all the features of early cyclotrons, accelerating protons to 80 keV using less than 1 kV on a semi-circular accelerating electrode, now called the ''dee''. Soon after, Lawrence constructed the first two-dee 27-Inch (69-cm) Cyclotron, which produced protons and deuterons of 4.8 MeV. In 1939, Lawrence constructed the 60-Inch (150-cm) Cyclotron, which accelerated deuterons to 19 MeV. Just before WWII, Lawrence designed a 184-inch cyclotron, but the war prevented the buildingmore » of this machine. Immediately after the war ended, the Veksler-McMillan principle of phase stability was put forward, which enabled the transformation of conventional cyclotrons to successful synchrocyclotrons. When completed, the 184-Inch Synchrocyclotron produced 340-MeV protons. Following it, more modern synchrocyclotrons were built around the globe, and the synchrocyclotrons in Berkeley and Uppsala, together with the Harvard cyclotron, would perform pioneering work in treatment of human cancer using accelerated hadrons (protons and light ions). When the 184-Inch Synchrocyclotron was built, Lawrence asked Robert Wilson, one of his former graduate students, to look into the shielding requirements for of the new accelerator. Wilson soon realized that the 184-Inch would produce a copious number of protons and other light ions that had enough energy to penetrate human body, and could be used for treatment of deep-seated diseases. Realizing the advantages of delivering a larger dose in the Bragg peak when placed inside deep-seated tumors, he published in a medical journal a seminal paper on the rationale to use accelerated protons and light ions for treatment of human cancer. The precise dose localization provided by protons and light ions means lower doses to normal tissues adjacent to the treatment volume compared to those in conventional (photon) treatments. Wilson wrote his personal account of this pioneering work in 1997. In 1954 Cornelius Tobias and John Lawrence at the Radiation Laboratory (former E.O. Lawrence Berkeley National Laboratory) of the University of California, Berkeley performed the first therapeutic exposure of human patients to hadron (deuteron and helium ion) beams at the 184-Inch Synchrocyclotron. By 1984, or 30 years after the first proton treatment at Berkeley, programs of proton radiation treatments had opened at: University of Uppsala, Sweden, 1957; the Massachusetts General Hospital-Harvard Cyclotron Laboratory (MGH/HCL), USA, 1961; Dubna (1967), Moscow (1969) and St Petersburg (1975) in Russia; Chiba (1979) and Tsukuba (1983) in Japan; and Villigen, Switzerland, 1984. These centers used the accelerators originally constructed for nuclear physics research. The experience at these centers has confirmed the efficacy of protons and light ions in increasing the tumor dose relative to normal tissue dose, with significant improvements in local control and patient survival for several tumor sites. M.R. Raju reviewed the early clinical studies. In 1990, the Loma Linda University Medical Center in California heralded in the age of dedicated medical accelerators when it commissioned its proton therapy facility with a 250-MeV synchrotron. Since then there has been a relatively rapid increase in the number of hospital-based proton treatment centers around the world, and by 2006 there are more than a dozen commercially-built facilities in use, five new facilities under construction, and more in planning stages. In the 1950s larger synchrotrons were built in the GeV region at Brookhaven (3-GeV Cosmotron) and at Berkeley (6-GeV Bevatron), and today most of the world's largest accelerators are synchrotrons. With advances in accelerator design in the early 1970s, synchrotrons at Berkeley and Princeton accelerated ions with atomic numbers between 6 and 18, at energies that permitted the initiation of several biological studies. It is worth noting that when the Bevatron was converted to accelerate light ions, the main push came from biomedical users who wanted to use high-LET radiation for treating human cancer.« less

Compression set in gas-blown condensation-cured polysiloxane elastomers

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

Patel, Mogon; Chinn, Sarah; Maxwell, Robert S.

2010-12-01

Accelerated thermal ageing studies on foamed condensation cured polysiloxane materials have been performed in support of life assessment and material replacement programmes. Two different types of filled hydrogen-blown and condensation cured polysiloxane foams were tested; commercial (RTV S5370), and an in-house formulated polysiloxane elastomer (Silfoam). Compression set properties were investigated using Thermomechanical (TMA) studies and compared against two separate longer term ageing trials carried out in air and in dry inert gas atmospheres using compression jigs. Isotherms measured from these studies were assessed using time-temperature (T/t) superposition. Acceleration factors were determined and fitted to Arrhenius kinetics. For both materials, themore » thermo-mechanical results were found to closely follow the longer term accelerated ageing trials. Comparison of the accelerated ageing data in dry nitrogen atmospheres against field trial results showed the accelerated ageing trends over predict, however the comparison is difficult as the field data suffer from significant component to component variability. Of the long term ageing trials reported here, those carried out in air deviate more significantly from field trials data compared to those carried out in dry nitrogen atmospheres. For field return samples, there is evidence for residual post-curing reactions influencing mechanical performance, which would accelerate compression set. Multiple quantum-NMR studies suggest that compression set is not associated with significant changes in net crosslink density, but that some degree of network rearrangement has occurred due to viscoelastic relaxation as well as bond breaking and forming processes, with possible post-curing reactions at early times.« less

Enhanced Phospholipase A2 Group 3 Expression by Oxidative Stress Decreases the Insulin-Degrading Enzyme

PubMed Central

Yui, Daishi; Nishida, Yoichiro; Nishina, Tomoko; Mogushi, Kaoru; Tajiri, Mio; Ishibashi, Satoru; Ajioka, Itsuki; Ishikawa, Kinya; Mizusawa, Hidehiro; Murayama, Shigeo; Yokota, Takanori

2015-01-01

Oxidative stress has a ubiquitous role in neurodegenerative diseases and oxidative damage in specific regions of the brain is associated with selective neurodegeneration. We previously reported that Alzheimer disease (AD) model mice showed decreased insulin-degrading enzyme (IDE) levels in the cerebrum and accelerated phenotypic features of AD when crossbred with alpha-tocopherol transfer protein knockout (Ttpa -/-) mice. To further investigate the role of chronic oxidative stress in AD pathophysiology, we performed DNA microarray analysis using young and aged wild-type mice and aged Ttpa -/- mice. Among the genes whose expression changed dramatically was Phospholipase A2 group 3 (Pla2g3); Pla2g3 was identified because of its expression profile of cerebral specific up-regulation by chronic oxidative stress in silico and in aged Ttpa -/- mice. Immunohistochemical studies also demonstrated that human astrocytic Pla2g3 expression was significantly increased in human AD brains compared with control brains. Moreover, transfection of HEK293 cells with human Pla2g3 decreased endogenous IDE expression in a dose-dependent manner. Our findings show a key role of Pla2g3 on the reduction of IDE, and suggest that cerebrum specific increase of Pla2g3 is involved in the initiation and/or progression of AD. PMID:26637123

Bio-Spectroscopic Imaging Provides Evidence of Hippocampal Zn Deficiency and Decreased Lipid Unsaturation in an Accelerated Ageing Mouse Model.

PubMed

Fimognari, Nicholas; Hollings, Ashley; Lam, Virginie; Tidy, Rebecca J; Kewish, Cameron M; Albrecht, Matthew A; Takechi, Ryu; Mamo, John C L; Hackett, Mark J

2018-06-14

Western society is facing a health epidemic due to the increasing incidence of dementia in ageing populations, and there are still few effective diagnostic methods, minimal treatment options, and no cure. Ageing is the greatest risk factor for memory loss that occurs during the natural ageing process, as well as being the greatest risk factor for neurodegenerative disease such as Alzheimer's disease. Therefore, greater understanding of the biochemical pathways that drive a healthy ageing brain towards dementia (pathological ageing or Alzheimer's disease), is required to accelerate the development of improved diagnostics and therapies. Unfortunately, many animal models of dementia model chronic amyloid precursor protein over-expression, which although highly relevant to mechanisms of amyloidosis and familial Alzheimer's disease, does not model well dementia during the natural ageing process. A promising animal model reported to model mechanisms of accelerated natural ageing and memory impairments, is the senescence accelerated murine prone strain 8 (SAMP8), which has been adopted by many research group to study the biochemical transitions that occur during brain ageing. A limitation to traditional methods of biochemical characterisation is that many important biochemical and elemental markers (lipid saturation, lactate, transition metals) cannot be imaged at meso- or micro-spatial resolution. Therefore, in this investigation we report the first multi-modal biospectroscopic characterisation of the SAMP8 model, and have identified important biochemical and elemental alterations, and co-localisations, between 4 month old SAMP8 mice and the relevant control (SAMR1) mice. Specifically, we demonstrate direct evidence of altered metabolism and disturbed lipid homeostasis within corpus callosum white matter, in addition to localised hippocampal metal deficiencies, in the accelerated ageing phenotype. Such findings have important implication for future research aimed at elucidating specific biochemical pathways for therapeutic intervention.

Accelerated Brain Aging in Schizophrenia: A Longitudinal Pattern Recognition Study.

PubMed

Schnack, Hugo G; van Haren, Neeltje E M; Nieuwenhuis, Mireille; Hulshoff Pol, Hilleke E; Cahn, Wiepke; Kahn, René S

2016-06-01

Despite the multitude of longitudinal neuroimaging studies that have been published, a basic question on the progressive brain loss in schizophrenia remains unaddressed: Does it reflect accelerated aging of the brain, or is it caused by a fundamentally different process? The authors used support vector regression, a supervised machine learning technique, to address this question. In a longitudinal sample of 341 schizophrenia patients and 386 healthy subjects with one or more structural MRI scans (1,197 in total), machine learning algorithms were used to build models to predict the age of the brain and the presence of schizophrenia ("schizophrenia score"), based on the gray matter density maps. Age at baseline ranged from 16 to 67 years, and follow-up scans were acquired between 1 and 13 years after the baseline scan. Differences between brain age and chronological age ("brain age gap") and between schizophrenia score and healthy reference score ("schizophrenia gap") were calculated. Accelerated brain aging was calculated from changes in brain age gap between two consecutive measurements. The age prediction model was validated in an independent sample. In schizophrenia patients, brain age was significantly greater than chronological age at baseline (+3.36 years) and progressively increased during follow-up (+1.24 years in addition to the baseline gap). The acceleration of brain aging was not constant: it decreased from 2.5 years/year just after illness onset to about the normal rate (1 year/year) approximately 5 years after illness onset. The schizophrenia gap also increased during follow-up, but more pronounced variability in brain abnormalities at follow-up rendered this increase nonsignificant. The progressive brain loss in schizophrenia appears to reflect two different processes: one relatively homogeneous, reflecting accelerated aging of the brain and related to various measures of outcome, and a more variable one, possibly reflecting individual variation and medication use. Differentiating between these two processes may not only elucidate the various factors influencing brain loss in schizophrenia, but also assist in individualizing treatment.

HIV-associated cellular senescence: A contributor to accelerated aging.

PubMed

Cohen, Justin; Torres, Claudio

2017-07-01

Due to the advent of antiretroviral therapy HIV is no longer a terminal disease and the HIV infected patients are becoming increasingly older. While this is a major success, with increasing age comes an increased risk for disease. The age-related comorbidities that HIV infected patients experience suggest that they suffer from accelerated aging. One possible contributor to this accelerated aging is cellular senescence, an age-associated response that can occur prematurely in response to stress, and that is emerging as a contributor to disease and aging. HIV patients experience several stressors such as the virus itself, antiretroviral drugs and to a lesser extent, substance abuse that can induce cellular senescence. This review summarizes the current knowledge of senescence induction in response to these stressors and their relation to the comorbidities in HIV patients. Cellular senescence may be a possible therapeutic target for these comorbidities. Copyright © 2016 Elsevier B.V. All rights reserved.

Solder joint aging characteristics from the MC2918 firing set of a B61 accelerated aging unit (AAU)

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

Vianco, P.T.; Rejent, J.A.

1997-10-01

The B61 accelerated aging unit (AAU) provided a unique opportunity to document the effects of a controlled, long-term thermal cycling environment on the aging of materials used in the device. This experiment was of particular interest to solder technologists because thermal cycling environments are a predominant source of solder joint failures in electronic assemblies. Observations of through hole solder joints in the MC2918 Firing Set from the B61 AAU did not reveal signs of catastrophic failure. Quantitative analyses of the microstructural metrics of intermetallic compound layer thickness and Pb-rich phase particle distributions indicated solder joint aging that was commensurate withmore » the accelerated aging environment. The effects of stress-enhanced coarsening of the Pb-rich phase were also documented.« less

Age-Related Differences in Spatiotemporal Variables and Ground Reaction Forces During Sprinting in Boys.

PubMed

Nagahara, Ryu; Takai, Yohei; Haramura, Miki; Mizutani, Mirai; Matsuo, Akifumi; Kanehisa, Hiroaki; Fukunaga, Tetsuo

2018-02-24

We aimed to elucidate age-related differences in spatiotemporal and ground reaction force variables during sprinting in boys over a broad range of chronological ages. Ground reaction force signals during 50-m sprinting were recorded in 99 boys aged 6.5-15.4 years. Step-to-step spatiotemporal variables and mean forces were then calculated. There was a slower rate of development in sprinting performance in the age span from 8.8 to 12.1 years compared with younger and older boys. During that age span, mean propulsive force was almost constant, and step frequency for older boys was lower regardless of sprinting phase. During the ages younger than 8.8 years and older than 12.1 years, sprint performance rapidly increased with increasing mean propulsive forces during the middle acceleration and maximal speed phases and during the initial acceleration phase. There was a stage of temporal slower development of sprinting ability from age 8.8 to 12.1 years, being characterized by unchanged propulsive force and decreased step frequency. Moreover, increasing propulsive forces during the middle acceleration and maximal speed phases and during the initial acceleration phase are probably responsible for the rapid development of sprinting ability before and after the period of temporal slower development of sprinting ability.

The cell biology of aging.

PubMed

Hayflick, L

1985-02-01

It is only within the past ten years that biogerontology has become attractive to a sufficient number of biologists so that the field can be regarded as a seriously studied discipline. Cytogerontology, or the study of aging at the cellular level, had its genesis about 20 years ago when the dogma that maintained that cultured normal cells could replicate forever was overturned. Normal human and animal cells have a finite capacity to replicate and function whether they are cultured in vitro or transplanted as grafts in vivo. This phenomenon has been interpreted to be aging at the cellular level. Only abnormal somatic cells are capable of immortality. In recent years it has been found that the number of population doublings of which cultured normal cells are capable is inversely proportional to donor age. There is also good evidence that the number of population doublings of cultured normal fibroblasts is directly proportional to the maximum lifespan of ten species that have been studied. Cultures prepared from patients with accelerated aging syndromes (progeria and Werner's syndrome) undergo far fewer doublings than do those of age-matched controls. The normal human fibroblast cell strain WI-38 was established in 1962 from fetal lung, and several hundred ampules of these cells were frozen in liquid nitrogen at that time. These ampules have been reconstituted periodically and shown to be capable of replication. This represents the longest period of time that a normal human cell has ever been frozen. Normal human fetal cell strains such as WI-38 have the capacity to double only about 50 times. If cultures are frozen at various population doublings, the number of doublings remaining after reconstitution is equal to 50 minus the number of doublings that occurred prior to freezing. The memory of the cells has been found to be accurate after 23 years of preservation in liquid nitrogen. Normal human cells incur many physiologic decrements that herald the approach of their failure to divide. Many of these functional decrements are identical to decrements found in humans as they age. Thus it is likely that these decrements are also the precursors of age changes in vivo. The finite replicative capacity of normal cells is never seen to occur in vivo because aging and death of the individual occurs well before the doubling limit is reached.

The effect of copper, MDA, and accelerated aging on jet fuel thermal stability as measured by the gravimetric JFTOT

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

Pande, S.G.; Hardy, D.R.

1995-05-01

Thermally unstable jet fuels pose operational problems. In order to adequately identify such fuels, factors that realistically impact on thermal stability were examined. Evaluation was based on a quantitative method of measuring thermal stability, viz., NRL`s recently developed gravimetric JFTOT. This method gives a quantitative measurement of both the strip deposit and filterables formed. The pertinent factors examined, included the individual and interactive effects of: soluble copper, MDA (metal deactivator), and aging. The latter was accelerated to simulate field conditions of approximately six months aging at ambient temperature and pressure. The results indicate that the individual and interactive effects ofmore » copper, MDA, and accelerated aging appear to be fuel dependent. Based on the results, the three test fuels examined (one JP-8 and two JP-5s) were categorized as exhibiting very good, typical, and poor thermal stabilities, respectively. For both the very good and poor thermal stability fuels, the effect of copper in conjunction with accelerated aging did not significantly increase the total thermal deposits of the neat fuels. In contrast, for the typical thermal stability fuel, the combined effects of copper and accelerated aging, did. Furthermore, the addition of MDA prior to aging of the copper-doped, typical stability fuel significantly counteracted the adverse effect of copper and aging. A similar beneficial effect of MDA was not observed for the poor stability fuel. These results focus on the compositional differences among fuels and the need to elucidate these differences (physical and chemical) for a better understanding and prediction of their performance.« less

Separating Movement and Gravity Components in an Acceleration Signal and Implications for the Assessment of Human Daily Physical Activity

PubMed Central

van Hees, Vincent T.; Gorzelniak, Lukas; Dean León, Emmanuel Carlos; Eder, Martin; Pias, Marcelo; Taherian, Salman; Ekelund, Ulf; Renström, Frida; Franks, Paul W.; Horsch, Alexander; Brage, Søren

2013-01-01

Introduction Human body acceleration is often used as an indicator of daily physical activity in epidemiological research. Raw acceleration signals contain three basic components: movement, gravity, and noise. Separation of these becomes increasingly difficult during rotational movements. We aimed to evaluate five different methods (metrics) of processing acceleration signals on their ability to remove the gravitational component of acceleration during standardised mechanical movements and the implications for human daily physical activity assessment. Methods An industrial robot rotated accelerometers in the vertical plane. Radius, frequency, and angular range of motion were systematically varied. Three metrics (Euclidian norm minus one [ENMO], Euclidian norm of the high-pass filtered signals [HFEN], and HFEN plus Euclidean norm of low-pass filtered signals minus 1 g [HFEN+]) were derived for each experimental condition and compared against the reference acceleration (forward kinematics) of the robot arm. We then compared metrics derived from human acceleration signals from the wrist and hip in 97 adults (22–65 yr), and wrist in 63 women (20–35 yr) in whom daily activity-related energy expenditure (PAEE) was available. Results In the robot experiment, HFEN+ had lowest error during (vertical plane) rotations at an oscillating frequency higher than the filter cut-off frequency while for lower frequencies ENMO performed better. In the human experiments, metrics HFEN and ENMO on hip were most discrepant (within- and between-individual explained variance of 0.90 and 0.46, respectively). ENMO, HFEN and HFEN+ explained 34%, 30% and 36% of the variance in daily PAEE, respectively, compared to 26% for a metric which did not attempt to remove the gravitational component (metric EN). Conclusion In conclusion, none of the metrics as evaluated systematically outperformed all other metrics across a wide range of standardised kinematic conditions. However, choice of metric explains different degrees of variance in daily human physical activity. PMID:23626718

Separating movement and gravity components in an acceleration signal and implications for the assessment of human daily physical activity.

PubMed

van Hees, Vincent T; Gorzelniak, Lukas; Dean León, Emmanuel Carlos; Eder, Martin; Pias, Marcelo; Taherian, Salman; Ekelund, Ulf; Renström, Frida; Franks, Paul W; Horsch, Alexander; Brage, Søren

2013-01-01

Human body acceleration is often used as an indicator of daily physical activity in epidemiological research. Raw acceleration signals contain three basic components: movement, gravity, and noise. Separation of these becomes increasingly difficult during rotational movements. We aimed to evaluate five different methods (metrics) of processing acceleration signals on their ability to remove the gravitational component of acceleration during standardised mechanical movements and the implications for human daily physical activity assessment. An industrial robot rotated accelerometers in the vertical plane. Radius, frequency, and angular range of motion were systematically varied. Three metrics (Euclidian norm minus one [ENMO], Euclidian norm of the high-pass filtered signals [HFEN], and HFEN plus Euclidean norm of low-pass filtered signals minus 1 g [HFEN+]) were derived for each experimental condition and compared against the reference acceleration (forward kinematics) of the robot arm. We then compared metrics derived from human acceleration signals from the wrist and hip in 97 adults (22-65 yr), and wrist in 63 women (20-35 yr) in whom daily activity-related energy expenditure (PAEE) was available. In the robot experiment, HFEN+ had lowest error during (vertical plane) rotations at an oscillating frequency higher than the filter cut-off frequency while for lower frequencies ENMO performed better. In the human experiments, metrics HFEN and ENMO on hip were most discrepant (within- and between-individual explained variance of 0.90 and 0.46, respectively). ENMO, HFEN and HFEN+ explained 34%, 30% and 36% of the variance in daily PAEE, respectively, compared to 26% for a metric which did not attempt to remove the gravitational component (metric EN). In conclusion, none of the metrics as evaluated systematically outperformed all other metrics across a wide range of standardised kinematic conditions. However, choice of metric explains different degrees of variance in daily human physical activity.

Immunity, ageing and cancer

PubMed Central

Derhovanessian, Evelyna; Solana, Rafael; Larbi, Anis; Pawelec, Graham

2008-01-01

Compromised immunity contributes to the decreased ability of the elderly to control infectious disease and to their generally poor response to vaccination. It is controversial as to how far this phenomenon contributes to the well-known age-associated increase in the occurrence of many cancers in the elderly. However, should the immune system be important in controlling cancer, for which there is a great deal of evidence, it is logical to propose that dysfunctional immunity in the elderly would contribute to compromised immunosurveillance and increased cancer occurrence. The chronological age at which immunosenescence becomes clinically important is known to be influenced by many factors, including the pathogen load to which individuals are exposed throughout life. It is proposed here that the cancer antigen load may have a similar effect on "immune exhaustion" and that pathogen load and tumor load may act additively to accelerate immunosenescence. Understanding how and why immune responsiveness changes in humans as they age is essential for developing strategies to prevent or restore dysregulated immunity and assure healthy longevity, clearly possible only if cancer is avoided. Here, we provide an overview of the impact of age on human immune competence, emphasizing T-cell-dependent adaptive immunity, which is the most sensitive to ageing. This knowledge will pave the way for rational interventions to maintain or restore appropriate immune function not only in the elderly but also in the cancer patient. PMID:18816370

Interaction of intraocular lenses with fibronectin and human lens epithelial cells: Effect of chemical composition and aging.

PubMed

Tortolano, Lionel; Serrano, Carole; Jubeli, Emile; Saunier, Johanna; Yagoubi, Najet

2015-12-01

The aim of this study is to investigate in vitro interactions between hydrophobic acrylate intraocular lenses (IOLs) and their biological environment. The influence of lens chemical composition and aging on fibronectin (FN) adsorption and on IOLs cytotoxicity on human lens epithelial cells was examined. Cytotoxicity of acrylate monomers used in IOLs manufacture was also investigated. Four different IOLs were included in the study: Acrysof(®), Tecnis(®), EnVista(®), and iSert(®). Implants were artificially aged in a xenon arc chamber to simulate 2 years of light exposure. Fibronectin adsorption on IOL surface was quantified using ELISA and correlated to surface roughness determined with AFM. Direct contact cytotoxicity was determined with the MTT assay and cell morphology was observed with light microscopy. Results showed that fibronectin adsorption did not differ significantly among IOLs, whatever their chemical composition. Moreover, aging conditions did not impact fibronectin adsorption. All IOLs were biocompatible even after applying 2-year aging conditions, with cell viability higher than 70%. Five acrylate monomers appeared to be toxic in the range of concentrations tested, but no monomer release from the IOLs could be detected during accelerated 2-year incubation with saline solution. This study did not reveal an influence of chemical composition and aging on protein adsorption and on biocompatibility. © 2015 Wiley Periodicals, Inc.

Combined effect of whole-body vibration and ambient lighting on human discomfort, heart rate, and reaction time.

PubMed

Monazzam, Mohammad Reza; Shoja, Esmaeil; Zakerian, Seyed Abolfazl; Foroushani, Abbas Rahimi; Shoja, Mohsen; Gharaee, Masoumeh; Asgari, Amin

2018-07-01

This study aimed to investigate the effect of whole-body vibration and ambient lighting, as well as their combined effect on human discomfort, heart rate, and reaction time in laboratory conditions. 44 men were recruited with an average age of 25.4 ± 1.9 years. Each participant was subjected to 12 experimental steps, each step lasting five minutes for four different vibration accelerations in X, Y, and Z axes at a fixed frequency; three different lighting intensities of 50, 500, and 1000 lx were also considered. At each step, a visual computerized reaction test was taken from subjects and their heart rate recorded by pulse oximeter. In addition, the discomfort rate of subjects was measured using Borg scale. Increasing vibration acceleration significantly increased the discomfort rate and heart beat but not the reaction time. Lack of lighting caused more discomfort in the subjects, but there was no significant correlation between lighting intensity with heart rate and reaction time. The results also showed that the combined effect of vibration and lighting had no significant effect on any of the discomfort, heart rate, and reaction time variables. Whole-body vibration is an important factor in the development of human subjective and physiological reactions compared to lighting. Therefore, consideration of the level of vibration to which an individual is exposed in workplaces subject to vibration plays an important role in reducing the level of human discomfort, but its interaction with ambient lighting does not have a significant effect on human subjective and physiological responses.

Fully reduced HMGB1 accelerates the regeneration of multiple tissues by transitioning stem cells to GAlert.

PubMed

Lee, Geoffrey; Espirito Santo, Ana Isabel; Zwingenberger, Stefan; Cai, Lawrence; Vogl, Thomas; Feldmann, Marc; Horwood, Nicole J; Chan, James K; Nanchahal, Jagdeep

2018-05-08

A major discovery of recent decades has been the existence of stem cells and their potential to repair many, if not most, tissues. With the aging population, many attempts have been made to use exogenous stem cells to promote tissue repair, so far with limited success. An alternative approach, which may be more effective and far less costly, is to promote tissue regeneration by targeting endogenous stem cells. However, ways of enhancing endogenous stem cell function remain poorly defined. Injury leads to the release of danger signals which are known to modulate the immune response, but their role in stem cell-mediated repair in vivo remains to be clarified. Here we show that high mobility group box 1 (HMGB1) is released following fracture in both humans and mice, forms a heterocomplex with CXCL12, and acts via CXCR4 to accelerate skeletal, hematopoietic, and muscle regeneration in vivo. Pretreatment with HMGB1 2 wk before injury also accelerated tissue regeneration, indicating an acquired proregenerative signature. HMGB1 led to sustained increase in cell cycling in vivo, and using Hmgb1 -/- mice we identified the underlying mechanism as the transition of multiple quiescent stem cells from G 0 to G Alert HMGB1 also transitions human stem and progenitor cells to G Alert Therefore, exogenous HMGB1 may benefit patients in many clinical scenarios, including trauma, chemotherapy, and elective surgery. Copyright © 2018 the Author(s). Published by PNAS.

Translucency of Zirconia Ceramics before and after Artificial Aging.

PubMed

Walczak, Katarzyna; Meißner, Heike; Range, Ursula; Sakkas, Andreas; Boening, Klaus; Wieckiewicz, Mieszko; Konstantinidis, Ioannis

2018-03-11

The aging of zirconia ceramics (Y-TZP) is associated with tetragonal to monoclinic phase transformation. This change in microstructure may affect the optical properties of the ceramic. This study examines the effect of aging on the translucency of different zirconia materials. 120 disc-shaped specimens were fabricated from four zirconia materials: Cercon ht white, BruxZir Solid Zirconia, Zenostar T0, Lava Plus (n = 30 per group). Accelerated aging was performed in a steam autoclave (134°C, 0.2 MPa, 5 hours). CIELab coordinates (L*, a*, b*) and luminous reflectance (Y) were measured with a spectrophotometer before and after aging. Contrast ratio (CR) and translucency parameter (TP) were calculated from the L*, a*, b*, and Y tristimulus values. The general linear model (Bonferroni adjusted) was used to compare both parameters before and after aging, as well as between the different zirconia materials (p ≤ 0.05). CR and TP differed significantly before and after aging in all groups tested. Before aging, Zenostar T showed the highest and Lava Plus showed the lowest translucency. After aging, Cercon ht and Zenostar T showed the highest and BruxZir and Lava Plus the lowest translucency. Aging reduced the translucency in all specimens tested. Furthermore, translucency differed between the zirconia brands tested. Nevertheless, the differences were below the detectability threshold of the human eye. The aging process can influence the translucency and thus the esthetic outcome of zirconia restorations; however, the changes in translucency were minimal and probably undetectable by the human eye. © 2018 by the American College of Prosthodontists.

Ensemble Manifold Rank Preserving for Acceleration-Based Human Activity Recognition.

PubMed

Tao, Dapeng; Jin, Lianwen; Yuan, Yuan; Xue, Yang

2016-06-01

With the rapid development of mobile devices and pervasive computing technologies, acceleration-based human activity recognition, a difficult yet essential problem in mobile apps, has received intensive attention recently. Different acceleration signals for representing different activities or even a same activity have different attributes, which causes troubles in normalizing the signals. We thus cannot directly compare these signals with each other, because they are embedded in a nonmetric space. Therefore, we present a nonmetric scheme that retains discriminative and robust frequency domain information by developing a novel ensemble manifold rank preserving (EMRP) algorithm. EMRP simultaneously considers three aspects: 1) it encodes the local geometry using the ranking order information of intraclass samples distributed on local patches; 2) it keeps the discriminative information by maximizing the margin between samples of different classes; and 3) it finds the optimal linear combination of the alignment matrices to approximate the intrinsic manifold lied in the data. Experiments are conducted on the South China University of Technology naturalistic 3-D acceleration-based activity dataset and the naturalistic mobile-devices based human activity dataset to demonstrate the robustness and effectiveness of the new nonmetric scheme for acceleration-based human activity recognition.

Is biological aging accelerated in drug addiction?

PubMed

Bachi, Keren; Sierra, Salvador; Volkow, Nora D; Goldstein, Rita Z; Alia-Klein, Nelly

2017-02-01

Drug-addiction may trigger early onset of age-related disease, due to drug-induced multi-system toxicity and perilous lifestyle, which remains mostly undetected and untreated. We present the literature on pathophysiological processes that may hasten aging and its relevance to addiction, including: oxidative stress and cellular aging, inflammation in periphery and brain, decline in brain volume and function, and early onset of cardiac, cerebrovascular, kidney, and liver disease. Timely detection of accelerated aging in addiction is crucial for the prevention of premature morbidity and mortality.

Cost of nitrogen use in the US

EPA Science Inventory

Growing human demands for food, fuel and fiber have accelerated the human-driven fixation of reactive nitrogen (N) by at least 10-fold over the last century. This acceleration is one of the most dramatic changes to the sustainability of Earth’s systems. Approximately 65% ...

Xeroderma pigmentosum and other diseases of human premature aging and DNA repair: Molecules to patients

PubMed Central

Niedernhofer, Laura J.; Bohr, Vilhelm A.; Sander, Miriam; Kraemer, Kenneth H.

2012-01-01

A workshop1 to share, consider and discuss the latest developments in understanding xeroderma pigmentosum and other human diseases caused by defects in nucleotide excision repair (NER) of DNA damage was held on September 21–24, 2010 in Virginia. It was attended by approximately 100 researchers and clinicians, as well as several patients and representatives of patient support groups. This was the third in a series of workshops with similar design and goals: to emphasize discussion and interaction among participants as well as open exchange of information and ideas. The participation of patients, their parents and physicians was an important feature of this and the preceding two workshops. Topics discussed included the natural history and clinical features of the diseases, clinical and laboratory diagnosis of these rare diseases, therapeutic strategies, mouse models of neurodegeneration, molecular analysis of accelerated aging, impact of transcriptional defects and mitochondrial dysfunction on neurodegeneration, and biochemical insights into mechanisms of NER and base excision repair. PMID:21708183

Experimental induction of type 2 diabetes in aging-accelerated mice triggered Alzheimer-like pathology and memory deficits.

PubMed

Mehla, Jogender; Chauhan, Balwantsinh C; Chauhan, Neelima B

2014-01-01

Alzheimer's disease (AD) is an age-dependent neurodegenerative disease constituting ~95% of late-onset non-familial/sporadic AD, and only ~5% accounting for early-onset familial AD. Availability of a pertinent model representing sporadic AD is essential for testing candidate therapies. Emerging evidence indicates a causal link between diabetes and AD. People with diabetes are >1.5-fold more likely to develop AD. Senescence-accelerated mouse model (SAMP8) of accelerated aging displays many features occurring early in AD. Given the role played by diabetes in the pre-disposition of AD, and the utility of SAMP8 non-transgenic mouse model of accelerated aging, we examined if high fat diet-induced experimental type 2 diabetes in SAMP8 mice will trigger pathological aging of the brain. Results showed that compared to non-diabetic SAMP8 mice, diabetic SAMP8 mice exhibited increased cerebral amyloid-β, dysregulated tau-phosphorylating glycogen synthase kinase 3β, reduced synaptophysin immunoreactivity, and displayed memory deficits, indicating Alzheimer-like changes. High fat diet-induced type 2 diabetic SAMP8 mice may represent the metabolic model of AD.

[PSYCHO PHYSIOLOGICAL MARKERS OF ACCELERATED AGING AMONG THOSE WORKING WITH OCCUPATIONAL HAZARDS].

PubMed

Bashkireva, A S; Kachan, Ye Yu; Kulapina, M E

2015-01-01

We assessed the significance of psycho physiological markers of accelerated aging of the function of attention using comparative analysis of two occupational groups in order to reveal how the working process affects mental work capacity. We revealed peculiarities of systemic structure of functions which determine mental work capacity depending on the age and length of service in lorry drivers. It was proved that decrease in the mnestic functions of lorry-drivers takes place 10-15 years earlier compared to the control group. Psycho physiological indices, reflecting the functioning of attention, decreased not only with aging but also with longer driving experience. Our results show that it is necessary to conduct further studies of psycho physiological markers of age-related decrease in short-term memory depending on the activities at work in order to prevent accelerated aging and achieve professional longevity.

Atherosclerosis in epilepsy: its causes and implications.

PubMed

Hamed, Sherifa A

2014-12-01

Evidence from epidemiological, longitudinal, prospective, double-blinded clinical trials as well as case reports documents age-accelerated atherosclerosis with increased carotid artery intima media thickness (CA-IMT) in patients with epilepsy. These findings raise concern regarding their implications for age-accelerated cognitive and behavioral changes in midlife and risk of later age-related cognitive disorders including neurodegenerative processes such as Alzheimer's disease (AD). Chronic epilepsy, cerebral atherosclerosis, and age-related cognitive disorders including AD share many clinical manifestations (e.g. characteristic cognitive deficits), risk factors, and structural and pathological brain abnormalities. These shared risk factors include increased CA-IMT, hyperhomocysteinemia (HHcy), lipid abnormalities, weight gain and obesity, insulin resistance (IR), and high levels of inflammatory and oxidative stresses. The resulting brain structural and pathological abnormalities include decreased volume of the hippocampus, increased cortical thinning of the frontal lobe, ventricular expansion and increased white matter ischemic disease, total brain atrophy, and β-amyloid protein deposition in the brain. The knowledge that age-accelerated atherosclerosis may contribute to age-accelerated cognitive and behavioral abnormalities and structural brain pathologies in patients with chronic epilepsy represents an important research path to pursue future clinical and management considerations. Copyright © 2014 Elsevier Inc. All rights reserved.

Accelerated epigenetic aging in Down syndrome

PubMed Central

Horvath, Steve; Garagnani, Paolo; Bacalini, Maria Giulia; Pirazzini, Chiara; Salvioli, Stefano; Gentilini, Davide; Di Blasio, Anna Maria; Giuliani, Cristina; Tung, Spencer; Vinters, Harry V; Franceschi, Claudio

2015-01-01

Down Syndrome (DS) entails an increased risk of many chronic diseases that are typically associated with older age. The clinical manifestations of accelerated aging suggest that trisomy 21 increases the biological age of tissues, but molecular evidence for this hypothesis has been sparse. Here, we utilize a quantitative molecular marker of aging (known as the epigenetic clock) to demonstrate that trisomy 21 significantly increases the age of blood and brain tissue (on average by 6.6 years, P = 7.0 × 10−14). PMID:25678027

Effect of animal products and extracts on wound healing promotion in topical applications: a review.

PubMed

Napavichayanun, Supamas; Aramwit, Pornanong

2017-06-01

Wound healing is a natural process of body reaction to repair itself after injury. Nonetheless, many internal and external factors such as aging, comorbidity, stress, smoking, alcohol drinking, infections, malnutrition, or wound environment significantly affect the quality and speed of wound healing. The unsuitable conditions may delay wound healing process and cause chronic wound or scar formation. Therefore, many researches have attempted to search for agents that can accelerate wound healing with safety and biocompatibility to human body. Widely studied wound healing agents are those derived from either natural sources including plants and animals or chemical synthesis. The natural products seem to be safer and more biocompatible to human tissue. This review paper demonstrated various kinds of the animal-derived products including chitosan, collagen, honey, anabolic steroids, silk sericin, peptides, and proteoglycan in term of mechanisms of action, advantages, and disadvantages when applied as wound healing accelerator. The benefits of these animal-derived products are wound healing promotion, anti-inflammatory, antimicrobial activity, moisturizing effect, biocompatibility, and safety. However, the drawbacks such as allergy, low stability, batch-to-batch variability, and high extraction and purification costs could not be avoided in some products.

Effects of Aging and Adult-Onset Hearing Loss on Cortical Auditory Regions

PubMed Central

Cardin, Velia

2016-01-01

Hearing loss is a common feature in human aging. It has been argued that dysfunctions in central processing are important contributing factors to hearing loss during older age. Aging also has well documented consequences for neural structure and function, but it is not clear how these effects interact with those that arise as a consequence of hearing loss. This paper reviews the effects of aging and adult-onset hearing loss in the structure and function of cortical auditory regions. The evidence reviewed suggests that aging and hearing loss result in atrophy of cortical auditory regions and stronger engagement of networks involved in the detection of salient events, adaptive control and re-allocation of attention. These cortical mechanisms are engaged during listening in effortful conditions in normal hearing individuals. Therefore, as a consequence of aging and hearing loss, all listening becomes effortful and cognitive load is constantly high, reducing the amount of available cognitive resources. This constant effortful listening and reduced cognitive spare capacity could be what accelerates cognitive decline in older adults with hearing loss. PMID:27242405

Chromatic stability of acrylic resins of artificial eyes submitted to accelerated aging and polishing.

PubMed

Goiato, Marcelo Coelho; Santos, Daniela Micheline dos; Souza, Josiene Firmino; Moreno, Amália; Pesqueira, Aldiéris Alves

2010-12-01

Esthetics and durability of materials used to fabricate artificial eyes has been an important issue since artificial eyes are essential to restore esthetics and function, protect the remaining tissues and help with patients' psychological therapy. However, these materials are submitted to degrading effects of environmental agents on the physical properties of the acrylic resin. This study assessed the color stability of acrylic resins used to fabricate sclera in three basic shades (N1, N2 and N3) when subjected to accelerated aging, mechanical and chemical polishing. Specimens of each resin were fabricated and submitted to mechanical and chemical polishing. Chromatic analysis was performed before and after accelerated aging through ultraviolet reflection spectrophotometry. All specimens revealed color alteration following polishing and accelerated aging. The resins presented statistically significant chromatic alteration (p<0.01) between the periods of 252 and 1008 h. Both polishing methods presented no significant difference between the values of color derivatives of resins.

Accelerated Testing Of Photothermal Degradation Of Polymers

NASA Technical Reports Server (NTRS)

Kim, Soon Sam; Liang, Ranty Hing; Tsay, Fun-Dow

1989-01-01

Electron-spin-resonance (ESR) spectroscopy and Arrhenius plots used to determine maximum safe temperature for accelerated testing of photothermal degradation of polymers. Aging accelerated by increasing illumination, temperature, or both. Results of aging tests at temperatures higher than those encountered in normal use valid as long as mechanism of degradation same throughout range of temperatures. Transition between different mechanisms at some temperature identified via transition between activation energies, manifesting itself as change in slope of Arrhenius plot at that temperature.

Towards Accelerated Aging Methodologies and Health Management of Power MOSFETs (Technical Brief)

NASA Technical Reports Server (NTRS)

Celaya, Jose R.; Patil, Nishad; Saha, Sankalita; Wysocki, Phil; Goebel, Kai

2009-01-01

Understanding aging mechanisms of electronic components is of extreme importance in the aerospace domain where they are part of numerous critical subsystems including avionics. In particular, power MOSFETs are of special interest as they are involved in high voltage switching circuits such as drivers for electrical motors. With increased use of electronics in aircraft control, it becomes more important to understand the degradation of these components in aircraft specific environments. In this paper, we present an accelerated aging methodology for power MOSFETs that subject the devices to indirect thermal overstress during high voltage switching. During this accelerated aging process, two major modes of failure were observed - latch-up and die attach degradation. In this paper we present the details of our aging methodology along with details of experiments and analysis of the results.

Computer modeling of photodegradation

NASA Technical Reports Server (NTRS)

Guillet, J.

1986-01-01

A computer program to simulate the photodegradation of materials exposed to terrestrial weathering environments is being developed. Input parameters would include the solar spectrum, the daily levels and variations of temperature and relative humidity, and materials such as EVA. A brief description of the program, its operating principles, and how it works was initially described. After that, the presentation focuses on the recent work of simulating aging in a normal, terrestrial day-night cycle. This is significant, as almost all accelerated aging schemes maintain a constant light illumination without a dark cycle, and this may be a critical factor not included in acceleration aging schemes. For outdoor aging, the computer model is indicating that the night dark cycle has a dramatic influence on the chemistry of photothermal degradation, and hints that a dark cycle may be needed in an accelerated aging scheme.

Acceleration characteristics of human ocular accommodation.

PubMed

Bharadwaj, Shrikant R; Schor, Clifton M

2005-01-01

Position and velocity of accommodation are known to increase with stimulus magnitude, however, little is known about acceleration properties. We investigated three acceleration properties: peak acceleration, time-to-peak acceleration and total duration of acceleration to step changes in defocus. Peak velocity and total duration of acceleration increased with response magnitude. Peak acceleration and time-to-peak acceleration remained independent of response magnitude. Independent first-order and second-order dynamic components of accommodation demonstrate that neural control of accommodation has an initial open-loop component that is independent of response magnitude and a closed-loop component that increases with response magnitude.

Short communication: Dating components of human atherosclerotic plaques.

PubMed

Gonçalves, Isabel; Stenström, Kristina; Skog, Göran; Mattsson, Sören; Nitulescu, Mihaela; Nilsson, Jan

2010-04-02

Atherosclerotic plaques that give rise to acute clinical symptoms are typically characterized by degradation of the connective tissue and plaque rupture. Experimental studies have shown that mechanisms to repair vulnerable lesions exist, but the rate of remodeling of human plaque tissue has not been studied. In the present study, we determined the biological age of different components of advanced human atherosclerotic plaques by analyzing tissue levels of (14)C released into the atmosphere during the nuclear weapons tests in the late 1950s and early 1960s. Atherosclerotic plaques were obtained from 10 patients (age 46 to 80 years) undergoing carotid surgery. Different regions of the plaques were dissected and analyzed for (14)C content using accelerator mass spectrometry. At the time of surgery, the mean biological age of the cap region was 6.4+/-3.2 years, which was significantly lower than that of the shoulder region (12.9+/-3.0 years, P<0.01), the interface toward the media (12.4+/-3.3 years, P<0.01), and the core (9.8+/-4.5 years, P<0.05). Analysis of proliferative activity and rate of apoptosis showed no signs of increased cellular turnover in the cap, suggesting that the lower (14)C content reflected a more recent time of formation. These results show that the turnover time of human plaque tissue is very long and may explain why regression of atherosclerotic plaque size rarely is observed in cardiovascular intervention trials.

Optimizations of Human Restraint Systems for Short-Period Acceleration

NASA Technical Reports Server (NTRS)

Payne, P. R.

1963-01-01

A restraint system's main function is to restrain its occupant when his vehicle is subjected to acceleration. If the restraint system is rigid and well-fitting (to eliminate slack) then it will transmit the vehicle acceleration to its occupant without modifying it in any way. Few present-day restraint systems are stiff enough to give this one-to-one transmission characteristic, and depending upon their dynamic characteristics and the nature of the vehicle's acceleration-time history, they will either magnify or attenuate the acceleration. Obviously an optimum restraint system will give maximum attenuation of an input acceleration. In the general case of an arbitrary acceleration input, a computer must be used to determine the optimum dynamic characteristics for the restraint system. Analytical solutions can be obtained for certain simple cases, however, and these cases are considered in this paper, after the concept of dynamic models of the human body is introduced. The paper concludes with a description of an analog computer specially developed for the Air Force to handle completely general mechanical restraint optimization programs of this type, where the acceleration input may be any arbitrary function of time.

Accelerated aging effects on surface hardness and roughness of lingual retainer adhesives.

PubMed

Ramoglu, Sabri Ilhan; Usumez, Serdar; Buyukyilmaz, Tamer

2008-01-01

To test the null hypothesis that accelerated aging has no effect on the surface microhardness and roughness of two light-cured lingual retainer adhesives. Ten samples of light-cured materials, Transbond Lingual Retainer (3M Unitek) and Light Cure Retainer (Reliance) were cured with a halogen light for 40 seconds. Vickers hardness and surface roughness were measured before and after accelerated aging of 300 hours in a weathering tester. Differences between mean values were analyzed for statistical significance using a t-test. The level of statistical significance was set at P < .05. The mean Vickers hardness of Transbond Lingual Retainer was 62.8 +/- 3.5 and 79.6 +/- 4.9 before and after aging, respectively. The mean Vickers hardness of Light Cure Retainer was 40.3 +/- 2.6 and 58.3 +/- 4.3 before and after aging, respectively. Differences in both groups were statistically significant (P < .001). Following aging, mean surface roughness was changed from 0.039 microm to 0.121 microm and from 0.021 microm to 0.031 microm for Transbond Lingual Retainer and Light Cure Retainer, respectively. The roughening of Transbond Lingual Retainer with aging was statistically significant (P < .05), while the change in the surface roughness of Light Cure Retainer was not (P > .05). Accelerated aging significantly increased the surface microhardness of both light-cured retainer adhesives tested. It also significantly increased the surface roughness of the Transbond Lingual Retainer.

76 FR 43347 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-Cooperative...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-20

... DEPARTMENT OF JUSTICE Antitrust Division Notice Pursuant to the National Cooperative Research and Production Act of 1993--Cooperative Research Group on Diesel Aftertreatment Accelerated Aging Cycles--Heavy... Institute-- Cooperative Research Group on Diesel Aftertreatment Accelerated Aging Cycles--Heavy-Duty...

Perception of linear acceleration in weightlessness

NASA Technical Reports Server (NTRS)

Arrott, A. P.; Young, L. R.

1987-01-01

Eye movements and subjective detection of acceleration were measured on human experimental subjects during vestibular sled acceleration during the D1 Spacelab Mission. Methods and results are reported on the time to detection of small acceleration steps, the threshold for detection of linear acceleration, perceived motion path, and CLOAT. A consistently shorter time to detection of small acceleration steps is found. Subjective reports of perceived motion during sinusoidal oscillation in weightlessness were qualitatively similar to reports on earth.

Accelerated longitudinal designs: An overview of modelling, power, costs and handling missing data.

PubMed

Galbraith, Sally; Bowden, Jack; Mander, Adrian

2017-02-01

Longitudinal studies are often used to investigate age-related developmental change. Whereas a single cohort design takes a group of individuals at the same initial age and follows them over time, an accelerated longitudinal design takes multiple single cohorts, each one starting at a different age. The main advantage of an accelerated longitudinal design is its ability to span the age range of interest in a shorter period of time than would be possible with a single cohort longitudinal design. This paper considers design issues for accelerated longitudinal studies. A linear mixed effect model is considered to describe the responses over age with random effects for intercept and slope parameters. Random and fixed cohort effects are used to cope with the potential bias accelerated longitudinal designs have due to multiple cohorts. The impact of other factors such as costs and the impact of dropouts on the power of testing or the precision of estimating parameters are examined. As duration-related costs increase relative to recruitment costs the best designs shift towards shorter duration and eventually cross-sectional design being best. For designs with the same duration but differing interval between measurements, we found there was a cutoff point for measurement costs relative to recruitment costs relating to frequency of measurements. Under our model of 30% dropout there was a maximum power loss of 7%.

Increased accumulation of the glycoxidation product N(epsilon)-(carboxymethyl)lysine in human tissues in diabetes and aging.

PubMed Central

Schleicher, E D; Wagner, E; Nerlich, A G

1997-01-01

N(epsilon)-(Carboxymethyl)lysine (CML), a major product of oxidative modification of glycated proteins, has been suggested to represent a general marker of oxidative stress and long-term damage to proteins in aging, atherosclerosis, and diabetes. To investigate the occurrence and distribution of CML in humans an antiserum specifically recognizing protein-bound CML was generated. The oxidative formation of CML from glycated proteins was reduced by lipoic acid, aminoguanidine, superoxide dismutase, catalase, and particularly vitamin E and desferrioxamine. Immunolocalization of CML in skin, lung, heart, kidney, intestine, intervertebral discs, and particularly in arteries provided evidence for an age-dependent increase in CML accumulation in distinct locations, and acceleration of this process in diabetes. Intense staining of the arterial wall and particularly the elastic membrane was found. High levels of CML modification were observed within atherosclerotic plaques and in foam cells. The preferential location of CML immunoreactivity in lesions may indicate the contribution of glycoxidation to the processes occurring in diabetes and aging. Additionally, we found increased CML content in serum proteins in diabetic patients. The strong dependence of CML formation on oxidative conditions together with the increased occurrence of CML in diabetic serum and tissue proteins suggest a role for CML as endogenous biomarker for oxidative damage. PMID:9022079

Early-life reproduction is associated with increased mortality risk but enhanced lifetime fitness in pre-industrial humans.

PubMed

Hayward, Adam D; Nenko, Ilona; Lummaa, Virpi

2015-04-07

The physiology of reproductive senescence in women is well understood, but the drivers of variation in senescence rates are less so. Evolutionary theory predicts that early-life investment in reproduction should be favoured by selection at the cost of reduced survival and faster reproductive senescence. We tested this hypothesis using data collected from preindustrial Finnish church records. Reproductive success increased up to age 25 and was relatively stable until a decline from age 41. Women with higher early-life fecundity (ELF; producing more children before age 25) subsequently had higher mortality risk, but high ELF was not associated with accelerated senescence in annual breeding success. However, women with higher ELF experienced faster senescence in offspring survival. Despite these apparent costs, ELF was under positive selection: individuals with higher ELF had higher lifetime reproductive success. These results are consistent with previous observations in both humans and wild vertebrates that more births and earlier onset of reproduction are associated with reduced survival, and with evolutionary theory predicting trade-offs between early reproduction and later-life survival. The results are particularly significant given recent increases in maternal ages in many societies and the potential consequences for offspring health and fitness. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Early-life reproduction is associated with increased mortality risk but enhanced lifetime fitness in pre-industrial humans

PubMed Central

Hayward, Adam D.; Nenko, Ilona; Lummaa, Virpi

2015-01-01

The physiology of reproductive senescence in women is well understood, but the drivers of variation in senescence rates are less so. Evolutionary theory predicts that early-life investment in reproduction should be favoured by selection at the cost of reduced survival and faster reproductive senescence. We tested this hypothesis using data collected from preindustrial Finnish church records. Reproductive success increased up to age 25 and was relatively stable until a decline from age 41. Women with higher early-life fecundity (ELF; producing more children before age 25) subsequently had higher mortality risk, but high ELF was not associated with accelerated senescence in annual breeding success. However, women with higher ELF experienced faster senescence in offspring survival. Despite these apparent costs, ELF was under positive selection: individuals with higher ELF had higher lifetime reproductive success. These results are consistent with previous observations in both humans and wild vertebrates that more births and earlier onset of reproduction are associated with reduced survival, and with evolutionary theory predicting trade-offs between early reproduction and later-life survival. The results are particularly significant given recent increases in maternal ages in many societies and the potential consequences for offspring health and fitness. PMID:25740893

Psychological Adjustment in a College-Level Program of Marked Academic Acceleration.

ERIC Educational Resources Information Center

Robinson, Nancy M.; Janos, Paul M.

1986-01-01

The questionnaire responses of 24 markedly accelerated young students at the University of Washington were compared with those of 24 regular-aged university students, 23 National Merit Scholors, and 27 students who had qualified for acceleration but instead elected to participate in high school. Accelerants appeared as well adjusted as all…

Perinatal Complications and Aging Indicators by Midlife

PubMed Central

Caspi, Avshalom; Ambler, Antony; Belsky, Daniel W.; Chapple, Simon; Cohen, Harvey Jay; Israel, Salomon; Poulton, Richie; Ramrakha, Sandhya; Rivera, Christine D.; Sugden, Karen; Williams, Benjamin; Wolke, Dieter; Moffitt, Terrie E.

2014-01-01

BACKGROUND: Perinatal complications predict increased risk for morbidity and early mortality. Evidence of perinatal programming of adult mortality raises the question of what mechanisms embed this long-term effect. We tested a hypothesis related to the theory of developmental origins of health and disease: that perinatal complications assessed at birth predict indicators of accelerated aging by midlife. METHODS: Perinatal complications, including both maternal and neonatal complications, were assessed in the Dunedin Multidisciplinary Health and Development Study cohort (N = 1037), a 38-year, prospective longitudinal study of a representative birth cohort. Two aging indicators were assessed at age 38 years, objectively by leukocyte telomere length (TL) and subjectively by perceived facial age. RESULTS: Perinatal complications predicted both leukocyte TL (β = −0.101; 95% confidence interval, −0.169 to −0.033; P = .004) and perceived age (β = 0.097; 95% confidence interval, 0.029 to 0.165; P = .005) by midlife. We repeated analyses with controls for measures of family history and social risk that could predispose to perinatal complications and accelerated aging, and for measures of poor health taken in between birth and the age-38 follow-up. These covariates attenuated, but did not fully explain the associations observed between perinatal complications and aging indicators. CONCLUSIONS: Our findings provide support for early-life developmental programming by linking newborns’ perinatal complications to accelerated aging at midlife. We observed indications of accelerated aging “inside,” as measured by leukocyte TL, an indicator of cellular aging, and “outside,” as measured by perceived age, an indicator of declining tissue integrity. A better understanding of mechanisms underlying perinatal programming of adult aging is needed. PMID:25349321

175.4 The Relationship of Aging and Inflammatory Biomarkers to Gray Matter Volume and Episodic Memory Performance in Schizophrenia: Evidence of Pathological Accelerated Aging

PubMed Central

Gama, Clarissa

2017-01-01

Abstract Background: Schizophrenia (SZ) is associated with increased somatic morbidity and mortality, in addition to cognitive impairments similar to those seen in normal aging, which may suggest that pathological accelerated aging occurs in SZ. Therefore, we aim to evaluate the relationships of age, telomere length (TL) and CCL11 (aging and inflammatory biomarkers), and gray matter volumes (GM) to episodic memory performance in individuals with SZ compared to healthy controls (HC). Methods: 112 participants (48 SZ and 64 HC) underwent clinical and memory assessments, structural MRI, and had their peripheral blood drawn for biomarkers analysis. Comparisons of group means and correlations were performed. Results: Participants with SZ had decreased TL and GM residual volume, increased CCL11, and worse memory performance compared to HC. In SZ, shorter TL was related to increased CCL11, and they were both related to reduced GM residual volume, all of which were related to worse memory performance. Older age was only associated with reduced GM, but longer duration of illness was related with all the aforementioned variables. Younger age of disease onset was related with increased CCL11 levels and worse memory performance. In HC, there were no significant correlations except for between memory and GM. Conclusion: Our results are consistent with accelerated aging in SZ. These results may indicate that it is not age itself, but the impact of the disease associated with a pathological accelerated aging that leads to impaired outcomes in SZ. Akira Sawa, johns Hopkins University, Johns Hopkins Hospital and Medical Institutions

75 FR 14191 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-Cooperative...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-24

... DEPARTMENT OF JUSTICE Antitrust Division Notice Pursuant to the National Cooperative Research and Production Act of 1993--Cooperative Research Group On: Diesel After Treatment Accelerated Aging Cycles--Heavy... Institute--Cooperative Research Group on Diesel After Treatment Accelerated Aging Cycles--Heavy-Duty...

Accelerated Reader: Evaluation Report and Executive Summary

ERIC Educational Resources Information Center

Gorard, Stephen; Siddiqui, Nadia; See, Beng Huat

2015-01-01

Accelerated Reader (AR) is a whole-group reading management and monitoring program that aims to foster the habit of independent reading among primary and early secondary age pupils. The internet-based software initially screens pupils according to their reading levels, and suggests books that match their reading age and reading interest. Pupils…

Nuclear power plant cable materials :

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

Celina, Mathias C.; Gillen, Kenneth T; Lindgren, Eric Richard

2013-05-01

A selective literature review was conducted to assess whether currently available accelerated aging and original qualification data could be used to establish operational margins for the continued use of cable insulation and jacketing materials in nuclear power plant environments. The materials are subject to chemical and physical degradation under extended radiationthermal- oxidative conditions. Of particular interest were the circumstances under which existing aging data could be used to predict whether aged materials should pass loss of coolant accident (LOCA) performance requirements. Original LOCA qualification testing usually involved accelerated aging simulations of the 40-year expected ambient aging conditions followed by amore » LOCA simulation. The accelerated aging simulations were conducted under rapid accelerated aging conditions that did not account for many of the known limitations in accelerated polymer aging and therefore did not correctly simulate actual aging conditions. These highly accelerated aging conditions resulted in insulation materials with mostly inert aging processes as well as jacket materials where oxidative damage dropped quickly away from the air-exposed outside jacket surface. Therefore, for most LOCA performance predictions, testing appears to have relied upon heterogeneous aging behavior with oxidation often limited to the exterior of the cable cross-section a situation which is not comparable with the nearly homogenous oxidative aging that will occur over decades under low dose rate and low temperature plant conditions. The historical aging conditions are therefore insufficient to determine with reasonable confidence the remaining operational margins for these materials. This does not necessarily imply that the existing 40-year-old materials would fail if LOCA conditions occurred, but rather that unambiguous statements about the current aging state and anticipated LOCA performance cannot be provided based on original qualification testing data alone. The non-availability of conclusive predictions for the aging conditions of 40-year-old cables implies that the same levels of uncertainty will remain for any re-qualification or extended operation of these cables. The highly variable aging behavior of the range of materials employed also implies that simple, standardized aging tests are not sufficient to provide the required aging data and performance predictions for all materials. It is recommended that focused studies be conducted that would yield the material aging parameters needed to predict aging behaviors under low dose, low temperature plant equivalent conditions and that appropriately aged specimens be prepared that would mimic oxidatively-aged 40- to 60- year-old materials for confirmatory LOCA performance testing. This study concludes that it is not sufficient to expose materials to rapid, high radiation and high temperature levels with subsequent LOCA qualification testing in order to predictively quantify safety margins of existing infrastructure with regard to LOCA performance. We need to better understand how cable jacketing and insulation materials have degraded over decades of power plant operation and how this aging history relates to service life prediction and the performance of existing equipment to withstand a LOCA situation.« less

Signaling pathway activation drift during aging: Hutchinson-Gilford Progeria Syndrome fibroblasts are comparable to normal middle-age and old-age cells.

PubMed

Aliper, Alexander M; Csoka, Antonei Benjamin; Buzdin, Anton; Jetka, Tomasz; Roumiantsev, Sergey; Moskalev, Alexy; Zhavoronkov, Alex

2015-01-01

For the past several decades, research in understanding the molecular basis of human aging has progressed significantly with the analysis of premature aging syndromes. Progerin, an altered form of lamin A, has been identified as the cause of premature aging in Hutchinson-Gilford Progeria Syndrome (HGPS), and may be a contributing causative factor in normal aging. However, the question of whether HGPS actually recapitulates the normal aging process at the cellular and organismal level, or simply mimics the aging phenotype is widely debated. In the present study we analyzed publicly available microarray datasets for fibroblasts undergoing cellular aging in culture, as well as fibroblasts derived from young, middle-age, and old-age individuals, and patients with HGPS. Using GeroScope pathway analysis and drug discovery platform we analyzed the activation states of 65 major cellular signaling pathways. Our analysis reveals that signaling pathway activation states in cells derived from chronologically young patients with HGPS strongly resemble cells taken from normal middle-aged and old individuals. This clearly indicates that HGPS may truly represent accelerated aging, rather than being just a simulacrum. Our data also points to potential pathways that could be targeted to develop drugs and drug combinations for both HGPS and normal aging.

Muscle-specific inositide phosphatase (MIP/MTMR14) is reduced with age and its loss accelerates skeletal muscle aging process by altering calcium homeostasis.

PubMed

Romero-Suarez, Sandra; Shen, Jinhua; Brotto, Leticia; Hall, Todd; Mo, Chenglin; Valdivia, Héctor H; Andresen, Jon; Wacker, Michael; Nosek, Thomas M; Qu, Cheng-Kui; Brotto, Marco

2010-08-01

We have recently reported that a novel muscle-specific inositide phosphatase (MIP/MTMR14) plays a critical role in [Ca2+]i homeostasis through dephosphorylation of sn-1-stearoyl-2-arachidonoyl phosphatidylinositol (3,5) bisphosphate (PI(3,5)P2). Loss of function mutations in MIP have been identified in human centronuclear myopathy. We developed a MIP knockout (MIPKO) animal model and found that MIPKO mice were more susceptible to exercise-induced muscle damage, a trademark of muscle functional changes in older subjects. We used wild-type (Wt) mice and MIPKO mice to elucidate the roles of MIP in muscle function during aging. We found MIP mRNA expression, MIP protein levels, and MIP phosphatase activity significantly decreased in old Wt mice. The mature MIPKO mice displayed phenotypes that closely resembled those seen in old Wt mice: i) decreased walking speed, ii) decreased treadmill activity, iii) decreased contractile force, and iv) decreased power generation, classical features of sarcopenia in rodents and humans. Defective Ca2+ homeostasis is also present in mature MIPKO and old Wt mice, suggesting a putative role of MIP in the decline of muscle function during aging. Our studies offer a new avenue for the investigation of MIP roles in skeletal muscle function and as a potential therapeutic target to treat aging sarcopenia.

Serum from calorie-restricted animals delays senescence and extends the lifespan of normal human fibroblasts in vitro.

PubMed

de Cabo, Rafael; Liu, Lijuan; Ali, Ahmed; Price, Nathan; Zhang, Jing; Wang, Mingyi; Lakatta, Edward; Irusta, Pablo M

2015-03-01

The cumulative effects of cellular senescence and cell loss over time in various tissues and organs are considered major contributing factors to the ageing process. In various organisms, caloric restriction (CR) slows ageing and increases lifespan, at least in part, by activating nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases of the sirtuin family. Here, we use an in vitro model of CR to study the effects of this dietary regime on replicative senescence, cellular lifespan and modulation of the SIRT1 signaling pathway in normal human diploid fibroblasts. We found that serum from calorie-restricted animals was able to delay senescence and significantly increase replicative lifespan in these cells, when compared to serum from ad libitum fed animals. These effects correlated with CR-mediated increases in SIRT1 and decreases in p53 expression levels. In addition, we show that manipulation of SIRT1 levels by either over-expression or siRNA-mediated knockdown resulted in delayed and accelerated cellular senescence, respectively. Our results demonstrate that CR can delay senescence and increase replicative lifespan of normal human diploid fibroblasts in vitro and suggest that SIRT1 plays an important role in these processes.

Serum from calorie-restricted animals delays senescence and extends the lifespan of normal human fibroblasts in vitro

PubMed Central

Ali, Ahmed; Price, Nathan; Zhang, Jing; Wang, Mingyi; Lakatta, Edward; Irusta, Pablo M.

2015-01-01

The cumulative effects of cellular senescence and cell loss over time in various tissues and organs are considered major contributing factors to the ageing process. In various organisms, caloric restriction (CR) slows ageing and increases lifespan, at least in part, by activating nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases of the sirtuin family. Here, we use an in vitro model of CR to study the effects of this dietary regime on replicative senescence, cellular lifespan and modulation of the SIRT1 signaling pathway in normal human diploid fibroblasts. We found that serum from calorie-restricted animals was able to delay senescence and significantly increase replicative lifespan in these cells, when compared to serum from ad libitum fed animals. These effects correlated with CR-mediated increases in SIRT1 and decreases in p53 expression levels. In addition, we show that manipulation of SIRT1 levels by either over-expression or siRNA-mediated knockdown resulted in delayed and accelerated cellular senescence, respectively. Our results demonstrate that CR can delay senescence and increase replicative lifespan of normal human diploid fibroblasts in vitro and suggest that SIRT1 plays an important role in these processes. (185 words). PMID:25855056

The evolutionary origin and significance of Menopause

PubMed Central

Pollycove, Ricki; Naftolin, Frederick; Simon, James A.

2010-01-01

Contemporary human females have long life expectancy (81y US), especially relative to age at menopause (51y US). Menopause is a consequence of reproductive aging and follicular depletion (ovarian failure), yielding very low circulating estrogen* serum concentrations and biologically disadvantageous metabolic alterations. Stated in terms of antagonistic pleiotropy, the ongoing hypoestrogenic endocrine environment, beneficial during lactation, results in acceleration of several age-related health conditions following menopause (i.e. late postmenopausal osteoporosis, cardiovascular disease and cognitive decline). In contrast, the complex hypoestrogenic hormonal milieu present during postpartum lactation provides biologic advantages to both mother and newborn. The lactational hormonal milieu causes symptoms similar to those of the late perimenopause and early postmenopause, prompting theories for their biologic selective advantage. The precepts of evolutionary medicine encourage a reassessment of hormone therapy. Based on data presented, the authors propose additional opportunities for disease prevention and morbidity reduction in postmenopausal women. PMID:21252729

Novel effects of diosgenin on skin aging.

PubMed

Tada, Yayoi; Kanda, Naoko; Haratake, Akinori; Tobiishi, Megumi; Uchiwa, Hideyo; Watanabe, Shinichi

2009-06-01

Extracts of Dioscorea coomposita or Dioscorea villosa are consumed as supplemental health foods at the time of climacteric. The extracts contain large amounts of the plant steroid, diosgenin. Here, we studied the safety and efficacy of diosgenin against skin aging at the time of climacteric. In vitro, diosgenin enhanced DNA synthesis in a human 3D skin equivalent model, and increased bromodeoxyuridine uptake and intracellular cAMP level in adult human keratinocytes. The increase of bromodeoxyuridine uptake by diosgenin was blocked by an adenylate cyclase inhibitor, but not by antisense oligonucleotides against estrogen receptor alpha, estrogen receptor beta or an orphan G-protein-coupled receptor, GPR30, indicating the involvement of cAMP but not estrogen receptor alpha, estrogen receptor beta or GPR30. In vivo, administration of diosgenin improved the epidermal thickness in the ovariectomized mice, a climacteric model, without altering the degree of fat accumulation. In order to examine the safety of diosgenin, diosgenin and 17beta-estradiol were administered to breast cancer-burdened mice. The results revealed that while 17beta-estradiol accelerated the tumor growth, diosgenin did not show this effect. Our finding, a restoration of keratinocyte proliferation in aged skin, suggests that diosgenin may have potential as a safe health food for climacteric.

Glucose-derived AGEs enhance human gastric cancer metastasis through RAGE/ERK/Sp1/MMP2 cascade.

PubMed

Deng, Ruyuan; Mo, Fengbo; Chang, Bowen; Zhang, Qi; Ran, Hui; Yang, Shuhua; Zhu, Zhiqiang; Hu, Lei; Su, Qing

2017-11-28

Advanced glycation end products (AGEs) have been reported to take part in many cancer processes. Whether AGEs contribute to gastric cancer (GC) course and the underlying mechanism are still unclear. Here, glucose-derived AGEs are detected to be accumulated in tumor tissues and blood of patients with GC. As the receptor for AGEs, RAGE is highly expressed in cancer tissues, and closely associated with the depth of cancer invasion, lymph node metastasis and TNM stage. Both in vivo and in vitro treatment of AGEs accelerate the tumor invasion and metastasis, with upregualtion of RAGE, Specificity Protein 1 (Sp1), and MMP2 protein expression, as well as enhancement of MMP2 activity. Either RAGE-blocking antibody or Sp1-knockdown can partially block the AGEs-induced effects. Moreover, AGEs increased the phosphorylation of ERK, and reducing the phosphorylation level of ERK by MEK1/2 inhibitor decreased the expression of Sp1. These results indicate that accumulation of glucose-derived AGEs may act as one of potential risk factors for GC progression and promote the invasion and metastasis of gastric cancer partially through the activation of RAGE/ERK/Sp1/MMP2 pathway.

Glucose-derived AGEs enhance human gastric cancer metastasis through RAGE/ERK/Sp1/MMP2 cascade

PubMed Central

Deng, Ruyuan; Mo, Fengbo; Chang, Bowen; Zhang, Qi; Ran, Hui; Yang, Shuhua; Zhu, Zhiqiang; Hu, Lei; Su, Qing

2017-01-01

Advanced glycation end products (AGEs) have been reported to take part in many cancer processes. Whether AGEs contribute to gastric cancer (GC) course and the underlying mechanism are still unclear. Here, glucose-derived AGEs are detected to be accumulated in tumor tissues and blood of patients with GC. As the receptor for AGEs, RAGE is highly expressed in cancer tissues, and closely associated with the depth of cancer invasion, lymph node metastasis and TNM stage. Both in vivo and in vitro treatment of AGEs accelerate the tumor invasion and metastasis, with upregualtion of RAGE, Specificity Protein 1 (Sp1), and MMP2 protein expression, as well as enhancement of MMP2 activity. Either RAGE-blocking antibody or Sp1-knockdown can partially block the AGEs-induced effects. Moreover, AGEs increased the phosphorylation of ERK, and reducing the phosphorylation level of ERK by MEK1/2 inhibitor decreased the expression of Sp1. These results indicate that accumulation of glucose-derived AGEs may act as one of potential risk factors for GC progression and promote the invasion and metastasis of gastric cancer partially through the activation of RAGE/ERK/Sp1/MMP2 pathway. PMID:29262634

Environmental Chemicals and Aging.

PubMed

Pearson, Brandon L; Ehninger, Dan

2017-03-01

Innovations in agriculture and medicine as well as industrial and domestic technologies are essential for the growing and aging global population. These advances generally require the use of novel natural or synthetic chemical agents with the potential to affect human health. Here, we attempt to highlight environmental chemicals and select drugs with the potential to exacerbate aging by directly affecting molecular aging cascades focusing particular attention on the brain. Finally, we call attention to some potential fruitful areas of research, particularly with advanced molecular profiling that could aid in prevention or mitigation of environmental chemical toxic influences in the periphery and the brain. We briefly summarize new research and highlight a recent study designed to prospectively identify agrochemicals with the potential to induce neurological diseases and place these discoveries into the already rich neurodegeneration and aging literature. Collectively, the research reviewed briefly here highlight chemicals with the true potential to accelerate aging, particularly in the brain, by eliciting elevated free radical stress and mitochondrial dysfunction. We make general recommendations about improved methodological approaches toward identification and regulation of chemicals that are gerontogenic to the brain.

Epidemiology of cognitive aging and Alzheimer's disease: contributions of the cache county utah study of memory, health and aging.

PubMed

Hayden, Kathleen M; Welsh-Bohmer, Kathleen A

2012-01-01

Epidemiological studies of Alzheimer's disease (AD) provide insights into changing public health trends and their contribution to disease incidence. The current chapter considers how the population-based approach has contributed to our understanding of lifetime exposures that contribute to later disease risk and may act to modify onset of symptoms. We focus on the findings from a recent survey of an exceptionally long-lived population, the Cache County Utah Study of Memory, Health, and Aging. This study is confined to a single geographic population has allowed estimation of the genetic and environmental influences on AD expression across the expected human lifespan of 95+ years. Given the emphasis of this text on the behavioral neurosciences of aging, we highlight within the current chapter the particular contributions of this population-based study to the neuropsychology of aging and AD. We also discuss hypotheses generated from this survey with respect to factors that may either accelerate or delay symptom onset in AD and the conditions that appear to be associated with successful cognitive aging.

Mercury accumulation and accelerated progression of carotid atherosclerosis: a population-based prospective 4-year follow-up study in men in eastern Finland.

PubMed

Salonen, J T; Seppänen, K; Lakka, T A; Salonen, R; Kaplan, G A

2000-02-01

Basic research and our previous studies have suggested that mercury exposure enhances lipid peroxidation and the risk of myocardial infarction, but there are no studies concerning the association between mercury accumulation and atherosclerosis. We therefore investigated whether high hair mercury content is associated with accelerated progression of carotid atherosclerosis, determined by ultrasonographic assessment of common carotid intima-media thickness (IMT), in a prospective study among 1014 men aged 42-60 years. In a linear regression model adjusting for other atherosclerotic risk factors, high hair mercury content was one of the strongest predictors of the 4-year increase in the mean IMT (P2.81 microg/g (fifths) had an IMT increase of 0.105, 0.102, 0.113, 0.107 and 0.140 mm/4 years, respectively (P=0.041 for heterogeneity between groups). The IMT increase was 0.034 mm/4 years (31.9%) greater in the highest fifth than in the other fifths (P<0.05 for the difference). These findings suggest that mercury accumulation in the human body is associated with accelerated progression of carotid atherosclerosis.

Synergistic function of Smad4 and PTEN in suppressing forestomach squamous cell carcinoma in the mouse.

PubMed

Teng, Yan; Sun, An-Na; Pan, Xiao-Chen; Yang, Guan; Yang, Lei-Lei; Wang, Ming-Rong; Yang, Xiao

2006-07-15

The genetic bases underlying esophageal tumorigenesis are poorly understood. Our previous studies have shown that coordinated deletion of the Smad4 and PTEN genes results in accelerated hair loss and skin tumor formation in mice. Herein, we exemplify that the concomitant inactivation of Smad4 and PTEN accelerates spontaneous forestomach carcinogenesis at complete penetrance during the first 2 months of age. All of the forestomach tumors were invasive squamous cell carcinomas (SCCs), which recapitulated the natural history and pathologic features of human esophageal SCCs. A small population of the SCC lesions was accompanied by adenocarcinomas at the adjacent submucosa region in the double mutant mice. The rapid progression of forestomach tumor formation in the Smad4 and PTEN double knockout mice corresponded to a dramatic increase in esophageal and forestomach epithelial proliferation. The decreased expression of p27, p21, and p16 together with the overexpression of cyclin D1 contributed cooperatively to the accelerated forestomach tumorigenesis in the double mutant mice. Our results point strongly to the crucial relevance of synergy between Smad4 and PTEN to suppress forestomach tumorigenesis through the cooperative induction of cell cycle inhibitors.

A Porcine Model of Traumatic Brain Injury via Head Rotational Acceleration

PubMed Central

Cullen, D. Kacy; Harris, James P.; Browne, Kevin D.; Wolf, John A; Duda, John E.; Meaney, David F.; Margulies, Susan S.; Smith, Douglas H.

2017-01-01

Unique from other brain disorders, traumatic brain injury (TBI) generally results from a discrete biomechanical event that induces rapid head movement. The large size and high organization of the human brain makes it particularly vulnerable to traumatic injury from rotational accelerations that can cause dynamic deformation of the brain tissue. Therefore, replicating the injury biomechanics of human TBI in animal models presents a substantial challenge, particularly with regard to addressing brain size and injury parameters. Here we present the historical development and use of a porcine model of head rotational acceleration. By scaling up the rotational forces to account for difference in brain mass between swine and humans, this model has been shown to produce the same tissue deformations and identical neuropathologies found in human TBI. The parameters of scaled rapid angular accelerations applied for the model reproduce inertial forces generated when the human head suddenly accelerates or decelerates in falls, collisions, or blunt impacts. The model uses custom-built linkage assemblies and a powerful linear actuator designed to produce purely impulsive nonimpact head rotation in different angular planes at controlled rotational acceleration levels. Through a range of head rotational kinematics, this model can produce functional and neuropathological changes across the spectrum from concussion to severe TBI. Notably, however, the model is very difficult to employ, requiring a highly skilled team for medical management, biomechanics, neurological recovery, and specialized outcome measures including neuromonitoring, neurophysiology, neuroimaging, and neuropathology. Nonetheless, while challenging, this clinically relevant model has proven valuable for identifying mechanisms of acute and progressive neuropathologies as well as for the evaluation of noninvasive diagnostic techniques and potential neuroprotective treatments following TBI. PMID:27604725

Representation of visual gravitational motion in the human vestibular cortex.

PubMed

Indovina, Iole; Maffei, Vincenzo; Bosco, Gianfranco; Zago, Myrka; Macaluso, Emiliano; Lacquaniti, Francesco

2005-04-15

How do we perceive the visual motion of objects that are accelerated by gravity? We propose that, because vision is poorly sensitive to accelerations, an internal model that calculates the effects of gravity is derived from graviceptive information, is stored in the vestibular cortex, and is activated by visual motion that appears to be coherent with natural gravity. The acceleration of visual targets was manipulated while brain activity was measured using functional magnetic resonance imaging. In agreement with the internal model hypothesis, we found that the vestibular network was selectively engaged when acceleration was consistent with natural gravity. These findings demonstrate that predictive mechanisms of physical laws of motion are represented in the human brain.

Issues on human acceleration tolerance after long-duration space flights

NASA Technical Reports Server (NTRS)

Kumar, K. Vasantha; Norfleet, William T.

1992-01-01

This report reviewed the literature on human tolerance to acceleration at 1 G and changes in tolerance after exposure to hypogravic fields. It was found that human tolerance decreased after exposure to hypokinetic and hypogravic fields, but the magnitude of such reduction ranged from 0 to 30 percent for plateau G forces and 30 to 70 percent for time tolerance on sustained G forces. A logistic regression model of the probability of individuals with 25 percent reduction in +Gz tolerance after 1 to 41 days of hypogravic exposures was constructed. The estimated values from the model showed a good correlation with the observed data. A brief review of the need for in-flight centrifuge during long-duration missions was also presented. Review of the available data showed that the use of countermeasures (such as anti-G suits, periodic acceleration, and exercise) reduced the decrement in acceleration tolerance after long-duration space flights. Areas of further research include quantification of the effect of countermeasures on tolerance, and methods to augment tolerance during and after exposures to hypogravic fields. Such data are essential for planning long-duration human missions.

Transgenic mice overexpressing glia maturation factor-β, an oxidative stress inducible gene, show premature aging due to Zmpste24 down-regulation.

PubMed

Imai, Rika; Asai, Kanae; Hanai, Jun-ichi; Takenaka, Masaru

2015-07-01

Glia Maturation Factor-β (GMF), a brain specific protein, is induced by proteinuria in renal tubules. Ectopic GMF overexpression causes apoptosisin vitro via cellular vulnerability to oxidative stress. In order to examine the roles of GMF in non-brain tissue, we constructed transgenic mice overexpressing GMF (GMF-TG). The GMF-TG mice exhibited appearance phenotypes associated with premature aging. The GMF-TG mice also demonstrated short lifespans and reduced hair regrowth, suggesting an accelerated aging process. The production of an abnormal lamin A, a nuclear envelope protein, plays a causal role in both normal aging and accelerated aging diseases, known as laminopathies. Importantly, we identified the abnormal lamin A (prelamin A), accompanied by a down-regulation of a lamin A processing enzyme (Zmpste24) in the kidney of the GMF-TG mice. The GMF-TG mice showed accelerated aging in the kidney, compared with wild-type mice, showing increased TGF-β1, CTGF gene and serum creatinine. The gene expression of p21/waf1 was increased at an earlier stage of life, at 10 weeks, which was in turn down-regulated at a later stage, at 60 weeks. In conclusion, we propose that GMF-TG mice might be a novel mouse model of accelerated aging, due to the abnormal lamin A.

An experimental study for determining human discomfort response to roll vibration

NASA Technical Reports Server (NTRS)

Leatherwood, J. D.; Dempsey, T. K.; Clevenson, S. A.

1976-01-01

An experimental study using a passenger ride quality apparatus (PRQA) was conducted to determine the subjective reactions of passengers to roll vibrations. The data obtained illustrate the effect upon human comfort of several roll-vibration parameters: namely, roll acceleration level, roll frequency, and seat location (i.e., distance from axis of rotation). Results of an analysis of variance indicated that seat location had no effect on discomfort ratings of roll vibrations. The effect of roll acceleration level was significant, and discomfort ratings increased markedly with increasing roll acceleration level at all roll frequencies investigated. Of particular interest, is the fact that the relationship between discomfort ratings and roll acceleration level was linear in nature. The effect of roll frequency also was significant as was the interaction between roll acceleration level and roll frequency.

Retinal pigment epithelium, age-related macular degeneration and neurotrophic keratouveitis.

PubMed

Bianchi, Enrica; Scarinci, Fabio; Ripandelli, Guido; Feher, Janos; Pacella, Elena; Magliulo, Giuseppe; Gabrieli, Corrado Balacco; Plateroti, Rocco; Plateroti, Pasquale; Mignini, Fiorenzo; Artico, Marco

2013-01-01

Age-related macular degeneration (AMD) is the leading cause of impaired vision and blindness in the aging population. The aims of our studies were to identify qualitative and quantitative alterations in mitochondria in human retinal pigment epithelium (RPE) from AMD patients and controls and to test the protective effects of pigment epithelium-derived factor (PEDF), a known neurotrophic and antiangiogenic substance, against neurotrophic keratouveitis. Histopathological alterations were studied by means of morphometry, light and electron microscopy. Unexpectedly, morphometric data showed that the RPE alterations noted in AMD may also develop in normal aging, 10-15 years later than appearing in AMD patients. Reduced tear secretion, corneal ulceration and leukocytic infiltration were found in capsaicin (CAP)-treated rats, but this effect was significantly attenuated by PEDF. These findings suggest that PEDF accelerated the recovery of tear secretion and also prevented neurotrophic keratouveitis and vitreoretinal inflammation. PEDF may have a clinical application in inflammatory and neovascular diseases of the eye.

Accelerated aging and stabilization of radiation-vulcanized EPDM rubber

NASA Astrophysics Data System (ADS)

Basfar, A. A.; Abdel-Aziz, M. M.; Mofti, S.

2000-03-01

The effect of different antioxidants and their mixtures on the thermal aging and accelerated weathering of γ-radiation vulcanized EPDM rubber in presence of crosslinking coagent, was investigated. The compounds used were either a synergistic blend of phenolic and phosphite antioxidants, i.e. 1:4 Irganox 1076: Irgafos 168 or a blend of arylamine and quinoline type antioxidants, i.e. 1:1 IPPD: TMQ, at fixed concentration. Tinuvin 622 LD hindered amine light stabilized (HALS) was also used. The response was evaluated by the tensile strength and elongation at break for irradiated samples after thermal aging at 100°C for 28 days and accelerated weathering (Xenon test) up to 200 h.

Colour stability of temporary restorations with different thicknesses submitted to artificial accelerated aging.

PubMed

Silame, F D J; Tonani, R; Alandia-Roman, C C; Chinelatti, M; Panzeri, H; Pires-de-Souza, F C P

2013-12-01

This study evaluated the colour stability of temporary prosthetic restorations with different thicknesses submitted to artificial accelerated aging. The occlusal surfaces of 40 molars were grinded to obtain flat enamel surfaces. Twenty acrylic resin specimens [Polymethyl methacrylate (Duralay) and Bis-methyl acrylate (Luxatemp)] were made with two different thicknesses, 0.5 mm and 1.0 mm. Temporary restorations were fixed on enamel and CIE L*a*b* colour parameters of each specimen were assessed before and after artificial accelerated aging. All groups showed colour alterations above the clinically acceptable limit. Luxatemp showed the lowest colour alteration regardless its thickness and Duralay showed the greatest alteration with 0.5 mm.

Body Acceleration as Indicator for Walking Economy in an Ageing Population.

PubMed

Valenti, Giulio; Bonomi, Alberto G; Westerterp, Klaas R

2015-01-01

In adults, walking economy declines with increasing age and negatively influences walking speed. This study aims at detecting determinants of walking economy from body acceleration during walking in an ageing population. 35 healthy elderly (18 males, age 51 to 83 y, BMI 25.5±2.4 kg/m2) walked on a treadmill. Energy expenditure was measured with indirect calorimetry while body acceleration was sampled at 60Hz with a tri-axial accelerometer (GT3X+, ActiGraph), positioned on the lower back. Walking economy was measured as lowest energy needed to displace one kilogram of body mass for one meter while walking (WCostmin, J/m/kg). Gait features were extracted from the acceleration signal and included in a model to predict WCostmin. On average WCostmin was 2.43±0.42 J/m/kg and correlated significantly with gait rate (r2 = 0.21, p<0.01) and regularity along the frontal (anteroposterior) and lateral (mediolateral) axes (r2 = 0.16, p<0.05 and r2 = 0.12, p<0.05 respectively). Together, the three variables explained 46% of the inter-subject variance (p<0.001) with a standard error of estimate of 0.30 J/m/kg. WCostmin and regularity along the frontal and lateral axes were related to age (WCostmin: r2 = 0.44, p<0.001; regularity: r2 = 0.16, p<0.05 and r2 = 0.12, p<0.05 respectively frontal and lateral). The age associated decline in walking economy is induced by the adoption of an increased gait rate and by irregular body acceleration in the horizontal plane.

Deficiency in DNA damage response of enterocytes accelerates intestinal stem cell aging in Drosophila.

PubMed

Park, Joung-Sun; Jeon, Ho-Jun; Pyo, Jung-Hoon; Kim, Young-Shin; Yoo, Mi-Ae

2018-03-07

Stem cell dysfunction is closely linked to tissue and organismal aging and age-related diseases, and heavily influenced by the niche cells' environment. The DNA damage response (DDR) is a key pathway for tissue degeneration and organismal aging; however, the precise protective role of DDR in stem cell/niche aging is unclear. The Drosophila midgut is an excellent model to study the biology of stem cell/niche aging because of its easy genetic manipulation and its short lifespan. Here, we showed that deficiency of DDR in Drosophila enterocytes (ECs) accelerates intestinal stem cell (ISC) aging. We generated flies with knockdown of Mre11 , Rad50 , Nbs1 , ATM , ATR , Chk1 , and Chk2 , which decrease the DDR system in ECs. EC-specific DDR depletion induced EC death, accelerated the aging of ISCs, as evidenced by ISC hyperproliferation, DNA damage accumulation, and increased centrosome amplification, and affected the adult fly's survival. Our data indicated a distinct effect of DDR depletion in stem or niche cells on tissue-resident stem cell proliferation. Our findings provide evidence of the essential role of DDR in protecting EC against ISC aging, thus providing a better understanding of the molecular mechanisms of stem cell/niche aging.

Updates to Blast Injury Criteria Models for Nuclear Casualty Estimation

DTIC Science & Technology

2015-12-01

the likelihood of blast-related injury use a two-step process. First, the maximum velocity obtained by the human body or secondary missile is determined...the human body . Secondary injuries are caused by missiles that are accelerated by the blast wave. Tertiary injuries are caused by the acceleration of...the human body and the ensuing deceleration. In this work, we focus on secondary and tertiary injuries. Because of the dramatic effects experienced

The Dawn of Human Matrilineal Diversity

PubMed Central

Behar, Doron M.; Villems, Richard; Soodyall, Himla; Blue-Smith, Jason; Pereira, Luisa; Metspalu, Ene; Scozzari, Rosaria; Makkan, Heeran; Tzur, Shay; Comas, David; Bertranpetit, Jaume; Quintana-Murci, Lluis; Tyler-Smith, Chris; Wells, R. Spencer; Rosset, Saharon

2008-01-01

The quest to explain demographic history during the early part of human evolution has been limited because of the scarce paleoanthropological record from the Middle Stone Age. To shed light on the structure of the mitochondrial DNA (mtDNA) phylogeny at the dawn of Homo sapiens, we constructed a matrilineal tree composed of 624 complete mtDNA genomes from sub-Saharan Hg L lineages. We paid particular attention to the Khoi and San (Khoisan) people of South Africa because they are considered to be a unique relic of hunter-gatherer lifestyle and to carry paternal and maternal lineages belonging to the deepest clades known among modern humans. Both the tree phylogeny and coalescence calculations suggest that Khoisan matrilineal ancestry diverged from the rest of the human mtDNA pool 90,000–150,000 years before present (ybp) and that at least five additional, currently extant maternal lineages existed during this period in parallel. Furthermore, we estimate that a minimum of 40 other evolutionarily successful lineages flourished in sub-Saharan Africa during the period of modern human dispersal out of Africa approximately 60,000–70,000 ybp. Only much later, at the beginning of the Late Stone Age, about 40,000 ybp, did introgression of additional lineages occur into the Khoisan mtDNA pool. This process was further accelerated during the recent Bantu expansions. Our results suggest that the early settlement of humans in Africa was already matrilineally structured and involved small, separately evolving isolated populations. PMID:18439549

The Role of Linear Acceleration in Visual-Vestibular Interactions and Implications in Aircraft Operations

NASA Technical Reports Server (NTRS)

Correia, Manning J.; Luke, Brian L.; McGrath, Braden J.; Clark, John B.; Rupert, Angus H.

1996-01-01

While considerable attention has been given to visual-vestibular interaction (VVI) during angular motion of the head as might occur during an aircraft spin, much less attention has been given to VVI during linear motion of the head. Such interaction might occur, for example, while viewing a stationary or moving display during vertical take-off and landing operations Research into linear VVI, particularly during prolonged periods of linear acceleration, has been hampered by the unavailability of a programmable translator capable of large excursions We collaborated with Otis Elevator Co. and used their research tower and elevator, whose motion could be digitally programmed, to vertically translate human subjects over a distance of 92.3 meters with a peak linear acceleration of 2 meters/sec(exp 2) During pulsatile or sinusoidal translation, the subjects viewed moving stripes (optokinetic stimulus) or a fixed point source (light emitting diode, led, display), respectively and it was generally found that. The direction of linear acceleration relative to the cardinal head axes and the direction of the slow component of optokinetic nystagmus (OKN) determined the extent of VVI during concomitant stripe motion and linear acceleration. Acceleration along the z head axis (A(sub z)) produced the largest VVI, particularly when the slow component of OKN was in the same direction as eye movements produced by the linear acceleration and Eye movements produced by linear acceleration are suppressed by viewing a fixed target at frequencies below 10 Hz But, above this frequency the suppression produced by VVI is removed. Finally, as demonstrated in non-human primates, vergence of the eyes appears to modulate the vertical eye movement response to linear acceleration in humans.

Timing paradox of stepping and falls in ageing: not so quick and quick(er) on the trigger.

PubMed

Rogers, Mark W; Mille, Marie-Laure

2016-08-15

Physiological and degenerative changes affecting human standing balance are major contributors to falls with ageing. During imbalance, stepping is a powerful protective action for preserving balance that may be voluntarily initiated in recognition of a balance threat, or be induced by an externally imposed mechanical or sensory perturbation. Paradoxically, with ageing and falls, initiation slowing of voluntary stepping is observed together with perturbation-induced steps that are triggered as fast as or faster than for younger adults. While age-associated changes in sensorimotor conduction, central neuronal processing and cognitive functions are linked to delayed voluntary stepping, alterations in the coupling of posture and locomotion may also prolong step triggering. It is less clear, however, how these factors may explain the accelerated triggering of induced stepping. We present a conceptual model that addresses this issue. For voluntary stepping, a disruption in the normal coupling between posture and locomotion may underlie step-triggering delays through suppression of the locomotion network based on an estimation of the evolving mechanical state conditions for stability. During induced stepping, accelerated step initiation may represent an event-triggering process whereby stepping is released according to the occurrence of a perturbation rather than to the specific sensorimotor information reflecting the evolving instability. In this case, errors in the parametric control of induced stepping and its effectiveness in stabilizing balance would be likely to occur. We further suggest that there is a residual adaptive capacity with ageing that could be exploited to improve paradoxical triggering and other changes in protective stepping to impact fall risk. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Bone mineral content and density of the lumbar spine of infants and toddlers: influence of age, sex, race, growth, and human milk feeding.

PubMed

Kalkwarf, Heidi J; Zemel, Babette S; Yolton, Kimberly; Heubi, James E

2013-01-01

Little is known about factors that affect bone mass and density of infants and toddlers and the means to assess their bone health owing to challenges in studying this population. The objectives of this study were to describe age, sex, race, growth, and human milk feeding effects on bone mineral content (BMC) and areal density (aBMD) of the lumbar spine, and determine precision of BMC and aBMD measurements. We conducted a cross-sectional study of 307 healthy participants (63 black), ages 1 to 36 months. BMC and aBMD of the lumbar spine were measured by dual-energy X-ray absorptiometry. Duplicate scans were obtained on 76 participants for precision determination. Age-specific Z-scores for aBMD, weight, and length (BMDZ, WAZ, LAZ) were calculated. Information on human milk feeding duration was ascertained by questionnaire. Between ages 1 and 36 months, lumbar spine BMC increased about fivefold and aBMD increased twofold (p < 0.0001). BMC was greater (5.8%) in males than in females (p = 0.001), but there was no difference in aBMD (p = 0.37). There was no difference in BMC or aBMD between whites and blacks (p ≥ 0.16). WAZ and LAZ were positively associated with BMDZ (r = 0.34 and 0.24, p < 0.001). Duration of human milk feeding was negatively associated with BMDZ in infants <12 months of age (r = -0.42, p < 0.001). Precision of BMC and aBMD measurements was good, 2.20% and 1.84%, respectively. Dramatic increases in BMC and aBMD of the lumbar spine occur in the first 36 months of life. We provide age-specific values for aBMD of healthy infants and toddlers that can be used to evaluate bone deficits. Future studies are needed to identify the age when sex and race differences in aBMD occur, and how best to account for delayed or accelerated growth in the context of bone health assessment of infants and toddlers. Copyright © 2013 American Society for Bone and Mineral Research.

Chemical vs. Physical Acceleration of Cement Hydration

PubMed Central

Bentz, Dale P.; Zunino, Franco; Lootens, Didier

2016-01-01

Cold weather concreting often requires the use of chemical accelerators to speed up the hydration reactions of the cement, so that setting and early-age strength development will occur in a timely manner. While calcium chloride (dihydrate – CaCl2·2H2O) is the most commonly used chemical accelerator, recent research using fine limestone powders has indicated their high proficiency for physically accelerating early-age hydration and reducing setting times. This paper presents a comparative study of the efficiency of these two approaches in accelerating hydration (as assessed via isothermal calorimetry), reducing setting times (Vicat needle), and increasing early-age mortar cube strength (1 d and 7 d). Both the CaCl2 and the fine limestone powder are used to replace a portion of the finest sand in the mortar mixtures, while keeping both the water-to-cement ratio and volume fractions of water and cement constant. Studies are conducted at 73.4 °F (23°C) and 50 °F (10 °C), so that activation energies can be estimated for the hydration and setting processes. Because the mechanisms of acceleration of the CaCl2 and limestone powder are different, a hybrid mixture with 1 % CaCl2 and 20 % limestone powder (by mass of cement) is also investigated. Both technologies are found to be viable options for reducing setting times and increasing early-age strengths, and it is hoped that concrete producers and contractors will consider the addition of fine limestone powder to their toolbox of techniques for assuring performance in cold weather and other concreting conditions where acceleration may be needed. PMID:28077884

75 FR 31816 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-Diesel After...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-04

... DEPARTMENT OF JUSTICE Antitrust Division Notice Pursuant to the National Cooperative Research and Production Act of 1993--Diesel After Treatment Accelerated Aging Cycles--Heavy-Duty Notice is hereby given... Group on Diesel After treatment Accelerated Aging Cycles--Heavy-Duty (``DAAAC-HD'') has filed written...

Accelerated aging of phenolic-bonded flakeboards

Treesearch

Andrew J. Baker; Robert H. Gillespie

1978-01-01

Specimens of phenolic-bonded flakeboard, vertical-grain southern pine and Douglas-fir, and marine-grade Douglas-fir plywood were exposed to four accelerated aging situations. These consisted of: 1) Multiple cycles of boiling and elevated-temperature drying, 2) multiple cycles of vacuum- pressure soaking and intermediate-temperature drying, 3) the six-cycle ASTM D-1037...

Man-systems evaluation of moving base vehicle simulation motion cues. [human acceleration perception involving visual feedback

NASA Technical Reports Server (NTRS)

Kirkpatrick, M.; Brye, R. G.

1974-01-01

A motion cue investigation program is reported that deals with human factor aspects of high fidelity vehicle simulation. General data on non-visual motion thresholds and specific threshold values are established for use as washout parameters in vehicle simulation. A general purpose similator is used to test the contradictory cue hypothesis that acceleration sensitivity is reduced during a vehicle control task involving visual feedback. The simulator provides varying acceleration levels. The method of forced choice is based on the theory of signal detect ability.

A novel approach on accelerated ageing towards reliability optimization of high concentration photovoltaic cells

NASA Astrophysics Data System (ADS)

Tsanakas, John A.; Jaffre, Damien; Sicre, Mathieu; Elouamari, Rachid; Vossier, Alexis; de Salins, Jean-Edouard; Bechou, Laurent; Levrier, Bruno; Perona, Arnaud; Dollet, Alain

2014-09-01

This paper presents a preliminary study upon a novel approach proposed for highly accelerated ageing and reliability optimization of high concentrating photovoltaic (HCPV) cells and assemblies. The intended approach aims to overcome several limitations of some current accelerated ageing tests (AAT) adopted up today, proposing the use of an alternative experimental set-up for performing faster and more realistic thermal cycles, under real sun, without the involvement of environmental chamber. The study also includes specific characterization techniques, before and after each AAT sequence, which respectively provide the initial and final diagnosis on the condition of the tested sample. The acquired data from these diagnostic/characterization methods are then used as indices to determine both quantitatively and qualitatively the severity of degradation and, thus, the ageing level for each tested HCPV assembly or cell sample. Ultimate goal of such "initial diagnosis - AAT - final diagnosis" sequences is to provide the basis for a future work on the reliability analysis of the main degradation mechanisms and confident prediction of failure propagation in HCPV cells, by means of acceleration factor (AF) and mean-time-to-failure (MTTF) estimations.

Long-time aging in 3 mol.% yttria-stabilized tetragonal zirconia polycrystals at human body temperature.

PubMed

Keuper, Melanie; Berthold, Christoph; Nickel, Klaus Georg

2014-02-01

We present new findings on the low-temperature degradation of yttria-stabilized zirconia at 37°C over several years and at high and low partial pressures of water. With the aid of focused ion beam cross-section confirmation studies we are able to show an extensive linear, continuous degradation without retardation, even at low temperatures and low water pressures. The characteristic layer growth and its inferred rate constant imply a lifetime of tens of years under simple tension and open the possibility of studying the longevity of these ceramics more rigorously. In addition, we show reproducibility complications of accelerated aging tests by the use of different autoclaves and possible implications for standardized procedures. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Decreased proteasomal function accelerates cigarette smoke-induced pulmonary emphysema in mice.

PubMed

Yamada, Yosuke; Tomaru, Utano; Ishizu, Akihiro; Ito, Tomoki; Kiuchi, Takayuki; Ono, Ayako; Miyajima, Syota; Nagai, Katsura; Higashi, Tsunehito; Matsuno, Yoshihiro; Dosaka-Akita, Hirotoshi; Nishimura, Masaharu; Miwa, Soichi; Kasahara, Masanori

2015-06-01

Chronic obstructive pulmonary disease (COPD) is a disease common in elderly people, characterized by progressive destruction of lung parenchyma and chronic inflammation of the airways. The pathogenesis of COPD remains unclear, but recent studies suggest that oxidative stress-induced apoptosis in alveolar cells contributes to emphysematous lung destruction. The proteasome is a multicatalytic enzyme complex that plays a critical role in proteostasis by rapidly destroying misfolded and modified proteins generated by oxidative and other stresses. Proteasome activity decreases with aging in many organs including lungs, and an age-related decline in proteasomal function has been implicated in various age-related pathologies. However, the role of the proteasome system in the pathogenesis of COPD has not been investigated. Recently, we have established a transgenic (Tg) mouse model with decreased proteasomal chymotrypsin-like activity, showing age-related phenotypes. Using this model, we demonstrate here that decreased proteasomal function accelerates cigarette smoke (CS)-induced pulmonary emphysema. CS-exposed Tg mice showed remarkable airspace enlargement and increased foci of inflammation compared with wild-type controls. Importantly, apoptotic cells were found in the alveolar walls of the affected lungs. Impaired proteasomal activity also enhanced apoptosis in cigarette smoke extract (CSE)-exposed fibroblastic cells derived from mice and humans in vitro. Notably, aggresome formation and prominent nuclear translocation of apoptosis-inducing factor were observed in CSE-exposed fibroblastic cells isolated from Tg mice. Collective evidence suggests that CS exposure and impaired proteasomal activity coordinately enhance apoptotic cell death in the alveolar walls that may be involved in the development and progression of emphysema in susceptible individuals such as the elderly.

Timing paradox of stepping and falls in ageing: not so quick and quick(er) on the trigger

PubMed Central

Mille, Marie‐Laure

2016-01-01

Abstract Physiological and degenerative changes affecting human standing balance are major contributors to falls with ageing. During imbalance, stepping is a powerful protective action for preserving balance that may be voluntarily initiated in recognition of a balance threat, or be induced by an externally imposed mechanical or sensory perturbation. Paradoxically, with ageing and falls, initiation slowing of voluntary stepping is observed together with perturbation‐induced steps that are triggered as fast as or faster than for younger adults. While age‐associated changes in sensorimotor conduction, central neuronal processing and cognitive functions are linked to delayed voluntary stepping, alterations in the coupling of posture and locomotion may also prolong step triggering. It is less clear, however, how these factors may explain the accelerated triggering of induced stepping. We present a conceptual model that addresses this issue. For voluntary stepping, a disruption in the normal coupling between posture and locomotion may underlie step‐triggering delays through suppression of the locomotion network based on an estimation of the evolving mechanical state conditions for stability. During induced stepping, accelerated step initiation may represent an event‐triggering process whereby stepping is released according to the occurrence of a perturbation rather than to the specific sensorimotor information reflecting the evolving instability. In this case, errors in the parametric control of induced stepping and its effectiveness in stabilizing balance would be likely to occur. We further suggest that there is a residual adaptive capacity with ageing that could be exploited to improve paradoxical triggering and other changes in protective stepping to impact fall risk. PMID:26915664

Methodology for the Calibration of the Data Acquisition with a Six-Degree-of-Freedom Acceleration Measurement Device

DOT National Transportation Integrated Search

1989-06-01

This report describes a methodology for calibrating and gathering data with a six-degree-of-freedom acceleration measurement device that is intended to measure head acceleration of anthropomorphic dummies and human volunteers in automotive crash test...

Evaluation of effect of laser etching on shear bond strength between maxillofacial silicone and acrylic resin subjected to accelerated aging process.

PubMed

Rhea, Antonette; Ahila, S C; Kumar, B Muthu

2017-01-01

Maxillofacial prosthesis are supported by implants, require a retentive matrix to retain the suprastructure. The retentive matrix is made up of acrylic resin to which the silicone prostheses are anchored by micro-mechanical bond. The delamination of silicone away from the retentive matrix is a persisting problem in implant-supported maxillofacial prosthesis. This study aimed to evaluate the effect of laser etching on the shear bond strength (BS) between acrylic resin and maxillofacial silicone, after 24 h of fabrication and after 200 h of accelerated aging. The samples were prepared according to ISO/TR 11405:1994 in maxillofacial silicone and polymethyl methacrylate resin. The untreated samples were Group A (control), Group B (silicon carbide [SiC] paper abrasion 80 grit size), and Group C (erbium-doped yttrium aluminum garnet laser etching). Then, the samples were coated with primer and bonded to maxillofacial silicone. The samples were subjected to shear BS test in an universal testing machine after 24 h of fabrication and after 200 h of accelerated aging. The results were statistically analyzed using one-way ANOVA and Tukey's HSD post hoc test. The shear BS test after 24 h of fabrication showed better BS in SiC paper abrasion. The shear BS test after 200 h of accelerated aging showed better BS in laser etching compared to SiC abrasion. Laser etching produced better shear BS compared to conventional SiC paper abrasion after 200 h of accelerated aging process.

Experimental evaluation of the Battelle accelerated test design for the solar array at Mead, Nebraska

NASA Technical Reports Server (NTRS)

Frickland, P. O.; Repar, J.

1982-01-01

A previously developed test design for accelerated aging of photovoltaic modules was experimentally evaluated. The studies included a review of relevant field experience, environmental chamber cycling of full size modules, and electrical and physical evaluation of the effects of accelerated aging during and after the tests. The test results indicated that thermally induced fatigue of the interconnects was the primary mode of module failure as measured by normalized power output. No chemical change in the silicone encapsulant was detectable after 360 test cycles.

Accelerated life testing of spacecraft subsystems

NASA Technical Reports Server (NTRS)

Wiksten, D.; Swanson, J.

1972-01-01

The rationale and requirements for conducting accelerated life tests on electronic subsystems of spacecraft are presented. A method for applying data on the reliability and temperature sensitivity of the parts contained in a sybsystem to the selection of accelerated life test parameters is described. Additional considerations affecting the formulation of test requirements are identified, and practical limitations of accelerated aging are described.

Comparing aging of graphite/LiFePO4 cells at 22 °C and 55 °C - Electrochemical and photoelectron spectroscopy studies

NASA Astrophysics Data System (ADS)

Hellqvist Kjell, Maria; Malmgren, Sara; Ciosek, Katarzyna; Behm, Mårten; Edström, Kristina; Lindbergh, Göran

2013-12-01

Accelerated aging at elevated temperature is commonly used to test lithium-ion battery lifetime, but the effect of an elevated temperature is still not well understood. If aging at elevated temperature would only be faster, but in all other respects equivalent to aging at ambient temperature, cells aged to end-of-life (EOL) at different temperatures would be very similar. The present study compares graphite/LiFePO4-based cells either cycle- or calendar-aged to EOL at 22 °C and 55 °C. Cells cycled at the two temperatures show differences in electrochemical impedance spectra as well as in X-ray photoelectron spectroscopy (XPS) spectra. These results show that lithium-ion cell aging is a complex set of processes. At elevated temperature, the aging is accelerated in process-specific ways. Furthermore, the XPS results of cycle-aged samples indicate increased deposition of oxygenated LiPF6 decomposition products in both the negative and positive electrode/electrolyte interfaces. The decomposition seems more pronounced at elevated temperature, and largely accelerated by cycling, which could contribute to the observed cell impedance increase.

DNA methylation age is elevated in breast tissue of healthy women.

PubMed

Sehl, Mary E; Henry, Jill E; Storniolo, Anna Maria; Ganz, Patricia A; Horvath, Steve

2017-07-01

Limited evidence suggests that female breast tissue ages faster than other parts of the body according to an epigenetic biomarker of aging known as the "epigenetic clock." However, it is unknown whether breast tissue samples from healthy women show a similar accelerated aging effect relative to other tissues, and what could drive this acceleration. The goal of this study is to validate our initial finding of advanced DNA methylation (DNAm) age in breast tissue, by directly comparing it to that of peripheral blood tissue from the same individuals, and to do a preliminary assessment of hormonal factors that could explain the difference. We utilized n = 80 breast and 80 matching blood tissue samples collected from 40 healthy female participants of the Susan G. Komen Tissue Bank at the Indiana University Simon Cancer Center who donated these samples at two time points spaced at least a year apart. DNA methylation levels (Illumina 450K platform) were used to estimate the DNAm age. DNAm age was highly correlated with chronological age in both peripheral blood (r = 0.94, p < 0.0001) and breast tissues (r = 0.86, p < 0.0001). A measure of epigenetic age acceleration (age-adjusted DNAm Age) was substantially increased in breast relative to peripheral blood tissue (p = 1.6 × 10 -11 ). The difference between DNAm age of breast and blood decreased with advancing chronologic age (r = -0.53, p = 4.4 × 10 -4 ). Our data clearly demonstrate that female breast tissue has a higher epigenetic age than blood collected from the same subject. We also observe that the degree of elevation in breast diminishes with advancing age. Future larger studies will be needed to examine associations between epigenetic age acceleration and cumulative hormone exposure.

Evaluating Weathering of Food Packaging Polyethylene-Nano-clay Composites: Release of Nanoparticles and their Impacts.

PubMed

Han, Changseok; Zhao, Amy; Varughese, Eunice; Sahle-Demessie, E

2018-01-01

Nano-fillers are increasingly incorporated into polymeric materials to improve the mechanical, barrier or other matrix properties of nanocomposites used for consumer and industrial applications. However, over the life cycle, these nanocomposites could degrade due to exposure to environmental conditions, resulting in the release of embedded nanomaterials from the polymer matrix into the environment. This paper presents a rigorous study on the degradation and the release of nanomaterials from food packaging composites. Films of nano-clay-loaded low-density polyethylene (LDPE) composite for food packaging applications were prepared with the spherilene technology and exposed to accelerated weathering of ultraviolet (UV) irradiation or low concentration of ozone at 40 °C. The changes in the structural, surface morphology, chemical and physical properties of the films during accelerated weathering were investigated. Qualitative and quantitative changes in properties of pristine and aged materials and the release of nano-clay proceeded slowly until 130 hr irradiation and then accelerated afterward resulting complete degradation. Although nano-clay increased the stability of LDPE and improved thermal and barrier properties, they accelerated the UV oxidation of LDPE. With increasing exposure to UV, the surface roughness, chemiluminescence index, and carbonyl index of the samples increased while decreasing the intensity of the wide-angle X-ray diffraction pattern. Nano-clay particles with sizes ranging from 2-8 nm were released from UV and ozone weathered composite. The concentrations of released nanoparticles increased with an increase in aging time. Various toxicity tests, including reactive oxygen species generation and cell activity/viability were also performed on the released nano-clay and clay polymer. The released nano-clays basically did not show toxicity. Our combined results demonstrated the degradation properties of nano-clay particle-embedded LDPE composites toxicity of released nano-clay particles to A594 adenocarcinomic human alveolar basal epithelial cells was observed, which will help with future risk based-formulations of exposure.

A novel diagnostic tool reveals mitochondrial pathology in human diseases and aging.

PubMed

Scheibye-Knudsen, Morten; Scheibye-Alsing, Karsten; Canugovi, Chandrika; Croteau, Deborah L; Bohr, Vilhelm A

2013-03-01

The inherent complex and pleiotropic phenotype of mitochondrial diseases poses a significant diagnostic challenge for clinicians as well as an analytical barrier for scientists. To overcome these obstacles we compiled a novel database, www.mitodb.com, containing the clinical features of primary mitochondrial diseases. Based on this we developed a number of qualitative and quantitative measures, enabling us to determine whether a disorder can be characterized as mitochondrial. These included a clustering algorithm, a disease network, a mitochondrial barcode and two scoring algorithms. Using these tools we detected mitochondrial involvement in a number of diseases not previously recorded as mitochondrial. As a proof of principle Cockayne syndrome, ataxia with oculomotor apraxia 1 (AOA1), spinocerebellar ataxia with axonal neuropathy 1 (SCAN1) and ataxia-telangiectasia have recently been shown to have mitochondrial dysfunction and those diseases showed strong association with mitochondrial disorders. We next evaluated mitochondrial involvement in aging and detected two distinct categories of accelerated aging disorders, one of them being associated with mitochondrial dysfunction. Normal aging seemed to associate stronger with the mitochondrial diseases than the non-mitochondrial partially supporting a mitochondrial theory of aging.

The Effects of a Cognitive Acceleration Intervention Programme on the Performance of Secondary School Pupils in Malawi.

ERIC Educational Resources Information Center

Mbano, Nellie

2003-01-01

Investigates whether the critical period for cognitive transition from concrete operations to formal operations at 12-14 years of age actually exists. Uses the Cognitive Acceleration through Science Education (CASE) intervention program in Malawi. Discusses the existence of the critical period, academic achievement, and explanations for age and…

Human female meiosis revised: new insights into the mechanisms of chromosome segregation and aneuploidies from advanced genomics and time-lapse imaging.

PubMed

Capalbo, Antonio; Hoffmann, Eva R; Cimadomo, Danilo; Ubaldi, Filippo Maria; Rienzi, Laura

2017-11-01

The unbalanced transmission of chromosomes in human gametes and early preimplantation embryos causes aneuploidy, which is a major cause of infertility and pregnancy failure. A baseline of 20% of human oocytes are estimated to be aneuploid and this increases exponentially from 30 to 35 years, reaching on average 80% by 42 years. As a result, reproductive senescence in human females is predominantly determined by the accelerated decline in genetic quality of oocytes from 30 years of age. Understanding mechanisms of chromosome segregation and aneuploidies in the female germline is a crucial step towards the development of new diagnostic approaches and, possibly, for the development of therapeutic targets and molecules. Here, we have reviewed emerging mechanisms that may drive human aneuploidy, in particular the maternal age effect. We conducted a systematic search in PubMed Central of the primary literature from 1990 through 2016 following the PRISMA guidelines, using MeSH terms related to human aneuploidy. For model organism research, we conducted a literature review based on references in human oocytes manuscripts and general reviews related to chromosome segregation in meiosis and mitosis. Advances in genomic and imaging technologies are allowing unprecedented insight into chromosome segregation in human oocytes. This includes the identification of a novel chromosome segregation error, termed reverse segregation, as well as sister kinetochore configurations that were not predicted based on murine models. Elucidation of mechanisms that result in errors in chromosome segregation in meiosis may lead to therapeutic developments that could improve reproductive outcomes by reducing aneuploidy. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Are Human influences responsible for the existence and possible drowning of (parts of) the Ebro Delta, Spain?

NASA Astrophysics Data System (ADS)

Kettner, A. J.; Xing, F.; Ashton, A. D.

2010-12-01

The modern Ebro Delta, Spain, has developed since the Holocene sea level stabilized around 6,000 years ago. Delta progradation rates since than have changed significantly. Historical charts dating from the Middle Ages suggest that the delta prograded from the Roman epoch until the 10th century at rates 2-3 times faster than before. The Romans deforested significant parts of the 80,093 km2 large hinterland, mainly to supply the ship industry, which induced severe erosion. In contrast, dams and reservoirs emplacements for irrigation works on the Ebro and its tributaries during the last 150 years led to the retention of almost the entire fluvial sediment normally transported to the Mediterranean, resulting in acceleration of coastal erosion. Climatic impact on the sediment load transported to the coast is less well understood but Paleohydrological reconstructions suggest that riverine sediment to the Mediterranean increased during the Middle Ages and the Little Ice Age. For this study, a numerical model, HydroTrend, is applied in a first attempt to unravel the impact of climate change and human impact of the Ebro basin over the last 2,000 years. HydroTrend is able to compute water discharge and sediment load in daily increments over centuries based on the geomorphic, geographic and geologic catchment parameters as well as human activities. For model input, a Holocene climate record is reconstructed, based on dendrochronology. Spatial and temporal human deforestation reconstructions are based on a high resolution simulations by Kaplan et al. (2009) who determined deforestation over time by population density, and land suitability.

Cycle-Powered Short Radius (1.9 m) Centrifuge: Effect of Exercise Versus Passive Acceleration on Heart Rate in Humans

NASA Technical Reports Server (NTRS)

Greenleaf, J. E.; Gundo, D. P.; Watenpaugh, D. E.; Mulenburg, G. M.; Mckenzie, M. A.; Looft-Wilson, R.; Hargens, A. R.

1997-01-01

In addition to extensive use of lower extremity physical exercise training as a countermeasure for the work capacity component of spaceflight deconditioning, some form of additional head-to-foot (+Gz) gravitational (orthostatic) stress may be required to further attenuate or prevent the signs and symptoms (nausea, vertigo, instability, fatigue) of the general reentry syndrome (GRS) that can reduce astronaut performance during landing. Orthostatic (head-to-foot) stress can be induced by standing, by lower body negative pressure, and by +Gz acceleration. One important question is whether acceleration training alone or with concurrent leg exercise would provide sufficient additive stimulation to attenuate the GRS. Use of a new human-powered centrifuge may be the answer. Thus, the purpose for this study was to compare heart rate (HR), i.e., a stress response during human-powered acceleration, in four men (35-62 yr) and two women (30-31 yr) during exercise acceleration versus passive acceleration (by an off-board operator) at 100% (maximal acceleration = A(max)), and at 25%, 50%, and 75% of A(max). Mean (+/-SE) A(max) was 43.7 +/- 1.3 rpm (+3.9 +/- 0.2Gz). Mean HR at exercise A(max) was 189 +/- 13 b/min (50-70 sec run time), and 142 +/- 22 b/min at passive A(max) (40-70 sec run time). Regression of mean HR on the various +Gz levels indicated explained variance (correlations squared) of r(exp 2) = 0.88 (exercise) and r(exp 2) = 0.96 (passive): exercise HR of 107 +/- 4 (25%) to 189 +/- 13 (100%) b/min were 43-50 b/min higher (p less than 0.05) than comparable passive HR of 64 +/- 2 to 142 +/- 22 b/min. Thus, exercise adds significant physiological stress during +Gz acceleration. Inflight use of this combined exercise and acceleration countermeasure may maintain work capacity as well as normalize acceleration and orthostatic tolerances which could attenuate or perhaps eliminate the GRS.

Why did children grow so well at hard times? The ultimate importance of pathogen control during puberty

PubMed Central

Hõrak, Peeter; Valge, Markus

2015-01-01

Background and objectives: Secular increase in human height and performance occurred in Europe throughout the 20th century despite the temporally worsening access to nutrients during and after World War II. This pattern is paradoxical under the assumption of the major impact of pre- and postnatal growth conditions for determination of adult size and human capital. Methodology: We examined the anthropometric parameters of Estonian girls born between 1938 and 1953, and measured around the age of 17 (n = 1475). This period involved two opposite trends in the economic and epidemiological situation: increasing birth-time economic hardships during the war and particularly in the post-war period, and decreasing infant mortality (a proxy of disease burden) after 1947. Results: Height of girls was negatively affected by the number of siblings and positively by parental socioeconomic position, but these effects were weaker than the secular trend. Leg length (an indicator of pre-pubertal growth conditions) was independent of age and birth date while all other traits, including measures of performance (cranial volume, lung capacity and handgrip strength) showed acceleration. The best predictor of size at age 17 was, in most cases, infant mortality in the year when the girls were aged 11. Conclusions and implications: Reduction of disease burden during pubertal growth can override effects of resource shortage at birth. Our results also support the idea that increasing efficiency of pathogen control can contribute to the secular increase in cognitive abilities, i.e. the Flynn effect, and that epidemiological transition is the main driver of secular increase in human capital. PMID:26198188

Evaluation of hardness and colour change of soft liners after accelerated ageing.

PubMed

Mancuso, Daniela Nardi; Goiato, Marcelo Coelho; Zuccolotti, Bruna Carolina Rossatti; Moreno, Amália; dos Santos, Daniela Micheline

2009-07-01

Soft liners have been developed to offer comfort to denture wearers. However, this comfort is compromised when there is a change in the properties of the material, causing colour change, solubility, absorption and hardening. These characteristics can compromise the longevity of soft liners. The aim of this in vitro study was to investigate the effect of ageing on both the hardness and colour change of two soft liners following accelerated ageing. Two denture liners, one resin based (Trusoft, Bosworth, Illinois, USA) and one silicone based (Ufi Gel P, Voco GMBH, Cuxhaven, Germany), were tested in this study for both hardness (using the Shore A scale) and colour change (using the CIE L*a*b* colour scale), initially and after 1008 hours (6 weeks) of accelerated ageing. Statistical analysis was performed using the unpaired t-test with the Welch correction. These indicated that both materials increased in hardness and underwent colour change after accelerated ageing. The initial hardness of Trusoft was far lower than that of Ufi Gel P (18.2 Shore A units vs 34.8 Shore A units). However, for Trusoft the changes for both hardness (from 18.2 to 52.1 Shore A units) and colour change (16.85 on the CIE L*a*b* colour scale) were greater than those for Ufi Gel P, for which hardness changed from 34.8 to 36.5 Shore A units and the colour change was 5.19 on the CIE L*a*b* colour scale. Ufi Gel P underwent less hardness and colour change after accelerated ageing than Trusoft. On the other hand, the use of Trusoft may be preferable in cases where initial softness is a major consideration, such as when relining an immediate denture after implant surgery.

42 CFR 484.245 - Accelerated payments for home health agencies.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 5 2011-10-01 2011-10-01 false Accelerated payments for home health agencies. 484... HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION HOME HEALTH SERVICES Prospective Payment System for Home Health Agencies § 484.245 Accelerated payments for home health agencies. (a) General rule...

42 CFR 484.245 - Accelerated payments for home health agencies.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 5 2012-10-01 2012-10-01 false Accelerated payments for home health agencies. 484... HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION HOME HEALTH SERVICES Prospective Payment System for Home Health Agencies § 484.245 Accelerated payments for home health agencies. (a) General rule...

42 CFR 484.245 - Accelerated payments for home health agencies.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Accelerated payments for home health agencies. 484... HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION HOME HEALTH SERVICES Prospective Payment System for Home Health Agencies § 484.245 Accelerated payments for home health agencies. (a) General rule...

Accelerating Technologies: Consequences for the Future Wellbeing of Students

ERIC Educational Resources Information Center

Saltinski, Ronald

2015-01-01

Today's students, K-12 and beyond, will face an ominous future unless educators quickly invest in preparing student perspectives for the accelerating technologies that will have global implications for the wellbeing of all humanity. Accelerating technologies are quietly, almost insidiously, transforming the world with little fanfare and certainly…

Fbxw7 Deletion Accelerates KrasG12D-Driven Pancreatic Tumorigenesis via Yap Accumulation.

PubMed

Zhang, Qiang; Zhang, Yaqing; Parsels, Joshua D; Lohse, Ines; Lawrence, Theodore S; Pasca di Magliano, Marina; Sun, Yi; Morgan, Meredith A

2016-11-01

Pancreatic cancers driven by KRAS mutations require additional mutations for tumor progression. The tumor suppressor FBXW7 is altered in pancreatic cancers, but its contribution to pancreatic tumorigenesis is unknown. To determine potential cooperation between Kras mutation and Fbxw7 inactivation in pancreatic tumorigenesis, we generated P48-Cre;LSL-Kras G12D ;Fbxw7 fl/fl (KFC fl/fl ) compound mice. We found that KFC fl/fl mice displayed accelerated tumorigenesis: all mice succumbed to pancreatic ductal adenocarcinoma (PDA) by 40 days of age, with PDA onset occurring by 2 weeks of age. PDA in KFC fl/fl mice was preceded by earlier onset of acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN) lesions, and associated with chromosomal instability and the accumulation of Fbxw7 substrates Yes-associated protein (Yap), c-Myc, and Notch. Using KFC fl/fl and FBXW7-deficient human pancreatic cancer cells, we found that Yap silencing attenuated growth promotion by Fbxw7 deletion. Our data demonstrate that Fbxw7 is a potent suppressor of Kras G12D -induced pancreatic tumorigenesis due, at least in part, to negative regulation of Yap. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Redox Active Transition Metal ions Make Melanin Susceptible to Chemical Degradation Induced by Organic Peroxide.

PubMed

Zadlo, Andrzej; Pilat, Anna; Sarna, Michal; Pawlak, Anna; Sarna, Tadeusz

2017-12-01

With aging, retinal pigment epithelium melanosomes, by fusion with the age pigment lipofuscin, form complex granules called melanolipofuscin. Lipofuscin granules may contain oxidized proteins and lipid hydroperoxides, which in melanolipofuscin could chemically modify melanin polymer, while transition metal ions present in melanin can accelerate such oxidative modifications. The aim of this research was to examine the effect of selected transition metal ions on melanin susceptibility to chemical modification induced by the water-soluble tert-butyl hydroperoxide used as an oxidizing agent. Synthetic melanin obtained by DOPA autooxidation and melanosomes isolated from bovine retinal pigment epithelium were analyzed. To monitor tert-butyl hydroperoxide-induced oxidative changes of DMa and BMs, electron paramagnetic resonance spectroscopy, UV-vis absorption spectroscopy, dynamic light scattering, atomic force microscopy and electron paramagnetic resonance oximetry were employed. These measurements revealed that both copper and iron ions accelerated chemical degradation induced by tert-butyl hydroperoxide, while zinc ions had no effect. Strong prooxidant action was detected only in the case of melanosomes and melanin degraded in the presence of iron. It can be postulated that similar chemical processes, if they occur in situ in melanolipofuscin granules of the human retinal pigment epithelium, would modify antioxidant properties of melanin and its reactivity.

Obesity-induced oxidative stress, accelerated functional decline with age and increased mortality in mice.

PubMed

Zhang, Yiqiang; Fischer, Kathleen E; Soto, Vanessa; Liu, Yuhong; Sosnowska, Danuta; Richardson, Arlan; Salmon, Adam B

2015-06-15

Obesity is a serious chronic disease that increases the risk of numerous co-morbidities including metabolic syndrome, cardiovascular disease and cancer as well as increases risk of mortality, leading some to suggest this condition represents accelerated aging. Obesity is associated with significant increases in oxidative stress in vivo and, despite the well-explored relationship between oxidative stress and aging, the role this plays in the increased mortality of obese subjects remains an unanswered question. Here, we addressed this by undertaking a comprehensive, longitudinal study of a group of high fat-fed obese mice and assessed both their changes in oxidative stress and in their performance in physiological assays known to decline with aging. In female C57BL/6J mice fed a high-fat diet starting in adulthood, mortality was significantly increased as was oxidative damage in vivo. High fat-feeding significantly accelerated the decline in performance in several assays, including activity, gait, and rotarod. However, we also found that obesity had little effect on other markers of function and actually improved performance in grip strength, a marker of muscular function. Together, this first comprehensive assessment of longitudinal, functional changes in high fat-fed mice suggests that obesity may induce segmental acceleration of some of the aging process. Published by Elsevier Inc.

Visual evaluation of color stability after accelerated aging of pigmented and nonpigmented silicones to be used in facial prostheses.

PubMed

Mancuso, Daniela Nardi; Goiato, Marcelo Coelho; Dekon, Stefan Fiuza de Carvalho; Gennari-Filho, Humberto

2009-01-01

The objective of this study was to evaluate by a visual method of comparison the color stability of nonpigmented and pigmented facial silicones after accelerated aging. Two kinds of silicones were used in this study; one specifically formulated for facial prostheses and the other an acetic silicone for industrial use. Twenty-four trial bodies were made for each silicone. These were divided into colorless and intrinsically pigmented groups: ceramic, make-up, and iron oxide. The groups were submitted to accelerated aging for nonmetallic materials. An initial reading and subsequent readings were made at 163, 351, 692, and 1000 hours using a visual method of comparison. The values were annotated in a spreadsheet by two observers, according to scores elaborated for this study. All groups presented color stability in the visual method. According to the results obtained and analyzed in this study, we can conclude that both silicones, Silastic 732 RTV and Silastic MDX 4-4210, behaved similarly, they can therefore be indicated for use in maxillofacial prosthesis. The time factor of aging influenced negatively, independently of the pigmentation, or lack of it, and of silicones and no group had visually noticeable alterations in any of the accelerated aging time, independently of the addition or not of pigments.

Obesity-induced oxidative stress, accelerated functional decline with age and increased mortality in mice

PubMed Central

Zhang, Yiqiang; Fischer, Kathleen E.; Soto, Vanessa; Liu, Yuhong; Sosnowska, Danuta; Richardson, Arlan; Salmon, Adam B.

2015-01-01

Obesity is a serious chronic disease that increases the risk of numerous co-morbidities including metabolic syndrome, cardiovascular disease and cancer as well as increases risk of mortality leading some to suggest this represents accelerated aging. Obesity is associated with significant increases in oxidative stress in vivo and, despite the well-explored relationship between oxidative stress and aging, the role this plays in the increased mortality of obese subjects remains an unanswered question. Here, we addressed this by undertaking a comprehensive, longitudinal study of a group of high fat-fed obese mice and assessed both their changes in oxidative stress and in their performance in physiological assays known to decline with aging. In female C57BL/6J mice fed a high-fat diet starting in adulthood, mortality was significantly increased in high fat-fed mice as was oxidative damage in vivo. High fat-feeding significantly accelerated the decline in performance in several assays, including activity, gait, and rotarod. However, we also found that obesity had little effect on other markers and actually improved performance in grip strength, a marker of muscular function. Together, this first comprehensive assessment of longitudinal functional changes in high fat-fed mice suggests that obesity may induce segmental acceleration of some of the aging process. PMID:25558793

Planning for an Accelerated School. A Two Day Workshop (Stanford, California, November 17-18, 1988). Illinois Network of Accelerated Schools.

ERIC Educational Resources Information Center

Illinois State Board of Education, Springfield. Dept. of School Improvement Services.

The thesis of this conference report is that acceleration is a much more effective method than remediation for bringing at-risk children into the educational mainstream at an early age. The papers summarized in the report provide a background on the history, politics, and demography of at-risk students and suggest applications of acceleration to…

Aroma profile and sensory characteristics of a sulfur dioxide-free mulberry (Morus nigra) wine subjected to non-thermal accelerating aging techniques.

PubMed

Tchabo, William; Ma, Yongkun; Kwaw, Emmanuel; Zhang, Haining; Xiao, Lulu; Tahir, Haroon Elrasheid

2017-10-01

The present study was undertaken to assess accelerating aging effects of high pressure, ultrasound and manosonication on the aromatic profile and sensorial attributes of aged mulberry wines (AMW). A total of 166 volatile compounds were found amongst the AMW. The outcomes of the investigation were presented by means of geometric mean (GM), cluster analysis (CA), principal component analysis (PCA), partial least squares regressions (PLSR) and principal component regression (PCR). GM highlighted 24 organoleptic attributes responsible for the sensorial profile of the AMW. Moreover, CA revealed that the volatile composition of the non-thermal accelerated aged wines differs from that of the conventional aged wines. Besides, PCA discriminated the AMW on the basis of their main sensorial characteristics. Furthermore, PLSR identified 75 aroma compounds which were mainly responsible for the olfactory notes of the AMW. Finally, the overall quality of the AMW was noted to be better predicted by PLSR than PCR. Copyright © 2017 Elsevier Ltd. All rights reserved.

Accelerated Post-Weld Natural Ageing in Ultrasonic Welding Aluminium 6111-T4 Automotive Sheet

NASA Astrophysics Data System (ADS)

Chen, Ying-Chun; Prangnell, Phil

In contrast to previously published reports, it is shown that there is an observable HAZ when ultrasonic spot welding (USW) automotive alloys, like AA6111-T4, the severity of which depends on the welding energy. Immediately after welding, softening is seen relative to the T4 condition, but this is rapidly recovered by natural ageing, which masks the presence of a HAZ, and the weld strength eventually exceeds that of the parent material. This behaviour is caused by dissolution of the solute clusters/GPZs in the T4 sheet, due to the high weld temperatures (> 400 °C), combined with accelerated post-weld natural ageing to a more advanced state than in the parent material. Modelling has demonstrated that this accelerated natural ageing behaviour can be attributed to an excess vacancy concentration generated by the USW process.

Uric acid, an important antioxidant contributing to survival in termites

PubMed Central

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

2017-01-01

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

Chronic skin inflammation accelerates macrophage cholesterol crystal formation and atherosclerosis

PubMed Central

Ng, Qimin; Sanda, Gregory E.; Dey, Amit K.; Teague, Heather L.; Sorokin, Alexander V.; Dagur, Pradeep K.; Silverman, Joanna I.; Harrington, Charlotte L.; Rodante, Justin A.; Rose, Shawn M.; Varghese, Nevin J.; Belur, Agastya D.; Goyal, Aditya; Gelfand, Joel M.; Springer, Danielle A.; Bleck, Christopher K.E.; Thomas, Crystal L.; Yu, Zu-Xi; Winge, Mårten C.G.; Kruth, Howard S.; Marinkovich, M. Peter; Joshi, Aditya A.; Playford, Martin P.; Mehta, Nehal N.

2018-01-01

Inflammation is critical to atherogenesis. Psoriasis is a chronic inflammatory skin disease that accelerates atherosclerosis in humans and provides a compelling model to understand potential pathways linking these diseases. A murine model capturing the vascular and metabolic diseases in psoriasis would accelerate our understanding and provide a platform to test emerging therapies. We aimed to characterize a new murine model of skin inflammation (Rac1V12) from a cardiovascular standpoint to identify novel atherosclerotic signaling pathways modulated in chronic skin inflammation. The RacV12 psoriasis mouse resembled the human disease state, including presence of systemic inflammation, dyslipidemia, and cardiometabolic dysfunction. Psoriasis macrophages had a proatherosclerotic phenotype with increased lipid uptake and foam cell formation, and also showed a 6-fold increase in cholesterol crystal formation. We generated a triple-genetic K14-RacV12–/+/Srb1–/–/ApoER61H/H mouse and confirmed psoriasis accelerates atherogenesis (~7-fold increase). Finally, we noted a 60% reduction in superoxide dismutase 2 (SOD2) expression in human psoriasis macrophages. When SOD2 activity was restored in macrophages, their proatherogenic phenotype reversed. We demonstrate that the K14-RacV12 murine model captures the cardiometabolic dysfunction and accelerates vascular disease observed in chronic inflammation and that skin inflammation induces a proatherosclerotic macrophage phenotype with impaired SOD2 function, which associated with accelerated atherogenesis. PMID:29321372

Comparison Between THOR Anthropomorphic Test Device and THOR Finite Element Model

NASA Technical Reports Server (NTRS)

Moore, Erik

2014-01-01

Extended time spent in reduced gravity can cause physiologic deconditioning of astronauts, reducing their ability to sustain excessive forces during dynamic phases of spaceflight such as landing. To make certain that the crew is safe during these phases, NASA must take caution when determining what types of landings are acceptable based on the accelerations applied to the astronaut. In order to test acceptable landings, various trials have been run accelerating humans, cadavers, and Anthropomorphic Test Devices (ATDs), or crash test dummies, at different acceleration and velocity rates on a sled testing platform. Using these tests, risks of injury will be created and metrics will be developed for the likelihood of injuries due to the acceleration. A finite element model (FEM) of the Test Device for Human Occupant Restraint (THOR) ATD has been developed that can simulate these test trials and others (Putnam, 2014), reducing the need for human and ATD testing. Additionally, this will give researchers a more effective way to test the accelerations and orientations encountered during spaceflight landings during design of new space vehicles for crewed missions. However, the FEM has not been proven and must be validated by comparing the forces, accelerations, and other measurements of all parts of the body between the physical tests already completed and computer simulated trials. The purpose of my research was to validate the FEM for the ATD using previously run trials with the physical THOR ATD.

Experimental models for aging and their potential for novel drug discovery.

PubMed

Folch, Jaume; Busquets, Oriol; Sánchez-López, Miren EttchetoElena; Pallàs, Mercè; Beas-Zarate, Carlos; Marin, Miguel; Casadesus, Gemma; Olloquequi, Jordi; Auladell, Carme; Camins, Antoni

2017-07-07

The development of antiaging drugs is an interesting area of scientific research. In order to evaluate the beneficial effects of new potential drugs, it is necessary to gather the specific knowledge on the adequate preclinical models that are available. This review focuses on invertebrate and vertebrate preclinical models used to evaluate the efficacy of antiaging compounds, with the objective to extend lifespan and health span. Dietary restriction (DR), a common experimental process to extend lifespan in all organisms, is also discussed. Besides, classical antiaging drugs such as resveratrol, rapamycin and metformin, denominated DR mimetics, are reviewed. The main therapeutic targets of these drugs include sirtuins, IGF-1, and mTOR, all of them being modulated by DR. The National Institute on Aging (NIA) developed the Interventions Testing Program (ITP). At the preclinical level, the ITP uses genetically heterogeneous mice model (HET), which is probably the most suitable rodent model to study potential drugs preventing aging-related diseases. The accelerated-senescence mouse P8 is also an interesting rodent model for the research in the field of aging. Notwithstanding, non-human primates are still necessary prior to clinical trials, since they allow an easier extrapolation to humans due to their anatomical and physiological similarities. In this review, the different models and approaches for antiaging studies were evaluated. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Influence of opacifiers on dimensional stability and detail reproduction of maxillofacial silicone elastomer

PubMed Central

2010-01-01

Background We evaluated the influence of chemical disinfection and accelerated aging on the dimensional stability and detail reproduction of a silicone elastomer containing one of two opacifiers. Methods A total of 90 samples were fabricated from Silastic MDX 4-4210 silicone and divided into groups (n = 10) according to opacifier content (barium sulfate or titanium dioxide) and disinfectant solution (neutral soap, Efferdent, or 4% chlorhexidine). The specimens were disinfected 3 times per week during 60 days and then subjected to accelerated aging for 1008 hours. Dimensional stability and detail reproduction tests were performed after specimens' fabrication (baseline), chemical disinfection and periodically during accelerated aging (252, 504, and 1008 hours). The results were analyzed using 3-way repeated-measures ANOVA and the Tukey HSD test (α = 0.05). Results All groups exhibited dimensional changes over time. The opacifier (p = .314), period (p < .0001) and their interactions (p = .0041) affected the dimensional stability of the silicone. Statistical significant dimensional differences occurred between groups with (0.071) and without opacifiers (0.053). Accelerated aging influenced the dimensional stability of the samples. All groups scored 2 in the detail reproduction tests, which represents the fully reproducing of three test grooves with accurate angles. Conclusions Incorporation of opacifiers alters the dimensional stability of silicones used in facial prosthetics, but seems to have no influence on detail reproduction. Accelerated aging is responsible for most of the dimensional changes in Silastic MDX4 4210, but all dimensional changes measured in this study remained within the limits of stability necessary for this application. PMID:21162729

[Autonomic regulation at emotional stress under hypoxic conditions in the elderly with physiological and accelerated aging: effect of hypoxic training].

PubMed

Os'mak, E D; Asanov, É O

2014-01-01

The effect of hypoxic training on autonomic regulation in psycho-emotional stress conditions in hypoxic conditions in older people with physiological (25 people) and accelerated (28 people) aging respiratory system. It is shown that hypoxic training leads to an increase in vagal activity indicators (HF) and reduced simpatovagal index (LF/HF), have a normalizing effect on the autonomic balance during stress loads in older people with different types of aging respiratory system.

Effects of accelerated ageing on viability, leachate exudation, and fatty acid content of Dalbergia sissoo Roxb

Treesearch

R.C. Thapliyal; K.F. Connor

1997-01-01

Accelerated ageing of seeds of Dalbergia sissoo Roxb., a multi-purpose tropical legume tree, was effective as a vigour test only at temperatures in excess of 43 deg C for 72 h. Increased leakage of solutes accompanied the decrease in viability, but there was no relationship between seed size and conductivity. Analyses of D. sissoo...

Accelerated Middle Schools. What Works Clearinghouse Intervention Report

ERIC Educational Resources Information Center

What Works Clearinghouse, 2008

2008-01-01

Accelerated middle schools are self-contained academic programs designed to help middle school students who are behind grade level catch up with their age peers. If these students begin high school with other students their age, the hope is that they will be more likely to stay in school and graduate. The programs serve students who are one to two…

Using the brain's fight-or-flight response for predicting mental illness on the human space flight program

NASA Astrophysics Data System (ADS)

Losik, L.

A predictive medicine program allows disease and illness including mental illness to be predicted using tools created to identify the presence of accelerated aging (a.k.a. disease) in electrical and mechanical equipment. When illness and disease can be predicted, actions can be taken so that the illness and disease can be prevented and eliminated. A predictive medicine program uses the same tools and practices from a prognostic and health management program to process biological and engineering diagnostic data provided in analog telemetry during prelaunch readiness and space exploration missions. The biological and engineering diagnostic data necessary to predict illness and disease is collected from the pre-launch spaceflight readiness activities and during space flight for the ground crew to perform a prognostic analysis on the results from a diagnostic analysis. The diagnostic, biological data provided in telemetry is converted to prognostic (predictive) data using the predictive algorithms. Predictive algorithms demodulate telemetry behavior. They illustrate the presence of accelerated aging/disease in normal appearing systems that function normally. Mental illness can predicted using biological diagnostic measurements provided in CCSDS telemetry from a spacecraft such as the ISS or from a manned spacecraft in deep space. The measurements used to predict mental illness include biological and engineering data from an astronaut's circadian and ultranian rhythms. This data originates deep in the brain that is also damaged from the long-term exposure to cortisol and adrenaline anytime the body's fight or flight response is activated. This paper defines the brain's FOFR; the diagnostic, biological and engineering measurements needed to predict mental illness, identifies the predictive algorithms necessary to process the behavior in CCSDS analog telemetry to predict and thus prevent mental illness from occurring on human spaceflight missions.

Influence of artificial accelerated aging on the color stability and opacity of composites of different shades.

PubMed

Mundim, F M; Da Fonseca Roberti Garcia, L; Silva Sousa, A B; Cruvinel, D R; De Carvalho Panzeri Pires-De-Souza, F

2010-10-01

The aim of this study was to evaluate the influence of artificial accelerated aging on the color stability and opacity of composites of different shades. Four composites for direct use (Heliomolar, 4 Seasons, Tetric EvoCeram; QuiXfil) and one for indirect use (SR Adoro) in two shades were used: light (A2) and dark (C3 for direct, and D4 for indirect composite). QuiXfil was obtained in Universal shade. A Teflon matrix (12 X 2 mm) was used to obtain 54 specimens (N=6), which were submitted to color and opacity analysis (Spectrophotometer PCB 6807, Byk Gardner) before and after artificial accelerated aging for 384 hours. After the statistical analysis (2-way ANOVA - Bonferroni - P<0.05), significant color alteration was observed in the light and dark composites studied (P<0.05), with the exception of QuiXfil. Composite 4 Seasons/C3 showed less color alteration (ΔE=0.91). The opacity alteration (ΔOP) was higher for light composites. Artificial accelerated aging interfered in the optical properties assessed; however, the alterations seemed to be more related to the composites composition than to their shade.

Daily Ingestion of Aloe Vera Gel Powder Containing Aloe Sterols Prevents Skin Photoaging in OVX Hairless Mice.

PubMed

Yao, Ruiqing; Tanaka, Miyuki; Misawa, Eriko; Saito, Marie; Nabeshima, Kazumi; Yamauchi, Koji; Abe, Fumiaki; Yamamoto, Yuki; Furukawa, Fukumi

2016-10-12

Estrogen deficiencies associated with menopause accelerate spontaneous skin aging and stimulate the ultraviolet (UV) irradiation-induced photoaging of skin. However, food compositions with the potential to ameliorate the UV irradiation-induced acceleration of skin aging with menopause have not yet been investigated in detail. In the present study, we examined the ability of plant sterols derived from Aloe vera gel to prevent the UV irradiation-induced acceleration of skin aging in ovariectomized mice. Skin transepidermal water loss (TEWL) was significantly higher in the ovariectomy group than in the sham operation group following UVB irradiation, whereas skin elasticity was significantly lower. Ultraviolet B (UVB) irradiation induced greater reductions in skin hyaluronic acid levels and more severe collagen fiber damage in the derims in the ovariectomy group than in the sham group. The intake of AVGP significantly ameliorated this acceleration in skin aging by reducing the expression of matrix metalloproteinases (MMPs) and increasing that of epidermal growth factor (EGF) and hyaluronan synthase (HAS) in the skin. These results indicate that AVGP supplementation prevents skin damage induced by UVB irradiation and ovariectomy in part by inhibiting damage to the extracellular matrix. © 2016 Institute of Food Technologists®.

Introduction

NASA Astrophysics Data System (ADS)

Assmann, R. W.; Ferrario, M.

2016-09-01

Particle accelerators are a field of continuing and growing success. Today about 30,000 accelerators are operated with various types of particles, including electrons, positrons, protons, neutrinos and various kinds of ions. These particles are used for the investigation of fundamental particles and forces in our universe. In parallel a fast growing field of accelerator-based photon science has developed since the 1970"s. Modern particle beams produce unique photon pulses that are used in ground-breaking studies on fast processes in chemistry and biology, on structures of viruses and bacteria, on the phenomenon of multi-resistivity to medication, on the functioning of photo-synthesis at the electronic level and on other important challenges for human mankind. Last not least, numerous particle accelerators are being used every day for industrial and medical applications, including the irradiation of tumors in human patients.

Human tissue inhibitor of metalloproteinases-1 improved wound healing in diabetes through its anti-apoptotic effect.

PubMed

Lao, Guojuan; Ren, Meng; Wang, Xiaoyi; Zhang, Jinglu; Huang, Yanrui; Liu, Dan; Luo, Hengcong; Yang, Chuan; Yan, Li

2017-09-08

Impaired wound healing accompanies severe cell apoptosis in diabetic patients. Tissue inhibitor of metalloproteinases-1 (TIMP-1) was known to have effects on promoting growth and anti-apoptosis for cells. We aimed to determine the actual levels of TIMP-1 and cell apoptosis in: (i) the biopsies of diabetic and non-diabetic foot tissue and (ii) the human fibroblasts with or without treatments of advanced glycation end-products (AGEs). Next, we aimed to determine the improved levels of cell apoptosis and wound healing after the treatments of either active protein of TIMP-1 or in vivo expression of gene therapy vector-mediated TIMP-1 in both the human fibroblasts and the animal model of diabetic rats. The levels of TIMP-1 were significantly reduced in diabetic skin tissues and in AGEs-treated fibroblasts. Both AGEs-treated cells were effectively protected from apoptosis by active protein of TIMP-1 at appropriate dose level. So did the induced in vivo TIMP-1 expression after gene delivery. Similar effects were also found on the significant improvement of impaired wound healing in diabetic rats. We concluded that TIMP-1 improved wound healing through its anti-apoptotic effect. Treatments with either active protein TIMP-1 or TIMP-1 gene therapy delivered in local wound sites may be used as a strategy for accelerating diabetic wound healing. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Nucleotide excision repair deficient mouse models and neurological disease

PubMed Central

Niedernhofer, Laura J.

2008-01-01

Nucleotide excision repair (NER) is a highly conserved mechanism to remove helix-distorting DNA base damage. A major substrate for NER is DNA damage caused by environmental genotoxins, most notably ultraviolet radiation. Xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy are three human diseases caused by inherited defects in NER. The symptoms and severity of these diseases vary dramatically, ranging from profound developmental delay to cancer predisposition and accelerated aging. All three syndromes include neurological disease, indicating an important role for NER in protecting against spontaneous DNA damage as well. To study the pathophysiology caused by DNA damage, numerous mouse models of NER deficiency were generated by knocking-out genes required for NER or knocking-in disease-causing human mutations. This review explores the utility of these mouse models to study neurological disease caused by NER deficiency. PMID:18272436

"What Is a Step?" Differences in How a Step Is Detected among Three Popular Activity Monitors That Have Impacted Physical Activity Research.

PubMed

John, Dinesh; Morton, Alvin; Arguello, Diego; Lyden, Kate; Bassett, David

2018-04-15

(1) Background: This study compared manually-counted treadmill walking steps from the hip-worn DigiwalkerSW200 and OmronHJ720ITC, and hip and wrist-worn ActiGraph GT3X+ and GT9X; determined brand-specific acceleration amplitude (g) and/or frequency (Hz) step-detection thresholds; and quantified key features of the acceleration signal during walking. (2) Methods: Twenty participants (Age: 26.7 ± 4.9 years) performed treadmill walking between 0.89-to-1.79 m/s (2-4 mph) while wearing a hip-worn DigiwalkerSW200, OmronHJ720ITC, GT3X+ and GT9X, and a wrist-worn GT3X+ and GT9X. A DigiwalkerSW200 and OmronHJ720ITC underwent shaker testing to determine device-specific frequency and amplitude step-detection thresholds. Simulated signal testing was used to determine thresholds for the ActiGraph step algorithm. Steps during human testing were compared using bias and confidence intervals. (3) Results: The OmronHJ720ITC was most accurate during treadmill walking. Hip and wrist-worn ActiGraph outputs were significantly different from the criterion. The DigiwalkerSW200 records steps for movements with a total acceleration of ≥1.21 g. The OmronHJ720ITC detects a step when movement has an acceleration ≥0.10 g with a dominant frequency of ≥1 Hz. The step-threshold for the ActiLife algorithm is variable based on signal frequency. Acceleration signals at the hip and wrist have distinctive patterns during treadmill walking. (4) Conclusions: Three common research-grade physical activity monitors employ different step-detection strategies, which causes variability in step output.

“What Is a Step?” Differences in How a Step Is Detected among Three Popular Activity Monitors That Have Impacted Physical Activity Research

PubMed Central

John, Dinesh; Arguello, Diego; Lyden, Kate; Bassett, David

2018-01-01

(1) Background: This study compared manually-counted treadmill walking steps from the hip-worn DigiwalkerSW200 and OmronHJ720ITC, and hip and wrist-worn ActiGraph GT3X+ and GT9X; determined brand-specific acceleration amplitude (g) and/or frequency (Hz) step-detection thresholds; and quantified key features of the acceleration signal during walking. (2) Methods: Twenty participants (Age: 26.7 ± 4.9 years) performed treadmill walking between 0.89-to-1.79 m/s (2–4 mph) while wearing a hip-worn DigiwalkerSW200, OmronHJ720ITC, GT3X+ and GT9X, and a wrist-worn GT3X+ and GT9X. A DigiwalkerSW200 and OmronHJ720ITC underwent shaker testing to determine device-specific frequency and amplitude step-detection thresholds. Simulated signal testing was used to determine thresholds for the ActiGraph step algorithm. Steps during human testing were compared using bias and confidence intervals. (3) Results: The OmronHJ720ITC was most accurate during treadmill walking. Hip and wrist-worn ActiGraph outputs were significantly different from the criterion. The DigiwalkerSW200 records steps for movements with a total acceleration of ≥1.21 g. The OmronHJ720ITC detects a step when movement has an acceleration ≥0.10 g with a dominant frequency of ≥1 Hz. The step-threshold for the ActiLife algorithm is variable based on signal frequency. Acceleration signals at the hip and wrist have distinctive patterns during treadmill walking. (4) Conclusions: Three common research-grade physical activity monitors employ different step-detection strategies, which causes variability in step output. PMID:29662048

The role of dietary carbohydrates in organismal aging.

PubMed

Lee, Dongyeop; Son, Heehwa G; Jung, Yoonji; Lee, Seung-Jae V

2017-05-01

Carbohydrates are essential nutrients that are used as a primary source of energy. Carbohydrate utilization should be properly controlled, as abnormal regulation of carbohydrate metabolism is associated with diseases, such as diabetes, cardiovascular diseases, and stroke. These metabolic syndromes have become a serious problem in developed countries, and there is an increased need for research examining the influence of carbohydrates on animal physiology. Diets enriched in glucose, a major carbohydrate, are also associated with accelerated aging in several model organisms, including yeast and Caenorhabditis elegans (C. elegans). Genetic factors that mediate the effects of high glucose diets on aging have been identified during the last decade, mostly through the use of C. elegans. In this review, we describe studies that determine the effects of carbohydrate-enriched diets on aging by focusing on the mechanisms through which evolutionarily conserved pathways mediate the lifespan-altering effects of glucose in C. elegans. These include the insulin/insulin-like growth factor-1, sterol-regulatory element-binding protein, and AMP-activated protein kinase signaling pathways. We also discuss the effects of various carbohydrates and carbohydrate-derived metabolites on aging in model organisms and cultured mammalian cells. Finally, we discuss how dietary carbohydrates influence health and aging in humans.

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

Won, Jong-Pil, E-mail: jpwon@konkuk.ac.kr; Hwang, Un-Jong; Lee, Su-Jin

This study evaluated the performance of shotcrete using high strength C{sub 12}A{sub 7} mineral-based accelerator that has been developed to improve the durability and long-term strength. Rebound, compressive strength and flexural strength were tested in the field. Test result showed that existing C{sub 12}A{sub 7} mineral-based accelerator exhibits better early strength than the high-strength C{sub 12}A{sub 7} mineral-based accelerator until the early age, but high-strength C{sub 12}A{sub 7} mineral-based accelerator shows about 29% higher at the long-term age of 28 days. Microstructural analysis such as scanning electron microscope (SEM), X-ray diffraction (XRD) and nitrogen adsorption method was evaluated to analyzemore » long-term strength development mechanism of high strength C{sub 12}A{sub 7} mineral-based accelerator. As analysis result, it had more dense structure due to the reaction product by adding material that used to enhanced strength. It had better resistance performance in chloride ion penetration, freezing–thawing and carbonation than shotcrete that used existing C{sub 12}A{sub 7} mineral-based accelerator.« less

A whole body vibration perception map and associated acceleration loads at the lower leg, hip and head.

PubMed

Sonza, Anelise; Völkel, Nina; Zaro, Milton A; Achaval, Matilde; Hennig, Ewald M

2015-07-01

Whole-body vibration (WBV) training has become popular in recent years. However, WBV may be harmful to the human body. The goal of this study was to determine the acceleration magnitudes at different body segments for different frequencies of WBV. Additionally, vibration sensation ratings by subjects served to create perception vibration magnitude and discomfort maps of the human body. In the first of two experiments, 65 young adults mean (± SD) age range of 23 (± 3.0) years, participated in WBV severity perception ratings, based on a Borg scale. Measurements were performed at 12 different frequencies, two intensities (3 and 5 mm amplitudes) of rotational mode WBV. On a separate day, a second experiment (n = 40) included vertical accelerometry of the head, hip and lower leg with the same WBV settings. The highest lower limb vibration magnitude perception based on the Borg scale was extremely intense for the frequencies between 21 and 25 Hz; somewhat hard for the trunk region (11-25 Hz) and fairly light for the head (13-25 Hz). The highest vertical accelerations were found at a frequency of 23 Hz at the tibia, 9 Hz at the hip and 13 Hz at the head. At 5 mm amplitude, 61.5% of the subjects reported discomfort in the foot region (21-25 Hz), 46.2% for the lower back (17, 19 and 21 Hz) and 23% for the abdominal region (9-13 Hz). The range of 3-7 Hz represents the safest frequency range with magnitudes less than 1 g(*)sec for all studied regions. Copyright © 2015 IPEM. Published by Elsevier Ltd. All rights reserved.

In vitro cytotoxicity of maxillofacial silicone elastomers: effect of accelerated aging.

PubMed

Bal, Bilge Turhan; Yilmaz, Handan; Aydin, Cemal; Karakoca, Seçil; Yilmaz, Sükran

2009-04-01

The purpose of this in vitro study was to evaluate the cytotoxicity of three maxillofacial silicone elastomers at 24, 48, and 72 h on L-929 cells and to determine the effect of accelerated aging on the cytotoxicity of these silicone elastomers. Disc-shaped test samples of maxillofacial silicone elastomers (Cosmesil, Episil, Multisil) were fabricated according to manufacturers' instructions under aseptic conditions. Samples were then divided into three groups: (1) not aged; (2) aged for 150 h with an accelerated weathering tester; and (3) aged for 300 h. Then the samples were placed in Dulbecco's Modified Eagle Medium/Ham's F12 (DMEM/F12) for 24, 48, and 72 h. After the incubation periods, cytotoxicity of the extracts to cultured fibroblasts (L-929) was measured by MTT assay. The degree of cytotoxicity of each sample was determined according to the reference value represented by the cells with a control (culture without sample). Statistical significance was determined by repeated measurement ANOVA (p < 0.01) followed by Duncan's test (p < 0.05). All test materials in each group demonstrated high survival rates in MTT assay (Episil; 93.84%, Multisil; 88.30%, Cosmesil; 87.50%, respectively); however, in all groups, Episil material demonstrated significantly higher cell survival rate after each of the experimental incubation periods (p < 0.05). Accelerated aging for 150 and 300 h had no significant effect on the biocompatibility of maxillofacial silicone elastomers tested (p > 0.05).

Accelerated Skeletal Maturation in Disorders of Retinoic Acid Metabolism: A Case Report and Focused Review of the Literature.

PubMed

Nilsson, O; Isoherranen, N; Guo, M H; Lui, J C; Jee, Y H; Guttmann-Bauman, I; Acerini, C; Lee, W; Allikmets, R; Yanovski, J A; Dauber, A; Baron, J

2016-11-01

Nutritional excess of vitamin A, a precursor for retinoic acid (RA), causes premature epiphyseal fusion, craniosynostosis, and light-dependent retinopathy. Similarly, homozygous loss-of-function mutations in CYP26B1, one of the major RA-metabolizing enzymes, cause advanced bone age, premature epiphyseal fusion, and craniosynostosis. In this paper, a patient with markedly accelerated skeletal and dental development, retinal scarring, and autism-spectrum disease is presented and the role of retinoic acid in longitudinal bone growth and skeletal maturation is reviewed. Genetic studies were carried out using SNP array and exome sequencing. RA isomers were measured in the patient, family members, and in 18 age-matched healthy children using high-performance liquid chromatography coupled to tandem mass spectrometry. A genomic SNP array identified a novel 8.3 megabase microdeletion on chromosome 10q23.2-23.33. The 79 deleted genes included CYP26A1 and C1 , both major RA-metabolizing enzymes. Exome sequencing did not detect any variants that were predicted to be deleterious in the remaining alleles of these genes or other known retinoic acid-metabolizing enzymes. The patient exhibited elevated plasma total RA (16.5 vs. 12.6±1.5 nM, mean±SD, subject vs. controls) and 13- cis RA (10.7 nM vs. 6.1±1.1). The findings support the hypothesis that elevated RA concentrations accelerate bone and dental maturation in humans. CYP26A1 and C1 haploinsufficiency may contribute to the elevated retinoic acid concentrations and clinical findings of the patient, although this phenotype has not been reported in other patients with similar deletions, suggesting that other unknown genetic or environmental factors may also contribute. © Georg Thieme Verlag KG Stuttgart · New York.

Cellular senescence and autophagy in the pathogenesis of chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).

PubMed

Kuwano, Kazuyoshi; Araya, Jun; Hara, Hiromichi; Minagawa, Shunsuke; Takasaka, Naoki; Ito, Saburo; Kobayashi, Kenji; Nakayama, Katsutoshi

2016-11-01

Aging is associated with impairments in homeostasis. Although aging and senescence are not equivalent, the number of senescent cells increases with aging. Cellular senescence plays important roles in tissue repair or remodeling, as well as embryonic development. Autophagy is a process of lysosomal self-degradation that maintains a homeostatic balance between the synthesis, degradation, and recycling of cellular proteins. Autophagy diminishes with aging; additionally, accelerated aging can be attributed to reduced autophagy. Cellular senescence has been widely implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD), a disease of accelerated lung aging, presumably by impairing cell repopulation and by aberrant cytokine secretion in the senescence-associated secretory phenotype. The possible participation of autophagy in the pathogenic sequence of COPD has been extensively explored. Although it has been reported that increased autophagy may induce epithelial cell death, an insufficient reserve of autophagy can induce cellular senescence in bronchial epithelial cells of COPD. Furthermore, advanced age is one of the most important risk factors for the development of idiopathic pulmonary fibrosis (IPF). Telomere shortening is found in blood leukocytes and alveolar epithelial cells from patients with IPF. Accelerated senescence of epithelial cells plays a role in IPF pathogenesis by perpetuating abnormal epithelial-mesenchymal interactions. Insufficient autophagy may be an underlying mechanism of accelerated epithelial cell senescence and myofibroblast differentiation in IPF. Herein, we review the molecular mechanisms of cellular senescence and autophagy and summarize the role of cellular senescence and autophagy in both COPD and IPF. Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Mechanical properties experimental investigation of HTPB propellant after thermal accelerated aging

NASA Astrophysics Data System (ADS)

Yang, Xiaohong; Sun, Chaoxiang; Zhang, Junfa; Xu, Jinsheng; Tan, Bingdong

2017-04-01

To get accurate aging mechanical properties of aged HTPB propellant, the thermal accelerated aging experiment method is utilized and the uniaxial tensile experiments were conducted to obtain the mechanical data of aged HTPB propellants, and the maximum tensile strength, σm, maximum tensile strain, ɛm, and the fracture tensile strain, ɛb, of HTPB propellant with different aging time and various aging temperatures,were obtained, using universal material testing machine. The experimental results show that the σm of HTPB propellant initially increases, subsequently decreases and finally increases with aging time. The ɛm and ɛb generally decrease with increasing aging time, what's more, the decrease rate of both ɛm and ɛb reduce with the aging time. What's more, the postcure effect and oxidation reaction occurred inside HTPB matrix, including the chain degradation reaction and oxidation-induced crosslinking, were discussed to explain the mechanical aging rule of HTPB propellant.

Influence of paints formulations on nanoparticles release during their life cycle

NASA Astrophysics Data System (ADS)

Fiorentino, Brice; Golanski, Luana; Guiot, Arnaud; Damlencourt, Jean-François; Boutry, Delphine

2015-03-01

Pristine nanoparticles (NPs) may present a hazard to humans and the environment, and hence it is important to know to what extent NPs can be freely released from commercialized products in which they are added. The purpose of this study was to identify the parameters of the paint formulation containing SiO2 NPs of 19-nm diameter that could have an impact on the release induced by aging and abrasion. In order to simulate outdoor aging during the life cycle of the product, painted panels were exposed to accelerated weathering experiments in accordance with the norm EN ISO 16474-3:2013. The surface modification of these paints was characterized by scanning electron microscope coupled with energy dispersive spectrometry (SEM-EDS). These analyses showed that the acrylic copolymer binder has undergone a more significant chemical degradation compared with the styrene-acrylic copolymer. To simulate a mechanical aging, abrasion tests were conducted using a Taber Abraser, simulating critical scenarios of the abrasion standard. The particle size distributions and particle concentrations of the abraded particles were measured using an electric low-pressure impactor. After accelerated aging and abrasion tests, we observed a link between the paint degradations occurring with the release of pristine NPs and the embedded pristine NPs. Surface degradation of acrylic copolymer paints was more significant than that of the styrene-acrylic copolymer paints, and this induced a release of NPs 2.7 times higher. Other parameters like TiO2 addition as pigments induced a strong stability of paint against light and water, decreasing the total number of NPs released from paints from 30,000 to 1200 particles/cm3. These results revealed that formulations can be tuned to decrease the number of free NPs released and get a "safe-by-design" product.

Aging Behavior and Performance Projections for a Polysulfide Elastomer

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

Celina, Mathias C.; Giron, Nicholas Henry; Quintana, Adam

The accelerated aging behavior and aging state of a 30 year old field retrieved polysulfide elastomer was examined. The material is used as an environmental thread sealant for a stainless steel bolt in a steel threaded insert in an aluminum assembly. It is a two component curable polysulfide elastomer that is commercially available in a similar formulation as was applied 30 years ago. The primary goal of this study was to establish if aging over 30 years under moderate aging conditions (mostly ambient temperature and humidity) resulted in significant property changes, or if accelerated aging could identify developing aging pathwaysmore » which would prevent the extended use of this material. The aging behavior of this material was examined in three ways: A traditional accelerated thermo-oxidative aging study between 95 to 140°C which focused on physical and chemical properties changes, an evaluation of the underlying oxidation rates between RT and 125°C, and an assessment of the aging state of a small 30 year old sample. All three data sets were used to establish aging characteristics, their time evolution, and to extrapolate the observed behavior to predict performance limits at RT. The accelerated aging study revealed a relatively high average activation energy of ~130 kJ/mol which gives overconfident performance predictions. Oxidation rates showed a decreasing behavior with aging time and a lower E a of ~84 kJ/mol from time - temperature superposition , but also predicted sufficient additional performance at RT. Consistent with these projections for extended RT performance, only small changes were observed for the 30 year old material. Extrapolations using this partially aged material also predict ongoing use as a viable option. Unexpected RT degradation could only develop into a concern should the oxidation rate not trend lower over time as was observed at elevated temperature. Considering all data acquired in this limited aging study , there are no immediately apparent concerns with this material for ongoing use. ACKNOWLEDGEMENTS We thank Lisa Deibler for providing us with a small sample of field aged and new commercial material.« less

Injury Risk Functions in Frontal Impacts Using Data from Crash Pulse Recorders

PubMed Central

Stigson, Helena; Kullgren, Anders; Rosén, Erik

2012-01-01

Knowledge of how crash severity influences injury risk in car crashes is essential in order to create a safe road transport system. Analyses of real-world crashes increase the ability to obtain such knowledge. The aim of this study was to present injury risk functions based on real-world frontal crashes where crash severity was measured with on-board crash pulse recorders. Results from 489 frontal car crashes (26 models of four car makes) with recorded acceleration-time history were analysed. Injury risk functions for restrained front seat occupants were generated for maximum AIS value of two or greater (MAIS2+) using multiple logistic regression. Analytical as well as empirical injury risk was plotted for several crash severity parameters; change of velocity, mean acceleration and peak acceleration. In addition to crash severity, the influence of occupant age and gender was investigated. A strong dependence between injury risk and crash severity was found. The risk curves reflect that small changes in crash severity may have a considerable influence on the risk of injury. Mean acceleration, followed by change of velocity, was found to be the single variable that best explained the risk of being injured (MAIS2+) in a crash. Furthermore, all three crash severity parameters were found to predict injury better than age and gender. However, age was an important factor. The very best model describing MAIS2+ injury risk included delta V supplemented by an interaction term of peak acceleration and age. PMID:23169136

Assessment of human exposure doses received by activation of medical linear accelerator components

NASA Astrophysics Data System (ADS)

Lee, D.-Y.; Kim, J.-H.; Park, E.-T.

2017-08-01

This study analyzes the radiation exposure dose that an operator can receive from radioactive components during maintenance or repair of a linear accelerator. This study further aims to evaluate radiological safety. Simulations are performed on 10 MV and 15 MV photon beams, which are the most frequently used high-energy beams in clinics. The simulation analyzes components in order of activity and the human exposure dose based on the amount of neutrons received. As a result, the neutron dose, radiation dose, and human exposure dose are ranked in order of target, primary collimator, flattening filter, multi-leaf collimator, and secondary collimator, where the minimum dose is 9.34E-07 mSv/h and the maximum is 1.71E-02 mSv/h. When applying the general dose limit (radiation worker 20 mSv/year, pubic 1 mSv/year) in accordance with the Nuclear Safety Act, all components of a linear accelerator are evaluated as below the threshold value. Therefore, the results suggest that there is no serious safety issue for operators in maintaining and repairing a linear accelerator. Nevertheless, if an operator recognizes an exposure from the components of a linear accelerator during operation and considers the operating time and shielding against external exposure, exposure of the operator is expected to be minimized.

Cumulative stress in research animals: Telomere attrition as a biomarker in a welfare context?

PubMed

Bateson, Melissa

2016-02-01

Progress in improving animal welfare is currently limited by the lack of objective methods for assessing lifetime experience. I propose that telomere attrition, a cellular biomarker of biological age, provides a molecular measure of cumulative experience that could be used to assess the welfare impact of husbandry regimes and/or experimental procedures on non-human animals. I review evidence from humans that telomere attrition is accelerated by negative experiences in a cumulative and dose-dependent manner, but that this attrition can be mitigated or even reversed by positive life-style interventions. Evidence from non-human animals suggests that despite some specific differences in telomere biology, stress-induced telomere attrition is a robust phenomenon, occurring in a range of species including mice and chickens. I conclude that telomere attrition apparently integrates positive and negative experience in an accessible common currency that translates readily to novel species--the Holy Grail of a cumulative welfare indicator. © 2015 The Author. BioEssays published by WILEY Periodicals, Inc.

Cumulative stress in research animals: Telomere attrition as a biomarker in a welfare context?

PubMed Central

2015-01-01

Progress in improving animal welfare is currently limited by the lack of objective methods for assessing lifetime experience. I propose that telomere attrition, a cellular biomarker of biological age, provides a molecular measure of cumulative experience that could be used to assess the welfare impact of husbandry regimes and/or experimental procedures on non‐human animals. I review evidence from humans that telomere attrition is accelerated by negative experiences in a cumulative and dose‐dependent manner, but that this attrition can be mitigated or even reversed by positive life‐style interventions. Evidence from non‐human animals suggests that despite some specific differences in telomere biology, stress‐induced telomere attrition is a robust phenomenon, occurring in a range of species including mice and chickens. I conclude that telomere attrition apparently integrates positive and negative experience in an accessible common currency that translates readily to novel species – the Holy Grail of a cumulative welfare indicator. PMID:26645576

Accelerated aging test results for aerospace wire insulation constructions

NASA Technical Reports Server (NTRS)

Dunbar, William G.

1995-01-01

Several wire insulation constructions were evaluated with and without continuous glow discharges at low pressure and high temperature to determine the aging characteristics of acceptable wire insulation constructions. It was known at the beginning of the test program that insulation aging takes several years when operated at normal ambient temperature and pressure of 20 C and 760 torr. Likewise, it was known that the accelerated aging process decreases insulation life by approximately 50% for each 10 C temperature rise. Therefore, the first phases of the program, not reported in these test results, were to select wire insulation constructions that could operate at high temperature and low pressure for over 10,000 hours with negligible shrinkage and little materials' deterioration.The final phase of the program was to determine accelerated aging characteristics. When an insulation construction is subjected to partial discharges the insulation is locally heated by the bombardment of the discharges, the insulation is also subjected to ozone and other deteriorating gas particles that may significantly increase the aging process. Several insulation systems using either a single material or combinations of teflon, kapton, and glass insulation constructions were tested. All constructions were rated to be partial discharge and/or corona-free at 240 volts, 400 Hz and 260 C (500 F) for 50, 000 hours at altitudes equivalent to the Paschen law. Minimum partial discharge aging tests were preceded by screening tests lasting 20 hours at 260 C. The aging process was accelerated by subjecting the test articles to temperatures up to 370 C (700 F) with and without partial discharges. After one month operation with continuous glow discharges surrounding the test articles, most insulation systems were either destroyed or became brittle, cracked, and unsafe for use. Time with space radiation as with partial discharges is accumulative.

Accelerated aging test results for aerospace wire insulation constructions

NASA Astrophysics Data System (ADS)

Dunbar, William G.

1995-11-01

Several wire insulation constructions were evaluated with and without continuous glow discharges at low pressure and high temperature to determine the aging characteristics of acceptable wire insulation constructions. It was known at the beginning of the test program that insulation aging takes several years when operated at normal ambient temperature and pressure of 20 C and 760 torr. Likewise, it was known that the accelerated aging process decreases insulation life by approximately 50% for each 10 C temperature rise. Therefore, the first phases of the program, not reported in these test results, were to select wire insulation constructions that could operate at high temperature and low pressure for over 10,000 hours with negligible shrinkage and little materials' deterioration.The final phase of the program was to determine accelerated aging characteristics. When an insulation construction is subjected to partial discharges the insulation is locally heated by the bombardment of the discharges, the insulation is also subjected to ozone and other deteriorating gas particles that may significantly increase the aging process. Several insulation systems using either a single material or combinations of teflon, kapton, and glass insulation constructions were tested. All constructions were rated to be partial discharge and/or corona-free at 240 volts, 400 Hz and 260 C (500 F) for 50, 000 hours at altitudes equivalent to the Paschen law. Minimum partial discharge aging tests were preceded by screening tests lasting 20 hours at 260 C. The aging process was accelerated by subjecting the test articles to temperatures up to 370 C (700 F) with and without partial discharges. After one month operation with continuous glow discharges surrounding the test articles, most insulation systems were either destroyed or became brittle, cracked, and unsafe for use. Time with space radiation as with partial discharges is accumulative.

The effect of accelerated ageing on colour stability of visible light-cured (VLC) chairside denture liners.

PubMed

Kostoulas, Ioannis; Polyzois, Gregory; Mitsoudis, Anastasios; Kavoura, Victoria; Frangou, Maria

2012-06-01

The purpose of this study was to assess the colour stability of seven visible light-cured (VLC) hard and soft denture liners by an in vitro accelerated ageing test and compare them with two autopolymerised hard and soft liners. Ten specimens of each material were fabricated. The initial colour was measured with a tri-stimulus colorimeter. One set of five specimens was placed in distilled water at 37°C in the dark for 15 days, while the remaining were subjected to UV/visible light-accelerated ageing initially for 24 h and then for 144 h. Colour change (ΔΕ) was calculated. Data were statistically analysed by anova, Tukey and t-tests at α = 0.05. All the liners showed clinically acceptable colour change (ΔΕ ≤ 6.8) in distilled water. The colour changes after ageing for Triad DuaLine, Lightdon U, Ufi Gel H and Light Liner Hard were clinically unacceptable (ΔΕ ≥ 6.8), whereas LightLiner Soft, Astron LC Soft, Triad Resiline and Flexacryl Soft presented slighter and clinically acceptable colour change (ΔΕ ≤ 6.8). Accelerated ageing affected significantly the colour stability of all denture liners tested except Astron LC Soft. Soft VLC denture liners were more colour-stable than hard VLC liners. © 2011 The Gerodontology Society and John Wiley & Sons A/S.

Birth-order differences can drive natural selection on aging.

PubMed

Gillespie, Duncan O S; Trotter, Meredith V; Krishna-Kumar, Siddharth; Tuljapurkar, Shripad D

2014-03-01

Senescence-the deterioration of survival and reproductive capacity with increasing age-is generally held to be an evolutionary consequence of the declining strength of natural selection with increasing age. The diversity in rates of aging observed in nature suggests that the rate at which age-specific selection weakens is determined by species-specific ecological factors. We propose that, in iteroparous species, relationships between parental age, offspring birth order, and environment may affect selection on senescence. Later-born siblings have, on average, older parents than do first borns. Offspring born to older parents may experience different environments in terms of family support or inherited resources, factors often mediated by competition from siblings. Thus, age-specific selection on parents may change if the environment produces birth-order related gradients in reproductive success. We use an age-and-stage structured population model to investigate the impact of sibling environmental inequality on the expected evolution of senescence. We show that accelerated senescence evolves when later-born siblings are likely to experience an environment detrimental to lifetime reproduction. In general, sibling inequality is likely to be of particular importance for the evolution of senescence in species such as humans, where family interactions and resource inheritance have important roles in determining lifetime reproduction. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

Dietary and genetic evidence for phosphate toxicity accelerating mammalian aging

PubMed Central

Ohnishi, Mutsuko; Razzaque, M. Shawkat

2010-01-01

Identifying factors that accelerate the aging process can provide important therapeutic targets for slowing down this process. Misregulation of phosphate homeostasis has been noted in various skeletal, cardiac, and renal diseases, but the exact role of phosphate toxicity in mammalian aging is not clearly defined. Phosphate is widely distributed in the body and is involved in cell signaling, energy metabolism, nucleic acid synthesis, and the maintenance of acid-base balance by urinary buffering. In this study, we used an in vivo genetic approach to determine the role of phosphate toxicity in mammalian aging. Klotho-knockout mice (klotho−/−) have a short life span and show numerous physical, biochemical, and morphological features consistent with premature aging, including kyphosis, uncoordinated movement, hypogonadism, infertility, severe skeletal muscle wasting, emphysema, and osteopenia, as well as generalized atrophy of the skin, intestine, thymus, and spleen. Molecular and biochemical analyses suggest that increased renal activity of sodium-phosphate cotransporters (NaPi2a) leads to severe hyperphosphatemia in klotho−/− mice. Genetically reducing serum phosphate levels in klotho−/− mice by generating a NaPi2a and klotho double-knockout (NaPi2a−/−/klotho−/−) strain resulted in amelioration of premature aging-like features. The NaPi2a−/−/klotho−/− double-knockout mice regained reproductive ability, recovered their body weight, reduced their organ atrophy, and suppressed ectopic calcifications, with the resulting effect being prolonged survival. More important, when hyperphosphatemia was induced in NaPi2a−/−/klotho−/− mice by feeding with a high-phosphate diet, premature aging-like features reappeared, clearly suggesting that phosphate toxicity is the main cause of premature aging in klotho−/− mice. The results of our dietary and genetic manipulation studies provide in vivo evidence for phosphate toxicity accelerating the aging process and suggest a novel role for phosphate in mammalian aging.—Ohnishi, M., Razzaque, M. S. Dietary and genetic evidence for phosphate toxicity accelerating mammalian aging. PMID:20418498

The relationship between infancy growth rate and the onset of puberty in both genders.

PubMed

Aydin, Banu Kucukemre; Devecioglu, Esra; Kadioglu, Alev; Cakmak, Ayca Erkin; Kisabacak, Sezin; Gokcay, Gulbin; Bas, Firdevs; Poyrazoglu, Sukran; Bundak, Ruveyde; Darendeliler, Feyza

2017-12-01

BackgroundIn this study, we examined the hypothesis that weight gain and linear growth during the first years of life influence the onset of puberty both in girls and in boys.MethodsA cohort of 157 healthy children, aged 6-9 years, was evaluated and their growth patterns were analyzed retrospectively. Repeated measures mixed model was used to examine the longitudinal anthropometric data.ResultsGirls with pubertal signs were heavier than their peers starting at 9 months of age (P=0.02), and the difference became more evident over time (P<0.001). Accelerated weight gain between 6 and 15 months of age was found to increase the odds of having a pubertal sign at the study visit (odds ratio (OR)=34.5) after adjusting for birth weight, gestational age and current age, height, weight, and BMI (P=0.004). Anthropometric indices of boys with or without pubertal signs were not significantly different at the study visit, but boys with accelerated height gain between 9 and 15 months of age were more likely to have pubertal signs (OR=15.8) after adjusting for birth weight, gestational age and current age, height, weight, and BMI (P=0.016).ConclusionEarly growth acceleration might be important for the timing of puberty in both genders.

Acceleration of leukocytes' epigenetic age as an early tumor and sex-specific marker of breast and colorectal cancer.

PubMed

Durso, Danielle Fernandes; Bacalini, Maria Giulia; Sala, Claudia; Pirazzini, Chiara; Marasco, Elena; Bonafé, Massimiliano; do Valle, Ítalo Faria; Gentilini, Davide; Castellani, Gastone; Faria, Ana Maria Caetano; Franceschi, Claudio; Garagnani, Paolo; Nardini, Christine

2017-04-04

Changes in blood epigenetic age have been associated with several pathological conditions and have recently been described to anticipate cancer development. In this work, we analyze a publicly available leukocytes methylation dataset to evaluate the relation between DNA methylation age and the prospective development of specific types of cancer. We calculated DNA methylation age acceleration using five state-of-the-art estimators (three multi-site: Horvath, Hannum, Weidner; and two CpG specific: ELOV2 and FHL2) in a cohort including 845 subjects from the EPIC-Italy project and we compared 424 samples that remained cancer-free over the approximately ten years of follow-up with 235 and 166 subjects who developed breast and colorectal cancer, respectively. We show that the epigenetic age estimated from blood DNA methylation data is statistically significantly associated to future breast and male colorectal cancer development. These results are corroborated by survival analysis that shows significant association between age acceleration and cancer incidence suggesting that the chance of developing age-related diseases may be predicted by circulating epigenetic markers, with a dependence upon tumor type, sex and age estimator. These are encouraging results towards the non-invasive and perspective usage of epigenetic biomarkers.

Oxidative stress and age-related changes in T cells: is thalassemia a model of accelerated immune system aging?

PubMed

Ghatreh-Samani, Mahdi; Esmaeili, Nafiseh; Soleimani, Masoud; Asadi-Samani, Majid; Ghatreh-Samani, Keihan; Shirzad, Hedayatolah

2016-01-01

Iron overload in β-thalassemia major occurs mainly due to blood transfusion, an essential treatment for β-thalassemia major patients, which results in oxidative stress. It has been thought that oxidative stress causes elevation of immune system senescent cells. Under this condition, cells normally enhance in aging, which is referred to as premature immunosenescence. Because there is no animal model for immunosenescence, most knowledge on the immunosenescence pattern is based on induction of immunosenescence. In this review, we describe iron overload and oxidative stress in β-thalassemia major patients and how they make these patients a suitable human model for immunosenescence. We also consider oxidative stress in some kinds of chronic virus infections, which induce changes in the immune system similar to β-thalassemia major. In conclusion, a therapeutic approach used to improve the immune system in such chronic virus diseases, may change the immunosenescence state and make life conditions better for β-thalassemia major patients.

Oxidative stress and age-related changes in T cells: is thalassemia a model of accelerated immune system aging?

PubMed Central

Ghatreh-Samani, Mahdi; Esmaeili, Nafiseh; Soleimani, Masoud; Asadi-Samani, Majid; Ghatreh-Samani, Keihan

2016-01-01

Iron overload in β-thalassemia major occurs mainly due to blood transfusion, an essential treatment for β-thalassemia major patients, which results in oxidative stress. It has been thought that oxidative stress causes elevation of immune system senescent cells. Under this condition, cells normally enhance in aging, which is referred to as premature immunosenescence. Because there is no animal model for immunosenescence, most knowledge on the immunosenescence pattern is based on induction of immunosenescence. In this review, we describe iron overload and oxidative stress in β-thalassemia major patients and how they make these patients a suitable human model for immunosenescence. We also consider oxidative stress in some kinds of chronic virus infections, which induce changes in the immune system similar to β-thalassemia major. In conclusion, a therapeutic approach used to improve the immune system in such chronic virus diseases, may change the immunosenescence state and make life conditions better for β-thalassemia major patients. PMID:27095931

Development and population growth: the Indian experience.

PubMed

Chandna, R C

1996-01-01

This paper analyzes the prevailing demographic trends and development processes in India. Data were taken from the World Development Report and the Human Development Reports of South Asia and India, Census of India, and Government of India's Economic Survey. A much slower economic progress and human development was observed in South Asia as compared to those in East Asia. At present, the income levels in East Asia are 27 times higher and have a human development index twice that of South Asia. India had a better economic performance as compared to other countries in South Asia. However, the human deprivations within India continue to hinder the country's emergence as a politico-economic power on the international scene. Investigation of the diversity in population growth and development in India was presented in this paper using indicators such as: average annual population growth; couple protection rate; female literacy; mean age at marriage for females; infrastructural facilities; proportion below poverty line; and the per capita income. Finally, specific suggestions on how to accelerate the fertility transition in the country were enumerated.

[Human bioaging acceleration as Chernobyl radiation consequence].

PubMed

Neĭfakh, E A; Liuman, G K

2013-01-01

To monitor human bioaging as a health integral index by blood plasma markers as a molar ratio for biochemically coupled monomers of intracellular lipofuscin, an intracellular polymeric aging pigment with free-radical crossed shifts, has been developed. Lipofuscin includes cell debris with catabolites of lipoperoxic cascade and lipid antioxidants. The latter were detected in the plasma samples of normal adults and children, as well as in Chernobyl clean-up workers (24-62 years old by 1990) with external total gamma-doses of 0.9-145 cSv for 4.2 years. Dynamics for bioaging markers as the molar ratio of blood levels of lipoperoxic catabolites to their antioxidants reflected normal physiologic peculiarities for the studied age periods: oxygen stress for newborns, adaptation during childhood, stability for the middle age and an increased lipoperoxidation (mainly for aging men) due to the age weakening of the antioxidant control. The ratio for the fractions of ma- lone dialdehyde (MDA), a lipoperoxic final catabolite, showed the increase of its binding by plasma proteins in proportions to calendar ages for the norm, as it is the case for lipofuscin; The graph of the age normal molar ratio of protein-bound MDA to the free one was pre-set for calibrations into the developed computer Program to calculate Relative Aging Velocities (Wrel) by bioage increments during the period of human exposure to radiation from the CAPS damage. Wrel were increasing logarithmically to the obtained doses if the total radiation exceeded 4 cSv and exceeded their normal velocities at 50 cSv 10 times or more. Slowing down of Wrel in relation to the calendar age increment was found if the sum doses were lower than 4 cSv. Levels of the studied plasma metabolites as their bioage Moles/Moles markers relative to their norms are dynamically stationary in contrast to the lipofuscin intracellular irreversible accumulation. Earlier it was shown that the decreased vitamin E and A levels with the increased lipoperoxic metabolite blood levels that indicate health consequences for the irradiated CAPS personell with related cytogenetic deviations, as well as for the adult population and children from radio-polluted regions, were restored to norms or corrected by adequate peroral therapy with bioantioxidants.

Effect of vibration duration on human discomfort. [passenger comfort and random vibration

NASA Technical Reports Server (NTRS)

Clevenson, S. A.; Dempsey, T. K.; Leatherwood, J. D.

1978-01-01

The duration effects of random vertical vibration on passenger discomfort were studied in a simulated section of an aircraft cabin configured to seat six persons in tourist-class style. Variables of the study included time of exposure (0.25 min to 60 min) and the rms amplitude of vibration (0.025g to 0.100g). The vibrations had a white noise spectrum with a bandwidth of 10 Hz centered at 5 Hz. Data indicate that the discomfort threshold occurred at an rms vertical acceleration level of 0.027g for all durations of vibration. However, for acceleration levels that exceeded the discomfort threshold, a systematic decrease in discomfort occurred as a function of increasing duration of vibration. For the range of accelerations used, the magnitude of the discomfort decrement was shown to be independent of acceleration level. The results suggest that discomfort from vertical vibration applied in the frequency range at which humans are most sensitive decreases with longer exposure, which is the opposite of the recommendation of the International Standard ISO 2631-1974 (E) Guide for the Evaluation of Human Exposure to Whole-Body Vibration.

An exploration of the perception of time from the perspective of the Science of Unitary Human Beings.

PubMed

Ring, Marcia E

2009-01-01

What is time? The science of unitary human beings describes pandimensional reality as a domain without spatial or temporal attributes. As part of this pandimensional reality, unitary human beings experience time as passing, and involving the past, present, and future. The theory of accelerating evolution describes changes in human and environmental energy fields that are always accelerating and are manifested as differences in the experience of time as being slow, fast, and still. Time, be it measured or experienced, has no meaning in and of itself, but can only be understood in terms of the ever-evolving life process.

Accumulation of severely atrophic myofibers marks the acceleration of sarcopenia in slow and fast twitch muscles.

PubMed

Rowan, Sharon L; Purves-Smith, Fennigje M; Solbak, Nathan M; Hepple, Russell T

2011-08-01

The age-related decline in muscle mass, known as sarcopenia, exhibits a marked acceleration in advanced age. Although many studies have remarked upon the accumulation of very small myofibers, particularly at advanced stages of sarcopenia, the significance of this phenomenon in the acceleration of sarcopenia has never been examined. Furthermore, although mitochondrial dysfunction characterized by a lack of cytochrome oxidase (COX) activity has been implicated in myofiber atrophy in sarcopenia, the contribution of this phenotype to the accumulation of severely atrophied fibers in aged muscles has never been determined. To this end, we examined the fiber size distribution in the slow twitch soleus (Sol) and fast twitch gastrocnemius (Gas) muscles between young adulthood (YA) and senescence (SEN). We also quantified the abundance of COX deficient myocytes and their size attributes to gain insight into the contribution of this phenotype to myofiber atrophy with aging. Our data showed that the progression of muscle atrophy, particularly its striking acceleration between late middle age and SEN, was paralleled by an accumulation of severely atrophic myofibers (≤ 1000 μm(2) in size) in both Sol and Gas. On the other hand, we observed no COX deficient myofibers in Sol, despite nearly 20% of the myofibers being severely atrophic. Similarly, only 0.17 ± 0.06% of all fibers in Gas were COX deficient, and their size was generally larger (2375 ± 319 μm(2)) than the severely atrophied myofibers noted above. Collectively, our results suggest that similar processes likely contribute to the acceleration of sarcopenia in both slow twitch and fast twitch muscles, and that COX deficiency is not a major contributor to this phenomenon. Copyright © 2011 Elsevier Inc. All rights reserved.

Does cyclic stress and accelerated ageing influence the wear behavior of highly crosslinked polyethylene?

PubMed

Affatato, Saverio; De Mattia, Jonathan Salvatore; Bracco, Pierangiola; Pavoni, Eleonora; Taddei, Paola

2016-06-01

First-generation (irradiated and remelted or annealed) and second-generation (irradiated and vitamin E blended or doped) highly crosslinked polyethylenes were introduced in the last decade to solve the problems of wear and osteolysis. In this study, the influence of the Vitamin-E addition on crosslinked polyethylene (XLPE_VE) was evaluated by comparing the in vitro wear behavior of crosslinked polyethylene (XLPE) versus Vitamin-E blended polyethylene XLPE and conventional ultra-high molecular weight polyethylene (STD_PE) acetabular cups, after accelerated ageing according to ASTM F2003-02 (70.0±0.1°C, pure oxygen at 5bar for 14 days). The test was performed using a hip joint simulator run for two millions cycles, under bovine calf serum as lubricant. Mass loss was found to decrease along the series XLPE_VE>STD_PE>XLPE, although no statistically significant differences were found between the mass losses of the three sets of cups. Micro-Raman spectroscopy was used to investigate at a molecular level the morphology changes induced by wear. The spectroscopic analyses showed that the accelerated ageing determined different wear mechanisms and molecular rearrangements during testing with regards to the changes in both the chain orientation and the distribution of the all-trans sequences within the orthorhombic, amorphous and third phases. The results of the present study showed that the addition of vitamin E was not effective to improve the gravimetric wear of PE after accelerated ageing. However, from a molecular point of view, the XLPE_VE acetabular cups tested after accelerated ageing appeared definitely less damaged than the STD_PE ones and comparable to XLPE samples. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ground-based research with heavy ions for space radiation protection

NASA Astrophysics Data System (ADS)

Durante, M.; Kronenberg, A.

Human exposure to ionizing radiation is one of the acknowledged potential showstoppers for long duration manned interplanetary missions. Human exploratory missions cannot be safely performed without a substantial reduction of the uncertainties associated with different space radiation health risks, and the development of effective countermeasures. Most of our knowledge of the biological effects of heavy charged particles comes from accelerator-based experiments. During the 35th COSPAR meeting, recent ground-based experiments with high-energy iron ions were discussed, and these results are briefly summarised in this paper. High-quality accelerator-based research with heavy ions will continue to be the main source of knowledge of space radiation health effects and will lead to reductions of the uncertainties in predictions of human health risks. Efforts in materials science, nutrition and pharmaceutical sciences and their rigorous evaluation with biological model systems in ground-based accelerator experiments will lead to the development of safe and effective countermeasures to permit human exploration of the Solar System.

Soil as a record of the past: Mass migration as the result of soil exhausting

NASA Astrophysics Data System (ADS)

van Mourik, Jan; Kluiving, Sjoerd

2014-05-01

An extensive area in Northwest Europe is covered by chemical poor Late Glacial aeolian sands. Till the Bronze Age the soils evolution in the coversand landscapes correlated with the geomorphological structure, Umbric Podzols on coversand ridges, Gleyic Podzols on coversand planes and Umbric or Histic Arenosols in brook valleys. Essential was the storage of nutrients in the biomass of the forest system. The nutrient cycle has been for long time a stabilizing factor in the forest ecosystems, repressing further soil acidification. Human occupation resulted in transformation of natural to cultural soilscapes. Agricultural management introduced lateral transport of nutrients from the soil system to the market and interrupted the natural vertical cycling. The results were soil exhaustion and acceleration of soil acidification. 1. In the early Bronze Age, shifting cultivation was applied to create small lots of arable land. Burning of forest means acceleration of the release of organic stored nutrients, available for crop production. However, the moderate rain climate of Northwest Europe caused leaching of released nutrients that were not quickly recycled. Nutrient losses stimulated the soil acidification and in very dry seasons even small scale sand drifting could occur. Without any nutrient addition (fertilization), shifting cultivation is not a form of sustainable land use and led to land degradation. 2. In the early Iron Age, the system Celtic field came in use. Systematic transport of nutrients from green strips to production lots and harvesting caused gradual nutrient losses of the soilscape and accelerated the soil acidification; Umbric Podzols degraded to Carbic Podzols. Celtic Field land management was also not a sustainable form of land use and led to land degradation. 3. Later in time, the lateral transport of nutrients increased during application of plaggic agriculture. Soil acidification continued on heath lands, the production area of organic manure. During the period with plaggic agriculture, the soils on arable fields development from Umbric Podzols to Plaggic podzols and Plaggic Anthrosols. Agriculture on such field became sustainable under conditions of a low productivity. In several archaeological studies there is evidence that the human impact on soils caused significant nutrient losses, soil degradation and diminishing crop production. People had to migrate to another area which a higher soil fertility to guarantee food production. Patterns of migration to fertile areas (if available) have been studied by archaeologists. Lack of space urged people to invent management techniques and equipment to increase crop production inside the occupied area.

Mass migration as the result of soil exhausting

NASA Astrophysics Data System (ADS)

van Mourik, Jan; Kluiving, Sjoerd

2014-05-01

An extensive area in Northwest Europe is covered by chemical poor Late Glacial aeolian sands. Till the Bronze Age the soils evolution in the coversand landscapes correlated with the geomorphological structure, Umbric Podzols on coversand ridges, Gleyic Podzols on coversand planes and Umbric or Histic Arenosols in brook valleys. Essential was the storage of nutrients in the biomass of the forest system. The nutrient cycle has been for long time a stabilizing factor in the forest ecosystems, repressing further soil acidification. Human occupation resulted in transformation of natural to cultural soilscapes. Agricultural management introduced lateral transport of nutrients from the soil system to the market and interrupted the natural vertical cycling. The results were soil exhaustion and acceleration of soil acidification. 1. In the early Bronze Age, shifting cultivation was applied to create small lots of arable land. Burning of forest means acceleration of the release of organic stored nutrients, available for crop production. However, the moderate rain climate of Northwest Europe caused leaching of released nutrients that were not quickly recycled. Nutrient losses stimulated the soil acidification and in very dry seasons even small scale sand drifting could occur. Without any nutrient addition (fertilization), shifting cultivation is not a form of sustainable land use and led to land degradation. 2. In the early Iron Age, the system Celtic field came in use. Systematic transport of nutrients from green strips to production lots and harvesting caused gradual nutrient losses of the soilscape and accelerated the soil acidification; Umbric Podzols degraded to Carbic Podzols. Celtic Field land management was also not a sustainable form of land use and led to land degradation. 3. Later in time, the lateral transport of nutrients increased during application of plaggic agriculture. Soil acidification continued on heath lands, the production area of organic manure. During the period with plaggic agriculture, the soils on arable fields development from Umbric Podzols to Plaggic podzols and Plaggic Anthrosols. Agriculture on such field became sustainable under conditions of a low productivity. In several archaeological studies there is evidence that the human impact on soils caused significant nutrient losses, soil degradation and diminishing crop production. People had to migrate to another area which a higher soil fertility to guarantee food production. Patterns of migration to fertile areas (if available) have been studied by archaeologists. Lack of space urged people to invent management techniques and equipment to increase crop production inside the occupied area.

Lifetime validation of high-reliability (>30,000hr) rotary cryocoolers for specific customer profiles

NASA Astrophysics Data System (ADS)

Cauquil, Jean-Marc; Seguineau, Cédric; Vasse, Christophe; Raynal, Gaetan; Benschop, Tonny

2018-05-01

The cooler reliability is a major performance requested by the customers, especially for 24h/24h applications, which are a growing market. Thales has built a reliability policy based on accelerate ageing and tests to establish a robust knowledge on acceleration factors. The current trend seems to prove that the RM2 mean time to failure is now higher than 30,000hr. Even with accelerate ageing; the reliability growth becomes hardly manageable for such large figures. The paper focuses on these figures and comments the robustness of such a method when projections over 30,000hr of MTTF are needed.

Age-Status Labeling in Homosexual Men

ERIC Educational Resources Information Center

Minnigerode, Fred A.

1976-01-01

Homosexual men (N=95) between 25 and 68 years of age were asked to classify themselves as young, middle-aged, or old. The popular suggestion of accelerated aging in homosexual men was not supported. (Author)

Fanconi Anemia: A DNA repair disorder characterized by accelerated decline of the hematopoietic stem cell compartment and other features of aging.

PubMed

Brosh, Robert M; Bellani, Marina; Liu, Yie; Seidman, Michael M

2017-01-01

Fanconi Anemia (FA) is a rare autosomal genetic disorder characterized by progressive bone marrow failure (BMF), endocrine dysfunction, cancer, and other clinical features commonly associated with normal aging. The anemia stems directly from an accelerated decline of the hematopoietic stem cell compartment. Although FA is a complex heterogeneous disease linked to mutations in 19 currently identified genes, there has been much progress in understanding the molecular pathology involved. FA is broadly considered a DNA repair disorder and the FA gene products, together with other DNA repair factors, have been implicated in interstrand cross-link (ICL) repair. However, in addition to the defective DNA damage response, altered epigenetic regulation, and telomere defects, FA is also marked by elevated levels of inflammatory mediators in circulation, a hallmark of faster decline in not only other hereditary aging disorders but also normal aging. In this review, we offer a perspective of FA as a monogenic accelerated aging disorder, citing the latest evidence for its multi-factorial deficiencies underlying its unique clinical and cellular features. Published by Elsevier B.V.

Interactions between creep, fatigue and strain aging in two refractory alloys

NASA Technical Reports Server (NTRS)

Sheffler, K. D.

1972-01-01

The application of low-amplitude, high-frequency fatigue vibrations during creep testing of two strain-aging refractory alloys (molybdenum-base TZC and tantalum-base T-111) significantly reduced the creep strength of these materials. This strength reduction caused dramatic increases in both the first stage creep strain and the second stage creep rate. The magnitude of the creep rate acceleration varied directly with both frequency and A ratio (ratio of alternating to mean stress), and also varied with temperature, being greatest in the range where the strain-aging phenomenon was most prominent. It was concluded that the creep rate acceleration resulted from a negative strain rate sensitivity which is associated with the strain aging phenomenon in these materials. (A negative rate sensitivity causes flow stress to decrease with increasing strain rate, instead of increasing as in normal materials). By combining two analytical expressions which are normally used to describe creep and strain aging behavior, an expression was developed which correctly described the influence of temperature, frequency, and A ratio on the TZC creep rate acceleration.

Characterization and Accelerated Ageing of UHMWPE Used in Orthopedic Prosthesis by Peroxide

PubMed Central

Rocha, Magda; Mansur, Alexandra; Mansur, Herman

2009-01-01

Ultra-high molecular weight polyethylene (UHMWPE) has been the most commonly used bearing material in total joint arthroplasty. Wear and oxidation fatigue resistance of UHMWPE are regarded as two important mechanical properties to extend the longevity of knee prostheses. Though accelerated in vitro protocols have been developed to test the relative oxidation resistance of various types of UHMWPE, its mechanism is not accurately understood yet. Thus, in the present study an accelerated ageing of UHMWPE in hydrogen peroxide solution was performed and relative oxidation was extensively characterized by Fourier Transformed Infrared Spectroscopy (FTIR) spectroscopy and the morphological changes were analyzed by Scanning Electron Microscopy (SEM). Different chemical groups of UHMWPE associated with the degradation reaction were monitored for over 120 days in order to evaluate the possible oxidation mechanism(s) which may have occurred. The results have provided strong evidence that the oxidation mechanism is rather complex, and two stages with their own particular first-order kinetics reaction patterns have been clearly identified. Furthermore, hydrogen peroxide has proven to be an efficient oxidative medium to accelerate ageing of UHMWPE.

Chronic pancreatitis: Do serum biomarkers provide an association with an inflammageing phenotype?

PubMed

Rasch, Sebastian; Valantiene, Irena; Mickevicius, Artautas; Beer, Sebastian; Rosendahl, Jonas; Charnley, Richard M; Robinson, Stuart M

2016-01-01

Chronic pancreatitis is an inflammatory disorder of the pancreas that is associated with accelerated mortality for patients suffering from this disease. The association between chronic inflammation and accelerated biological ageing has been well described and is often referred to as "inflammageing". In this review we seek to determine how systemic inflammation in chronic pancreatitis may contribute to an accelerated ageing phenotype. A systematic literature search with a predefined search protocol was performed on Medline, Embase and Cochrane libraries according to the PRISMA guidelines. The initial search identified 499 studies. After title, abstract and full text screen of the search results, 20 were included for further evaluation. In the 20 remaining articles 41 inflammatory mediators were identified - mainly involved in chronic inflammation, fibrosis and particularly cardinal features of inflammageing such as sarcopenia and osteoporosis. Chronic pancreatitis is associated with elevated levels of inflammatory mediators many of which are associated with an accelerated ageing phenotype and may explain some of the clinical sequelae of this disease. Copyright © 2016 IAP and EPC. All rights reserved.

Effects of Aged Stored Autologous Red Blood Cells on Human Endothelial Function

PubMed Central

Kanias, Tamir; Triulzi, Darrel; Donadee, Chenell; Barge, Suchitra; Badlam, Jessica; Jain, Shilpa; Belanger, Andrea M.; Kim-Shapiro, Daniel B.

2015-01-01

Rationale: A major abnormality that characterizes the red cell “storage lesion” is increased hemolysis and reduced red cell lifespan after infusion. Low levels of intravascular hemolysis after transfusion of aged stored red cells disrupt nitric oxide (NO) bioavailabity, via accelerated NO scavenging reaction with cell-free plasma hemoglobin. The degree of intravascular hemolysis post-transfusion and effects on endothelial-dependent vasodilation responses to acetylcholine have not been fully characterized in humans. Objectives: To evaluate the effects of blood aged to the limits of Food and Drug Administration–approved storage time on the human microcirculation and endothelial function. Methods: Eighteen healthy individuals donated 1 U of leukopheresed red cells, divided and autologously transfused into the forearm brachial artery 5 and 42 days after blood donation. Blood samples were obtained from stored blood bag supernatants and the antecubital vein of the infusion arm. Forearm blood flow measurements were performed using strain-gauge plethysmography during transfusion, followed by testing of endothelium-dependent blood flow with increasing doses of intraarterial acetylcholine. Measurements and Main Results: We demonstrate that aged stored blood has higher levels of arginase-1 and cell-free plasma hemoglobin. Compared with 5-day blood, the transfusion of 42-day packed red cells decreases acetylcholine-dependent forearm blood flows. Intravascular venous levels of arginase-1 and cell-free plasma hemoglobin increase immediately after red cell transfusion, with more significant increases observed after infusion of 42-day-old blood. Conclusions: We demonstrate that the transfusion of blood at the limits of Food and Drug Administration–approved storage has a significant effect on the forearm circulation and impairs endothelial function. Clinical trial registered with www.clinicaltrials.gov (NCT 01137656) PMID:26222884

Number of Children and Telomere Length in Women: A Prospective, Longitudinal Evaluation

PubMed Central

Barha, Cindy K.; Hanna, Courtney W.; Salvante, Katrina G.; Wilson, Samantha L.; Robinson, Wendy P.; Altman, Rachel M.; Nepomnaschy, Pablo A.

2016-01-01

Life history theory (LHT) predicts a trade-off between reproductive effort and the pace of biological aging. Energy invested in reproduction is not available for tissue maintenance, thus having more offspring is expected to lead to accelerated senescence. Studies conducted in a variety of non-human species are consistent with this LHT prediction. Here we investigate the relationship between the number of surviving children born to a woman and telomere length (TL, a marker of cellular aging) over 13 years in a group of 75 Kaqchikel Mayan women. Contrary to LHT’s prediction, women who had fewer children exhibited shorter TLs than those who had more children (p = 0.045) after controlling for TL at the onset of the 13-year study period. An “ultimate” explanation for this apparently protective effect of having more children may lay with human’s cooperative-breeding strategy. In a number of socio-economic and cultural contexts, having more chilren appears to be linked to an increase in social support for mothers (e.g., allomaternal care). Higher social support, has been argued to reduce the costs of further reproduction. Lower reproductive costs may make more metabolic energy available for tissue maintenance, resulting in a slower pace of cellular aging. At a “proximate” level, mechanisms involved may include the actions of the gonadal steroid estradiol, which increases dramatically during pregnancy. Estradiol is known to protect TL from the effects of oxidative stress as well as increase telomerase activity, an enzyme that maintains TL. Future research should explore the potential role of social support as well as that of estradiol and other potential biological pathways in the trade-offs between reproductive effort and the pace of cellular aging within and among human as well as in non-human populations. PMID:26731744

Mated Progeny Production Is a Biomarker of Aging in Caenorhabditis elegans

PubMed Central

Pickett, Christopher L.; Dietrich, Nicholas; Chen, Junfang; Xiong, Chengjie; Kornfeld, Kerry

2013-01-01

The relationships between reproduction and aging are important for understanding the mechanisms of aging and evaluating evolutionary theories of aging. To investigate the effects of progeny production on reproductive and somatic aging, we conducted longitudinal studies of Caenorhabditis elegans hermaphrodites. For mated wild-type animals that were not sperm limited and survived past the end of the reproductive period, high levels of cross-progeny production were positively correlated with delayed reproductive and somatic aging. In this group of animals, individuals that generated more cross progeny also reproduced and lived longer than individuals that generated fewer cross progeny. These results indicate that progeny production does not accelerate reproductive or somatic aging. This longitudinal study demonstrated that cumulative cross progeny production through day four is an early-stage biomarker that is a positive predictor of longevity. Furthermore, in mated animals, high levels of early cross progeny production were positively correlated with high levels of late cross progeny production, indicating that early progeny production does not accelerate reproductive aging. The relationships between progeny production and aging were further evaluated by comparing self-fertile hermaphrodites that generated relatively few self progeny with mated hermaphrodites that generated many cross progeny. The timing of age-related somatic degeneration was similar in these groups, suggesting progeny production does not accelerate somatic aging. These studies rigorously define relationships between progeny production, reproductive aging, and somatic aging and identify new biomarkers of C. elegans aging. These results indicate that some mechanisms or pathways control age-related degeneration of both reproductive and somatic tissues in C. elegans. PMID:24142929

Accelerated Aging Experiments for Capacitor Health Monitoring and Prognostics

NASA Technical Reports Server (NTRS)

Kulkarni, Chetan S.; Celaya, Jose Ramon; Biswas, Gautam; Goebel, Kai

2012-01-01

This paper discusses experimental setups for health monitoring and prognostics of electrolytic capacitors under nominal operation and accelerated aging conditions. Electrolytic capacitors have higher failure rates than other components in electronic systems like power drives, power converters etc. Our current work focuses on developing first-principles-based degradation models for electrolytic capacitors under varying electrical and thermal stress conditions. Prognostics and health management for electronic systems aims to predict the onset of faults, study causes for system degradation, and accurately compute remaining useful life. Accelerated life test methods are often used in prognostics research as a way to model multiple causes and assess the effects of the degradation process through time. It also allows for the identification and study of different failure mechanisms and their relationships under different operating conditions. Experiments are designed for aging of the capacitors such that the degradation pattern induced by the aging can be monitored and analyzed. Experimental setups and data collection methods are presented to demonstrate this approach.

Regional alveolar partial pressure of oxygen measurement with parallel accelerated hyperpolarized gas MRI.

PubMed

Kadlecek, Stephen; Hamedani, Hooman; Xu, Yinan; Emami, Kiarash; Xin, Yi; Ishii, Masaru; Rizi, Rahim

2013-10-01

Alveolar oxygen tension (Pao2) is sensitive to the interplay between local ventilation, perfusion, and alveolar-capillary membrane permeability, and thus reflects physiologic heterogeneity of healthy and diseased lung function. Several hyperpolarized helium ((3)He) magnetic resonance imaging (MRI)-based Pao2 mapping techniques have been reported, and considerable effort has gone toward reducing Pao2 measurement error. We present a new Pao2 imaging scheme, using parallel accelerated MRI, which significantly reduces measurement error. The proposed Pao2 mapping scheme was computer-simulated and was tested on both phantoms and five human subjects. Where possible, correspondence between actual local oxygen concentration and derived values was assessed for both bias (deviation from the true mean) and imaging artifact (deviation from the true spatial distribution). Phantom experiments demonstrated a significantly reduced coefficient of variation using the accelerated scheme. Simulation results support this observation and predict that correspondence between the true spatial distribution and the derived map is always superior using the accelerated scheme, although the improvement becomes less significant as the signal-to-noise ratio increases. Paired measurements in the human subjects, comparing accelerated and fully sampled schemes, show a reduced Pao2 distribution width for 41 of 46 slices. In contrast to proton MRI, acceleration of hyperpolarized imaging has no signal-to-noise penalty; its use in Pao2 measurement is therefore always beneficial. Comparison of multiple schemes shows that the benefit arises from a longer time-base during which oxygen-induced depolarization modifies the signal strength. Demonstration of the accelerated technique in human studies shows the feasibility of the method and suggests that measurement error is reduced here as well, particularly at low signal-to-noise levels. Copyright © 2013 AUR. Published by Elsevier Inc. All rights reserved.

Human Tolerance to Rapidly Applied Accelerations: A Summary of the Literature

NASA Technical Reports Server (NTRS)

Eiband, A. Martin

1959-01-01

The literature is surveyed to determine human tolerance to rapidly applied accelerations. Pertinent human and animal experiments applicable to space flight and to crash impact forces are analyzed and discussed. These data are compared and presented on the basis of a trapezoidal pulse. The effects of body restraint and of acceleration direction, onset rate, and plateau duration on the maximum tolerable and survivable rapidly applied accelerations are shown. Results of the survey indicate that adequate torso and extremity restraint is the primary variable in tolerance to rapidly applied accelerations. The harness, or restraint system, must be arranged to transmit the major portion of the accelerating force directly to the pelvic structure and not via the vertebral column. When the conditions of adequate restraint have been met, then the other variables, direction, magnitude, and onset rate of rapidly applied accelerations, govern maximum tolerance and injury limits. The results also indicate that adequately stressed aft-faced passenger seats offer maximum complete body support with minimum objectionable harnessing. Such a seat, whether designed for 20-, 30-, or 40-G dynamic loading, would include lap strap, chest (axillary) strap, and winged-back seat to increase headward and lateral G protection, full-height integral head rest, arm rests (load-bearing) with recessed hand-holds and provisions to prevent arms from slipping either laterally or beyond the seat back, and leg support to keep the legs from being wedged under the seat. For crew members and others whose duties require forward-facing seats, maximum complete body support requires lap, shoulder, and thigh straps, lap-belt tie-down strap, and full-height seat back with integral head support.

FRAS1-related extracellular matrix 3 (FREM3) single-nucleotide polymorphism effects on gene expression, amygdala reactivity and perceptual processing speed: An accelerated aging pathway of depression risk

PubMed Central

Nikolova, Yuliya S.; Iruku, Swetha P.; Lin, Chien-Wei; Conley, Emily Drabant; Puralewski, Rachel; French, Beverly; Hariri, Ahmad R.; Sibille, Etienne

2015-01-01

The A allele of the FRAS1-related extracellular matrix protein 3 (FREM3) rs7676614 single nucleotide polymorphism (SNP) was linked to major depressive disorder (MDD) in an early genome-wide association study (GWAS), and to symptoms of psychomotor retardation in a follow-up investigation. In line with significant overlap between age- and depression-related molecular pathways, parallel work has shown that FREM3 expression in postmortem human brain decreases with age. Here, we probe the effect of rs7676614 on amygdala reactivity and perceptual processing speed, both of which are altered in depression and aging. Amygdala reactivity was assessed using a face-matching BOLD fMRI paradigm in 365 Caucasian participants in the Duke Neurogenetics Study (DNS) (192 women, mean age 19.7 ± 1.2). Perceptual processing speed was indexed by reaction times in the same task and the Trail Making Test (TMT). The effect of rs7676614 on FREM3 mRNA brain expression levels was probed in a postmortem cohort of 169 Caucasian individuals (44 women, mean age 50.8 ± 14.9). The A allele of rs7676614 was associated with blunted amygdala reactivity to faces, slower reaction times in the face-matching condition (p < 0.04), as well as marginally slower performance on TMT Part B (p = 0.056). In the postmortem cohort, the T allele of rs6537170 (proxy for the rs7676614 A allele), was associated with trend-level reductions in gene expression in Brodmann areas 11 and 47 (p = 0.066), reminiscent of patterns characteristic of older age. The low-expressing allele of another FREM3 SNP (rs1391187) was similarly associated with reduced amygdala reactivity and slower TMT Part B speed, in addition to reduced BA47 activity and extraversion (p < 0.05). Together, these results suggest common genetic variation associated with reduced FREM3 expression may confer risk for a subtype of depression characterized by reduced reactivity to environmental stimuli and slower perceptual processing speed, possibly suggestive of accelerated aging. PMID:26441752

Progress in Characterizing Thermal Degradation of Ethylene-Propylene Rubber

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

Fifield, Leonard S.; Huang, Qian; Childers, Matthew I.

Ethylene-propylene rubber (EPR) is one of the two most common nuclear cable insulation materials. A large fraction of EPR-insulated cables in use in the nuclear industry were manufactured by The Okonite Company. Okoguard® is the name of the medium voltage thermoset EPR manufactured by The Okonite Company. Okoguard® has been produced with silane-treated clay filler and the characteristic pink color since the 1970’s. EPR is complex material that undergoes simultaneous reactions during thermal aging including oxidative and thermal cleavage and oxidative and thermal crosslinking. This reaction complexity makes precise EPR service life prediction from accelerated aging using approaches designed formore » single discreet reactions such as the Arrhenius approach problematic. Performance data and activation energies for EPR aged at conditions closer to service conditions will improve EPR lifetime prediction. In this report pink Okoguard® EPR insulation material has been thermally aged at elevated temperatures. A variety of characterization techniques have been employed to track material changes with aging. It was noted that EPR aged significant departure in aging behavior seemed to occur at accelerated aging temperatures between 140°C and 150°C at around 20 days of exposure. This may be due to alternative degradation mechanisms being accessed at this higher temperature and reinforces the need to perform accelerated aging for Okoguard® EPR service life prediction at temperatures below 150°C.« less

Detection of a novel, integrative aging process suggests complex physiological integration.

PubMed

Cohen, Alan A; Milot, Emmanuel; Li, Qing; Bergeron, Patrick; Poirier, Roxane; Dusseault-Bélanger, Francis; Fülöp, Tamàs; Leroux, Maxime; Legault, Véronique; Metter, E Jeffrey; Fried, Linda P; Ferrucci, Luigi

2015-01-01

Many studies of aging examine biomarkers one at a time, but complex systems theory and network theory suggest that interpretations of individual markers may be context-dependent. Here, we attempted to detect underlying processes governing the levels of many biomarkers simultaneously by applying principal components analysis to 43 common clinical biomarkers measured longitudinally in 3694 humans from three longitudinal cohort studies on two continents (Women's Health and Aging I & II, InCHIANTI, and the Baltimore Longitudinal Study on Aging). The first axis was associated with anemia, inflammation, and low levels of calcium and albumin. The axis structure was precisely reproduced in all three populations and in all demographic sub-populations (by sex, race, etc.); we call the process represented by the axis "integrated albunemia." Integrated albunemia increases and accelerates with age in all populations, and predicts mortality and frailty--but not chronic disease--even after controlling for age. This suggests a role in the aging process, though causality is not yet clear. Integrated albunemia behaves more stably across populations than its component biomarkers, and thus appears to represent a higher-order physiological process emerging from the structure of underlying regulatory networks. If this is correct, detection of this process has substantial implications for physiological organization more generally.

Mechanisms of skin aging induced by EGFR inhibitors.

PubMed

Gerber, Peter Arne; Buhren, Bettina Alexandra; Schrumpf, Holger; Hevezi, Peter; Bölke, Edwin; Sohn, Dennis; Jänicke, Reiner U; Belum, Viswanath Reddy; Robert, Caroline; Lacouture, Mario E; Homey, Bernhard

2016-10-01

The mechanisms of skin aging have not been completely elucidated. Anecdotal data suggests that EGFR inhibition accelerates aging-like skin changes. The objective of the study was to evaluate the clinical characteristics and investigate the cellular and molecular mechanisms underlying skin changes associated with the use of EFGRIs. Patients during prolonged treatment with EGFRIs (>3 months) were analyzed for aging-like skin changes. Baseline EGFR expression was compared in young (<25 years old) vs. old (> 65 years old) skin. In addition, the regulation of extracellular matrix, senescence-associated genes, and cell cycle status was measured in primary human keratinocytes treated with erlotinib in vitro. There were progressive signs of skin aging, including xerosis cutis, atrophy, rhytide formation, and/or actinic purpura in 12 patients. Keratinocytes treated with erlotinib in vitro showed a significant down-modulation of hyaluronan synthases (HAS2 and HAS3), whereas senescence-associated genes (p21, p53, IL-6, maspin) were upregulated, along with a G1 cell cycle arrest and stronger SA β-Gal activity. There was significantly decreased baseline expression in EGFR density in aged skin, when compared to young controls. EGFR inhibition results in molecular alterations in keratinocytes that may contribute to the observed skin aging of patients treated with respective targeted agents.

Mechanisms of skin aging induced by EGFR inhibitors

PubMed Central

Gerber, Peter Arne; Buhren, Bettina Alexandra; Schrumpf, Holger; Hevezi, Peter; Bölke, Edwin; Sohn, Dennis; Jänicke, Reiner; Belum, Viswanath Reddy; Robert, Caroline; Lacouture, Mario E.; Homey, Bernhard

2017-01-01

BACKGROUND The mechanisms of skin aging have not been completely elucidated. Anecdotal data suggests that EGFR inhibition accelerates aging-like skin changes. OBJECTIVE To evaluate the clinical characteristics and investigate the cellular and molecular mechanisms underlying skin changes associated with the use of EFGRIs. PATIENTS AND METHODS Patients during prolonged treatment with EGFRIs (>3 months) were analyzed for aging-like skin changes. Baseline EGFR expression was compared in young (< 25 years old) vs. old (> 65 years old) skin. In addition, the regulation of extracellular matrix, senescence-associated genes, and cell cycle status was measured in primary human keratinocytes treated with erlotinib in vitro. RESULTS Progressive signs of skin aging, including xerosis cutis, atrophy, rhytide formation and/or actinic purpura in 12 patients. Keratinocytes treated with erlotinib in vitro showed a significant down-modulation of hyaluronan synthases (HAS2 and HAS3), whereas senescence-associated genes (p21, p53, IL-6, maspin) were upregulated, along with a G1 cell cycle arrest and stronger SA β-Gal activity. There was significantly decreased baseline expression in EGFR-density in aged skin, when compared to young controls. CONCLUSIONS EGFR inhibition results in molecular alterations in keratinocytes that may contribute to the observed skin aging of patients treated with respective targeted agents. PMID:27165055

D-Galactose High-Dose Administration Failed to Induce Accelerated Aging Changes in Neurogenesis, Anxiety, and Spatial Memory on Young Male Wistar Rats.

PubMed

Cardoso, Armando; Magano, Sara; Marrana, Francisco; Andrade, José P

2015-12-01

The model of accelerated senescence with the prolonged administration of d-galactose is used in anti-aging studies because it mimics several aging-associated alterations such as increase of oxidative stress and decline of cognition. However, there is no standardized protocol for this aging model, and recently some reports have questioned its effectiveness. To clarify this issue, we used a model of high-dose d-galactose on 1-month-old male Wistar rats and studied the hippocampus, one of the most affected brain regions. In one group (n = 10), d-galactose was daily administered intraperitoneally (300 mg/kg) during 8 weeks whereas age-matched controls (n = 10) were injected intraperitoneally with saline. A third group (n = 10) was treated with the same dose of d-galactose and with oral epigallocatechin-3-gallate (EGCG) (2 grams/L), a green tea catechin with anti-oxidant and neuroprotective properties. After treatments, animals were submitted to open-field, elevated plus-maze and Morris water maze tests, and neurogenesis in the dentate gyrus subgranular layer was quantified. There were no significant alterations when the three groups were compared in the number of doublecortin- and Ki-67-immunoreactive cells, and also on anxiety levels, spatial learning, and memory. Therefore, d-galactose was not effective in the induction of accelerated aging, and EGCG administered to d-galactose-treated animals did not improve behavior and had no effects on neurogenesis. We conclude that daily 300 mg/kg of d-galactose administered intraperitoneally may not be a suitable model for inducing age-related neurobehavioral alterations in young male Wistar rats. More studies are necessary to obtain a reliable and reproducible model of accelerated senescence in rodents using d-galactose.

Resin composite characterizations following a simplified protocol of accelerated aging as a function of the expiration date.

PubMed

D'Alpino, Paulo Henrique Perlatti; Vismara, Marcus Vinícius Gonçalves; Mello, Luciano Marcelo de Medeiros; Di Hipólito, Vinicius; González, Alejandra Hortencia Miranda; Graeff, Carlos Frederico de Oliveira

2014-07-01

This study evaluated the mechanical, thermal, and morphological characteristics of different classifications of dental composites as a function of the material condition (new, aged and expired). Specimens were obtained according to these factors: Composites: Filtek P60, Filtek Z250, Filtek Z350XT, and Filtek Silorane; and Material conditions: new, aged, and expired. The syringe composites underwent an accelerated aging protocol (Arrhenius model). The flexural strength (FS) and flexural modulus (E) were obtained. The thermogravimetric analysis (TGA) and differential thermal analysis (DTA) were also performed and the glass transition temperature (Tg) and the weight loss calculated. Topographic analysis of the composites was performed under SEM. The material conditions influenced the mechanical properties of the composites. The silorane composite exhibited a characteristic thermal behavior different from that of the methacrylates. In general, the Tg increased after the accelerated aging protocol and decreased for expired ones, compared to the new composites. A significant increase in FS of Filtek Z350XT after aging was accompanied by an increase in the Tg. The filler packings were in accordance with the manufacture׳s information. The topographic aspects of the composites were modified as a function of the material condition. The mechanical properties of the composites following a simplified protocol of accelerated aging varied as a function of the expiration date. The silorane composite presented a characteristic thermal behavior. Although the dental manufacturers may not be able to control variables as storage temperature and transportation conditions, these effects on the composite clinical performance can be minimized if properly considered. Copyright © 2014 Elsevier Ltd. All rights reserved.

Bloom’s Syndrome: Why Not Premature Aging? A comparison of the BLM and WRN helicases

PubMed Central

de Renty, Christelle; Ellis, Nathan A.

2016-01-01

Genomic instability is a hallmark of cancer and aging. Premature aging (progeroid) syndromes are often caused by mutations in genes whose function is to ensure genomic integrity. The RecQ family of DNA helicases is highly conserved and plays crucial roles as genome caretakers. In human, mutations in three RecQ genes — BLM, WRN, and RECQL4 — give rise to Bloom’s syndrome (BS), Werner syndrome (WS), and Rothmund-Thomson’s syndrome (RTS), respectively. WS is a prototypic premature aging disorder; however, the clinical features present in BS and RTS do not indicate accelerated aging. The BLM helicase has pivotal functions at the crossroads of DNA replication, recombination, and repair. BS cells exhibit a characteristic form of genomic instability that includes excessive recombination. The excessive homologous recombination drives the development of the many types of cancers that affect persons in the normal population. Replication delay and slower cell turnover rates have been proposed to explain many features of Bloom’s syndrome, such as short stature. More recently, aberrant transcriptional regulation of growth and survival genes has been proposed as a hypothesis. PMID:27238185

Premature aging and cancer in nucleotide excision repair-disorders

PubMed Central

Diderich, K.; Alanazi, M.; Hoeijmakers, J.H.J.

2014-01-01

During past decades the major impact of DNA damage on cancer as ‘disease of the genes’ has become abundantly apparent. In addition to cancer recent years have also uncovered a very strong association of DNA damage with many features of (premature) aging. The notion that DNA repair systems not only protect against cancer but equally against too fast aging has become evident from a systematic, integral analysis of a variety of mouse mutants carrying defects in e.g. transcription-coupled repair with or without an additional impairment of global genome nucleotide excision repair and the corresponding segmental premature aging syndromes in man. A striking correlation between the degree of the DNA repair deficiency and the acceleration of specific progeroid symptoms has been discovered for those repair systems that primarily protect from the cytotoxic and cytostatic effects of DNA damage. These observations are explained from the perspective of nucleotide excision repair mouse mutant and human syndromes. However, similar principles likely apply to other DNA repair pathways including interstrand crosslink repair and double strand break repair and genome maintenance systems in general, supporting the notion that DNA damage constitutes an important intermediate in the process of aging. PMID:21680258

Accelerating Precision Drug Development and Drug Repurposing by Leveraging Human Genetics

PubMed Central

Shirey-Rice, Jana K.; Lavieri, Robert R.; Jerome, Rebecca N.; Zaleski, Nicole M.; Aronoff, David M.; Bastarache, Lisa; Niu, Xinnan; Holroyd, Kenneth J.; Roden, Dan M.; Skaar, Eric P.; Niswender, Colleen M.; Marnett, Lawrence J.; Lindsley, Craig W.; Ekstrom, Leeland B.; Bentley, Alan R.; Bernard, Gordon R.; Hong, Charles C.; Denny, Joshua C.

2017-01-01

Abstract The potential impact of using human genetic data linked to longitudinal electronic medical records on drug development is extraordinary; however, the practical application of these data necessitates some organizational innovations. Vanderbilt has created resources such as an easily queried database of >2.6 million de-identified electronic health records linked to BioVU, which is a DNA biobank with more than 230,000 unique samples. To ensure these data are used to maximally benefit and accelerate both de novo drug discovery and drug repurposing efforts, we created the Accelerating Drug Development and Repurposing Incubator, a multidisciplinary think tank of experts in various therapeutic areas within both basic and clinical science as well as experts in legal, business, and other operational domains. The Incubator supports a diverse pipeline of drug indication finding projects, leveraging the natural experiment of human genetics. PMID:28379727

Developmental origins of NAFLD: a womb with a clue

PubMed Central

Wesolowski, Stephanie R.; El Kasmi, Karim C.; Jonscher, Karen R.; Friedman, Jacob E.

2017-01-01

Changes in the maternal environment leading to an altered intrauterine milieu can result in subtle insults to the fetus, promoting increased lifetime disease risk and/or disease acceleration in childhood and later in life. Particularly worrisome is that the prevalence of NAFLD is rapidly increasing among children and adults, and is being diagnosed at increasingly younger ages, pointing towards an early-life origin. A wealth of evidence, in humans and non-human primates, suggests that maternal nutrition affects the placenta and fetal tissues, leading to persistent changes in hepatic metabolism, mitochondrial function, the intestinal microbiota, liver macrophage activation and susceptibility to NASH postnatally. Deleterious exposures in utero include fetal hypoxia, increased nutrient supply, inflammation and altered gut microbiota that might produce metabolic clues, including fatty acids, metabolites, endotoxins, bile acids and cytokines, which prime the infant liver for NAFLD in a persistent manner and increase susceptibility to NASH. Mechanistic links to early disease pathways might involve shifts in lipid metabolism, mitochondrial dysfunction, pioneering gut microorganisms, macrophage programming and epigenetic changes that alter the liver microenvironment, favouring liver injury. In this Review, we discuss how maternal, fetal, neonatal and infant exposures provide developmental clues and mechanisms to help explain NAFLD acceleration and increased disease prevalence. Mechanisms identified in clinical and preclinical models suggest important opportunities for prevention and intervention that could slow down the growing epidemic of NAFLD in the next generation. PMID:27780972

Laser-wakefield accelerators as hard x-ray sources for 3D medical imaging of human bone

PubMed Central

Cole, J. M.; Wood, J. C.; Lopes, N. C.; Poder, K.; Abel, R. L.; Alatabi, S.; Bryant, J. S. J.; Jin, A.; Kneip, S.; Mecseki, K.; Symes, D. R.; Mangles, S. P. D.; Najmudin, Z.

2015-01-01

A bright μm-sized source of hard synchrotron x-rays (critical energy Ecrit > 30 keV) based on the betatron oscillations of laser wakefield accelerated electrons has been developed. The potential of this source for medical imaging was demonstrated by performing micro-computed tomography of a human femoral trabecular bone sample, allowing full 3D reconstruction to a resolution below 50 μm. The use of a 1 cm long wakefield accelerator means that the length of the beamline (excluding the laser) is dominated by the x-ray imaging distances rather than the electron acceleration distances. The source possesses high peak brightness, which allows each image to be recorded with a single exposure and reduces the time required for a full tomographic scan. These properties make this an interesting laboratory source for many tomographic imaging applications. PMID:26283308

Boosting Adolescent and Young Adult Literacy: An Examination of Literacy Teaching and Learning in Philadelphia's Accelerated High Schools

ERIC Educational Resources Information Center

Gold, Eva; Edmunds, Kimberly; Maluk, Holly; Reumann-Moore, Rebecca

2011-01-01

In 2010-11, the School District of Philadelphia (the District) operated thirteen accelerated high schools that served approximately 2,000 under-credited, over-age students. Each of the accelerated schools was managed by one of seven external providers, each with its own educational approach, and each with a contractual agreement with the…

Molecular mechanisms of green tea polyphenols with protective effects against skin photoaging.

PubMed

Roh, Eunmiri; Kim, Jong-Eun; Kwon, Jung Yeon; Park, Jun Seong; Bode, Ann M; Dong, Zigang; Lee, Ki Won

2017-05-24

Whereas green tea has historically been consumed in high quantities in Northeast Asia, its popularity is also increasing in many Western countries. Green tea is an abundant source of plant polyphenols exhibiting numerous effects that are potentially beneficial for human health. Accumulating evidence suggests that green tea polyphenols confer protective effects on the skin against ultraviolet (UV) irradiation-induced acceleration of skin aging, involving antimelanogenic, antiwrinkle, antioxidant, and anti-inflammatory effects as well as prevention of immunosuppression. Melanin pigmentation in the skin is a major defense mechanism against UV irradiation, but pigmentation abnormalities such as melasma, freckles, senile lentigines, and other forms of melanin hyperpigmentation can also cause serious health and aesthetic issues. Furthermore, UV irradiation initiates the degradation of fibrillar collagen and elastic fibers, promoting the process of skin aging through deep wrinkle formation and loss of tissue elasticity. UV irradiation-induced formation of free radicals also contributes to accelerated photoaging. Additionally, immunosuppression caused by UV irradiation plays an important role in photoaging and skin carcinogenesis. In this review, we summarize the current literature regarding the antimelanogenic, antiwrinkle, antioxidant, and immunosuppression preventive mechanisms of green tea polyphenols that have been demonstrated to protect against UV irradiation-stimulated skin photoaging, and gauge the quality of evidence supporting the need for clinical studies using green tea polyphenols as anti-photoaging agents in novel cosmeceuticals.

Methamphetamine Accelerates Cellular Senescence through Stimulation of De Novo Ceramide Biosynthesis

PubMed Central

Astarita, Giuseppe; Avanesian, Agnesa; Grimaldi, Benedetto; Realini, Natalia; Justinova, Zuzana; Panlilio, Leight V.; Basit, Abdul; Piomelli, Daniele

2015-01-01

Methamphetamine is a highly addictive psychostimulant that causes profound damage to the brain and other body organs. Post mortem studies of human tissues have linked the use of this drug to diseases associated with aging, such as coronary atherosclerosis and pulmonary fibrosis, but the molecular mechanism underlying these findings remains unknown. Here we used functional lipidomics and transcriptomics experiments to study abnormalities in lipid metabolism in select regions of the brain and, to a greater extent, peripheral organs and tissues of rats that self-administered methamphetamine. Experiments in various cellular models (primary mouse fibroblasts and myotubes) allowed us to investigate the molecular mechanisms of systemic inflammation and cellular aging related to methamphetamine abuse. We report now that methamphetamine accelerates cellular senescence and activates transcription of genes involved in cell-cycle control and inflammation by stimulating production of the sphingolipid messenger ceramide. This pathogenic cascade is triggered by reactive oxygen species, likely generated through methamphetamine metabolism via cytochrome P450, and involves the recruitment of nuclear factor-κB (NF-κB) to induce expression of enzymes in the de novo pathway of ceramide biosynthesis. Inhibitors of NF-κB signaling and ceramide formation prevent methamphetamine-induced senescence and systemic inflammation in rats self-administering the drug, attenuating their health deterioration. The results suggest new therapeutic strategies to reduce the adverse consequences of methamphetamine abuse and improve effectiveness of abstinence treatments. PMID:25671639

Soiling of building envelope surfaces and its effect on solar reflectance – Part III: Interlaboratory study of an accelerated aging method for roofing materials

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

Sleiman, Mohamad; Chen, Sharon; Gilbert, Haley E.

A laboratory method to simulate natural exposure of roofing materials has been reported in a companion article. Here in the current article, we describe the results of an international, nine-participant interlaboratory study (ILS) conducted in accordance with ASTM Standard E691-09 to establish the precision and reproducibility of this protocol. The accelerated soiling and weathering method was applied four times by each laboratory to replicate coupons of 12 products representing a wide variety of roofing categories (single-ply membrane, factory-applied coating (on metal), bare metal, field-applied coating, asphalt shingle, modified-bitumen cap sheet, clay tile, and concrete tile). Participants reported initial and laboratory-agedmore » values of solar reflectance and thermal emittance. Measured solar reflectances were consistent within and across eight of the nine participating laboratories. Measured thermal emittances reported by six participants exhibited comparable consistency. For solar reflectance, the accelerated aging method is both repeatable and reproducible within an acceptable range of standard deviations: the repeatability standard deviation sr ranged from 0.008 to 0.015 (relative standard deviation of 1.2–2.1%) and the reproducibility standard deviation sR ranged from 0.022 to 0.036 (relative standard deviation of 3.2–5.8%). The ILS confirmed that the accelerated aging method can be reproduced by multiple independent laboratories with acceptable precision. In conclusion, this study supports the adoption of the accelerated aging practice to speed the evaluation and performance rating of new cool roofing materials.« less

Mitochondrial damage and ageing using skin as a model organ.

PubMed

Hudson, Laura; Bowman, Amy; Rashdan, Eyman; Birch-Machin, Mark A

2016-11-01

Ageing describes the progressive functional decline of an organism over time, leading to an increase in susceptibility to age-related diseases and eventually to death, and it is a phenomenon observed across a wide range of organisms. Despite a vast repertoire of ageing studies performed over the past century, the exact causes of ageing remain unknown. For over 50 years it has been speculated that mitochondria play a key role in the ageing process, due mainly to correlative data showing an increase in mitochondrial dysfunction, mitochondrial DNA (mtDNA) damage, and reactive oxygen species (ROS) with age. However, the exact role of the mitochondria in the ageing process remains unknown. The skin is often used to study human ageing, due to its easy accessibility, and the observation that the ageing process is able to be accelerated in this organ via environmental insults, such as ultra violet radiation (UVR). This provides a useful tool to investigate the mechanisms regulating ageing and, in particular, the role of the mitochondria. Observations from dermatological and photoageing studies can provide useful insights into chronological ageing of the skin and other organs such as the brain and liver. Moreover, a wide range of diseases are associated with ageing; therefore, understanding the cause of the ageing process as well as regulatory mechanisms involved could provide potentially advantageous therapeutic targets for the prevention or treatment of such diseases. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

End-stage renal disease and diabetes catalyze the formation of a pentose-derived crosslink from aging human collagen.

PubMed

Sell, D R; Monnier, V M

1990-02-01

Structure elucidation of a specific fluorophore from the aging extracellular matrix revealed the presence of a protein crosslink formed through nonenzymatic glycosylation of lysine and arginine residues. The unexpected finding that a pentose instead of a hexose is involved in the crosslinking process suggested that the crosslink, named pentosidine, might provide insight into abnormalities of pentose metabolism in aging and disease. This hypothesis was investigated by quantitating pentosidine in hydrolysates of 103 human skin specimens obtained randomly at autopsy. Pentosidine level was found to increase exponentially from 5 to 75 pmol/mg collagen over lifespan (r = 0.86, P less than 0.001). A three- to tenfold increase was noted in insulin-dependent diabetic and nondiabetic subjects with severe end-stage renal disease requiring hemodialysis (P less than 0.001). Moderately elevated levels were also noted in some very old subjects, some subjects with non-insulin dependent diabetes, and two subjects with cystic fibrosis and diabetes. The cause of the abnormal pentose metabolism in these conditions is unknown but may relate to hemolysis, impaired pentose excretion, cellular stress, and accelerated breakdown of ribonucleotides. Thus, pentosidine emerges as a useful tool for assessment of previously unrecognized disorders of pentose metabolism in aging and disease. Its presence in red blood cells and plasma proteins suggests that it might be used as a measure of integrated pentosemia in analogy to glycohemoglobin for the assessment of cumulative glycemia.

Anthropometrics and maturity status: A preliminary study of youth football head impact biomechanics.

PubMed

Yeargin, Susan W; Kingsley, Payton; Mensch, Jim M; Mihalik, Jason P; Monsma, Eva V

2017-10-03

There is a paucity of head impact biomechanics research focusing on youth athletes. Little is known about how youth subconcussive head impact tolerances are related to physical size and maturation. To examine the effects of age, anthropometric and maturational status variability on head impact biomechanics. Cross-sectional. Outdoor youth football facilities in South Carolina. Thirty-four male recreational youth football players, 8 to 13yrs. Categorized by CDC standards, independent variables were: age, height, mass, BMI, and estimated peak height velocity (PHV). Participants wore a designated head impact sensor (xPatch) on their mastoid process during practices and games. Linear acceleration (g) and rotational acceleration (rad/s 2 ). Boys in the older age category had a greater linear (F=17.72; P<0.001) and rotational acceleration (F=10.74; P<0.001) than those in the younger category. Post-PHV boys had higher linear (F=9.09, P=0.002) and rotational (F=5.57, P=0.018) accelerations than those who were pre-PHV. Rotational, but not linear acceleration differed by height category with lowest impacts found for the tallest category, whereas both linear and rotational accelerations by mass differences favored average and heavy categories. BMI overweight boys, had the greatest linear (F=5.25; P=0.011) and rotational acceleration (F=4.13; P=0.260) means. Post-PHV boys who were older, taller and had longer legs, but who were not heavier, had higher impacts perhaps due to the type of impacts sustained. Taller boys' heads are above their peers possibly encouraging hits in the torso region resulting in lower impact accelerations. Obese boys did not have sequential results compared to boys in the other BMI categories probably due to league rules, player position, and lack of momentum produced. Copyright © 2017 Elsevier B.V. All rights reserved.

On the Use of Accelerated Aging Methods for Screening High Temperature Polymeric Composite Materials

NASA Technical Reports Server (NTRS)

Gates, Thomas S.; Grayson, Michael A.

1999-01-01

A rational approach to the problem of accelerated testing of high temperature polymeric composites is discussed. The methods provided are considered tools useful in the screening of new materials systems for long-term application to extreme environments that include elevated temperature, moisture, oxygen, and mechanical load. The need for reproducible mechanisms, indicator properties, and real-time data are outlined as well as the methodologies for specific aging mechanisms.

Andy Sessler: The Full Life of an Accelerator Physicist

NASA Astrophysics Data System (ADS)

Kim, Kwang-Je; Budnitz, Robert J.; Winick, Herman

2015-02-01

This article describes the distinguished career of Andrew M. Sessler, the visionary former director of the Lawrence Berkeley National Laboratory (LBNL), one of the most influential accelerator physicists, and a strong, dedicated human-rights activist. Andy died on 17 April 2014 from cancer at age 85. He grew up in New York City, and attended Harvard (BA in Mathematics, 1949) and then Columbia (PhD in Physics, 1953.) After an NSF postdoc at Cornell with Hans Bethe and a stint on the faculty at the Ohio State University in 1954-59, he joined the Lawrence Radiation Laboratory (now LBNL) in 1959, and spent the remainder of his career there. Although Andy l his mark on several areas of physics, including nuclear structure theory, elementary-particle physics, and many-body problems, his lasting and most important contributions came from his efforts in accelerator physics and engineering, to which he devoted most of his life's work. In collaboration with his colleagues of the legendary Midwestern Universities Research Association, he developed theories for the RF acceleration process and the collective instability phenomena, helping to realize the colliding-beam accelerators with which most of the high-energy-physics discoveries of the last few decades have been made. His work in connection with the free-electron-laser (FEL) amplifier for high-power microwave generation constructed at the Lawrence Livermore National Laboratory anticipated the optical-guiding and the self-amplified spontaneous-emission principles, upon which the success of the X-ray FELs as the fourth-generation light sources is based. Throughout his career Andy made major contributions to issues related to the impact of science and technology on society. He helped usher in a new era of research on energy efficiency and sustainable-energy technology and was instrumental in building the research agendas in those areas for the Atomic Energy Commission (AEC) and later the Department of Energy. With a lifelong interest in promoting the human rights of scientists, Andy was instrumental in initiating the American Physical Society's Committee on International Freedom of Scientists and in raising funds to endow the APS Andrei Sakharov Prize. He and Moishe Pripstein cofounded Scientists for Sakharov, Orlov, and Sharansky; the group's protests along with those of other groups led to the release of the three Soviet dissidents. More importantly, Andy's voice and example became a major force in helping call the world's attention to the plight of scientists trapped in places where their human rights and their ability to do science were severely compromised. Andy received many honors, including the AEC's Ernest Orlando Lawrence Award in 1970, the APS's Dwight Nicholson Medal in 1994, and the Enrico Fermi Award from the US Department of Energy in 2014.

Andy Sessler: The Full Life of an Accelerator Physicist

NASA Astrophysics Data System (ADS)

Kim, Kwang-Je; Budnitz, Robert J.; Winick, Herman

2014-04-01

This article describes the distinguished career of Andrew M. Sessler, the visionary former director of the Lawrence Berkeley National Laboratory (LBNL), one of the most influential accelerator physicists, and a strong, dedicated human-rights activist. Andy died on 17 April 2014 from cancer at age 85. He grew up in New York City, and attended Harvard (BA in Mathematics, 1949) and then Columbia (PhD in Physics, 1953.) After an NSF postdoc at Cornell with Hans Bethe and a stint on the faculty at the Ohio State University in 1954-59, he joined the Lawrence Radiation Laboratory (now LBNL) in 1959, and spent the remainder of his career there. Although Andy l his mark on several areas of physics, including nuclear structure theory, elementary-particle physics, and many-body problems, his lasting and most important contributions came from his efforts in accelerator physics and engineering, to which he devoted most of his life's work. In collaboration with his colleagues of the legendary Midwestern Universities Research Association, he developed theories for the RF acceleration process and the collective instability phenomena, helping to realize the colliding-beam accelerators with which most of the high-energy-physics discoveries of the last few decades have been made. His work in connection with the free-electron-laser (FEL) amplifier for high-power microwave generation constructed at the Lawrence Livermore National Laboratory anticipated the optical-guiding and the self-amplified spontaneous-emission principles, upon which the success of the X-ray FELs as the fourth-generation light sources is based. Throughout his career Andy made major contributions to issues related to the impact of science and technology on society. He helped usher in a new era of research on energy efficiency and sustainable-energy technology and was instrumental in building the research agendas in those areas for the Atomic Energy Commission (AEC) and later the Department of Energy. With a lifelong interest in promoting the human rights of scientists, Andy was instrumental in initiating the American Physical Society's Committee on International Freedom of Scientists and in raising funds to endow the APS Andrei Sakharov Prize. He and Moishe Pripstein cofounded Scientists for Sakharov, Orlov, and Sharansky; the group's protests along with those of other groups led to the release of the three Soviet dissidents. More importantly, Andy's voice and example became a major force in helping call the world's attention to the plight of scientists trapped in places where their human rights and their ability to do science were severely compromised. Andy received many honors, including the AEC's Ernest Orlando Lawrence Award in 1970, the APS's Dwight Nicholson Medal in 1994, and the Enrico Fermi Award from the US Department of Energy in 2014.

Andy Sessler: The Full Life of an Accelerator Physicist

NASA Astrophysics Data System (ADS)

Kim, Kwang-Je; Budnitz, Robert J.; Winick, Herman

This article describes the distinguished career of Andrew M. Sessler, the visionary former director of the Lawrence Berkeley National Laboratory (LBNL), one of the most influential accelerator physicists, and a strong, dedicated human-rights activist. Andy died on 17 April 2014 from cancer at age 85. He grew up in New York City, and attended Harvard (BA in Mathematics, 1949) and then Columbia (PhD in Physics, 1953.) After an NSF postdoc at Cornell with Hans Bethe and a stint on the faculty at the Ohio State University in 1954-59, he joined the Lawrence Radiation Laboratory (now LBNL) in 1959, and spent the remainder of his career there. Although Andy left his mark on several areas of physics, including nuclear structure theory, elementary-particle physics, and many-body problems, his lasting and most important contributions came from his efforts in accelerator physics and engineering, to which he devoted most of his life's work. In collaboration with his colleagues of the legendary Midwestern Universities Research Association, he developed theories for the RF acceleration process and the collective instability phenomena, helping to realize the colliding-beam accelerators with which most of the high-energy-physics discoveries of the last few decades have been made. His work in connection with the free-electron-laser (FEL) amplifier for high-power microwave generation constructed at the Lawrence Livermore National Laboratory anticipated the optical-guiding and the self-amplified spontaneous-emission principles, upon which the success of the X-ray FELs as the fourth-generation light sources is based. Throughout his career Andy made major contributions to issues related to the impact of science and technology on society. He helped usher in a new era of research on energy efficiency and sustainable-energy technology and was instrumental in building the research agendas in those areas for the Atomic Energy Commission (AEC) and later the Department of Energy. With a lifelong interest in promoting the human rights of scientists, Andy was instrumental in initiating the American Physical Society's Committee on International Freedom of Scientists and in raising funds to endow the APS Andrei Sakharov Prize. He and Moishe Pripstein cofounded Scientists for Sakharov, Orlov, and Sharansky; the group's protests along with those of other groups led to the release of the three Soviet dissidents. More importantly, Andy's voice and example became a major force in helping call the world's attention to the plight of scientists trapped in places where their human rights and their ability to do science were severely compromised. Andy received many honors, including the AEC's Ernest Orlando Lawrence Award in 1970, the APS's Dwight Nicholson Medal in 1994, and the Enrico Fermi Award from the US Department of Energy in 2014.

The sense of balance in humans: Structural features of otoconia and their response to linear acceleration

PubMed Central

Kniep, Rüdiger; Zahn, Dirk; Wulfes, Jana

2017-01-01

We explored the functional role of individual otoconia within the otolith system of mammalians responsible for the detection of linear accelerations and head tilts in relation to the gravity vector. Details of the inner structure and the shape of intact human and artificial otoconia were studied using environmental scanning electron microscopy (ESEM), including decalcification by ethylenediaminetetraacetic acid (EDTA) to discriminate local calcium carbonate density. Considerable differences between the rhombohedral faces of human and artificial otoconia already indicate that the inner architecture of otoconia is not consistent with the point group -3m. This is clearly confirmed by decalcified otoconia specimen which are characterized by a non-centrosymmetric volume distribution of the compact 3+3 branches. This structural evidence for asymmetric mass distribution was further supported by light microscopy in combination with a high speed camera showing the movement of single otoconia specimen (artificial specimen) under gravitational influence within a viscous medium (artificial endolymph). Moreover, the response of otoconia to linear acceleration forces was investigated by particle dynamics simulations. Both, time-resolved microscopy and computer simulations of otoconia acceleration show that the dislocation of otoconia include significant rotational movement stemming from density asymmetry. Based on these findings, we suggest an otolith membrane expansion/stiffening mechanism for enhanced response to linear acceleration transmitted to the vestibular hair cells. PMID:28406968

Early age strength increase of fly ash blended cement by a ternary hardening accelerating admixture

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

Hoang, Kien; Justnes, Harald; SINTEF Building and Infrastructure

The applicability of a combination of sodium thiocyanate (NaSCN), diethanolamine (DEA) and glycerol (Gly) with small dosages as a ternary hardening accelerating admixture for fly ash blended cement (OPC-FA) was studied. The ternary admixture induced higher early and later age mortar strength at both low (5 °C) and normal (20 °C) temperature. Despite used in lower dosage the ternary admixture led to higher strength of the investigated OPC-FA system than other chemicals (e.g. sodium sulfate). Results obtained from isothermal calorimetry, thermogravimetric analysis (TGA) and X-ray diffraction (XRD) showed that the ternary admixture accelerated the cement hydration and increased the amountmore » of AFm (notably calcium hemicarboaluminate hydrate) in the hydration products. A synergistic effect between the three components of the accelerator on the hydration of OPC-FA system was observed.« less

Effect of accelerated ageing and surface sealing on the permanent deformation of auto-polymerising soft linings.

PubMed

da Silva, Joaquim; Takahashi, Jessica; Nuňez, Juliana; Consani, Rafael; Mesquita, Marcelo

2012-09-01

To compare the effects of different ageing methods on the permanent deformation of two permanent soft liners. The materials selected were auto-polymerising acrylic resin and silicone-based reliners. Sealer coating was also evaluated. Sixty specimens of each reliner were manufactured (12.7 mm diameter and 19 mm length). Specimens were randomly distributed into 12 groups (n = 10) and submitted to one of the accelerated ageing processes. Permanent deformation tests were conducted with a mechanical device described within the American Dental Association specification number 18 with a compressive load of 750 gf applied for 30 s. All data were submitted for statistical analysis. Mann-Whitney test compared the effect of the surface sealer on each material and the permanent deformation of the materials in the same ageing group (p = 0.05). Kruskal-Wallis and Dunn tests compared all ageing groups of each material (p = 0.05). The silicone-based reliner presented a lower permanent deformation than the acrylic resin-based reliner, regardless of the ageing procedure. The surface sealer coating was effective only for the thermocycled silicone group and the accelerated ageing processes affected only the permanent deformation of the acrylic resin-based material. The silicone-based reliner presented superior elastic properties and the thermocycling was more effective in ageing the materials. © 2010 The Gerodontology Society and John Wiley & Sons A/S.

Accelerated aging in schizophrenia patients: the potential role of oxidative stress.

PubMed

Okusaga, Olaoluwa O

2014-08-01

Several lines of evidence suggest that schizophrenia, a severe mental illness characterized by delusions, hallucinations and thought disorder is associated with accelerated aging. The free radical (oxidative stress) theory of aging assumes that aging occurs as a result of damage to cell constituents and connective tissues by free radicals arising from oxygen-associated reactions. Schizophrenia has been associated with oxidative stress and chronic inflammation, both of which also appear to reciprocally induce each other in a positive feedback manner. The buildup of damaged macromolecules due to increased oxidative stress and failure of protein repair and maintenance systems is an indicator of aging both at the cellular and organismal level. When compared with age-matched healthy controls, schizophrenia patients have higher levels of markers of oxidative cellular damage such as protein carbonyls, products of lipid peroxidation and DNA hydroxylation. Potential confounders such as antipsychotic medication, smoking, socio-economic status and unhealthy lifestyle make it impossible to solely attribute the earlier onset of aging-related changes or oxidative stress to having a diagnosis of schizophrenia. Regardless of whether oxidative stress can be attributed solely to a diagnosis of schizophrenia or whether it is due to other factors associated with schizophrenia, the available evidence is in support of increased oxidative stress-induced cellular damage of macromolecules which may play a role in the phenomenon of accelerated aging presumed to be associated with schizophrenia.

Progeric effects of catalase inactivation in human cells

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

Koepke, Jay I.; Wood, Christopher S.; Terlecky, Laura J.

2008-10-01

Peroxisomes generate hydrogen peroxide, a reactive oxygen species, as part of their normal metabolism. A number of pathological situations exist in which the organelle's capacity to degrade the potentially toxic oxidant is compromised. It is the peroxidase, catalase, which largely determines the functional antioxidant capacity of the organelle, and it is this enzyme that is affected in aging, in certain diseases, and in response to exposure to specific chemical agents. To more tightly control the enzymatic activity of peroxisomal catalase and carefully document the effects of its impaired action on human cells, we employed the inhibitor 3-amino-1,2,4-triazole. We show thatmore » by chronically reducing catalase activity to approximately 38% of normal, cells respond in a dramatic manner, displaying a cascade of accelerated aging reactions. Hydrogen peroxide and related reactive oxygen species are produced, protein and DNA are oxidatively damaged, import into peroxisomes and organelle biogenesis is corrupted, and matrix metalloproteinases are hyper-secreted from cells. In addition, mitochondria are functionally impaired, losing their ability to maintain a membrane potential and synthesize reactive oxygen species themselves. These latter results suggest an important redox-regulated connection between the two organelle systems, a topic of considerable interest for future study.« less

Anti-glycation and anti-oxidative effects of a phenolic-enriched maple syrup extract and its protective effects on normal human colon cells.

PubMed

Liu, Weixi; Wei, Zhengxi; Ma, Hang; Cai, Ang; Liu, Yongqiang; Sun, Jiadong; DaSilva, Nicholas A; Johnson, Shelby L; Kirschenbaum, Louis J; Cho, Bongsup P; Dain, Joel A; Rowley, David C; Shaikh, Zahir A; Seeram, Navindra P

2017-02-22

Oxidative stress and free radical generation accelerate the formation of advanced glycation endproducts (AGEs) which are linked to several chronic diseases. Published data suggest that phenolic-rich plant foods, show promise as natural anti-AGEs agents due to their anti-oxidation capacities. A phenolic-enriched maple syrup extract (MSX) has previously been reported to show anti-inflammatory and neuroprotective effects but its anti-AGE effects remain unknown. Therefore, herein, we investigated the anti-glycation and anti-oxidation effects of MSX using biochemical and biophysical methods. MSX (500 μg mL -1 ) reduced the formation of AGEs by 40% in the bovine serum albumin (BSA)-fructose assay and by 30% in the BSA-methylglyoxal (MGO) assay. MSX also inhibited the formation of crosslinks typically seen in the late stage of glycation. Circular dichroism and differential scanning calorimeter analyses demonstrated that MSX maintained the structure of BSA during glycation. In the anti-oxidant assays, MSX (61.7 μg mL -1 ) scavenged 50% of free radicals (DPPH assay) and reduced free radical generation by 20% during the glycation process (electron paramagnetic resonance time scan). In addition, the intracellular levels of hydrogen peroxide induced reactive oxygen species were reduced by 27-58% with MSX (50-200 μg mL -1 ) in normal/non-tumorigenic human colon CCD-18Co cells. Moreover, in AGEs and MGO challenged CCD-18Co cells, higher cellular viabilities and rapid extracellular signal-regulated kinase (ERK) phosphorylation were observed in MSX treated cells, indicating its protective effects against AGEs-induced cytotoxicity. Overall, this study supports the biological effects of MSX, and warrants further investigation of its potential as a dietary agent against diseases mediated by oxidative stress and inflammation.

Behavior of human horizontal vestibulo-ocular reflex in response to high-acceleration stimuli

NASA Technical Reports Server (NTRS)

Maas, E. F.; Huebner, W. P.; Seidman, S. H.; Leigh, R. J.

1989-01-01

The horizontal vestibulo-ocular reflex (VOR) during transient, high-acceleration (1900-7100 deg/sec-squared) head rotations was studied in four human subjects. Such stimuli perturbed the angle of gaze and caused illusory movement of a viewed target (oscillopsia). The disturbance of gaze could be attributed to the latency of the VOR (which ranged from 6-15 ms) and inadequate compensatory eye rotations (median VOR gain ranged from 0.61-0.83).

The attenuation of strike acceleration with the use of safety equipment in tae kwon do.

PubMed

Gupta, Sanjey

2011-12-01

THE OBJECTIVES OF THIS STUDY INCLUDE: (1) Determination of the attenuation of strike acceleration that Tae Kwon Do sparring safety pads provide from kicks from Olympic style TKD fighters, (2) The sex and weight differentiation in acceleration achieved within the thorax model with the roundhouse kicks. This prospective, observational study utilized 15 Olympic style fighters from an "elite" team kicking a water core heavy bag thorax model with roundhouse kicks. The model was fitted with a tri-axial accelerometer (GCDC, model X250-2) to measure g acceleration from strikes to the bag. The bag was kicked in three, 10 kick phases by all subjects: kicks without padding; kicks with hogu on heavy bag, and kicks with hogu and instep guards on feet. The g acceleration readings were recorded in all phases. Kolmogorov-Smirnov failed for all variables. There were 8 female subjects: median age 14 years, median weight 53.4 kg and 7 male subjects: median age 17 years, median weight 70.45 kg. The ANOVA on ranks of the acceleration from kicks against the bag achieved significance, P=0.001. Spearman rank order correlation between the weights of players and acceleration of strike against the hogu without and with insteps pads was significant, P=0.035/r=0.54 and P=0.018/r=0.59, respectively. Heavier and male subjects tend to produce more force in strikes. Protective chest guard reduces acceleration to the thorax model, but the utility of instep guards is questionable.

A Hybrid CPU-GPU Accelerated Framework for Fast Mapping of High-Resolution Human Brain Connectome

PubMed Central

Ren, Ling; Xu, Mo; Xie, Teng; Gong, Gaolang; Xu, Ningyi; Yang, Huazhong; He, Yong

2013-01-01

Recently, a combination of non-invasive neuroimaging techniques and graph theoretical approaches has provided a unique opportunity for understanding the patterns of the structural and functional connectivity of the human brain (referred to as the human brain connectome). Currently, there is a very large amount of brain imaging data that have been collected, and there are very high requirements for the computational capabilities that are used in high-resolution connectome research. In this paper, we propose a hybrid CPU-GPU framework to accelerate the computation of the human brain connectome. We applied this framework to a publicly available resting-state functional MRI dataset from 197 participants. For each subject, we first computed Pearson’s Correlation coefficient between any pairs of the time series of gray-matter voxels, and then we constructed unweighted undirected brain networks with 58 k nodes and a sparsity range from 0.02% to 0.17%. Next, graphic properties of the functional brain networks were quantified, analyzed and compared with those of 15 corresponding random networks. With our proposed accelerating framework, the above process for each network cost 80∼150 minutes, depending on the network sparsity. Further analyses revealed that high-resolution functional brain networks have efficient small-world properties, significant modular structure, a power law degree distribution and highly connected nodes in the medial frontal and parietal cortical regions. These results are largely compatible with previous human brain network studies. Taken together, our proposed framework can substantially enhance the applicability and efficacy of high-resolution (voxel-based) brain network analysis, and have the potential to accelerate the mapping of the human brain connectome in normal and disease states. PMID:23675425

Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing and Potentially Promotes Neoplasia

PubMed Central

Smout, Michael J.; Sotillo, Javier; Laha, Thewarach; Papatpremsiri, Atiroch; Rinaldi, Gabriel; Pimenta, Rafael N.; Chan, Lai Yue; Johnson, Michael S.; Turnbull, Lynne; Whitchurch, Cynthia B.; Giacomin, Paul R.; Moran, Corey S.; Golledge, Jonathan; Daly, Norelle; Sripa, Banchob; Mulvenna, Jason P.

2015-01-01

Abstract Infection with the human liver fluke Opisthorchis viverrini induces cancer of the bile ducts, cholangiocarcinoma (CCA). Injury from feeding activities of this parasite within the human biliary tree causes extensive lesions, wounds that undergo protracted cycles of healing, and re-injury over years of chronic infection. We show that O. viverrini secreted proteins accelerated wound resolution in human cholangiocytes, an outcome that was compromised following silencing of expression of the fluke-derived gene encoding the granulin-like growth factor, Ov-GRN-1. Recombinant Ov-GRN-1 induced angiogenesis and accelerated mouse wound healing. Ov-GRN-1 was internalized by human cholangiocytes and induced gene and protein expression changes associated with wound healing and cancer pathways. Given the notable but seemingly paradoxical properties of liver fluke granulin in promoting not only wound healing but also a carcinogenic microenvironment, Ov-GRN-1 likely holds marked potential as a therapeutic wound-healing agent and as a vaccine against an infection-induced cancer of major public health significance in the developing world. PMID:26485648

Effect of Gravity on the Mammalian Cell Deformation

NASA Technical Reports Server (NTRS)

Hung, R. J.; Tsao, Y.; Gonda, Steven

1995-01-01

The effect of human cell immersed in culture liquid under a micro-gravity environment has been investigated. The study is based on the numerical simulation of the configuration of human cell affected by the time dependent variation of gravity acceleration ranging from 10(exp -3) to 2 g(sub o) (g(sub o) = 9.81 m/s(exp 2)) in 15 seconds. Both the free floating cell and the cell contacted to the upper and lower inclined walls imposed by the time-dependent reduced gravity acceleration are considered in this study. The results show that the cell configuration changes from spherical to horizontally elongated ellipsoid for both the free floating cell and the cell sitting on the lower inclined wall while the cell configuration varies from spherical to vertically elongated ellipsoid for the cell hanging to the upper inclined wall when the gravity acceleration increases. Experimental observations, carried out of human cells exposed to the variation of gravity levels, show that the results of experimental observations agree exactly with the theoretical model computation described in this paper. These results sre significant for humans exposed to the micro-gravity environment.

Accelerated telomere attrition is associated with relative household income, diet and inflammation in the pSoBid cohort.

PubMed

Shiels, Paul G; McGlynn, Liane M; MacIntyre, Alan; Johnson, Paul C D; Batty, G David; Burns, Harry; Cavanagh, Jonathan; Deans, Kevin A; Ford, Ian; McConnachie, Alex; McGinty, Agnes; McLean, Jennifer S; Millar, Keith; Sattar, Naveed; Tannahill, Carol; Velupillai, Yoga N; Packard, Chris J

2011-01-01

It has previously been hypothesized that lower socio-economic status can accelerate biological ageing, and predispose to early onset of disease. This study investigated the association of socio-economic and lifestyle factors, as well as traditional and novel risk factors, with biological-ageing, as measured by telomere length, in a Glasgow based cohort that included individuals with extreme socio-economic differences. A total of 382 blood samples from the pSoBid study were available for telomere analysis. For each participant, data was available for socio-economic status factors, biochemical parameters and dietary intake. Statistical analyses were undertaken to investigate the association between telomere lengths and these aforementioned parameters. The rate of age-related telomere attrition was significantly associated with low relative income, housing tenure and poor diet. Notably, telomere length was positively associated with LDL and total cholesterol levels, but inversely correlated to circulating IL-6. These data suggest lower socio-economic status and poor diet are relevant to accelerated biological ageing. They also suggest potential associations between elevated circulating IL-6, a measure known to predict cardiovascular disease and diabetes with biological ageing. These observations require further study to tease out potential mechanistic links.

Aging-related renal injury and inflammation are associated with downregulation of Klotho and induction of RIG-I/NF-κB signaling pathway in senescence-accelerated mice.

PubMed

Zeng, Yi; Wang, Ping-Han; Zhang, Mao; Du, Jun-Rong

2016-02-01

The predominant distribution of the antiaging Klotho protein in both the kidneys and brain may point to its essential role in protecting against dysfunction of the kidney-brain axis during the aging process. Our previous study showed that the downregulation of Klotho was involved in aging-related cognitive impairment in aged senescence-accelerated mouse prone-8 (SAMP8) mice. The present study investigated the potential role of Klotho in aging-associated inflammation and renal injury. Age- and gender-matched groups of SAMP8 mice and their corresponding normal control senescence-accelerated mouse resistant-1 (SAMR1) were used to investigate the potential role of Klotho in aging-associated inflammation and renal injury. Compared with aged SAMR1 controls, early-stage chronic kidney disease (CKD), which is associated with an increase in the urinary albumin-to-creatinine ratio, inflammatory cell infiltration, glomerulosclerosis, and tubulointerstitial fibrosis, was observed in aged SAMP8 mice. Furthermore, the aging-related loss of Klotho-induced activation of the retinoic acid-inducible gene 1/nuclear factor-κB (RIG-I/NF-κB) signaling pathway and subsequent production of the proinflammatory mediators tumor necrosis factor α, interleukin-6, and inducible nitric oxide synthase in the kidneys of aged SAMP8 mice compared with SAMR1 controls. The present results suggest that aging-related inflammation and the development of early-stage CKD are likely associated with the downregulation of Klotho and induction of the RIG-I/NF-κB signaling pathway in 12-month-old SAMP8 mice. Moreover, aged SAMP8 mice with cognitive deficits and renal damage may be a potential mouse model for investigating the kidney-brain axis in the aging process.

Evidence for the Cost of Reproduction in Humans: High Lifetime Reproductive Effort Is Associated with Greater Oxidative Stress in Post-Menopausal Women

PubMed Central

Sancilio, Amelia; Galbarczyk, Andrzej; Klimek, Magdalena

2016-01-01

Life history theory predicts trade-offs between reproductive effort and maternal survivorship in energy-restricted environments. However, empirical evidence for the positive association between maternal mortality and reproductive effort from energetically challenged human populations are mixed and physiological mechanisms that may underlie this association are poorly understood. We hypothesized that increases in aerobic metabolism during repeated periods of pregnancy and lactation result in increased oxidative stress that may contribute to somatic deterioration, vulnerability to illness, and accelerated aging. We therefore predicted that lifetime gravidity and parity would be related to levels of biomarkers of oxidative stress, as well as antioxidative defence enzymes in post-menopausal women. Our hypothesis was supported by positive linear associations between levels of 8-OHdG, a biomarker of DNA oxidative damage (β = 0.21, p<0.05), levels of antioxidative defence enzyme Cu-Zn SOD (β = 0.25, p<0.05), and number of lifetime pregnancies. Furthermore, independent of age and health status, post-menopausal women with higher gravidity and parity (> = 4 pregnancies per lifetime) had 20% higher levels of 8-OHdG and 60% higher levels of Cu-Zn SOD compared to women with lower gravidity and parity (<4 pregnancies per lifetime). Our results present the first evidence for oxidative stress as a possible cost of reproductive effort in humans. PMID:26761206

Evidence for the Cost of Reproduction in Humans: High Lifetime Reproductive Effort Is Associated with Greater Oxidative Stress in Post-Menopausal Women.

PubMed

Ziomkiewicz, Anna; Sancilio, Amelia; Galbarczyk, Andrzej; Klimek, Magdalena; Jasienska, Grazyna; Bribiescas, Richard G

2016-01-01

Life history theory predicts trade-offs between reproductive effort and maternal survivorship in energy-restricted environments. However, empirical evidence for the positive association between maternal mortality and reproductive effort from energetically challenged human populations are mixed and physiological mechanisms that may underlie this association are poorly understood. We hypothesized that increases in aerobic metabolism during repeated periods of pregnancy and lactation result in increased oxidative stress that may contribute to somatic deterioration, vulnerability to illness, and accelerated aging. We therefore predicted that lifetime gravidity and parity would be related to levels of biomarkers of oxidative stress, as well as antioxidative defence enzymes in post-menopausal women. Our hypothesis was supported by positive linear associations between levels of 8-OHdG, a biomarker of DNA oxidative damage (β = 0.21, p<0.05), levels of antioxidative defence enzyme Cu-Zn SOD (β = 0.25, p<0.05), and number of lifetime pregnancies. Furthermore, independent of age and health status, post-menopausal women with higher gravidity and parity (> = 4 pregnancies per lifetime) had 20% higher levels of 8-OHdG and 60% higher levels of Cu-Zn SOD compared to women with lower gravidity and parity (<4 pregnancies per lifetime). Our results present the first evidence for oxidative stress as a possible cost of reproductive effort in humans.

Activation of tyrosine kinase c-Abl contributes to α-synuclein–induced neurodegeneration

PubMed Central

Lee, Su Hyun; Kim, Donghoon; Karuppagounder, Senthilkumar S.; Kumar, Manoj; Mao, Xiaobo; Shin, Joo Ho; Lee, Yunjong; Pletnikova, Olga; Troncoso, Juan C.; Dawson, Valina L.; Dawson, Ted M.; Ko, Han Seok

2016-01-01

Aggregation of α-synuclein contributes to the formation of Lewy bodies and neurites, the pathologic hallmarks of Parkinson disease (PD) and α-synucleinopathies. Although a number of human mutations have been identified in familial PD, the mechanisms that promote α-synuclein accumulation and toxicity are poorly understood. Here, we report that hyperactivity of the nonreceptor tyrosine kinase c-Abl critically regulates α-synuclein–induced neuropathology. In mice expressing a human α-synucleinopathy–associated mutation (hA53Tα-syn mice), deletion of the gene encoding c-Abl reduced α-synuclein aggregation, neuropathology, and neurobehavioral deficits. Conversely, overexpression of constitutively active c-Abl in hA53Tα-syn mice accelerated α-synuclein aggregation, neuropathology, and neurobehavioral deficits. Moreover, c-Abl activation led to an age-dependent increase in phosphotyrosine 39 α-synuclein. In human postmortem samples, there was an accumulation of phosphotyrosine 39 α-synuclein in brain tissues and Lewy bodies of PD patients compared with age-matched controls. Furthermore, in vitro studies show that c-Abl phosphorylation of α-synuclein at tyrosine 39 enhances α-synuclein aggregation. Taken together, this work establishes a critical role for c-Abl in α-synuclein–induced neurodegeneration and demonstrates that selective inhibition of c-Abl may be neuroprotective. This study further indicates that phosphotyrosine 39 α-synuclein is a potential disease indicator for PD and related α-synucleinopathies. PMID:27348587

Visceral adipose tissue modulates mammalian longevity

PubMed Central

Muzumdar, Radhika; Allison, David B.; Huffman, Derek M.; Ma, Xiaohui; Atzmon, Gil; Einstein, Francine H.; Fishman, Sigal; Poduval, Aruna D.; McVei, Theresa; Keith, Scott W.; Barzilai, Nir

2008-01-01

Summary Caloric restriction (CR) can delay many age-related diseases and extend lifespan, while an increase in adiposity is associated with enhanced disease risk and accelerated aging. Among the various fat depots, the accrual of visceral fat (VF) is a common feature of aging, and has been shown to be the most detrimental on metabolic syndrome of aging in humans. We have previously demonstrated that surgical removal of VF in rats improves insulin action; thus, we set out to determine if VF removal affects longevity. We prospectively studied lifespan in three groups of rats: ad libitum-fed (AL-fed), CR (Fed 60% of AL) and a group of AL-fed rats with selective removal of VF at 5 months of age (VF-removed rats). We demonstrate that compared to AL-fed rats, VF-removed rats had a significant increase in mean (p < 0.001) and maximum lifespan (p < 0.04) and significant reduction in the incidence of severe renal disease (p < 0.01). CR rats demonstrated the greatest mean and maximum lifespan (p < 0.001) and the lowest rate of death as compared to AL-fed rats (0.13). Taken together, these observations provide the most direct evidence to date that a reduction in fat mass, specifically VF, may be one of the possible underlying mechanisms of the anti-aging effect of CR. PMID:18363902

Traffic-related air pollution impact on mouse brain accelerates myelin and neuritic aging changes with specificity for CA1 neurons

PubMed Central

Woodward, NC; Pakbin, P; Saffari, A; Shirmohammadi, F; Haghani, A; Sioutas, C; Cacciottolo, M; Morgan, TE; Finch, CE

2017-01-01

Traffic-related air pollution (TRAP) is associated with lower cognition and reduced white matter volume in older adults, specifically for particulate matter <2.5 μm diameter (PM2.5). Rodents exposed to TRAP have shown microglial activation and neuronal atrophy. We further investigated age differences of TRAP exposure, with focus on hippocampus for neuritic atrophy, white matter degeneration, and microglial activation. Young and middle-aged mice (3 and 18 month female C57BL/6J) were exposed to nanoscale-PM (nPM, <0.2 μm diameter). Young mice showed selective changes in the hippocampal CA1 region, with neurite atrophy (−25%), decreased MBP (−50%), and increased Iba1 (+50%), with dentate gyrus relatively unaffected. Exposure to nPM of young mice decreased GluA1 protein (−40%) and increased TNFa mRNA (10×). Older controls had age changes approximating nPM effects on young, with no response to nPM, suggesting an age ceiling effect. The CA1 selective vulnerability in young mice parallels CA1 vulnerability in Alzheimer’s disease. We propose that TRAP associated human cognitive and white matter changes involve hippocampal responses to nPM that begin at younger ages. PMID:28212893

Accelerated Telomere Shortening in Acromegaly; IGF-I Induces Telomere Shortening and Cellular Senescence.

PubMed

Matsumoto, Ryusaku; Fukuoka, Hidenori; Iguchi, Genzo; Odake, Yukiko; Yoshida, Kenichi; Bando, Hironori; Suda, Kentaro; Nishizawa, Hitoshi; Takahashi, Michiko; Yamada, Shozo; Ogawa, Wataru; Takahashi, Yutaka

2015-01-01

Patients with acromegaly exhibit reduced life expectancy and increased prevalence of age-related diseases, such as diabetes, hypertension, and cardiovascular disease. However, the underlying mechanism has not been fully elucidated. Telomere shortening is reportedly associated with reduced life expectancy and increased prevalence of these age-related diseases. We measured telomere length in patients with acromegaly using quantitative PCR method. The effect of GH and IGF-I on telomere length and cellular senescence was examined in human skin fibroblasts. Patients with acromegaly exhibited shorter telomere length than age-, sex-, smoking-, and diabetes-matched control patients with non-functioning pituitary adenoma (0.62 ± 0.23 vs. 0.75 ± 0.35, respectively, P = 0.047). In addition, telomere length in acromegaly was negatively correlated with the disease duration (R2 = 0.210, P = 0.003). In vitro analysis revealed that not GH but IGF-I induced telomere shortening in human skin fibroblasts. Furthermore, IGF-I-treated cells showed increased senescence-associated β-galactosidase activity and expression of p53 and p21 protein. IGF-I-treated cells reached the Hayflick limit earlier than GH- or vehicle-treated cells, indicating that IGF-I induces cellular senescence. Shortened telomeres in acromegaly and cellular senescence induced by IGF-I can explain, in part, the underlying mechanisms by which acromegaly exhibits an increased morbidity and mortality in association with the excess secretion of IGF-I.

Flt3 is a target of coumestrol in protecting against UVB-induced skin photoaging.

PubMed

Park, Gaeun; Baek, Sohee; Kim, Jong-Eun; Lim, Tae-gyu; Lee, Charles C; Yang, Hee; Kang, Young-Gyu; Park, Jun Seong; Augustin, Martin; Mrosek, Michael; Lee, Chang Yong; Dong, Zigang; Huber, Robert; Lee, Ki Won

2015-12-01

While skin aging is a naturally occurring process by senescence, exposure to ultraviolet (UV) radiation accelerates wrinkle formation and sagging of skin. UV induces skin aging by degrading collagen via activating matrix metalloproteinases (MMPs). In this study, we show that coumestrol, a metabolite of the soybean isoflavone daidzein, has a preventive effect on skin photoaging in three-dimensional human skin equivalent model. Coumestrol inhibited UVB-induced MMP-1 expression and activity. Whole human kinase profiling assay identified FLT3 kinase as a novel target protein of coumestrol in UVB-induced signaling pathway in skin. Coumestrol suppresses FLT3 kinase activity, and subsequently, Ras/MEK/ERK and Akt/p70 ribosomal S6 kinase pathway. This suppresses AP-1 activity and in turn, diminishes MMP-1 gene transcription. Using X-ray crystallography, the binding of coumestrol to FLT3 was defined and implied ATP-competitive inhibition. Residues Lys644 and Phe830 showed local changes to accommodate coumestrol in the ATP-binding pocket. 4-APIA, a pharmacological inhibitor of FLT3, inhibited MMP-1 expression and induced signal transduction changes similar to coumestrol. Taken together, coumestrol inhibits UVB-induced MMP-1 expression by suppressing FLT3 kinase activity. These findings suggest that coumestrol is a novel dietary compound with potential application in preventing and improving UVB-associated skin aging. Copyright © 2015 Elsevier Inc. All rights reserved.

Miniature piezoelectric triaxial accelerometer measures cranial accelerations

NASA Technical Reports Server (NTRS)

Deboo, G. J.; Rogallo, V. L.

1966-01-01

Tiny triaxial accelerometer whose sensing elements are piezoelectric ceramic beams measures human cranial accelerations when a subject is exposed to a centrifuge or other simulators of g environments. This device could be considered for application in dental, medical, and automotive safety research.

Sod2 haploinsufficiency does not accelerate aging of telomere dysfunctional mice

PubMed Central

Guachalla, Luis Miguel; Ju, Zhenyu; Koziel, Rafal; von Figura, Guido; Song, Zhangfa; Fusser, Markus; Epe, Bernd; Jansen-Dűrr, Pidder; Rudolph, K. Lenhard

2009-01-01

Telomere shortening represents a causal factor of cellular senescence. At the same time, several lines of evidence indicate a pivotal role of oxidative DNA damage for the aging process in vivo. A causal connection between the two observations was suggested by experiments showing accelerated telomere shorting under conditions of oxidative stress in cultured cells, but has never been studied in vivo. We therefore have analysed whether an increase in mitochondrial derived oxidative stress in response to heterozygous deletion of superoxide dismutase (Sod2+/-) would exacerbate aging phenotypes in telomere dysfunctional (mTerc-/-) mice. Heterozygous deletion of Sod2 resulted in reduced SOD2 protein levels and increased oxidative stress in aging telomere dysfunctional mice, but this did not lead to an increase in basal levels of oxidative nuclear DNA damage, an accumulation of nuclear DNA breaks, or an increased rate of telomere shortening in the mice. Moreover, heterozygous deletion of Sod2 did not accelerate the depletion of stem cells and the impairment in organ maintenance in aging mTerc-/- mice. In agreement with these observations, Sod2 haploinsufficiency did not lead to a further reduction in lifespan of mTerc-/- mice. Together, these results indicate that a decrease in SOD2-dependent antioxidant defence does not exacerbate aging in the context of telomere dysfunction. PMID:20195488

Subjective acceleration of time experience in everyday life across adulthood.

PubMed

John, Dennis; Lang, Frieder R

2015-12-01

Most people believe that time seems to pass more quickly as they age. Building on assumptions of socioemotional selectivity theory, we investigated whether awareness that one's future lifetime is limited is associated with one's experience of time during everyday activities across adulthood in 3 studies. In the first 2 studies (Study 1: N = 608; Study 2: N = 398), participants completed a web-based version of the day reconstruction method. In Study 3 (N = 392) participants took part in a newly developed tomorrow construction method, a web-based experimental method for assessing everyday life plans. Results confirmed that older adults' subjective interpretation of everyday episodes is that these episodes pass more quickly compared with younger adults. The subjective acceleration of time experience in old age was more pronounced during productive activities than during regenerative-consumptive activities. The age differences were partly related to limited time remaining in life. In addition, subjective acceleration of time experience was associated with positive evaluations of everyday activities. Findings suggest that subjective acceleration of time in older adults' daily lives reflects an adaptation to limitations in time remaining in life. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Sonar Transducer Reliability Improvement Program, FY79 First Quarter Progress

DTIC Science & Technology

1979-06-01

The mst significant aspects are improve- ments in the gas-filling procedures for the TR155 transducers, results of accelerated aging of the TR215...thus saved the Navy approximately $19,000 during 4 months of operation. See Section 3.3.2. b. The accelerated aging of the TR-215 ( ) transducers (AN...incompatible with the various plastics and rubbers in the transducer. Further research is necessary to find and qualify fill fluids which represent the best

Modeling the Biodynamical Response of the Human Head for Injury Analysis

DTIC Science & Technology

2001-09-01

1 II. BACKGROUND ..............................................5 A. HUMAN ANATOMY ......................................5...facilitate the simulation of the sled acceleration test used for model validation. A. HUMAN ANATOMY 1. The Spine The muscles and other soft tissue

Anti-wrinkle effects of a tuna heart H2O fraction on Hs27 human fibroblasts.

PubMed

Kim, Young-Min; Jung, Hee-Jin; Choi, Jae-Sue; Nam, Taek-Jeong

2016-01-01

With the increase in life expectancy, there is also growing interest in anti-aging treatments and technologies. The development of anti-aging functional drugs for the skin, and foods from natural sources, may offer solutions to this global matter. Aging involves structural, functional and biochemical changes that occur throughout cells and bodily tissues; the amount of hormones secreted from of all human organs, including the skin, decreases over time. Matrix metalloproteinase (MMP) genes (MMP-1 and -8) play an important role in the aging of skin fibroblasts. For example, an increased MMP expression causes accelerated aging and the degradation of skin elasticity-related genes. In the present study, we examined the anti-wrinkle effects of tuna heart extract which are mediated through the inhibition of MMPs in skin cells. Generally, tuna contains high concentrations of selenium and antioxidants, which serve to remove free radicals, and is known to delay skin and body aging. In addition, unsaturated fatty acids in tuna help to maintain the natural glossy look of skin, and increase skin elasticity, providing moisture for dry skin. A recent study confirmed the various bio-effects of boiled tuna extract and muscle. However, bioactivity studies using tuna heart are limited. Thus, in the present study, we obtained extracts and fractions of tuna heart, and examined their effects on Hs27 human fibroblast proliferation using an MTS assay. In addition, we measured procollagen type 1 levels and elastase activity, and performed β-galactosidase staining. We then measured the expression levels of phosphatidylinositol 3-kinase/Akt and MMP-related genes by western blot analysis and RT-PCR. Our results revealed that tuna heart extract decreased MMP expression by upregulating tissue inhibitors of metalloproteinase-1 (TIMP-1) and decreasing elastase activity, thus exerting anti-aging and anti-wrinkle effects by increasing collagen synthesis and promoting skin fibroblast proliferation. Thus, our data suggest that tuna heart (TH)-H2O fractions exert anti-wrinkle effects on Hs27 cells.

Surface degradation of polymer insulators under accelerated climatic aging in weather-ometer

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

Xu, G.; McGrath, P.B.; Burns, C.W.

1996-12-31

Climatic aging experiments were conducted on two types of outdoor polymer insulators by using a programmable weather-ometer. The housing materials for the insulators were silicone rubber (SR) and ethylene propylene diene monomer (EPDM). The accelerated aging stresses were comprised of ultraviolet radiation, elevated temperature, temperature cycling, thermal shock and high humidity. Their effects on the insulator surface conditions and electrical performance wee examined through visual inspection and SEM studies, contact angle measurements, thermogravimetric analysis (TGA), energy dispersive spectroscopy (EDS) analysis, and 50% impulse flashover voltage tests. The results showed a significant damage on the insulator surface caused by some ofmore » the imposed aging stresses. The EDS analysis suggested a photooxidation process that happened on the insulator surface during the aging period.« less

Sensing Passive Eye Response to Impact Induced Head Acceleration Using MEMS IMUs.

PubMed

Meng, Yuan; Bottenfield, Brent; Bolding, Mark; Liu, Lei; Adams, Mark L

2018-02-01

The eye may act as a surrogate for the brain in response to head acceleration during an impact. Passive eye movements in a dynamic system are sensed by microelectromechanical systems (MEMS) inertial measurement units (IMU) in this paper. The technique is validated using a three-dimensional printed scaled human skull model and on human volunteers by performing drop-and-impact experiments with ribbon-style flexible printed circuit board IMUs inserted in the eyes and reference IMUs on the heads. Data are captured by a microcontroller unit and processed using data fusion. Displacements are thus estimated and match the measured parameters. Relative accelerations and displacements of the eye to the head are computed indicating the influence of the concussion causing impacts.

Acceleration feedback improves balancing against reflex delay

PubMed Central

Insperger, Tamás; Milton, John; Stépán, Gábor

2013-01-01

A model for human postural balance is considered in which the time-delayed feedback depends on position, velocity and acceleration (proportional–derivative–acceleration (PDA) feedback). It is shown that a PDA controller is equivalent to a predictive controller, in which the prediction is based on the most recent information of the state, but the control input is not involved into the prediction. A PDA controller is superior to the corresponding proportional–derivative controller in the sense that the PDA controller can stabilize systems with approximately 40 per cent larger feedback delays. The addition of a sensory dead zone to account for the finite thresholds for detection by sensory receptors results in highly intermittent, complex oscillations that are a typical feature of human postural sway. PMID:23173196

A multi-ingredient dietary supplement abolishes large-scale brain cell loss, improves sensory function, and prevents neuronal atrophy in aging mice.

PubMed

Lemon, J A; Aksenov, V; Samigullina, R; Aksenov, S; Rodgers, W H; Rollo, C D; Boreham, D R

2016-06-01

Transgenic growth hormone mice (TGM) are a recognized model of accelerated aging with characteristics including chronic oxidative stress, reduced longevity, mitochondrial dysfunction, insulin resistance, muscle wasting, and elevated inflammatory processes. Growth hormone/IGF-1 activate the Target of Rapamycin known to promote aging. TGM particularly express severe cognitive decline. We previously reported that a multi-ingredient dietary supplement (MDS) designed to offset five mechanisms associated with aging extended longevity, ameliorated cognitive deterioration and significantly reduced age-related physical deterioration in both normal mice and TGM. Here we report that TGM lose more than 50% of cells in midbrain regions, including the cerebellum and olfactory bulb. This is comparable to severe Alzheimer's disease and likely explains their striking age-related cognitive impairment. We also demonstrate that the MDS completely abrogates this severe brain cell loss, reverses cognitive decline and augments sensory and motor function in aged mice. Additionally, histological examination of retinal structure revealed markers consistent with higher numbers of photoreceptor cells in aging and supplemented mice. We know of no other treatment with such efficacy, highlighting the potential for prevention or amelioration of human neuropathologies that are similarly associated with oxidative stress, inflammation and cellular dysfunction. Environ. Mol. Mutagen. 57:382-404, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

How accelerated biological aging can affect solar reflective polymeric based building materials

NASA Astrophysics Data System (ADS)

Ferrari, C.; Santunione, G.; Libbra, A.; Muscio, A.; Sgarbi, E.

2017-11-01

Among the main issues concerning building materials, in particular outdoor ones, one can identify the colonization by microorganisms referred to as biological aggression. This can affect not only the aesthetical aspect but also the thermal performance of solar reflective materials. In order to improve the reliability of tests aimed to assess the resistance to biological aggression and contextually reduce the test duration, an accelerated test method has been developed. It is based on a lab reproducible setup where specific and controlled environmental and boundary conditions are imposed to accelerate as much as possible biological growth on building materials. Due to their widespread use, polymeric materials have been selected for the present analysis, in the aim of reaching an advanced bio-aged level in a relatively short time (8 weeks or less) and at the same time comparatively evaluate different materials under a given set of ageing conditions. Surface properties before, during and after ageing have been investigated by surface, microstructural and chemical analyses, as well as by examination of time progressive images to assess bacterial and algal growth rate.

Toward Successful Implementation of Prefabricated Deck Panels to Accelerate the Bridge Construction Process

DOT National Transportation Integrated Search

2016-08-01

The development of accelerated bridge construction (ABC) techniques and connection details has become a national research focus. With the aging of the interstate system and many bridges on key routes requiring extensive rehabilitation or replacement,...

Highly accelerated lifetime for externally applied bond critical fiber-reinforced polymer (FRP) infrastructure materials.

DOT National Transportation Integrated Search

2014-03-01

This report describes a research project to investigate accelerated aging protocols for fiber-reinforced : polymer (FRP) reinforcement of concrete. This research was conducted in three stages. In the first : stage, various spectroscopic techniques we...

Influence of surface sealing on color stability and roughness of composite submitted to ultraviolet-accelerated aging.

PubMed

Catelan, Anderson; Suzuki, Thaís Yumi Umeda; Becker, Francisco; Briso, André Luiz Fraga; Dos Santos, Paulo Henrique

2017-05-01

In the present study, we evaluated the influence of surface sealing on color stability and surface roughness of a composite resin after accelerated artificial aging. Thirty-two specimens of a composite were prepared. After 24 h, the specimens were polished and divided into four groups (n = 8), according to the surface sealant used, including the control, which had no sealant application. Baseline color was measured according to the CIELab system using a reflection spectrophotometer. Surface roughness was determined using a profilometer with a cut-off of 0.25 mm. After these tests, specimens were aged for 252 h in an ultraviolet (UV)-accelerated aging chamber. Color stability was determined by difference between coordinates obtained before and after the aging procedure. Data of color change and roughness were evaluated by anova and Fisher's exact test (α = 0.05). The results showed that the unsealed group had the highest color change compared to other groups (P = 0.0289), and there was no significant difference between groups sealed with surface sealant (P > 0.05). The artificial aging caused an increase in roughness values independent of the experimental group studied (P = 0.0015). The sealed composites showed lower color change after UV aging, but all groups showed clinically-acceptable color change, and only liquid polish decreased roughness. © 2016 John Wiley & Sons Australia, Ltd.

Effect of light aging on silicone-resin bond strength in maxillofacial prostheses.

PubMed

Polyzois, Gregory; Pantopoulos, Antonis; Papadopoulos, Triantafillos; Hatamleh, Muhanad

2015-04-01

The aim of this study was to investigate the effect of accelerated light aging on bond strength of a silicone elastomer to three types of denture resin. A total of 60 single lap joint specimens were fabricated with auto-, heat-, and photopolymerized (n = 20) resins. An addition-type silicone elastomer (Episil-E) was bonded to resins treated with the same primer (A330-G). Thirty specimens served as controls and were tested after 24 hours, and the remaining were aged under accelerated exposure to daylight for 546 hours (irradiance 765 W/m(2) ). Lap shear joint tests were performed to evaluate bond strength at 50 mm/min crosshead speed. Two-way ANOVA and Tukey's test were carried out to detect statistical significance (p < 0.05). ANOVA showed that the main effect of light aging was the most important factor determining the shear bond strength. The mean bond strength values ranged from 0.096 to 0.136 MPa. The highest values were recorded for auto- (0.131 MPa) and photopolymerized (0.136 MPa) resins after aging. Accelerated light aging for 546 hours affects the bond strength of an addition-type silicone elastomer to three different denture resins. The bond strength significantly increased after aging for photo- and autopolymerized resins. All the bonds failed adhesively. © 2014 by the American College of Prosthodontists.

Is Chronic Obstructive Pulmonary Disease an Accelerated Aging Disease?

PubMed

MacNee, William

2016-12-01

Aging is one of the most important risk factors for most chronic diseases. The worldwide increase in life expectancy has been accompanied by an increase in the prevalence of age-related diseases that result in significant morbidity and mortality and place an enormous burden on healthcare and resources. Aging is a progressive degeneration of the tissues that has a negative impact on the structure and function of vital organs. The lung ages, resulting in decreased function and reduced capacity to respond to environmental stresses and injury. Many of the changes that occur in the lungs with normal aging, such as decline in lung function, increased gas trapping, loss of lung elastic recoil, and enlargement of the distal air spaces, also are present in chronic obstructive pulmonary disease (COPD). The prevalence of COPD is two to three times higher in people over the age of 60 years than in younger age groups. Indeed, COPD has been considered a condition of accelerated lung aging. Several mechanisms associated with aging are present in the lungs of patients with COPD. Cell senescence is present in emphysematous lungs and is associated with shortened telomeres and decreased antiaging molecules, suggesting accelerated aging in the lungs of patients with COPD. Increasing age leads to elevated basal levels of inflammation and oxidative stress (inflammaging) and to increased immunosenescence associated with changes in both the innate and adaptive immune responses. These changes are similar to those that occur in COPD and may enhance the activity of the disease as well as increase susceptibility to exacerbations in patients with COPD. Understanding the mechanism of age-related changes in COPD may identify novel therapies for this condition.

Estimating the brain pathological age of Alzheimer’s disease patients from MR image data based on the separability distance criterion

NASA Astrophysics Data System (ADS)

Li, Yongming; Li, Fan; Wang, Pin; Zhu, Xueru; Liu, Shujun; Qiu, Mingguo; Zhang, Jingna; Zeng, Xiaoping

2016-10-01

Traditional age estimation methods are based on the same idea that uses the real age as the training label. However, these methods ignore that there is a deviation between the real age and the brain age due to accelerated brain aging. This paper considers this deviation and searches for it by maximizing the separability distance value rather than by minimizing the difference between the estimated brain age and the real age. Firstly, set the search range of the deviation as the deviation candidates according to prior knowledge. Secondly, use the support vector regression (SVR) as the age estimation model to minimize the difference between the estimated age and the real age plus deviation rather than the real age itself. Thirdly, design the fitness function based on the separability distance criterion. Fourthly, conduct age estimation on the validation dataset using the trained age estimation model, put the estimated age into the fitness function, and obtain the fitness value of the deviation candidate. Fifthly, repeat the iteration until all the deviation candidates are involved and get the optimal deviation with maximum fitness values. The real age plus the optimal deviation is taken as the brain pathological age. The experimental results showed that the separability was apparently improved. For normal control-Alzheimer’s disease (NC-AD), normal control-mild cognition impairment (NC-MCI), and MCI-AD, the average improvements were 0.178 (35.11%), 0.033 (14.47%), and 0.017 (39.53%), respectively. For NC-MCI-AD, the average improvement was 0.2287 (64.22%). The estimated brain pathological age could be not only more helpful to the classification of AD but also more precisely reflect accelerated brain aging. In conclusion, this paper offers a new method for brain age estimation that can distinguish different states of AD and can better reflect the extent of accelerated aging.

Guidelines for investigating causality of sequence variants in human disease

PubMed Central

MacArthur, D. G.; Manolio, T. A.; Dimmock, D. P.; Rehm, H. L.; Shendure, J.; Abecasis, G. R.; Adams, D. R.; Altman, R. B.; Antonarakis, S. E.; Ashley, E. A.; Barrett, J. C.; Biesecker, L. G.; Conrad, D. F.; Cooper, G. M.; Cox, N. J.; Daly, M. J.; Gerstein, M. B.; Goldstein, D. B.; Hirschhorn, J. N.; Leal, S. M.; Pennacchio, L. A.; Stamatoyannopoulos, J. A.; Sunyaev, S. R.; Valle, D.; Voight, B. F.; Winckler, W.; Gunter, C.

2014-01-01

The discovery of rare genetic variants is accelerating, and clear guidelines for distinguishing disease-causing sequence variants from the many potentially functional variants present in any human genome are urgently needed. Without rigorous standards we risk an acceleration of false-positive reports of causality, which would impede the translation of genomic research findings into the clinical diagnostic setting and hinder biological understanding of disease. Here we discuss the key challenges of assessing sequence variants in human disease, integrating both gene-level and variant-level support for causality. We propose guidelines for summarizing confidence in variant pathogenicity and highlight several areas that require further resource development. PMID:24759409

Guidelines for investigating causality of sequence variants in human disease.

PubMed

MacArthur, D G; Manolio, T A; Dimmock, D P; Rehm, H L; Shendure, J; Abecasis, G R; Adams, D R; Altman, R B; Antonarakis, S E; Ashley, E A; Barrett, J C; Biesecker, L G; Conrad, D F; Cooper, G M; Cox, N J; Daly, M J; Gerstein, M B; Goldstein, D B; Hirschhorn, J N; Leal, S M; Pennacchio, L A; Stamatoyannopoulos, J A; Sunyaev, S R; Valle, D; Voight, B F; Winckler, W; Gunter, C

2014-04-24

The discovery of rare genetic variants is accelerating, and clear guidelines for distinguishing disease-causing sequence variants from the many potentially functional variants present in any human genome are urgently needed. Without rigorous standards we risk an acceleration of false-positive reports of causality, which would impede the translation of genomic research findings into the clinical diagnostic setting and hinder biological understanding of disease. Here we discuss the key challenges of assessing sequence variants in human disease, integrating both gene-level and variant-level support for causality. We propose guidelines for summarizing confidence in variant pathogenicity and highlight several areas that require further resource development.

Relationship between Body Mass Index, Skeletal Maturation and Dental Development in 6- to 15- Year Old Orthodontic Patients in a Sample of Iranian Population.

PubMed

Hedayati, Zohreh; Khalafinejad, Fatemeh

2014-12-01

The prevalence of overweight and obesity has been increasing markedly in recent years. It may influence growth in pre pubertal children. The purpose of this study was to determine whether increased Body Mass Index (BMI) is associated with accelerated skeletal maturation and dental maturation in six to fifteen years old orthodontic patients in Shiraz, Iran. Skeletal maturation and dental development of 95 orthodontic patients (65 females and 30 males), aged 6 to 15 years, were determined. Dental development was assessed using the Demerjian method and skeletal maturation was evaluated by cervical vertebral method as presented by Bacetti. The BMI was determined for each patient. T-test was applied to compare the mean difference between chronologic and dental age among the study groups. A regression model was used to assess the relationship between BMI percentile, skeletal maturation, and dental development. 18.9% of subjects were overweight and obese. The mean differences between dental age and chronologic age were 0.73±1.3 for underweight and normal weight children and 1.8±1.08 for overweight and obese children. These results highlighted the correlation between accelerated dental maturity and increasing BMI percentile (p= 0.002). A new formula was introduced for this relationship. There was not any significant relationship between BMI percentile and skeletal maturation. Children who were overweight or obese had accelerated dental development whereas they did not have accelerated skeletal maturation significantly after being adjusted for age and gender.

Trace concentrations of vitamin E protect radiation crosslinked UHMWPE from oxidative degradation.

PubMed

Kurtz, S M; Dumbleton, J; Siskey, R S; Wang, A; Manley, M

2009-08-01

The effect of very low concentrations of Vitamin E on the stability and mechanical behavior of UHMWPE remains unknown. We tested the hypothesis that the oxidation resistance of Vitamin E-blended UHMWPE would be influenced by trace doses of antioxidant, resin, and radiation treatment. Trace concentrations (< or =500 ppm w/w%) of alpha-tocopherol (Vitamin E) were blended separately with GUR 1020 and 1050 resins and molded into disks. From each disk, three groups of 10 mm thick blocks were machined: (1) no irradiation (control); (2) 30 kGy of gamma irradiation in nitrogen; and (3) 75 kGy of gamma irradiation in air. Specimens were subjected to three aging protocols: (a) no aging (control); (b) two weeks and (c) four weeks of accelerated aging in accordance with ASTM F 2003 (i.e., 70 degrees C and 5 atm oxygen). The minimum concentration of Vitamin E needed to stabilize UHMWPE during our accelerated tests depended upon the method of radiation processing. For the 30 and 75 kGy irradiated materials, the addition of 125 ppm or more Vitamin E was sufficient to maintain baseline mechanical and chemical properties through two weeks of accelerated aging. For these groups, the addition of 375 ppm or 500 ppm, respectively, was necessary to maintain baseline mechanical and chemical properties throughout the four-week accelerated aging period. UHMWPE resin molecular weight did not have an effect on oxidation behavior. The results of this experiment therefore supported our hypotheses that trace concentrations of Vitamin E, coupled with radiation treatment-but not resin grade-influence the mechanical and oxidative degradation behavior of UHMWPE.

Accelerated Evolution of the Pituitary Adenylate Cyclase-Activating Polypeptide Precursor Gene During Human Origin

PubMed Central

Wang, Yin-qiu; Qian, Ya-ping; Yang, Su; Shi, Hong; Liao, Cheng-hong; Zheng, Hong-Kun; Wang, Jun; Lin, Alice A.; Cavalli-Sforza, L. Luca; Underhill, Peter A.; Chakraborty, Ranajit; Jin, Li; Su, Bing

2005-01-01

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide abundantly expressed in the central nervous system and involved in regulating neurogenesis and neuronal signal transduction. The amino acid sequence of PACAP is extremely conserved across vertebrate species, indicating a strong functional constraint during the course of evolution. However, through comparative sequence analysis, we demonstrated that the PACAP precursor gene underwent an accelerated evolution in the human lineage since the divergence from chimpanzees, and the amino acid substitution rate in humans is at least seven times faster than that in other mammal species resulting from strong Darwinian positive selection. Eleven human-specific amino acid changes were identified in the PACAP precursors, which are conserved from murine to African apes. Protein structural analysis suggested that a putative novel neuropeptide might have originated during human evolution and functioned in the human brain. Our data suggested that the PACAP precursor gene underwent adaptive changes during human origin and may have contributed to the formation of human cognition. PMID:15834139

Effects of different surface treatments and accelerated artificial aging on the bond strength of composite resin repairs.

PubMed

Melo, Marco Aurélio Veiga de; Moysés, Marcos Ribeiro; Santos, Saulo Galvão dos; Alcântara, Carlos Eduardo Pinto; Ribeiro, José Carlos Rabelo

2011-01-01

The purpose of the present study was to assess the bond strength of composite resin repairs subjected to different surface treatments and accelerated artificial aging. 192 cylindrical samples (CSs) were prepared and divided into 24 groups (n = 8). Half of the CSs were stored in water for 24 h, and the other half were subjected to C-UV accelerated aging for non-metallic specimens. The treatments were phosphoric acid + silane + adhesive (PSA); phosphoric acid + adhesive (PA); diamond bur + phosphoric acid + silane + adhesive (DPSA); diamond bur + phosphoric acid + adhesive (DPA); air abrasion + phosphoric acid + silane + adhesive (APSA); and air abrasion + phosphoric acid + adhesive (APA). The repair was performed and the specimens were again aged as described above. A control group (n = 8) was established and did not receive any type of aging or surface treatment. The specimens were loaded to failure in shear mode with a crosshead speed of 0.5 mm/min until fracture. Data were analyzed by one-way ANOVA/Tukey's test (p < 0.05). No statistically significant differences were found among DPSA, DPA, APSA, APA, and the control group. The aged PSA and PA achieved low bonding values and were statistically different from the control group, whereas the non-aged PSA and PA presented no statistically significant difference from the control group. Repairs with the proposed surface treatments were viable on both recent and aged restorations; however, phosphoric acid + adhesive alone were effective only on recent restorations.

Radioisotope Dating with Accelerators.

ERIC Educational Resources Information Center

Muller, Richard A.

1979-01-01

Explains a new method of detecting radioactive isotopes by counting their accelerated ions rather than the atoms that decay during the counting period. This method increases the sensitivity by several orders of magnitude, and allows one to find the ages of much older and smaller samples. (GA)

[A paradox of a parasite prolonging the life of its host. Pearl mussel can cancel the accelerated aging program in salmon].

PubMed

Ziuganov, V V

2005-01-01

A unique case is analyzed when the accelerated aging program (progeria) in salmons (Salmonidae) can be canceled by larval parasite of the gills--freshwater pearl mussel Margaritifera margaritifera. As a result, the maximum age of Salmo fishes hosting the mussel can be as high as 13 years. The mollusk-fish system made it possible to demonstrate that the parasite can inhibit aging of the host and stimulate nonspecific resistance to stress, i.e., can control longevity. The mussel proved to increase the resistance to epitheliomata and cutaneous mycoses. The parasite is perceived to neutralize the senile changes in the regulatory system hypothalamus-pituitary-peripheral endocrine glands-hypothalamus of salmon.

The dynamic contributions of the otolith organs to human ocular torsion

NASA Technical Reports Server (NTRS)

Merfeld, D. M.; Teiwes, W.; Clarke, A. H.; Scherer, H.; Young, L. R.

1996-01-01

We measured human ocular torsion (OT) monocularly (using video) and binocularly (using search coils) while sinusoidally accelerating (0.7 g) five human subjects along an earth-horizontal axis at five frequencies (0.35, 0.4, 0.5, 0.75, and 1.0 Hz). The compensatory nature of OT was investigated by changing the relative orientation of the dynamic (linear acceleration) and static (gravitational) cues. Four subject orientations were investigated: (1) Y-upright-acceleration along the interaural (y) axis while upright; (2) Y-supine-acceleration along the y-axis while supine; (3) Z-RED-acceleration along the dorsoventral (z) axis with right ear down; (4) Z-supine-acceleration along the z-axis while supine. Linear acceleration in the Y-upright, Y-supine and Z-RED orientations elicited conjugate OT. The smaller response in the Z-supine orientation appeared disconjugate. The amplitude of the response decreased and the phase lag increased with increasing frequency for each orientation. This frequency dependence does not match the frequency response of the regular or irregular afferent otolith neurons; therefore the response dynamics cannot be explained by simple peripheral mechanisms. The Y-upright responses were larger than the Y-supine responses (P < 0.05). This difference indicates that OT must be more complicated than a simple low-pass filtered response to interaural shear force, since the dynamic shear force along the interaural axis was identical in these two orientations. The Y-supine responses were, in turn, larger than the Z-RED responses (P < 0.01). Interestingly, the vector sum of the Y-supine responses plus Z-RED responses was not significantly different (P = 0.99) from the Y-upright responses. This suggests that, in this frequency range, the conjugate OT response during Y-upright stimulation might be composed of two components: (1) a response to shear force along the y-axis (as in Y-supine stimulation), and (2) a response to roll tilt of gravitoinertial force (as in Z-RED stimulation).

Compressed sensing for high-resolution nonlipid suppressed 1 H FID MRSI of the human brain at 9.4T.

PubMed

Nassirpour, Sahar; Chang, Paul; Avdievitch, Nikolai; Henning, Anke

2018-04-29

The aim of this study was to apply compressed sensing to accelerate the acquisition of high resolution metabolite maps of the human brain using a nonlipid suppressed ultra-short TR and TE 1 H FID MRSI sequence at 9.4T. X-t sparse compressed sensing reconstruction was optimized for nonlipid suppressed 1 H FID MRSI data. Coil-by-coil x-t sparse reconstruction was compared with SENSE x-t sparse and low rank reconstruction. The effect of matrix size and spatial resolution on the achievable acceleration factor was studied. Finally, in vivo metabolite maps with different acceleration factors of 2, 4, 5, and 10 were acquired and compared. Coil-by-coil x-t sparse compressed sensing reconstruction was not able to reliably recover the nonlipid suppressed data, rather a combination of parallel and sparse reconstruction was necessary (SENSE x-t sparse). For acceleration factors of up to 5, both the low-rank and the compressed sensing methods were able to reconstruct the data comparably well (root mean squared errors [RMSEs] ≤ 10.5% for Cre). However, the reconstruction time of the low rank algorithm was drastically longer than compressed sensing. Using the optimized compressed sensing reconstruction, acceleration factors of 4 or 5 could be reached for the MRSI data with a matrix size of 64 × 64. For lower spatial resolutions, an acceleration factor of up to R∼4 was successfully achieved. By tailoring the reconstruction scheme to the nonlipid suppressed data through parameter optimization and performance evaluation, we present high resolution (97 µL voxel size) accelerated in vivo metabolite maps of the human brain acquired at 9.4T within scan times of 3 to 3.75 min. © 2018 International Society for Magnetic Resonance in Medicine.

Human Pathophysiological Adaptations to the Space Environment

PubMed Central

Demontis, Gian C.; Germani, Marco M.; Caiani, Enrico G.; Barravecchia, Ivana; Passino, Claudio; Angeloni, Debora

2017-01-01

Space is an extreme environment for the human body, where during long-term missions microgravity and high radiation levels represent major threats to crew health. Intriguingly, space flight (SF) imposes on the body of highly selected, well-trained, and healthy individuals (astronauts and cosmonauts) pathophysiological adaptive changes akin to an accelerated aging process and to some diseases. Such effects, becoming manifest over a time span of weeks (i.e., cardiovascular deconditioning) to months (i.e., loss of bone density and muscle atrophy) of exposure to weightlessness, can be reduced through proper countermeasures during SF and in due time are mostly reversible after landing. Based on these considerations, it is increasingly accepted that SF might provide a mechanistic insight into certain pathophysiological processes, a concept of interest to pre-nosological medicine. In this article, we will review the main stress factors encountered in space and their impact on the human body and will also discuss the possible lessons learned with space exploration in reference to human health on Earth. In fact, this is a productive, cross-fertilized, endeavor in which studies performed on Earth yield countermeasures for protection of space crew health, and space research is translated into health measures for Earth-bound population. PMID:28824446

Human Pathophysiological Adaptations to the Space Environment.

PubMed

Demontis, Gian C; Germani, Marco M; Caiani, Enrico G; Barravecchia, Ivana; Passino, Claudio; Angeloni, Debora

2017-01-01

Space is an extreme environment for the human body, where during long-term missions microgravity and high radiation levels represent major threats to crew health. Intriguingly, space flight (SF) imposes on the body of highly selected, well-trained, and healthy individuals (astronauts and cosmonauts) pathophysiological adaptive changes akin to an accelerated aging process and to some diseases. Such effects, becoming manifest over a time span of weeks (i.e., cardiovascular deconditioning) to months (i.e., loss of bone density and muscle atrophy) of exposure to weightlessness, can be reduced through proper countermeasures during SF and in due time are mostly reversible after landing. Based on these considerations, it is increasingly accepted that SF might provide a mechanistic insight into certain pathophysiological processes, a concept of interest to pre-nosological medicine. In this article, we will review the main stress factors encountered in space and their impact on the human body and will also discuss the possible lessons learned with space exploration in reference to human health on Earth. In fact, this is a productive, cross-fertilized, endeavor in which studies performed on Earth yield countermeasures for protection of space crew health, and space research is translated into health measures for Earth-bound population.

To what extent can we attribute accelerated landscape change to human activity? A cautionary tale from the drylands of the South African interior

NASA Astrophysics Data System (ADS)

Tooth, Stephen; Lyons, Richard; Duller, Geoff; McCarthy, Terence

2013-04-01

Across many parts of interior South Africa, alluvial and colluvial sediments are currently subject to widespread erosion by rivers, dongas (gullies), sheetwash and wind. This creates an impression of accelerated landscape change that is commonly attributed to factors such as poor land management by European settlers (mid 18th century onwards) or indigenous peoples, possibly in combination with decadal-scale climatic fluctuations and/or susceptible soil characteristics. Many resources are devoted to managing degrading lands, but effective conservation and restoration efforts are contingent on correctly identifying the underlying causes of erosion. Across South Africa, varied population densities, and diverse climates and soil types, mean that the causes of erosion are likely to be complex and to vary regionally. In some regions, examples of accelerated erosion resulting from vegetation clearance, overburning, overstocking, artificial drainage or land abandonment can be demonstrated. In other regions, however, our geomorphological, sedimentological and geochronological investigations provide an alternative 'geological' perspective on this erosion 'problem' by demonstrating that erosion may be a recurring, natural process linked to late Quaternary climate change and/or longer term landscape denudation. In particular, luminescence chronologies for hillslopes, alluvial fans and river floodplains/terraces at various locations across interior South Africa have enabled comparison with other regional/global palaeoenvironmental records. These comparisons reveal that climatically-controlled changes in runoff and sediment supply, mediated through vegetation cover changes, resulted in shifts between sedimentation (relative aridity), soil formation (relative humidity) and minor channel/donga erosion (semiaridity) from at least 40 kyr until the late Holocene. By contrast, major erosion involving sustained channel incision and associated donga formation appears to have been initiated during the last few thousand years, at some sites apparently corresponding with rapid climatic fluctuations associated with the Mediaeval Warm Period and Little Ice Age. In some instances, channel incision depth has been controlled by the stability of downstream resistant rock barriers (e.g. dolerite sills and dykes) that form local baselevels in river long profiles; upstream of stable barriers, incision has been restricted but where barriers have been partially or fully breached, then deep incision into bedrock is characteristic. These findings provide evidence that: 1) during the late Quaternary, erosional phases have occurred independently of human activity, in different climatic settings, and across different soil types; and 2) in many regions, even the present phase of deep channel incision and donga formation predates the advent of European settlement or indigenous population expansion. These 'geological' perspectives on the age and history of major erosional features demonstrate that accelerated landscape change in South Africa is not necessarily a consequence of human activities, and cannot be assumed to represent an unequivocal signature of the Anthropocene. These perspectives also have implications for land management. Where erosion is indisputably occurring as a result of land mismanagement, then alternative land use practices and erosion-control measures may succeed in slowing or reversing erosion, but where erosion results from natural climatic or denudational processes, then such schemes are unlikely to succeed in the medium- or long-term.

Colour stability of denture teeth submitted to different cleaning protocols and accelerated artificial aging.

PubMed

Freire, T S; Aguilar, F G; Garcia, L da Fonseca Roberti; Pires-de-Souza, F de Carvalho Panzeri

2014-03-01

Acrylic resin is widely used for artificial teeth manufacturing due to several important characteristics; however, this material do not present acceptable colour stability over the course of time. This study evaluated the effect of different cleaning protocols and accelerated artificial aging on colour stability of denture teeth made of acrylic resin. Sixty denture teeth in dark and light shades were used, and separated according to the treatment to which they were submitted. Results demonstrated that colour stability of artificial teeth is influenced by the cleaning solution and artificial aging, being dark teeth more susceptible to colour alteration than lighter ones.

Electronic Health Management

NASA Technical Reports Server (NTRS)

Celaya, Jose R.; Saha, Sankalita; Goebel, Kai

2011-01-01

Accelerated aging methodologies for electrolytic components have been designed and accelerated aging experiments have been carried out. The methodology is based on imposing electrical and/or thermal overstresses via electrical power cycling in order to mimic the real world operation behavior. Data are collected in-situ and offline in order to periodically characterize the devices' electrical performance as it ages. The data generated through these experiments are meant to provide capability for the validation of prognostic algorithms (both model-based and data-driven). Furthermore, the data allow validation of physics-based and empirical based degradation models for this type of capacitor. A first set of models and algorithms has been designed and tested on the data.

Poor maternal nutrition and accelerated postnatal growth induces an accelerated aging phenotype and oxidative stress in skeletal muscle of male rats

PubMed Central

Fernandez-Twinn, Denise S.; Chen, Jian Hua; Hargreaves, Iain P.; Neergheen, Viruna; Aiken, Catherine E.; Ozanne, Susan E.

2016-01-01

ABSTRACT ‘Developmental programming’, which occurs as a consequence of suboptimal in utero and early environments, can be associated with metabolic dysfunction in later life, including an increased incidence of cardiovascular disease and type 2 diabetes, and predisposition of older men to sarcopenia. However, the molecular mechanisms underpinning these associations are poorly understood. Many conditions associated with developmental programming are also known to be associated with the aging process. We therefore utilized our well-established rat model of low birth weight and accelerated postnatal catch-up growth (termed ‘recuperated’) in this study to establish the effects of suboptimal maternal nutrition on age-associated factors in skeletal muscle. We demonstrated accelerated telomere shortening (a robust marker of cellular aging) as evidenced by a reduced frequency of long telomeres (48.5-8.6 kb) and an increased frequency of short telomeres (4.2-1.3 kb) in vastus lateralis muscle from aged recuperated offspring compared to controls. This was associated with increased protein expression of the DNA-damage-repair marker 8-oxoguanine-glycosylase (OGG1) in recuperated offspring. Recuperated animals also demonstrated an oxidative stress phenotype, with decreased citrate synthase activity, increased electron-transport-complex activities of complex I, complex II-III and complex IV (all markers of functional mitochondria), and increased xanthine oxidase (XO), p67phox and nuclear-factor kappa-light-chain-enhancer of activated B-cells (NF-κB). Recuperated offspring also demonstrated increased antioxidant defense capacity, with increased protein expression of manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), catalase and heme oxygenase-1 (HO1), all of which are known targets of NF-κB and can be upregulated as a consequence of oxidative stress. Recuperated offspring also had a pro-inflammatory phenotype, as evidenced by increased tumor necrosis factor-α (TNFα) and interleukin-1β (IL1β) protein levels. Taken together, we demonstrate, for the first time to our knowledge, an accelerated aging phenotype in skeletal muscle in the context of developmental programming. These findings may pave the way for suitable interventions in at-risk populations. PMID:27585884

Early Induction of NRF2 Antioxidant Pathway by RHBDF2 Mediates Rapid Cutaneous Wound Healing

PubMed Central

Hosur, Vishnu; Burzenski, Lisa M.; Stearns, Timothy M.; Farley, Michelle L.; Sundberg, John P.; Wiles, Michael V.; Shultz, Leonard D.

2017-01-01

Rhomboid family protein RHBDF2, an upstream regulator of the epidermal growth factor (EGF) receptor signaling, has been implicated in cutaneous wound healing. However, the underlying molecular mechanisms are still emerging. In humans, a gain-of-function mutation in the RHBDF2 gene accelerates cutaneous wound healing in an EGFR-dependent manner. Likewise, a gain-of-function mutation in the mouse Rhbdf2 gene (Rhbdf2cub/cub) shows a regenerative phenotype (rapid ear-hole closure) resulting from constitutive activation of the EGFR pathway. Because the RHBDF2-regulated EGFR pathway is relevant to cutaneous wound healing in humans, we used Rhbdf2cub/cub mice to investigate the biological networks and pathways leading to accelerated ear-hole closure, with the goal of identifying therapeutic targets potentially effective in promoting wound healing in humans. Comparative transcriptome analysis of ear pinna tissue from Rhbdf2cub/cub and Rhbdf2+/+ mice at 0h, 15 min, 2h, and 24h post-wounding revealed an early induction of the nuclear factor E2-related factor 2 (NRF2)-mediated anti-oxidative pathway (0h and 15 min), followed by the integrin-receptor aggregation pathway (2h) as early-stage events immediately and shortly after wounding in Rhbdf2cub/cub mice. Additionally, we observed genes enriched for the Fc fragment of the IgG receptor IIIa (FCGR3A)-mediated phagocytosis pathway 24h post-wounding. Although cutaneous wound repair in healthy individuals is generally non-problematic, it can be severely impaired due to aging, diabetes, and chronic inflammation. This study suggests that activation of the NRF2-antioxidant pathway by rhomboid protein RHBDF2 might be beneficial in treating chronic non-healing wounds. PMID:28268192

Early induction of NRF2 antioxidant pathway by RHBDF2 mediates rapid cutaneous wound healing.

PubMed

Hosur, Vishnu; Burzenski, Lisa M; Stearns, Timothy M; Farley, Michelle L; Sundberg, John P; Wiles, Michael V; Shultz, Leonard D

2017-04-01

Rhomboid family protein RHBDF2, an upstream regulator of the epidermal growth factor (EGF) receptor signaling, has been implicated in cutaneous wound healing. However, the underlying molecular mechanisms are still emerging. In humans, a gain-of-function mutation in the RHBDF2 gene accelerates cutaneous wound healing in an EGFR-dependent manner. Likewise, a gain-of-function mutation in the mouse Rhbdf2 gene (Rhbdf2 cub/cub ) shows a regenerative phenotype (rapid ear-hole closure) resulting from constitutive activation of the EGFR pathway. Because the RHBDF2-regulated EGFR pathway is relevant to cutaneous wound healing in humans, we used Rhbdf2 cub/cub mice to investigate the biological networks and pathways leading to accelerated ear-hole closure, with the goal of identifying therapeutic targets potentially effective in promoting wound healing in humans. Comparative transcriptome analysis of ear pinna tissue from Rhbdf2 cub/cub and Rhbdf2 +/+ mice at 0h, 15min, 2h, and 24h post-wounding revealed an early induction of the nuclear factor E2-related factor 2 (NRF2)-mediated anti-oxidative pathway (0h and 15min), followed by the integrin-receptor aggregation pathway (2h) as early-stage events immediately and shortly after wounding in Rhbdf2 cub/cub mice. Additionally, we observed genes enriched for the Fc fragment of the IgG receptor IIIa (FCGR3A)-mediated phagocytosis pathway 24h post-wounding. Although cutaneous wound repair in healthy individuals is generally non-problematic, it can be severely impaired due to aging, diabetes, and chronic inflammation. This study suggests that activation of the NRF2-antioxidant pathway by rhomboid protein RHBDF2 might be beneficial in treating chronic non-healing wounds. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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

2014-01-01

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

Introducing the North Water: Histories of exploration, ice dynamics, living resources, and human settlement in the Thule Region.

PubMed

Hastrup, Kirsten; Mosbech, Anders; Grønnow, Bjarne

2018-04-01

The North Water is a recurrent polynya in the High Arctic situated between Northwest Greenland and Ellesmere Island of Canada. The North Water makes a dynamic space, where various processes may enhance or obstruct each other, accelerating or halting particular modes of human-animal relations in the region, where life itself depends on the North Water. This will be discussed in four steps. The first step posits the North Water as a perceived oasis for explorers and whalers hailing from Europe or America in the nineteenth century. The second step concentrates on the diverse rhythms inherent in the ice conditions, as affected by trends that are set in motion elsewhere. The third step highlights the implications of the dynamics of the ice and sea currents for animal life in the region. The fourth step gives an overview of human settlement patterns around the North Water across the ages. The article shows how natural and social features are deeply implicated in each other, even if they are not directly co-variant.

Task-control of arousal and the effects of repeated unidirectional angular acceleration on human vestibular responses.

DOT National Transportation Integrated Search

1963-11-01

Subjects were exposed to a 10-day habituation series of 200 CW accelerations in total darkness while performing attention-demanding tasks. Decelerations were sub-threshold. Preliminary and post-tests indicated that slow-phase nystagmus and duration o...

Responses to rotating linear acceleration vectors considered in relation to a model of the otolith organs. [human oculomotor response to transverse acceleration stress

NASA Technical Reports Server (NTRS)

Benson, A. J.; Barnes, G. R.

1973-01-01

Human subjects were exposed to a linear acceleration vector that rotated in the transverse plane of the skull without angular counterrotation. Lateral eye movements showed a sinusoidal change in slow phase velocity and an asymmetry or bias in the same direction as vector rotation. A model is developed that attributes the oculomotor response to otolithic mechanisms. It is suggested that the bias component is the manifestation of torsion of the statoconial plaque relative to the base of the utricular macula and that the sinusoidal component represents the translational oscillation of the statoconia. The model subsumes a hypothetical neural mechanism which allows x- and y-axis accelerations to be resolved. Derivation of equations of motion for the statoconial plaque in torsion and translation, which take into account forces acting in shear and normal to the macula, yield estimates of bias and sinusoidal components that are in qualitative agreement with the diverse experimental findings.

[Changes of axial dimensions of the eye during growth in emmetropia, myopia and hyperopia].

PubMed

Katuzny, Bartłomiej J; Koszewska-Kołodziejczak, Aleksandra

2005-01-01

The aim ot this study was to evaluate changes ot axial dimensions ot the eye during growth in emmetropia, myopia and hyperopia. We examined 183 children (363 eyes) aged 4 to 19 with emmetropia, myopia and hyperopia. All measurements were performed after cycloplegia with 1% tropicamidum (Polfa Warszawa). Total and corneal refraction was examined with autokeratorefractometer (Nikon NRK-8000). Then we used ultrasound biometer Ocuscan (Alcon, USA), to measure axial length of the eye, axial length of the vitreous cavity, axial dimension of the lens and axial depth of the anterior chamber. 1. Growth of the axial length of the emmetropic eyes is finished at the age of 12, in hyperopic eyes in the age of 11 and in myopic eyes growth is proportional until the age of 14 and then significantly accelerates. 2. Growth of the axial length is mainly caused by increasing axial length of vitreous cavity. A little role in human eye growth is also played by increasing depth of the anterior chamber. 3. Between 4 and 19 years old, mean cycloplegic axial dimension of the lens is slightly decreasing in emmetropic and hyperopic eyes, whereas in myopic eyes is constant.

The role of estrogen in cutaneous ageing and repair.

PubMed

Wilkinson, Holly N; Hardman, Matthew J

2017-09-01

Combined advances in modern medical practice and increased human longevity are driving an ever-expanding elderly population. Females are particularly at risk of age-associated pathology, spending more of their lives in a post-menopausal state. Menopause, denoted by a rapid decline in serum sex steroid levels, accelerates biological ageing across the body's tissues. Post-menopause physiological changes are particularly noticeable in the skin, which loses structural architecture and becomes prone to damage. The sex steroid most widely discussed as an intrinsic contributor to skin ageing and pathological healing is 17β-estradiol (or estrogen), although many others are involved. Estrogen deficiency is detrimental to many wound-healing processes, notably inflammation and re-granulation, while exogenous estrogen treatment widely reverses these effects. Over recent decades, many of the molecular and cellular correlates to estrogen's beneficial effect on normal skin homeostasis and wound healing have been reported. However, disparities still exist, particularly in the context of mechanistic studies investigating estrogen receptor signalling and its potential cellular effects. New molecular techniques, coupled with increased understanding of estrogen in skin biology, will provide further opportunities to develop estrogen receptor-targeted therapeutics. Copyright © 2017 Elsevier B.V. All rights reserved.

Reduced hematopoietic reserves in DNA interstrand crosslink repair-deficient Ercc1−/− mice

PubMed Central

Prasher, Joanna M; Lalai, Astrid S; Heijmans-Antonissen, Claudia; Ploemacher, Robert E; Hoeijmakers, Jan H J; Touw, Ivo P; Niedernhofer, Laura J

2005-01-01

The ERCC1-XPF heterodimer is a structure-specific endonuclease involved in both nucleotide excision repair and interstrand crosslink repair. Mice carrying a genetic defect in Ercc1 display symptoms suggestive of a progressive, segmental progeria, indicating that disruption of one or both of these DNA damage repair pathways accelerates aging. In the hematopoietic system, there are defined age-associated changes for which the cause is unknown. To determine if DNA repair is critical to prolonged hematopoietic function, hematopoiesis in Ercc1−/− mice was compared to that in young and old wild-type mice. Ercc1−/− mice (3-week-old) exhibited multilineage cytopenia and fatty replacement of bone marrow, similar to old wild-type mice. In addition, the proliferative reserves of hematopoietic progenitors and stress erythropoiesis were significantly reduced in Ercc1−/− mice compared to age-matched controls. These features were not seen in nucleotide excision repair-deficient Xpa−/− mice, but are characteristic of Fanconi anemia, a human cancer syndrome caused by defects in interstrand crosslink repair. These data support the hypothesis that spontaneous interstrand crosslink damage contributes to the functional decline of the hematopoietic system associated with aging. PMID:15692571

The Attenuation of Strike Acceleration with the Use of Safety Equipment in Tae Kwon Do

PubMed Central

Gupta, Sanjey

2011-01-01

Purpose The objectives of this study include: (1) Determination of the attenuation of strike acceleration that Tae Kwon Do sparring safety pads provide from kicks from Olympic style TKD fighters, (2) The sex and weight differentiation in acceleration achieved within the thorax model with the roundhouse kicks. Methods This prospective, observational study utilized 15 Olympic style fighters from an “elite” team kicking a water core heavy bag thorax model with roundhouse kicks. The model was fitted with a tri-axial accelerometer (GCDC, model X250-2) to measure g acceleration from strikes to the bag. The bag was kicked in three, 10 kick phases by all subjects: kicks without padding; kicks with hogu on heavy bag, and kicks with hogu and instep guards on feet. The g acceleration readings were recorded in all phases. Results Kolmogorov-Smirnov failed for all variables. There were 8 female subjects: median age 14 years, median weight 53.4 kg and 7 male subjects: median age 17 years, median weight 70.45 kg. The ANOVA on ranks of the acceleration from kicks against the bag achieved significance, P=0.001. Spearman rank order correlation between the weights of players and acceleration of strike against the hogu without and with insteps pads was significant, P=0.035/r=0.54 and P=0.018/r=0.59, respectively. Conclusion Heavier and male subjects tend to produce more force in strikes. Protective chest guard reduces acceleration to the thorax model, but the utility of instep guards is questionable. PMID:22375244

Pro- and Antioxidant Functions of the Peroxisome-Mitochondria Connection and Its Impact on Aging and Disease

PubMed Central

Pascual-Ahuir, Amparo; Manzanares-Estreder, Sara

2017-01-01

Peroxisomes and mitochondria are the main intracellular sources for reactive oxygen species. At the same time, both organelles are critical for the maintenance of a healthy redox balance in the cell. Consequently, failure in the function of both organelles is causally linked to oxidative stress and accelerated aging. However, it has become clear that peroxisomes and mitochondria are much more intimately connected both physiologically and structurally. Both organelles share common fission components to dynamically respond to environmental cues, and the autophagic turnover of both peroxisomes and mitochondria is decisive for cellular homeostasis. Moreover, peroxisomes can physically associate with mitochondria via specific protein complexes. Therefore, the structural and functional connection of both organelles is a critical and dynamic feature in the regulation of oxidative metabolism, whose dynamic nature will be revealed in the future. In this review, we will focus on fundamental aspects of the peroxisome-mitochondria interplay derived from simple models such as yeast and move onto discussing the impact of an impaired peroxisomal and mitochondrial homeostasis on ROS production, aging, and disease in humans. PMID:28811869

Improved Prediction of Falls in Community-Dwelling Older Adults Through Phase-Dependent Entropy of Daily-Life Walking

PubMed Central

Ihlen, Espen A. F.; van Schooten, Kimberley S.; Bruijn, Sjoerd M.; van Dieën, Jaap H.; Vereijken, Beatrix; Helbostad, Jorunn L.; Pijnappels, Mirjam

2018-01-01

Age and age-related diseases have been suggested to decrease entropy of human gait kinematics, which is thought to make older adults more susceptible to falls. In this study we introduce a new entropy measure, called phase-dependent generalized multiscale entropy (PGME), and test whether this measure improves fall-risk prediction in community-dwelling older adults. PGME can assess phase-dependent changes in the stability of gait dynamics that result from kinematic changes in events such as heel strike and toe-off. PGME was assessed for trunk acceleration of 30 s walking epochs in a re-analysis of 1 week of daily-life activity data from the FARAO study, originally described by van Schooten et al. (2016). The re-analyzed data set contained inertial sensor data from 52 single- and 46 multiple-time prospective fallers in a 6 months follow-up period, and an equal number of non-falling controls matched by age, weight, height, gender, and the use of walking aids. The predictive ability of PGME for falls was assessed using a partial least squares regression. PGME had a superior predictive ability of falls among single-time prospective fallers when compared to the other gait features. The single-time fallers had a higher PGME (p < 0.0001) of their trunk acceleration at 60% of their step cycle when compared with non-fallers. No significant differences were found between PGME of multiple-time fallers and non-fallers, but PGME was found to improve the prediction model of multiple-time fallers when combined with other gait features. These findings suggest that taking into account phase-dependent changes in the stability of the gait dynamics has additional value for predicting falls in older people, especially for single-time prospective fallers. PMID:29556188

Improved Prediction of Falls in Community-Dwelling Older Adults Through Phase-Dependent Entropy of Daily-Life Walking.

PubMed

Ihlen, Espen A F; van Schooten, Kimberley S; Bruijn, Sjoerd M; van Dieën, Jaap H; Vereijken, Beatrix; Helbostad, Jorunn L; Pijnappels, Mirjam

2018-01-01

Age and age-related diseases have been suggested to decrease entropy of human gait kinematics, which is thought to make older adults more susceptible to falls. In this study we introduce a new entropy measure, called phase-dependent generalized multiscale entropy (PGME), and test whether this measure improves fall-risk prediction in community-dwelling older adults. PGME can assess phase-dependent changes in the stability of gait dynamics that result from kinematic changes in events such as heel strike and toe-off. PGME was assessed for trunk acceleration of 30 s walking epochs in a re-analysis of 1 week of daily-life activity data from the FARAO study, originally described by van Schooten et al. (2016). The re-analyzed data set contained inertial sensor data from 52 single- and 46 multiple-time prospective fallers in a 6 months follow-up period, and an equal number of non-falling controls matched by age, weight, height, gender, and the use of walking aids. The predictive ability of PGME for falls was assessed using a partial least squares regression. PGME had a superior predictive ability of falls among single-time prospective fallers when compared to the other gait features. The single-time fallers had a higher PGME ( p < 0.0001) of their trunk acceleration at 60% of their step cycle when compared with non-fallers. No significant differences were found between PGME of multiple-time fallers and non-fallers, but PGME was found to improve the prediction model of multiple-time fallers when combined with other gait features. These findings suggest that taking into account phase-dependent changes in the stability of the gait dynamics has additional value for predicting falls in older people, especially for single-time prospective fallers.

T-cell differentiation and CD56+ levels in polypoidal choroidal vasculopathy and neovascular age-related macular degeneration.

PubMed

Subhi, Yousif; Nielsen, Marie Krogh; Molbech, Christopher Rue; Oishi, Akio; Singh, Amardeep; Nissen, Mogens Holst; Sørensen, Torben Lykke

2017-11-20

Polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (AMD) are prevalent age-related diseases characterized by exudative changes in the macula. Although they share anatomical and clinical similarities, they are also distinctly characterized by their own features, e.g. vascular abnormalities in PCV and drusen-mediated progression in neovascular AMD. PCV remains etiologically uncharacterized, and ongoing discussion is whether PCV and neovascular AMD share the same etiology or constitute two substantially different diseases. In this study, we investigated T-cell differentiation and aging profile in human patients with PCV, patients with neovascular AMD, and age-matched healthy control individuals. Fresh venous blood was prepared for flow cytometry to investigate CD4 + and CD8 + T-cell differentiation (naïve, central memory, effector memory, effector memory CD45ra + ), loss of differentiation markers CD27 and CD28, and expression of aging marker CD56. Patients with PCV were similar to the healthy controls in all aspects. In patients with neovascular AMD we found significantly accelerated T-cell differentiation (more CD28 - CD27 - cells) and aging (more CD56 + cells) in the CD8 + T-cell compartment. These findings suggest that PCV and neovascular AMD are etiologically different in terms of T cell immunity, and that neovascular AMD is associated with T-cell immunosenescence.

The Human Hazard.

ERIC Educational Resources Information Center

Tickell, Crispin

1995-01-01

Examines the plight of environmental refugees and the adequacy of political responses to the situation. Discusses the consequences of accelerated environmental change, particularly the impact of global warming on human migration. (LZ)

Detection of linear ego-acceleration from optic flow.

PubMed

Festl, Freya; Recktenwald, Fabian; Yuan, Chunrong; Mallot, Hanspeter A

2012-07-20

Human observers are able to estimate various ego-motion parameters from optic flow, including rotation, translational heading, time-to-collision (TTC), time-to-passage (TTP), etc. The perception of linear ego-acceleration or deceleration, i.e., changes of translational velocity, is less well understood. While time-to-passage experiments indicate that ego-acceleration is neglected, subjects are able to keep their (perceived) speed constant under changing conditions, indicating that some sense of ego-acceleration or velocity change must be present. In this paper, we analyze the relation of ego-acceleration estimates and geometrical parameters of the environment using simulated flights through cylindrical and conic (narrowing or widening) corridors. Theoretical analysis shows that a logarithmic ego-acceleration parameter, called the acceleration rate ρ, can be calculated from retinal acceleration measurements. This parameter is independent of the geometrical layout of the scene; if veridical ego-motion is known at some instant in time, acceleration rate allows updating of ego-motion without further depth-velocity calibration. Results indicate, however, that subjects systematically confuse ego-acceleration with corridor narrowing and ego-deceleration with corridor widening, while veridically judging ego-acceleration in straight corridors. We conclude that judgments of ego-acceleration are based on first-order retinal flow and do not make use of acceleration rate or retinal acceleration.

Accelerated Gray and White Matter Deterioration With Age in Schizophrenia.

PubMed

Cropley, Vanessa L; Klauser, Paul; Lenroot, Rhoshel K; Bruggemann, Jason; Sundram, Suresh; Bousman, Chad; Pereira, Avril; Di Biase, Maria A; Weickert, Thomas W; Weickert, Cynthia Shannon; Pantelis, Christos; Zalesky, Andrew

2017-03-01

Although brain changes in schizophrenia have been proposed to mirror those found with advancing age, the trajectory of gray matter and white matter changes during the disease course remains unclear. The authors sought to measure whether these changes in individuals with schizophrenia remain stable, are accelerated, or are diminished with age. Gray matter volume and fractional anisotropy were mapped in 326 individuals diagnosed with schizophrenia or schizoaffective disorder and in 197 healthy comparison subjects aged 20-65 years. Polynomial regression was used to model the influence of age on gray matter volume and fractional anisotropy at a whole-brain and voxel level. Between-group differences in gray matter volume and fractional anisotropy were regionally localized across the lifespan using permutation testing and cluster-based inference. Significant loss of gray matter volume was evident in schizophrenia, progressively worsening with age to a maximal loss of 8% in the seventh decade of life. The inferred rate of gray matter volume loss was significantly accelerated in schizophrenia up to middle age and plateaued thereafter. In contrast, significant reductions in fractional anisotropy emerged in schizophrenia only after age 35, and the rate of fractional anisotropy deterioration with age was constant and best modeled with a straight line. The slope of this line was 60% steeper in schizophrenia relative to comparison subjects, indicating a significantly faster rate of white matter deterioration with age. The rates of reduction of gray matter volume and fractional anisotropy were significantly faster in males than in females, but an interaction between sex and diagnosis was not evident. The findings suggest that schizophrenia is characterized by an initial, rapid rate of gray matter loss that slows in middle life, followed by the emergence of a deficit in white matter that progressively worsens with age at a constant rate.

Hydrophobic Characteristics of Composite Insulators in Simulated Inland Arid Desert Environment

NASA Astrophysics Data System (ADS)

Khan, Yasin; Al-Arainy, Abdulrehman Ali; Malik, Nazar Hussain; Qureshi, Muhammad Iqbal

2010-06-01

Presently along with traditional insulators i.e. glass and porcelain, etc., the polymeric insulators are also used world widely. These polymeric insulators are very sensitive to various environmental parameters e.g. UV radiations, heat, etc. The UV radiation level in the central region of Saudi Arabia is high as compared to the recommended IEC-61109 standard for the accelerated aging of the composite insulators. In this study, thermoplastic elastomer (TPE) and Ethylene Propylene Diene Monomer (EPDM) insulators were subjected to accelerated aging stress as per IEC standard as well as modified IEC standard simulating the inland arid desert's atmospheric conditions. The hydrophobic characteristics were studied by measuring the contact angle along the insulator surface before and after the accelerated aging of the samples. It was found that TPE loses its hydrophobic properties more as compared to EPDM insulator. This loss was proportional to the intensity of UV irradiation. The rate of recovery is also low for both the tested materials as compared to Silicone Rubber insulators.

Parasite infection accelerates age polyethism in young honey bees

PubMed Central

Lecocq, Antoine; Jensen, Annette Bruun; Kryger, Per; Nieh, James C.

2016-01-01

Honey bees (Apis mellifera) are important pollinators and their health is threatened worldwide by persistent exposure to a wide range of factors including pesticides, poor nutrition, and pathogens. Nosema ceranae is a ubiquitous microsporidian associated with high colony mortality. We used lab micro-colonies of honey bees and video analyses to track the effects of N. ceranae infection and exposure on a range of individual and social behaviours in young adult bees. We provide detailed data showing that N. ceranae infection significantly accelerated the age polyethism of young bees, causing them to exhibit behaviours typical of older bees. Bees with high N. ceranae spore counts had significantly increased walking rates and decreased attraction to queen mandibular pheromone. Infected bees also exhibited higher rates of trophallaxis (food exchange), potentially reflecting parasite manipulation to increase colony infection. However, reduction in queen contacts could help bees limit the spread of infection. Such accelerated age polyethism may provide a form of behavioural immunity, particularly if it is elicited by a wide variety of pathogens. PMID:26912310

Parasite infection accelerates age polyethism in young honey bees.

PubMed

Lecocq, Antoine; Jensen, Annette Bruun; Kryger, Per; Nieh, James C

2016-02-25

Honey bees (Apis mellifera) are important pollinators and their health is threatened worldwide by persistent exposure to a wide range of factors including pesticides, poor nutrition, and pathogens. Nosema ceranae is a ubiquitous microsporidian associated with high colony mortality. We used lab micro-colonies of honey bees and video analyses to track the effects of N. ceranae infection and exposure on a range of individual and social behaviours in young adult bees. We provide detailed data showing that N. ceranae infection significantly accelerated the age polyethism of young bees, causing them to exhibit behaviours typical of older bees. Bees with high N. ceranae spore counts had significantly increased walking rates and decreased attraction to queen mandibular pheromone. Infected bees also exhibited higher rates of trophallaxis (food exchange), potentially reflecting parasite manipulation to increase colony infection. However, reduction in queen contacts could help bees limit the spread of infection. Such accelerated age polyethism may provide a form of behavioural immunity, particularly if it is elicited by a wide variety of pathogens.

HYDROPHOBIC CHARACTERISTICS OF COMPOSITE INSULATORS IN SIMULATED INLAND ARID DESERT ENVIRONMENT

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

Khan, Yasin; Al-Arainy, Abdulrehman Ali; Malik, Nazar Hussain

2010-06-15

Presently along with traditional insulators i.e. glass and porcelain, etc., the polymeric insulators are also used world widely. These polymeric insulators are very sensitive to various environmental parameters e.g. UV radiations, heat, etc. The UV radiation level in the central region of Saudi Arabia is high as compared to the recommended IEC-61109 standard for the accelerated aging of the composite insulators. In this study, thermoplastic elastomer (TPE) and Ethylene Propylene Diene Monomer (EPDM) insulators were subjected to accelerated aging stress as per IEC standard as well as modified IEC standard simulating the inland arid desert's atmospheric conditions. The hydrophobic characteristicsmore » were studied by measuring the contact angle along the insulator surface before and after the accelerated aging of the samples. It was found that TPE loses its hydrophobic properties more as compared to EPDM insulator. This loss was proportional to the intensity of UV irradiation. The rate of recovery is also low for both the tested materials as compared to Silicone Rubber insulators.« less

Biological age and tempos of aging in women over 60 in connection with their morphofunctional characteristics.

PubMed

Negasheva, Marina; Lapshina, Natalia; Okushko, Rostislav; Godina, Elena

2014-05-19

The study of aging processes and the changes in morphological, physiological, and functional characteristics that are associated with aging is of great interest not only for researchers, but also for the general public. The aim of the present paper is to study the biological age and tempos of aging in women older than 60 years, including long-lived females (over 90-years-old), and their associations with morphofunctional characteristics. Somatic traits, body mass components, and functional characteristics were investigated in 119 elderly (between 60 and 74-years-old) and long-lived (over 90-years-old) women in Tiraspol. With the special PC software 'Diagnostics of Aging: BioAge' (National Gerontological Center, Moscow, Russia) the biological age and tempos of aging were evaluated in the study participants. The results show close connections between morphofunctional changes, particularly in body mass components, and biological age. The software demonstrated its validity in the estimation of biological age in the group of elderly women. In the homogenous (according to their chronological age) group of women, three subgroups were separated with different tempos of aging: those with lower rates of aging (biological age less than chronological age by two years or more); those consistent with their chronological age, and those with accelerated tempos of aging (biological age higher than chronological age by two years or more). Morphofunctional characteristics in the studied groups of women demonstrate the trends of age-involutive changes which can be traced through all groups, from those with slow rates of aging, to those with average rates, to those with accelerated tempos of aging, and finally in long-lived women. The results of comparative analysis show that women with accelerated aging are characterized with such traits as lower skeletal muscle mass, lower hand grip strength, and higher metabolic rate. Canonical discriminant analysis revealed a number of morphofunctional characteristics which differentiate the early-aging women from women with average rates of aging: higher BMI values, excessive fat mass, lower skeletal muscle mass and low values of hand grip strength. Thus the presence of such characteristics in elderly women can be considered as additional risk factor towards the early onset of the aging process.

Re-dating Zhoukoudian Upper Cave, northern China and its regional significance.

PubMed

Li, Feng; Bae, Christopher J; Ramsey, Christopher B; Chen, Fuyou; Gao, Xing

2018-05-31

Due to the presence of multiple partial modern human skeletons thought to have been interred along with a diversity of evidence of symbolic behavior, Zhoukoudian Upper Cave (ZKD UC; formally "Choukoutien") from northern China has long been a critical site for understanding Late Quaternary human evolution and particularly the role eastern Asia played. Unfortunately, uncertainty regarding ZKD UC's chronology has long hindered determination of its importance in the debate over modern human origins. This situation has been particularly problematic because dates from the primary archaeological layers of ZKD UC have ranged from the Late Pleistocene to the Early Holocene (∼34-10 ka), with clearly different implications depending on which age is used. Here, we present a new set of accelerator mass spectrometry radiocarbon dating results from ZKD UC. Based on this new set of dates and further re-evaluations of the previous dating analyses, archaeological materials, published excavation reports and stratigraphy, we conclude that the ZKD UC archaeological layers minimally date to 35.1-33.5 ka. Given the similarities between the human fossils and archaeology between ZKD UC and western Eurasia, it is likely that the ZKD UC human foragers were part of dispersal events across northern Eurasia toward Siberia and eventually reaching into northern China. Copyright © 2018 Elsevier Ltd. All rights reserved.

Accelerating Drug Development: Antiviral Therapies for Emerging Viruses as a Model.

PubMed

Everts, Maaike; Cihlar, Tomas; Bostwick, J Robert; Whitley, Richard J

2017-01-06

Drug discovery and development is a lengthy and expensive process. Although no one, simple, single solution can significantly accelerate this process, steps can be taken to avoid unnecessary delays. Using the development of antiviral therapies as a model, we describe options for acceleration that cover target selection, assay development and high-throughput screening, hit confirmation, lead identification and development, animal model evaluations, toxicity studies, regulatory issues, and the general drug discovery and development infrastructure. Together, these steps could result in accelerated timelines for bringing antiviral therapies to market so they can treat emerging infections and reduce human suffering.

Whole-genome sequencing of Atacama skeleton shows novel mutations linked with dysplasia.

PubMed

Bhattacharya, Sanchita; Li, Jian; Sockell, Alexandra; Kan, Matthew J; Bava, Felice A; Chen, Shann-Ching; Ávila-Arcos, María C; Ji, Xuhuai; Smith, Emery; Asadi, Narges B; Lachman, Ralph S; Lam, Hugo Y K; Bustamante, Carlos D; Butte, Atul J; Nolan, Garry P

2018-04-01

Over a decade ago, the Atacama humanoid skeleton (Ata) was discovered in the Atacama region of Chile. The Ata specimen carried a strange phenotype-6-in stature, fewer than expected ribs, elongated cranium, and accelerated bone age-leading to speculation that this was a preserved nonhuman primate, human fetus harboring genetic mutations, or even an extraterrestrial. We previously reported that it was human by DNA analysis with an estimated bone age of about 6-8 yr at the time of demise. To determine the possible genetic drivers of the observed morphology, DNA from the specimen was subjected to whole-genome sequencing using the Illumina HiSeq platform with an average 11.5× coverage of 101-bp, paired-end reads. In total, 3,356,569 single nucleotide variations (SNVs) were found as compared to the human reference genome, 518,365 insertions and deletions (indels), and 1047 structural variations (SVs) were detected. Here, we present the detailed whole-genome analysis showing that Ata is a female of human origin, likely of Chilean descent, and its genome harbors mutations in genes ( COL1A1 , COL2A1 , KMT2D , FLNB , ATR , TRIP11 , PCNT ) previously linked with diseases of small stature, rib anomalies, cranial malformations, premature joint fusion, and osteochondrodysplasia (also known as skeletal dysplasia). Together, these findings provide a molecular characterization of Ata's peculiar phenotype, which likely results from multiple known and novel putative gene mutations affecting bone development and ossification. © 2018 Bhattacharya et al.; Published by Cold Spring Harbor Laboratory Press.

Cycle-powered short radius (1.9M) centrifuge: exercise vs. passive acceleration

NASA Technical Reports Server (NTRS)

Greenleaf, J. E.; Gundo, D. P.; Watenpaugh, D. E.; Mulenburg, G. M.; Marchman, N.; Looft-Wilson, R.; Hargens, A. R.

1996-01-01

A human-powered short-arm centrifuge is described. This centrifuge could be used during spaceflight to provide +Gz acceleration while subjects performed exercise, thus supplying two forms of weightlessness countermeasures. Results from a study of cardiovascular responses while using the centrifuge are presented.

Glucose metabolite glyoxal induces senescence in telomerase-immortalized human mesenchymal stem cells

PubMed Central

2012-01-01

Background Various by-products of the cellular metabolism, such as reactive carbonyl species (RCS) are potentially harmful to cells and tissues, and play a role in many physiological and pathological processes. Among various RCS is the highly reactive dicarbonyl glyoxal (GO), which is a natural physiological metabolite produced by the auto-oxidation of glucose, and can form covalent adducts known as advanced glycation endproducts (AGE). We have previously reported that GO accelerates ageing and causes premature senescence in normal human skin fibroblasts. Results Using a bone marrow-derived telomerase-immortalised mesenchymal stem cell line hMSC-TERT we have observed that an exposure of cells to 0.75 mM and 1 mM GO induces irreversible cellular senescence within 3 days. Induction of senescence in hMSC-TERT was demonstrated by a variety of markers, including characteristic cell morphology and enlargement, vacuolisation, multinucleation, induction of senescence associated β-galactosidase, cell cycle arrest, and increased levels of a cell cycle inhibitor p16. These changes were accompanied by increased extent of DNA breaks as measured by the comet assay, and increased levels of the AGE product, carboxymethyl-lysine (CML). Furthermore, the in vitro differentiation potential of hMSC-TERT to become functional osteoblasts was highly reduced in GO-treated stem cells, as determined by alkaline phosphatase (ALP) activity and mineralized matrix (MM) formation. Conclusions The results of our study imply that an imbalanced glucose metabolism can reduce the functioning ability of stem cells in vivo both during ageing and during stem cell-based therapeutic interventions. PMID:22424056

Acceleration of the aging process by oxygen

NASA Technical Reports Server (NTRS)

Miquel, J.; Lunderen, P. R.; Bensch, K. G.

1975-01-01

Tissue changes induced by hyperoxia have been compared with those of normal aging. Results of investigations using male flies prompt conclusion that normal aging, radiation syndrome, and hyperoxic injury share at least one common feature--lipid peroxidation damage to all mambranes resulting in accumulation of age pigment.

Heavy Ion Acceleration at J-PARC

NASA Astrophysics Data System (ADS)

SATO, Susumu

2018-02-01

J-PARC, the Japan Proton Accelerator Research Complex, is an accelerator, which provides a high-intensity proton beam. Recently as a very attractive project, the acceleration of heavy ions produced by supplementary ion sources, called J-PARC-HI, is seriously contemplated by domestic as well as international communities. The planned facility would accelerate heavy ions up to U92+ with a beam energy 20 AGeV ( of 6.2 AGeV). The highlight of the J-PARC-HI project is its very high beam rate up to 1011 Hz, which will enable the study of very rare events. Taking advantage of this high intensity, J-PARC-HI will carry out frontier studies of new and rare observables in this energy region: (i) nuclear medium modification of chiral property of vector mesons through low-mass di-lepton signal, (ii) QCD critical pointcharacterization through event-by-event fluctuation signals of particle production, (iii) systematic measurements related to the equation of state through collective flow signal or two-particle momentum correlation signal, or (iv) the search of hyper nuclei with multi strangeness including or exceeding S = 3. The current plan of J-PARC-HI aims to carrying out the first experimental measurements in 2025.

Accelerated Aging in Electrolytic Capacitors for Prognostics

NASA Technical Reports Server (NTRS)

Celaya, Jose R.; Kulkarni, Chetan; Saha, Sankalita; Biswas, Gautam; Goebel, Kai Frank

2012-01-01

The focus of this work is the analysis of different degradation phenomena based on thermal overstress and electrical overstress accelerated aging systems and the use of accelerated aging techniques for prognostics algorithm development. Results on thermal overstress and electrical overstress experiments are presented. In addition, preliminary results toward the development of physics-based degradation models are presented focusing on the electrolyte evaporation failure mechanism. An empirical degradation model based on percentage capacitance loss under electrical overstress is presented and used in: (i) a Bayesian-based implementation of model-based prognostics using a discrete Kalman filter for health state estimation, and (ii) a dynamic system representation of the degradation model for forecasting and remaining useful life (RUL) estimation. A leave-one-out validation methodology is used to assess the validity of the methodology under the small sample size constrain. The results observed on the RUL estimation are consistent through the validation tests comparing relative accuracy and prediction error. It has been observed that the inaccuracy of the model to represent the change in degradation behavior observed at the end of the test data is consistent throughout the validation tests, indicating the need of a more detailed degradation model or the use of an algorithm that could estimate model parameters on-line. Based on the observed degradation process under different stress intensity with rest periods, the need for more sophisticated degradation models is further supported. The current degradation model does not represent the capacitance recovery over rest periods following an accelerated aging stress period.

Loss of circadian clock accelerates aging in neurodegeneration-prone mutants

PubMed Central

Krishnan, Natraj; Rakshit, Kuntol; Chow, Eileen S.; Wentzell, Jill S.; Kretzschmar, Doris; Giebultowicz, Jadwiga M.

2012-01-01

Circadian clocks generate rhythms in molecular, cellular, physiological, and behavioral processes. Recent studies suggest that disruption of the clock mechanism accelerates organismal senescence and age-related pathologies in mammals. Impaired circadian rhythms are observed in many neurological diseases; however, it is not clear whether loss of rhythms is the cause or result of neurodegeneration, or both. To address this important question, we examined the effects of circadian disruption in Drosophila melanogaster mutants that display clock-unrelated neurodegenerative phenotypes. We combined a null mutation in the clock gene period (per01) that abolishes circadian rhythms, with a hypomorphic mutation in the carbonyl reductase gene sniffer (sni1), which displays oxidative stress induced neurodegeneration. We report that disruption of circadian rhythms in sni1 mutants significantly reduces their lifespan compared to single mutants. Shortened lifespan in double mutants was coupled with accelerated neuronal degeneration evidenced by vacuolization in the adult brain. In addition, per01 sni1 flies showed drastically impaired vertical mobility and increased accumulation of carbonylated proteins compared to age-matched single mutant flies. Loss of per function does not affect sni mRNA expression, suggesting that these genes act via independent pathways producing additive effects. Finally, we show that per01 mutation accelerates the onset of brain pathologies when combined with neurodegeneration-prone mutation in another gene, swiss cheese (sws1), which does not operate through the oxidative stress pathway. Taken together, our data suggest that the period gene may be causally involved in neuroprotective pathways in aging Drosophila. PMID:22227001

A New Formulation of Equivalent Effective Stratospheric Chlorine (EESC)

NASA Technical Reports Server (NTRS)

Newman, P. A.; Daniel, J. S.; Waugh, D. W.; Nash, E. R.

2007-01-01

Equivalent effective stratospheric chlorine (EESC) is a convenient parameter to quantify the effects of halogens (chlorine and bromine) on ozone depletion in the stratosphere. We show and discuss a new formulation of EESC that now includes the effects of age-of-air dependent fractional release values and an age-of-air spectrum. This new formulation provides quantitative estimates of EESC that can be directly related to inorganic chlorine and bromine throughout the stratosphere. Using this EESC formulation, we estimate that human-produced ozone depleting substances will recover to 1980 levels in 2041 in the midlatitudes, and 2067 over Antarctica. These recovery dates are based upon the assumption that the international agreements for regulating ozone-depleting substances are adhered to. In addition to recovery dates, we also estimate the uncertainties in the estimated time of recovery. The midlatitude recovery of 2041 has a 95% confidence uncertainty from 2028 to 2049, while the 2067 Antarctic recovery has a 95% confidence uncertainty from 2056 to 2078. The principal uncertainties are from the estimated mean age-of-air, and the assumption that the mean age-of-air and fractional release values are time independent. Using other model estimates of age decrease due to climate change, we estimate that midlatitude recovery may be accelerated from 2041 to 2031.

Accelerated optical polymer aging studies for LED luminaire applications

NASA Astrophysics Data System (ADS)

Estupiñán, Edgar; Wendling, Peter; Kostrun, Marijan; Garner, Richard

2013-09-01

There is a need in the lighting industry to design and implement accelerated aging methods that accurately simulate the aging process of LED luminaire components. In response to this need, we have built a flexible and reliable system to study the aging characteristics of optical polymer materials, and we have employed it to study a commercially available LED luminaire diffuser made of PMMA. The experimental system consists of a "Blue LED Emitter" and a working surface. Both the temperatures of the samples and the optical powers of the LEDs are appropriately characterized in the system. Several accelerated aging experiments are carried out at different temperatures and optical powers over a 90 hour period and the measured transmission values are used as inputs to a degradation model derived using plausibility arguments. This model seems capable of predicting the behavior of the material as a function of time, temperature and optical power. The model satisfactorily predicts the measured transmission values of diffusers aged in luminaires at two different times and thus can be used to make application recommendations for this material. Specifically, at 35000 hours (the manufacturer's stated life of the luminaire) and at the typical operational temperature of the diffuser, the model predicts a transmission loss of only a few percent over the original transmission of the material at 450 nm, which renders this material suitable for this application.

Assessment of surface hardness of acrylic resins submitted to accelerated artificial aging.

PubMed

Tornavoi, D C; Agnelli, J A M; Lepri, C P; Mazzetto, M O; Botelho, A L; Soares, R G; Dos Reis, A C

2012-06-01

The aim of this study was to assess the influence of accelerated artificial aging (AAA) on the surface hardness of acrylic resins. The following three commercial brands of acrylic resins were tested: Vipi Flash (autopolymerized resin), Vipi Wave (microwave heat-polymerized resin) and Vipi Cril (conventional heat-polymerized resin). To perform the tests, 21 test specimens (65x10x3 mm) were made, 7 for each resin. Three surface hardness readings were performed for each test specimen, before and after AAA, and the means were submitted to the following tests: Kolmogorov-Smirnov (P>0.05), Levene Statistic, Two-way ANOVA, Tukey Post Hoc (P<0.05) with the SPSS Statistical Software 17.0. The analysis of the factors showed significant differences in the hardness values (P<0.05). Before aging, the autopolymerized acrylic resin Vipi Flash showed lower hardness values when compared with the heat-polymerized resin Vipi Cril (P=0.001). After aging, the 3 materials showed similar performance when compared among them. The Vipi Cril was the only one affected by AAA and showed lower hardness values after this procedure (Pp=0.003). It may be concluded that accelerated artificial aging influenced surface hardness of heat-polymerized acrylic resin Vipi Cril.

Effects of tartrazine on exploratory behavior in a three-generation toxicity study in mice.

PubMed

Tanaka, Toyohito; Takahashi, Osamu; Oishi, Shinshi; Ogata, Akio

2008-10-01

Tartrazine was given to mice in the diet at levels of 0 (control), 0.05%, 0.15%, and 0.45% from 5 weeks of age of the F(0) generation to 9 weeks of age of the F(2) generation, and selected reproductive and neurobehavioral parameters were measured. In the F(1) generation, the development of swimming direction at postnatal day (PND) 7 was accelerated significantly in male offspring in a dose-related manner. Surface righting at PND 7 was affected significantly in female offspring in dose-related manner. Several variables in exploratory behavior showed significant tendencies to be affected in the treatment groups in male offspring at 3 weeks of age. In the F(2) generation, the development of swimming direction at PND 7 was accelerated significantly in the high-dosed group in male offspring. Time taken of olfactory orientation at PND 14 was accelerated significantly in male offspring in a dose-related manner. Several variables in exploratory behavior showed significant tendencies to be affected in the treatment groups in male offspring at 3 weeks of age, and in males at 8 weeks of age. The dose levels of tartrazine in the present study produced a few adverse effects on neurobehavioral parameters throughout generations in mice.

Influence of Different Types of Resin Luting Agents on Color Stability of Ceramic Laminate Veneers Subjected to Accelerated Artificial Aging.

PubMed

Silami, Francisca Daniele Jardilino; Tonani, Rafaella; Alandia-Román, Carla Cecilia; Pires-de-Souza, Fernanda de Carvalho Panzeri

2016-01-01

The aim of this study was to evaluate the influence of accelerated aging (AAA) on the color stability of resin cements for bonding ceramic laminate veneers of different thicknesses. The occlusal surfaces of 80 healthy human molars were flattened. Ceramic laminate veneers (IPS e-max Ceram) of two thicknesses (0.5 and 1.0 mm) were bonded with three types of luting agents: light-cured, conventional dual and self-adhesive dual cement. Teeth without restorations and cement samples (0.5 mm) were used as control. After initial color evaluations, the samples were subjected to AAA for 580 h. After this, new color readouts were made, and the color stability (ΔE) and luminosity (ΔL) data were analyzed. The greatest color changes (p<0.05) occurred when 0.5 mm veneers were fixed with light-cured cement and the lowest when 1.0 mm veneers were fixed with conventional dual cement. There was no influence of the restoration thickness when the self-adhesive dual cement was used. When veneers were compared with the control groups, it was verified that the cement samples presented the greatest alterations (p<0.05) in comparison with both substrates and restored teeth. Therefore, it was concluded that the thickness of the restoration influences color and luminosity changes for conventional dual and light-cured cements. The changes in self-adhesive cement do not depend on restoration thickness.

Aging of the Immune System. Mechanisms and Therapeutic Targets.

PubMed

Weyand, Cornelia M; Goronzy, Jörg J

2016-12-01

Beginning with the sixth decade of life, the human immune system undergoes dramatic aging-related changes, which continuously progress to a state of immunosenescence. The aging immune system loses the ability to protect against infections and cancer and fails to support appropriate wound healing. Vaccine responses are typically impaired in older individuals. Conversely, inflammatory responses mediated by the innate immune system gain in intensity and duration, rendering older individuals susceptible to tissue-damaging immunity and inflammatory disease. Immune system aging functions as an accelerator for other age-related pathologies. It occurs prematurely in some clinical conditions, most prominently in patients with the autoimmune syndrome rheumatoid arthritis (RA); and such patients serve as an informative model system to study molecular mechanisms of immune aging. T cells from patients with RA are prone to differentiate into proinflammatory effector cells, sustaining chronic-persistent inflammatory lesions in the joints and many other organ systems. RA T cells have several hallmarks of cellular aging; most importantly, they accumulate damaged DNA. Because of deficiency of the DNA repair kinase ataxia telangiectasia mutated, RA T cells carry a higher burden of DNA double-strand breaks, triggering cell-indigenous stress signals that shift the cell's survival potential and differentiation pattern. Immune aging in RA T cells is also associated with metabolic reprogramming; specifically, with reduced glycolytic flux and diminished ATP production. Chronic energy stress affects the longevity and the functional differentiation of older T cells. Altered metabolic patterns provide opportunities to therapeutically target the immune aging process through metabolic interference.

A common brain network links development, aging, and vulnerability to disease.

PubMed

Douaud, Gwenaëlle; Groves, Adrian R; Tamnes, Christian K; Westlye, Lars Tjelta; Duff, Eugene P; Engvig, Andreas; Walhovd, Kristine B; James, Anthony; Gass, Achim; Monsch, Andreas U; Matthews, Paul M; Fjell, Anders M; Smith, Stephen M; Johansen-Berg, Heidi

2014-12-09

Several theories link processes of development and aging in humans. In neuroscience, one model posits for instance that healthy age-related brain degeneration mirrors development, with the areas of the brain thought to develop later also degenerating earlier. However, intrinsic evidence for such a link between healthy aging and development in brain structure remains elusive. Here, we show that a data-driven analysis of brain structural variation across 484 healthy participants (8-85 y) reveals a largely--but not only--transmodal network whose lifespan pattern of age-related change intrinsically supports this model of mirroring development and aging. We further demonstrate that this network of brain regions, which develops relatively late during adolescence and shows accelerated degeneration in old age compared with the rest of the brain, characterizes areas of heightened vulnerability to unhealthy developmental and aging processes, as exemplified by schizophrenia and Alzheimer's disease, respectively. Specifically, this network, while derived solely from healthy subjects, spatially recapitulates the pattern of brain abnormalities observed in both schizophrenia and Alzheimer's disease. This network is further associated in our large-scale healthy population with intellectual ability and episodic memory, whose impairment contributes to key symptoms of schizophrenia and Alzheimer's disease. Taken together, our results suggest that the common spatial pattern of abnormalities observed in these two disorders, which emerge at opposite ends of the life spectrum, might be influenced by the timing of their separate and distinct pathological processes in disrupting healthy cerebral development and aging, respectively.

Walking stability and sensorimotor function in older people with diabetic peripheral neuropathy.

PubMed

Menz, Hylton B; Lord, Stephen R; St George, Rebecca; Fitzpatrick, Richard C

2004-02-01

To evaluate, in older people with diabetic peripheral neuropathy (DPN) and in age-matched controls, acceleration patterns of the head and pelvis when walking to determine the effect of lower-limb sensory loss on walking stability. Case-control study. Falls and balance laboratory in Australia. Thirty persons with diabetes mellitus (age range, 55-91 y) and 30 age-matched controls. Acceleration patterns of the head and pelvis were measured while participants walked on a level surface and an irregular walkway. Participants also underwent tests of vision, sensation, strength, reaction time, and balance. Temporospatial gait parameters and variables derived from acceleration signals. Participants with DPN had reduced walking speed, cadence, and step length, and less rhythmic acceleration patterns at the head and pelvis compared with controls. These differences were particularly evident when participants walked on the irregular surface. Participants with DPN also had impaired peripheral sensation, reaction time, and balance. Older people with DPN have an impaired ability to stabilize their body when walking on irregular surfaces, even if they adopt a more conservative gait pattern. These results provide further insights into the role of peripheral sensory input in the control of gait stability, and suggest possible mechanisms underlying the increased risk of falling in older people with diabetic neuropathy.

Prognostics of Power Electronics, Methods and Validation Experiments

NASA Technical Reports Server (NTRS)

Kulkarni, Chetan S.; Celaya, Jose R.; Biswas, Gautam; Goebel, Kai

2012-01-01

Abstract Failure of electronic devices is a concern for future electric aircrafts that will see an increase of electronics to drive and control safety-critical equipment throughout the aircraft. As a result, investigation of precursors to failure in electronics and prediction of remaining life of electronic components is of key importance. DC-DC power converters are power electronics systems employed typically as sourcing elements for avionics equipment. Current research efforts in prognostics for these power systems focuses on the identification of failure mechanisms and the development of accelerated aging methodologies and systems to accelerate the aging process of test devices, while continuously measuring key electrical and thermal parameters. Preliminary model-based prognostics algorithms have been developed making use of empirical degradation models and physics-inspired degradation model with focus on key components like electrolytic capacitors and power MOSFETs (metal-oxide-semiconductor-field-effect-transistor). This paper presents current results on the development of validation methods for prognostics algorithms of power electrolytic capacitors. Particularly, in the use of accelerated aging systems for algorithm validation. Validation of prognostics algorithms present difficulties in practice due to the lack of run-to-failure experiments in deployed systems. By using accelerated experiments, we circumvent this problem in order to define initial validation activities.

Impact of soybean aging conditions on tofu sensory characteristics and acceptance.

PubMed

Kamizake, Neide Kiyoko Kondo; Silva, Lilian Catarini Pereira; Prudencio, Sandra Helena

2018-02-01

Tofu from aged soybeans is of poor quality, mainly with respect to texture. Texture defects described in the literature are contradictory. No study has investigated all sensory properties simultaneously. The objective of the present study was to evaluate the effect of soybean aging conditions [natural: ambient temperature and RH, 18 months, and accelerated: 30 °C, 84% relative humidity (RH), 6 months] on all of the sensory characteristics and the acceptance of tofu. Texture and color were also evaluated via an instrumental method. The control condition was -20 °C and 47% RH. Coodetec 214 and BRS 267 cultivars were studied. The effect of soybean accelerated aging on tofu sensory characteristics and acceptance was more pronounced compared to the natural condition. The two cultivars had a similar behavior. Tofu control exhibited a light, uniform and bright color, cohesive appearance, sweet aroma and flavor, as well as a firm and elastic texture. Tofu made from both aged cultivars showed a gray color with dark spots, a rough appearance, fermented aroma, rancid flavor, an astringent and bitter taste, a fracturable texture and adherence to the oral cavity after chewing. These characteristics of tofu from aged soybeans implied a low acceptance by consumers. Tofu from natural and accelerated aged soybeans has sensory attributes of appearance, as well as aroma, flavor and damaged texture, that are unacceptable by consumers. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Age-related cognitive decline coincides with accelerated volume loss of the dorsal but not ventral hippocampus in mice.

PubMed

Reichel, J M; Bedenk, B T; Czisch, M; Wotjak, C T

2017-01-01

Even in the absence of neurodegenerative diseases, progressing age often coincides with cognitive decline and morphological changes. However, longitudinal studies that directly link these two processes are missing. In this proof-of-concept study we therefore performed repeated within-subject testing of healthy male R26R mice in a spatial learning task in combination with manganese-enhanced volumetric MRI analyses at the ages of 8, 16, and 24 months. We grouped the mice into good and poor performers (n = 6, each), based on their spatial learning abilities at the age of 24 months. Using this stratification, we failed to detect a priori volume differences, but observed a significant decrease in total hippocampal volume over time for both groups. Interestingly, this volume decrease was specific for the dorsal hippocampus and significantly accelerated in poor performers between 16 and 24 months of age. This is the first time that individual changes in hippocampal volume were traced alongside cognitive performance within the same subjects over 1½ years. Our study points to a causal link between volume loss of the dorsal hippocampus and cognitive impairments. In addition, it suggests accelerated degenerative processes rather than a priori volume differences as determining trajectories of age-related cognitive decline. Despite the relatively small sample sizes, the strong behavioral and moderate morphological alterations demonstrate the general feasibility of longitudinal studies of age-related decline in cognition and hippocampus integrity. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Reproducing ten years of road ageing--accelerated carbonation and leaching of EAF steel slag.

PubMed

Suer, Pascal; Lindqvist, Jan-Erik; Arm, Maria; Frogner-Kockum, Paul

2009-09-01

Reuse of industrial aggregates is still hindered by concern for their long-term properties. This paper proposes a laboratory method for accelerated ageing of steel slag, to predict environmental and technical properties, starting from fresh slag. Ageing processes in a 10-year old asphalt road with steel slag of electric arc furnace (EAF) type in the subbase were identified by scanning electron microscopy (SEM) and leaching tests. Samples from the road centre and the pavement edge were compared with each other and with samples of fresh slag. It was found that slag from the pavement edge showed traces of carbonation and leaching processes, whereas the road centre material was nearly identical to fresh slag, in spite of an accessible particle structure. Batches of moisturized road centre material exposed to oxygen, nitrogen or carbon dioxide (CO2) were used for accelerated ageing. Time (7-14 days), temperature (20-40 degrees C) and initial slag moisture content (8-20%) were varied to achieve the carbonation (decrease in pH) and leaching that was observed in the pavement edge material. After ageing, water was added to assess leaching of metals and macroelements. 12% moisture, CO2 and seven days at 40 degrees C gave the lowest pH value. This also reproduced the observed ageing effect for Ca, Cu, Ba, Fe, Mn, Pb, Ca (decreased leaching) and for V, Si, and Al (increased leaching). However, ageing effects on SO4, DOC and Cr were not reproduced.

Human milk adiponectin affects infant weight trajectory during the second year of life.

PubMed

Woo, Jessica G; Guerrero, M Lourdes; Guo, Fukun; Martin, Lisa J; Davidson, Barbara S; Ortega, Hilda; Ruiz-Palacios, Guillermo M; Morrow, Ardythe L

2012-04-01

Serum adiponectin (APN) is associated with lower childhood obesity, and APN concentration in human milk is associated with slower growth during active breast-feeding. We examined infant weight gain in the second year of life after exposure to high or low levels of mother's milk APN. Breast-feeding mother-infant pairs were recruited in Mexico City and studied for 2 years; 192 infants with at least 12 months' follow-up were analyzed. Monthly milk samples were assayed for APN; mothers were classified as producing high or low levels of milk APN. Infant and maternal serum APN were assessed during year 1. Infant anthropometry was measured monthly (year 1) or bimonthly (year 2), and World Health Organization z scores were calculated. Longitudinal adjusted models assessed weight-for-age and weight-for-length z score trajectories from 1 to 2 years. Maternal serum APN modestly correlated with milk APN (r=0.37, P<0.0001) and infant serum APN (r=0.29, P=0.01). Infants exposed to high milk APN experienced increasing weight-for-age and weight-for-length z scores between age 1 and 2 years in contrast to low milk APN exposure (P for group × time=0.02 and 0.054, respectively), adjusting for growth in the first 6 months and other covariates. In contrast, infant serum APN in year 1 was not associated with the rate of weight gain in year 2. High human milk APN exposure was associated with accelerated weight trajectory during the second year of life, suggesting its role in catch-up growth after slower weight gain during the first year of life.

Models of subjective response to in-flight motion data

NASA Technical Reports Server (NTRS)

Rudrapatna, A. N.; Jacobson, I. D.

1973-01-01

Mathematical relationships between subjective comfort and environmental variables in an air transportation system are investigated. As a first step in model building, only the motion variables are incorporated and sensitivities are obtained using stepwise multiple regression analysis. The data for these models have been collected from commercial passenger flights. Two models are considered. In the first, subjective comfort is assumed to depend on rms values of the six-degrees-of-freedom accelerations. The second assumes a Rustenburg type human response function in obtaining frequency weighted rms accelerations, which are used in a linear model. The form of the human response function is examined and the results yield a human response weighting function for different degrees of freedom.

Comparative study of ageing, heat treatment and accelerated carbonation for stabilization of municipal solid waste incineration bottom ash in view of reducing regulated heavy metal/metalloid leaching.

PubMed

Santos, Rafael M; Mertens, Gilles; Salman, Muhammad; Cizer, Özlem; Van Gerven, Tom

2013-10-15

This study compared the performance of four different approaches for stabilization of regulated heavy metal and metalloid leaching from municipal solid waste incineration bottom ash (MSWI-BA): (i) short term (three months) heap ageing, (ii) heat treatment, (iii) accelerated moist carbonation, and (iv) accelerated pressurized slurry carbonation. Two distinct types of MSWI-BA were tested in this study: one originating from a moving-grate furnace incineration operation treating exclusively household refuse (sample B), and another originating from a fluid-bed furnace incineration operation that treats a mixture of household and light industrial wastes (sample F). The most abundant elements in the ashes were Si (20-27 wt.%) and Ca (16-19 wt.%), followed by significant quantities of Fe, Al, Na, S, K, Mg, Ti, and Cl. The main crystalline substances present in the fresh ashes were Quartz, Calcite, Apatite, Anhydrite and Gehlenite, while the amorphous fraction ranged from 56 to 73 wt.%. The leaching values of all samples were compared to the Flemish (NEN 7343) and the Walloon (DIN 38414) regulations from Belgium. Batch leaching of the fresh ashes at natural pH showed that seven elements exceeded at least one regulatory limit (Ba, Cr, Cu, Mo, Pb, Se and Zn), and that both ashes had excess basicity (pH > 12). Accelerated carbonation achieved significant reduction in ash basicity (9.3-9.9); lower than ageing (10.5-12.2) and heat treatment (11.1-12.1). For sample B, there was little distinction between the leaching results of ageing and accelerated carbonation with respect to regulatory limits; however carbonation achieved comparatively lower leaching levels. Heat treatment was especially detrimental to the leaching of Cr. For sample F, ageing was ineffective and heat treatment had marginally better results, while accelerated carbonation delivered the most effective performance, with slurry carbonation meeting all DIN limits. Slurry carbonation was deemed the most effective treatment process, achieving consistently significant leaching stabilization, while also effectively washing out Cl ions, a requirement for the utilization of the ashes in construction applications. The benefits of carbonation were linked to the formation of significant quantities of Ca-carbonates, including appreciable quantities of the Aragonite polymorph formed in the slurry carbonated samples. Copyright © 2013 Elsevier Ltd. All rights reserved.

Assessment of Homomorphic Analysis for Human Activity Recognition from Acceleration Signals.

PubMed

Vanrell, Sebastian Rodrigo; Milone, Diego Humberto; Rufiner, Hugo Leonardo

2017-07-03

Unobtrusive activity monitoring can provide valuable information for medical and sports applications. In recent years, human activity recognition has moved to wearable sensors to deal with unconstrained scenarios. Accelerometers are the preferred sensors due to their simplicity and availability. Previous studies have examined several \\azul{classic} techniques for extracting features from acceleration signals, including time-domain, time-frequency, frequency-domain, and other heuristic features. Spectral and temporal features are the preferred ones and they are generally computed from acceleration components, leaving the acceleration magnitude potential unexplored. In this study, based on homomorphic analysis, a new type of feature extraction stage is proposed in order to exploit discriminative activity information present in acceleration signals. Homomorphic analysis can isolate the information about whole body dynamics and translate it into a compact representation, called cepstral coefficients. Experiments have explored several configurations of the proposed features, including size of representation, signals to be used, and fusion with other features. Cepstral features computed from acceleration magnitude obtained one of the highest recognition rates. In addition, a beneficial contribution was found when time-domain and moving pace information was included in the feature vector. Overall, the proposed system achieved a recognition rate of 91.21% on the publicly available SCUT-NAA dataset. To the best of our knowledge, this is the highest recognition rate on this dataset.

The Identification of Zebrafish Mutants Showing Alterations in Senescence-Associated Biomarkers

PubMed Central

Uchiyama, Junzo; Koshimizu, Eriko; Qi, Jie; Nanjappa, Purushothama; Imamura, Shintaro; Islam, Asiful; Neuberg, Donna; Amsterdam, Adam; Roberts, Thomas M.

2008-01-01

There is an interesting overlap of function in a wide range of organisms between genes that modulate the stress responses and those that regulate aging phenotypes and, in some cases, lifespan. We have therefore screened mutagenized zebrafish embryos for the altered expression of a stress biomarker, senescence-associated β-galactosidase (SA-β-gal) in our current study. We validated the use of embryonic SA-β-gal production as a screening tool by analyzing a collection of retrovirus-insertional mutants. From a pool of 306 such mutants, we identified 11 candidates that showed higher embryonic SA-β-gal activity, two of which were selected for further study. One of these mutants is null for a homologue of Drosophila spinster, a gene known to regulate lifespan in flies, whereas the other harbors a mutation in a homologue of the human telomeric repeat binding factor 2 (terf2) gene, which plays roles in telomere protection and telomere-length regulation. Although the homozygous spinster and terf2 mutants are embryonic lethal, heterozygous adult fish are viable and show an accelerated appearance of aging symptoms including lipofuscin accumulation, which is another biomarker, and shorter lifespan. We next used the same SA-β-gal assay to screen chemically mutagenized zebrafish, each of which was heterozygous for lesions in multiple genes, under the sensitizing conditions of oxidative stress. We obtained eight additional mutants from this screen that, when bred to homozygosity, showed enhanced SA-β-gal activity even in the absence of stress, and further displayed embryonic neural and muscular degenerative phenotypes. Adult fish that are heterozygous for these mutations also showed the premature expression of aging biomarkers and the accelerated onset of aging phenotypes. Our current strategy of mutant screening for a senescence-associated biomarker in zebrafish embryos may thus prove to be a useful new tool for the genetic dissection of vertebrate stress response and senescence mechanisms. PMID:18704191

A Prediction of Response of the Head and Neck of the U.S. Adult Military Population to Dynamic Impact Acceleration from Selected Dynamic Test Subjects.

DTIC Science & Technology

1976-05-01

to Review Grants for Clinical Research and Investigation Involving Human Beings, Medical School, The University of Michigan. 3 of biomechanical models...human volunteers in dynamic sled tests found no clinically observable effects. due to acceleration on a subject in which the peak mouth angular...minutes cf rest between trials , and the average fo-ce of each set computed. Figure 2.7 shows typi- cal forcc curves and the EMG signal resulting from

Evidence of accelerated aging among African Americans and its implications for mortality.

PubMed

Levine, M E; Crimmins, E M

2014-10-01

Blacks experience morbidity and mortality earlier in the life course compared to whites. Such premature declines in health may be indicative of an acceleration of the aging process. The current study uses data on 7644 black and white participants, ages 30 and above, from the third National Health and Nutrition Examination Survey, to compare the biological ages of blacks and whites as indicated from a combination of ten biomarkers and to determine if such differences in biological age relative to chronological age account for racial disparities in mortality. At a specified chronological age, blacks are approximately 3 years older biologically than whites. Differences in biological age between blacks and whites appear to increase up until ages 60-65 and then decline, presumably due to mortality selection. Finally, differences in biological age were found to completely account for higher levels of all-cause, cardiovascular and cancer mortality among blacks. Overall, these results suggest that being black is associated with significantly higher biological age at a given chronological age and that this is a pathway to early death both overall and from the major age-related diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

Colour stability and opacity of resin cements and flowable composites for ceramic veneer luting after accelerated ageing.

PubMed

Archegas, Lucí Regina Panka; Freire, Andrea; Vieira, Sergio; Caldas, Danilo Biazzetto de Menezes; Souza, Evelise Machado

2011-11-01

Colour changes of the luting material can become clinically visible affecting the aesthetic appearance of thin ceramic laminates. The aim of this in vitro study was to evaluate the colour stability and opacity of light- and dual-cured resin cements and flowable composites after accelerated ageing. The luting agents were bonded (0.2 mm thick) to ceramic disks (0.75 mm thick) built with the pressed-ceramic IPS Aesthetic Empress (n=7). Colour measurements were determined using a FTIR spectrophotometer before and after accelerated ageing in a weathering machine with a total energy of 150 kJ. Changes in colour (ΔE) and opacity (ΔO) were obtained using the CIE L*a*b* system. The results were submitted to one-way ANOVA, Tukey HSD test and Student's t test (α=5%). All the materials showed significant changes in colour and opacity. The ΔE of the materials ranged from 0.41 to 2.40. The highest colour changes were attributed to RelyX ARC and AllCem, whilst lower changes were found in Variolink Veneer, Tetric Flow and Filtek Z350 Flow. The opacity of the materials ranged from -0.01 to 1.16 and its variation was not significant only for Opallis Flow and RelyX ARC. The accelerated ageing led to colour changes in all the evaluated materials, although they were considered clinically acceptable (ΔE<3). Amongst the dual-cured resin cements, Variolink II demonstrated the highest colour stability. All the flowable composites showed proper colour stability for the luting of ceramic veneers. After ageing, an increase in opacity was observed for most of the materials. Copyright © 2011 Elsevier Ltd. All rights reserved.

Soiling of building envelope surfaces and its effect on solar reflectance – Part II: Development of an accelerated aging method for roofing materials

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

Sleiman, Mohamad; Kirchstetter, Thomas W.; Berdahl, Paul

2014-01-09

Highly reflective roofs can decrease the energy required for building air conditioning, help mitigate the urban heat island effect, and slow global warming. However, these benefits are diminished by soiling and weathering processes that reduce the solar reflectance of most roofing materials. Soiling results from the deposition of atmospheric particulate matter and the growth of microorganisms, each of which absorb sunlight. Weathering of materials occurs with exposure to water, sunlight, and high temperatures. This study developed an accelerated aging method that incorporates features of soiling and weathering. The method sprays a calibrated aqueous soiling mixture of dust minerals, black carbon,more » humic acid, and salts onto preconditioned coupons of roofing materials, then subjects the soiled coupons to cycles of ultraviolet radiation, heat and water in a commercial weatherometer. Three soiling mixtures were optimized to reproduce the site-specific solar spectral reflectance features of roofing products exposed for 3 years in a hot and humid climate (Miami, Florida); a hot and dry climate (Phoenix, Arizona); and a polluted atmosphere in a temperate climate (Cleveland, Ohio). A fourth mixture was designed to reproduce the three-site average values of solar reflectance and thermal emittance attained after 3 years of natural exposure, which the Cool Roof Rating Council (CRRC) uses to rate roofing products sold in the US. This accelerated aging method was applied to 25 products₋single ply membranes, factory and field applied coatings, tiles, modified bitumen cap sheets, and asphalt shingles₋and reproduced in 3 days the CRRC's 3-year aged values of solar reflectance. In conclusion, this accelerated aging method can be used to speed the evaluation and rating of new cool roofing materials.« less

Trends in cervical cancer incidence and mortality in Poland: is there an impact of the introduction of the organised screening?

PubMed

Nowakowski, Andrzej; Wojciechowska, Urszula; Wieszczy, Paulina; Cybulski, Marek; Kamiński, Michał F; Didkowska, Joanna

2017-06-01

Aside from existing opportunistic screening, an organised screening programme (OSP) for cervical cancer (CC) was implemented in 2006/2007 in Poland. We applied joinpoint regression and age-period-cohort model to look for the impact of the OSP on CC incidence/mortality trends. Decline of age-standardised incidence rates (ASIRs) in the screening-age group (25-59 years) accelerated from -2.2% (95% CI -2.7 to -1.7%) between 1993 and 2008 to -6.1% (95% CI -7.7 to -4.4%) annually after 2008. In women aged 60+ years, ASIRs declined from 1986 until 2005 [annual percent change (APC) = -2.6%, 95% CI -2.9 to -2.4%] and stabilised thereafter. Decline of age-standardised mortality rates (ASMRs) in the screening-age group accelerated from -1.3% (95% CI -1.5 to -1.1%) between 1980 and 2005 to -4.7% (95% CI -5.6 to -3.8%) annually after 2005. In women aged 60+ ASMR declined between 1991 and 2004 (APC = -2.9%, 95% CI -3.5 to -2.3%) and stabilised thereafter. Relative risks of CC diagnosis and death were 0.63 (95% CI 0.62-0.65) and 0.61 (95% CI 0.59-0.63), respectively, for the most recent period compared to the reference around 1982. Implementation of the OSP possibly accelerated downward trends in the burden of CC in Polish women under the age of 60, but recent stabilisation of trends in older women requires actions.

Benchmark Accelerated Aging of Harvested Hypalon/Epr and Cspe/Xlpe Power and I&C Cable in Nuclear Power Plants

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

Duckworth, Robert C.; Frame, Emily; Fifield, Leonard S.

As part of the Light Water Reactor and Sustainability (LWRS) program in the U.S. Department of Energy (DOE) Office of Nuclear Energy, material aging and degradation research is currently geared to support the long-term operation of existing nuclear power plants (NPPs) as they move beyond their initial 40 year licenses. The goal of this research is to provide information so that NPPs can develop aging management programs (AMPs) to address replacement and monitoring needs as they look to operate for 20 years, and in some cases 40 years, beyond their initial operating lifetimes. For cable insulation and jacket materials thatmore » support instrument, control, and safety systems, accelerated aging data are needed to determine priorities in cable aging management programs. Before accelerated thermal and radiation aging of harvested, representative cable insulation and jacket materials, the benchmark performance of a new test capability at Oak Ridge National Laboratory (ORNL) was evaluated for temperatures between 70 and 135°C, dose rates between 100 and 500 Gy/h, and accumulated doses up to 20 kGy, Samples that were characterized and are representative of current materials in use were harvested from the Callaway NPP near Fulton, Missouri, and the San Onofre NPP north of San Diego, California. From the Callaway NPP, a multiconductor control rod cable manufactured by Boston Insulated Wire (BIW), with a Hypalon/ chorolosulfonated polyethylene (CSPE) jacket and ethylene-propylene rubber (EPR) insulation, was harvested from the auxiliary space during a planned outage in 2013. This cable was placed into service when the plant was started in 1984. From the San Onofre NPP, a Rockbestos Firewall III (FRIII) cable with a Hypalon/ CSPE jacket with cross-linked polyethylene (XLPE) insulation was harvested from an on-site, climate-controlled storage area. This conductor, which was never placed into service, was procured around 2007 in anticipation of future operation that did not occur. Benchmark aging for both jacket and insulation material was carried out in air at a temperature of 125°C or in uniform 140 Gy/h gamma irradiation over a period of 60 days. Their mechanical properties over the course of their exposures were compared with reference data from comparable cable jacket/insulation compositions and aging conditions. For both accelerated thermal and radiation aging, it was observed that the mechanical properties for the Callaway BIW control rod cable were consistent with those previously measured. However, for the San Onofre Rockbestos FRIII, there was an observable functional difference for accelerated thermal aging at 125°C. Details on possible sources for this difference and plans for resolving each source are given in this paper.« less

BENCHMARK ACCELERATED AGING OF HARVESTED HYPALON/EPR AND CSPE/XLPE POWER AND I&C CABLE IN NUCLEAR POWER PLANTS

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

Duckworth, Robert C; Fifield, Dr Leonard S

As part of the Light Water Reactor and Sustainability (LWRS) program in the U.S. Department of Energy (DOE) Office of Nuclear Energy, material aging and degradation research is currently geared to support the long-term operation of existing nuclear power plants (NPPs) as they move beyond their initial 40 year licenses. The goal of this research is to provide information so that NPPs can develop aging management programs (AMPs) to address replacement and monitoring needs as they look to operate for 20 years, and in some cases 40 years, beyond their initial operating lifetimes. For cable insulation and jacket materials thatmore » support instrument, control, and safety systems, accelerated aging data are needed to determine priorities in cable aging management programs. Before accelerated thermal and radiation aging of harvested, representative cable insulation and jacket materials, the benchmark performance of a new test capability at Oak Ridge National Laboratory (ORNL) was evaluated for temperatures between 70 and 135 C, dose rates between 100 and 500 Gy/h, and accumulated doses up to 20 kGy, Samples that were characterized and are representative of current materials in use were harvested from the Callaway NPP near Fulton, Missouri, and the San Onofre NPP north of San Diego, California. From the Callaway NPP, a multiconductor control rod cable manufactured by Boston Insulated Wire (BIW), with a Hypalon/ chorolosulfonated polyethylene (CSPE) jacket and ethylene-propylene rubber (EPR) insulation, was harvested from the auxiliary space during a planned outage in 2013. This cable was placed into service when the plant was started in 1984. From the San Onofre NPP, a Rockbestos Firewall III (FRIII) cable with a Hypalon/ CSPE jacket with cross-linked polyethylene (XLPE) insulation was harvested from an on-site, climate-controlled storage area. This conductor, which was never placed into service, was procured around 2007 in anticipation of future operation that did not occur. Benchmark aging for both jacket and insulation material was carried out in air at a temperature of 125 C or in uniform 140 Gy/h gamma irradiation over a period of 60 days. Their mechanical properties over the course of their exposures were compared with reference data from comparable cable jacket/insulation compositions and aging conditions. For both accelerated thermal and radiation aging, it was observed that the mechanical properties for the Callaway BIW control rod cable were consistent with those previously measured. However, for the San Onofre Rockbestos FRIII, there was an observable functional difference for accelerated thermal aging at 125 C. Details on possible sources for this difference and plans for resolving each source are given in this paper.« less

Life stress, glucocorticoid signaling, and the aging epigenome: Implications for aging-related diseases.

PubMed

Gassen, Nils C; Chrousos, George P; Binder, Elisabeth B; Zannas, Anthony S

2017-03-01

Life stress has been associated with accelerated cellular aging and increased risk for developing aging-related diseases; however, the underlying molecular mechanisms remain elusive. A highly relevant process that may underlie this association is epigenetic regulation. In this review, we build upon existing evidence to propose a model whereby exposure to life stress, in part via its effects on the hypothalamic-pituitary axis and the glucocorticoid signaling system, may alter the epigenetic landscape across the lifespan and, consequently, influence genomic regulation and function in ways that are conducive to the development of aging-related diseases. This model is supported by recent studies showing that life stressors and stress-related phenotypes can accelerate epigenetic aging, a measure that is based on DNA methylation prediction of chronological age and has been associated with several aging-related disease phenotypes. We discuss the implications of this model for the prevention and treatment of aging-related diseases, as well as the challenges and limitations of this line of research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Parent Book Talk to Accelerate Spanish Content Vocabulary Knowledge

ERIC Educational Resources Information Center

Pollard-Durodola, Sharolyn D.; Gonzalez, Jorge E.; Satterfield, Teresa; Benki, José R.; Vaquero, Juana; Ungco, Camille

2017-01-01

This article bridges research to practice by summarizing an interactive content-enriched shared book reading approach that Spanish-speaking parents of preschool-age children can easily use in the home to accelerate content vocabulary knowledge in Spanish. The approach was implemented in preschool classrooms using a transitional bilingual education…

Contrast-enhanced MR Angiography of the Abdomen with Highly Accelerated Acquisition Techniques

PubMed Central

Mostardi, Petrice M.; Glockner, James F.; Young, Phillip M.

2011-01-01

Purpose: To demonstrate that highly accelerated (net acceleration factor [Rnet] ≥ 10) acquisition techniques can be used to generate three-dimensional (3D) subsecond timing images, as well as diagnostic-quality high-spatial-resolution contrast material–enhanced (CE) renal magnetic resonance (MR) angiograms with a single split dose of contrast material. Materials and Methods: All studies were approved by the institutional review board and were HIPAA compliant; written consent was obtained from all participants. Twenty-two studies were performed in 10 female volunteers (average age, 47 years; range, 27–62 years) and six patients with renovascular disease (three women; average age, 48 years; range, 37–68 years; three men; average age, 60 years; range, 50–67 years; composite average age, 54 years; range, 38–68 years). The two-part protocol consisted of a low-dose (2 mL contrast material) 3D timing image with approximate 1-second frame time, followed by a high-spatial-resolution (1.0–1.6-mm isotropic voxels) breath-hold 3D renal MR angiogram (18 mL) over the full abdominal field of view. Both acquisitions used two-dimensional (2D) sensitivity encoding acceleration factor (R) of eight and 2D homodyne (HD) acceleration (RHD) of 1.4–1.8 for Rnet = R · RHD of 10 or higher. Statistical analysis included determination of mean values and standard deviations of image quality scores performed by two experienced reviewers with use of eight evaluation criteria. Results: The 2-mL 3D time-resolved image successfully portrayed progressive arterial filling in all 22 studies and provided an anatomic overview of the vasculature. Successful timing was also demonstrated in that the renal MR angiogram showed adequate or excellent portrayal of the main renal arteries in 21 of 22 studies. Conclusion: Two-dimensional acceleration techniques with Rnet of 10 or higher can be used in CE MR angiography to acquire (a) a 3D image series with 1-second frame time, allowing accurate bolus timing, and (b) a high-spatial-resolution renal angiogram. © RSNA, 2011 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11110242/-/DC1 PMID:21900616

Occlusal disharmony induces spatial memory impairment and hippocampal neuron degeneration via stress in SAMP8 mice.

PubMed

Kubo, Kin-ya; Yamada, Yukiko; Iinuma, Mitsuo; Iwaku, Fumihiko; Tamura, Yasuo; Watanabe, Kazuko; Nakamura, Hiroyuki; Onozuka, Minoru

2007-03-06

We examined the effect of occlusal disharmony in senescence-accelerated (SAMP8) mice on plasma corticosterone levels, hippocampal neuron number, and spatial performance in the water maze. The bite-raised condition was associated with an accelerated age-related decline in spatial memory, increased plasma corticosterone levels, and a decreased number of neurons in the hippocampal CA3 region. The findings suggest that the bite-raised condition in aged SAMP8 mice induces hippocampal neuron loss, thereby leading to senile memory deficits.

Epigenetic Aging and Immune Senescence in Women With Insomnia Symptoms: Findings From the Women's Health Initiative Study.

PubMed

Carroll, Judith E; Irwin, Michael R; Levine, Morgan; Seeman, Teresa E; Absher, Devin; Assimes, Themistocles; Horvath, Steve

2017-01-15

Insomnia symptoms are associated with vulnerability to age-related morbidity and mortality. Cross-sectional data suggest that accelerated biological aging may be a mechanism through which sleep influences risk. A novel method for determining age acceleration using epigenetic methylation to DNA has demonstrated predictive utility as an epigenetic clock and prognostic of age-related morbidity and mortality. We examined the association of epigenetic age and immune cell aging with sleep in the Women's Health Initiative study (N = 2078; mean 64.5 ± 7.1 years of age) with assessment of insomnia symptoms (restlessness, difficulty falling asleep, waking at night, trouble getting back to sleep, and early awakenings), sleep duration (short sleep 5 hours or less; long sleep greater than 8 hours), epigenetic age, naive T cell (CD8+CD45RA+CCR7+), and late differentiated T cells (CD8+CD28-CD45RA-). Insomnia symptoms were related to advanced epigenetic age (β ± SE = 1.02 ± 0.37, p = .005) after adjustments for covariates. Insomnia symptoms were also associated with more late differentiated T cells (β ± SE = 0.59 ± 0.21, p = .006), but not with naive T cells. Self-reported short and long sleep duration were unrelated to epigenetic age. Short sleep, but not long sleep, was associated with fewer naive T cells (p < .005) and neither was related to late differentiated T cells. Symptoms of insomnia were associated with increased epigenetic age of blood tissue and were associated with higher counts of late differentiated CD8+ T cells. Short sleep was unrelated to epigenetic age and late differentiated cell counts, but was related to a decline in naive T cells. In this large population-based study of women in the United States, insomnia symptoms are implicated in accelerated aging. Copyright © 2016. Published by Elsevier Inc.

Service Lifetime Estimation of EPDM Rubber Based on Accelerated Aging Tests

NASA Astrophysics Data System (ADS)

Liu, Jie; Li, Xiangbo; Xu, Likun; He, Tao

2017-04-01

Service lifetime of ethylene propylene diene monomer (EPDM) rubber at room temperature (25 °C) was estimated based on accelerated aging tests. The study followed sealing stress loss on compressed cylinder samples by compression stress relaxation methods. The results showed that the cylinder samples of EPDM can quickly reach the physical relaxation equilibrium by using the over-compression method. The non-Arrhenius behavior occurred at the lowest aging temperature. A significant linear relationship was observed between compression set values and normalized stress decay results, and the relationship was not related to the ambient temperature of aging. It was estimated that the sealing stress loss in view of practical application would occur after around 86.8 years at 25 °C. The estimations at 25 °C based on the non-Arrhenius behavior were in agreement with compression set data from storage aging tests in natural environment.

Dissociating Normal Aging from Alzheimer’s Disease: A View from Cognitive Neuroscience

PubMed Central

Toepper, Max

2017-01-01

Both normal aging and Alzheimer’s disease (AD) are associated with changes in cognition, grey and white matter volume, white matter integrity, neural activation, functional connectivity, and neurotransmission. Obviously, all of these changes are more pronounced in AD and proceed faster providing the basis for an AD diagnosis. Since these differences are quantitative, however, it was hypothesized that AD might simply reflect an accelerated aging process. The present article highlights the different neurocognitive changes associated with normal aging and AD and shows that, next to quantitative differences, there are multiple qualitative differences as well. These differences comprise different neurocognitive dissociations as different cognitive deficit profiles, different weights of grey and white matter atrophy, and different gradients of structural decline. These qualitative differences clearly indicate that AD cannot be simply described as accelerated aging process but on the contrary represents a solid entity. PMID:28269778

[Age-related aspects of the extent of lipid metabolism and post-traumatic stress disorders among veterans of modern warfare].

PubMed

Torgashov, M N; Miakotnykh, V S; Pal'tsev, A I

2013-01-01

The peculiarities of violations of lipid metabolism and symptoms of post-traumatic stress disorder (PTSD) in 161 patients of 25-69 years, veterans of the military actions on the territory of Afghanistan and the Northern Caucasus were investigated. The dependence of the formation of dyslipidemia and related changes of atherosclerosis in the young age on neuroendocrine effects, accompanying the effects of combat stress and promoting accelerated aging was determined. On the other hand, with the time, after 15-25 years after participating in hostilities, the intensity of PTSD and its influence on the development of violations of lipid spectrum may decline. The leading role in the pathogenesis of dyslipidemia goes to age-related changes, accompanying a process of accelerated aging of veterans of combat operations, and to pathological disorders of metabolism in liver associated with alcohol abuse and the consequences of infectious diseases.

The Influence of Passive Acceleration and Exercise+Acceleration on Work Capacity and Orthostasis

NASA Technical Reports Server (NTRS)

Simonson, S. R.; Cowell, S. A.; Stocks, J. M.; Biagini, H. W.; Vener, J. M.; Evetts, S. N.; Bailey, K. N.; Evans, J.; Knapp, C.; Greenleaf, J. E.

1999-01-01

The losses of aerobic power and orthostatic tolerance are significant effects of manned C) spaceflight that can negatively impact crew health and safety. Daily acceleration and aerobic training may ameliorate these effects. To determine the influence of passive intermittent +Gz acceleration (PA) training and active acceleration + interval exercise (AE) training on work 0 0 capacity and the acute (1 min) response to 70 deg head-up tilt, 6 men (X-Bar SD: age, 33 +/- 6 y; height, 178.3 +/- 4.6 cm; mass, 86.3 +/- 6.6 kg) participated in two 3-wk training protocols. It was hypothesized that PA and AE training would improve orthostatic tolerance and that the addition of aerobic conditioning, would not alter this effect.

Directional asymmetries and age effects in human self-motion perception.

PubMed

Roditi, Rachel E; Crane, Benjamin T

2012-06-01

Directional asymmetries in vestibular reflexes have aided the diagnosis of vestibular lesions; however, potential asymmetries in vestibular perception have not been well defined. This investigation sought to measure potential asymmetries in human vestibular perception. Vestibular perception thresholds were measured in 24 healthy human subjects between the ages of 21 and 68 years. Stimuli consisted of a single cycle of sinusoidal acceleration in a single direction lasting 1 or 2 s (1 or 0.5 Hz), delivered in sway (left-right), surge (forward-backward), heave (up-down), or yaw rotation. Subject identified self-motion directions were analyzed using a forced choice technique, which permitted thresholds to be independently determined for each direction. Non-motion stimuli were presented to measure possible response bias. A significant directional asymmetry in the dynamic response occurred in 27% of conditions tested within subjects, and in at least one type of motion in 92% of subjects. Directional asymmetries were usually consistent when retested in the same subject but did not occur consistently in one direction across the population with the exception of heave at 0.5 Hz. Responses during null stimuli presentation suggested that asymmetries were not due to biased guessing. Multiple models were applied and compared to determine if sensitivities were direction specific. Using Akaike information criterion, it was found that the model with direction specific sensitivities better described the data in 86% of runs when compared with a model that used the same sensitivity for both directions. Mean thresholds for yaw were 1.3±0.9°/s at 0.5 Hz and 0.9±0.7°/s at 1 Hz and were independent of age. Thresholds for surge and sway were 1.7±0.8 cm/s at 0.5 Hz and 0.7±0.3 cm/s at 1.0 Hz for subjects <50 and were significantly higher in subjects >50 years old. Heave thresholds were higher and were independent of age.

Cow milk consumption, insulin-like growth factor-I, and human biology: a life history approach.

PubMed

Wiley, Andrea S

2012-01-01

To assess the life history consequences of cow milk consumption at different stages in early life (prenatal to adolescence), especially with regard to linear growth and age at menarche and the role of insulin-like growth factor I (IGF-I) in mediating a relationship among milk, growth and development, and long-term biological outcomes. United States National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004 and review of existing literature. The literature tends to support milk's role in enhancing growth early in life (prior to age 5 years), but there is less support for this relationship during middle childhood. Milk has been associated with early menarche and with acceleration of linear growth in adolescence. NHANES data show a positive relationship between milk intake and linear growth in early childhood and adolescence, but not middle childhood, a period of relatively slow growth. IGF-I is a candidate bioactive molecule linking milk consumption to more rapid growth and development, although the mechanism by which it may exert such effects is unknown. Routine milk consumption is an evolutionarily novel dietary behavior that has the potential to alter human life history parameters, especially vis-à-vis linear growth, which in turn may have negative long-term biological consequences. Copyright © 2011 Wiley Periodicals, Inc.

Labor Market Progeria.

ERIC Educational Resources Information Center

Rodeheaver, Dean

1990-01-01

Social ambivalence toward women's roles, sexuality, appearance, and aging combine with social standards of attractiveness to create both age and sex discrimination in the workplace. The life expectancy of presentability is shorter among women than men, thus creating an accelerated aging process termed labor market progeria. (SK)

Carbon turnover in the water-soluble protein of the adult human lens

PubMed Central

Stewart, Daniel N.; Lango, Jozsef; Nambiar, Krishnan P.; Falso, Miranda J. S.; FitzGerald, Paul G.; Rocke, David M.; Hammock, Bruce D.

2013-01-01

Purpose Human eye lenses contain cells that persist from embryonic development. These unique, highly specialized fiber cells located at the core (nucleus) of the lens undergo pseudo-apoptosis to become devoid of cell nuclei and most organelles. Ostensibly lacking in protein transcriptional capabilities, it is currently believed that these nuclear fiber cells owe their extreme longevity to the perseverance of highly stable and densely packed crystallin proteins. Maintaining the structural and functional integrity of lenticular proteins is necessary to sustain cellular transparency and proper vision, yet the means by which the lens actually copes with a lifetime of oxidative stress, seemingly without any capacity for protein turnover and repair, is not completely understood. Although many years of research have been predicated upon the assumption that there is no protein turnover or renewal in nuclear fiber cells, we investigated whether or not different protein fractions possess protein of different ages by using the 14C bomb pulse. Methods Adult human lenses were concentrically dissected by gently removing the cell layers in water or shaving to the nucleus with a curved micrometer-controlled blade. The cells were lysed, and the proteins were separated into water-soluble and water-insoluble fractions. The small molecules were removed using 3 kDa spin filters. The 14C/C was measured in paired protein fractions by accelerator mass spectrometry, and an average age for the material within the sample was assigned using the 14C bomb pulse. Results The water-insoluble fractions possessed 14C/C ratios consistent with the age of the cells. In all cases, the water-soluble fractions contained carbon that was younger than the paired water-insoluble fraction. Conclusions As the first direct evidence of carbon turnover in protein from adult human nuclear fiber cells, this discovery supports the emerging view of the lens nucleus as a dynamic system capable of maintaining homeostasis in part due to intricate protein transport mechanisms and possibly protein repair. This finding implies that the lens plays an active role in the aversion of age-related nuclear (ARN) cataract. PMID:23441119

Adrenal maturation, nutritional status, and mucosal immunity in Bolivian youth.

PubMed

Hodges-Simeon, Carolyn R; Prall, Sean P; Blackwell, Aaron D; Gurven, Michael; Gaulin, Steven J C

2017-09-10

Humans-and several other apes-exhibit a unique pattern of post-natal adrenal maturation; however, the causes and consequences of variation in adrenal development are not well understood. In this study, we examine developmental and age-related maturation of the adrenal gland (measured via dehydroepiandrosterone-sulfate [DHEA-S]) for potential life-history associations with growth and mucosal immunity in a rural population of immune-challenged Bolivian juveniles and adolescents. Salivary DHEA-S, anthropometrics, and salivary mucosal immunity (secretory IgA [sIgA]) were measured in 171 males and females, aged 8-23. Males with greater energy (i.e. fat) stores showed higher DHEA-S levels. Controlling for age and energetic condition (to control for phenotypic correlation), higher DHEA-S was associated with higher mucosal immunity (sIgA) among both males and females. Higher DHEA-S levels were positively associated with growth (i.e. height and strength) in males. In accordance with predictions derived from life-history theory, males with higher energy stores secrete more adrenal androgens. This suggests that adrenal maturation is costly and subject to constraints; that is, only males with sufficient reserves will invest in accelerated adrenal maturation. Further, DHEA-S appears to have a measureable influence on immunocompetence in adolescent males and females; therefore, deficits in DHEA-S may have important consequences for health and maturation during this period. Adrenal maturation is an important, but understudied component of human growth and development. © 2017 Wiley Periodicals, Inc.

[Challenges of lopinavir/ritonavir in the chronicity of human immunodeficiency virus infection].

PubMed

Aguirrebengoa, Koldo

2014-11-01

Combination antiretroviral therapy (ART) has increased patient survival, which is currently similar to that of the general population in western countries. However, ART is unable to completely restore normal health, given the persistence of chronic immune activation. Human immunodeficiency virus (HIV) infection has become a chronic disease and 50% of patients will soon be older than 50 years. Currently, there is a debate on the possibility of accelerated aging in the HIV-infected population. An overlap has been observed between chronic inflammation, age-related comorbidities, lifestyle, and the long-term toxicity of ART. ART-related toxicity can encourage the development of comorbidities, especially cardiovascular and renal complications, while toxicity-especially that of thymidine analogs-can also contribute to inflammation and aging. Evidence is available on simplification strategies with boosted protease inhibitor monotherapy aiming to avoid or reduce potential or demonstrated toxicity. Currently, studies are underway of dual therapy strategies with lopinavir/ritonavir (LPV/r) with distinct antiretroviral agents. The studies with the largest samples are those with raltegravir and lamivudine. The GARDEL trial has demonstrated that dual therapy with LPV/r plus a generic drug such as lamivudine is non-inferior to triple therapy in treatment- naïve patients. All of the above indicates the response to the challenge posed to LPV/r by the chronic phase of the disease and by the need to reduce costs. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Accelerated Telomere Shortening in Acromegaly; IGF-I Induces Telomere Shortening and Cellular Senescence

PubMed Central

Matsumoto, Ryusaku; Fukuoka, Hidenori; Iguchi, Genzo; Odake, Yukiko; Yoshida, Kenichi; Bando, Hironori; Suda, Kentaro; Nishizawa, Hitoshi; Takahashi, Michiko; Yamada, Shozo; Ogawa, Wataru; Takahashi, Yutaka

2015-01-01

Objective Patients with acromegaly exhibit reduced life expectancy and increased prevalence of age-related diseases, such as diabetes, hypertension, and cardiovascular disease. However, the underlying mechanism has not been fully elucidated. Telomere shortening is reportedly associated with reduced life expectancy and increased prevalence of these age-related diseases. Methods We measured telomere length in patients with acromegaly using quantitative PCR method. The effect of GH and IGF-I on telomere length and cellular senescence was examined in human skin fibroblasts. Results Patients with acromegaly exhibited shorter telomere length than age-, sex-, smoking-, and diabetes-matched control patients with non-functioning pituitary adenoma (0.62 ± 0.23 vs. 0.75 ± 0.35, respectively, P = 0.047). In addition, telomere length in acromegaly was negatively correlated with the disease duration (R 2 = 0.210, P = 0.003). In vitro analysis revealed that not GH but IGF-I induced telomere shortening in human skin fibroblasts. Furthermore, IGF-I-treated cells showed increased senescence-associated β-galactosidase activity and expression of p53 and p21 protein. IGF-I-treated cells reached the Hayflick limit earlier than GH- or vehicle-treated cells, indicating that IGF-I induces cellular senescence. Conclusion Shortened telomeres in acromegaly and cellular senescence induced by IGF-I can explain, in part, the underlying mechanisms by which acromegaly exhibits an increased morbidity and mortality in association with the excess secretion of IGF-I. PMID:26448623

Paleodiet characterisation of an Etrurian population of Pontecagnano (Italy) by Isotope Ratio Mass Spectrometry (IRMS) and Atomic Absorption Spectrometry (AAS)(#).

PubMed

Scarabino, Carla; Lubritto, Carmine; Proto, Antonio; Rubino, Mauro; Fiengo, Gilda; Marzaioli, Fabio; Passariello, Isabella; Busiello, Gaetano; Fortunato, Antonietta; Alfano, Davide; Sabbarese, Carlo; Rogalla, Detlef; De Cesare, Nicola; d'Onofrio, Antonio; Terrasi, Filippo

2006-06-01

Human bones recovered from the archaeological site of Pontecagnano (Salerno, Italy) have been studied to reconstruct the diet of an Etrurian population. Two different areas were investigated, named Library and Sant' Antonio, with a total of 44 tombs containing human skeletal remains, ranging in age from the 8th to the 3rd century B.C. This time span was confirmed by 14C dating obtained using Accelerator Mass Spectrometry (AMS) on one bone sample from each site. Atomic Absorption Spectrometry (AAS) was used to extract information about the concentration of Sr, Zn, Ca elements in the bone inorganic fraction, whilst stable isotope ratio measurements (IRMS) were carried out on bone collagen to obtain the delta13C and delta15N. A reliable technique has been used to extract and separate the inorganic and organic fractions of the bone remains. Both IRMS and AAS results suggest a mixed diet including C3 plant food and herbivore animals, consistent with archaeological indications.

Effects of Sex and Education on Cognitive Change Over a 27-Year Period in Older Adults: The Rancho Bernardo Study.

PubMed

Reas, Emilie T; Laughlin, Gail A; Bergstrom, Jaclyn; Kritz-Silverstein, Donna; Barrett-Connor, Elizabeth; McEvoy, Linda K

2017-08-01

This study investigated how cognitive function changes with age and whether rates of decline vary by sex or education in a large, homogenous longitudinal cohort characterized by high participation rates, long duration of follow-up, and minimal loss to follow-up. Between 1988 and 2016, 2,225 community-dwelling participants of the Rancho Bernardo Study, aged 31 to 99 years at their initial cognitive assessment, completed neuropsychological testing approximately every 4 years, over a maximum 27-year follow-up. Linear mixed effects regression models defined sex-specific cognitive trajectories, adjusting for education and retest effects. Significant decline across all cognitive domains began around age 65 years and accelerated after age 80 years. Patterns of decline were generally similar between sexes, although men declined more rapidly than women on the global function test. Higher education was associated with slower decline on the tests of executive and global functions. After excluding 517 participants with evidence of cognitive impairment, accelerating decline with age remained for all tests, and women declined more rapidly than men on the executive function test. Accelerating decline with advancing age occurs across multiple cognitive domains in community-dwelling older adults, with few differences in rates of decline between men and women. Higher education may provide some protection against executive and global function decline with age. These findings better characterize normal cognitive aging, a critical prerequisite for identifying individuals at risk for cognitive impairment, and lay the groundwork for future studies of health and behavioral factors that affect age-related decline in this cohort. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Accelerating the Development of 21st-Century Toxicology: Outcome of a Human Toxicology Project Consortium Workshop

PubMed Central

Stephens, Martin L.; Barrow, Craig; Andersen, Melvin E.; Boekelheide, Kim; Carmichael, Paul L.; Holsapple, Michael P.; Lafranconi, Mark

2012-01-01

The U.S. National Research Council (NRC) report on “Toxicity Testing in the 21st century” calls for a fundamental shift in the way that chemicals are tested for human health effects and evaluated in risk assessments. The new approach would move toward in vitro methods, typically using human cells in a high-throughput context. The in vitro methods would be designed to detect significant perturbations to “toxicity pathways,” i.e., key biological pathways that, when sufficiently perturbed, lead to adverse health outcomes. To explore progress on the report’s implementation, the Human Toxicology Project Consortium hosted a workshop on 9–10 November 2010 in Washington, DC. The Consortium is a coalition of several corporations, a research institute, and a non-governmental organization dedicated to accelerating the implementation of 21st-century Toxicology as aligned with the NRC vision. The goal of the workshop was to identify practical and scientific ways to accelerate implementation of the NRC vision. The workshop format consisted of plenary presentations, breakout group discussions, and concluding commentaries. The program faculty was drawn from industry, academia, government, and public interest organizations. Most presentations summarized ongoing efforts to modernize toxicology testing and approaches, each with some overlap with the NRC vision. In light of these efforts, the workshop identified recommendations for accelerating implementation of the NRC vision, including greater strategic coordination and planning across projects (facilitated by a steering group), the development of projects that test the proof of concept for implementation of the NRC vision, and greater outreach and communication across stakeholder communities. PMID:21948868

Ancient DNA and Population Turnover in Southern Levantine Pigs- Signature of the Sea Peoples Migration?

PubMed Central

Meiri, Meirav; Huchon, Dorothée; Bar-Oz, Guy; Boaretto, Elisabetta; Horwitz, Liora Kolska; Maeir, Aren M.; Sapir-Hen, Lidar; Larson, Greger; Weiner, Steve; Finkelstein, Israel

2013-01-01

Near Eastern wild boars possess a characteristic DNA signature. Unexpectedly, wild boars from Israel have the DNA sequences of European wild boars and domestic pigs. To understand how this anomaly evolved, we sequenced DNA from ancient and modern pigs from Israel. Pigs from Late Bronze Age (until ca. 1150 BCE) in Israel shared haplotypes of modern and ancient Near Eastern pigs. European haplotypes became dominant only during the Iron Age (ca. 900 BCE). This raises the possibility that European pigs were brought to the region by the Sea Peoples who migrated to the Levant at that time. Then, a complete genetic turnover took place, most likely because of repeated admixture between local and introduced European domestic pigs that went feral. Severe population bottlenecks likely accelerated this process. Introductions by humans have strongly affected the phylogeography of wild animals, and interpretations of phylogeography based on modern DNA alone should be taken with caution. PMID:24186332

Mechanism and preclinical prevention of increased breast cancer risk caused by pregnancy.

PubMed

Haricharan, Svasti; Dong, Jie; Hein, Sarah; Reddy, Jay P; Du, Zhijun; Toneff, Michael; Holloway, Kimberly; Hilsenbeck, Susan G; Huang, Shixia; Atkinson, Rachel; Woodward, Wendy; Jindal, Sonali; Borges, Virginia F; Gutierrez, Carolina; Zhang, Hong; Schedin, Pepper J; Osborne, C Kent; Tweardy, David J; Li, Yi

2013-12-31

While a first pregnancy before age 22 lowers breast cancer risk, a pregnancy after age 35 significantly increases life-long breast cancer risk. Pregnancy causes several changes to the normal breast that raise barriers to transformation, but how pregnancy can also increase cancer risk remains unclear. We show in mice that pregnancy has different effects on the few early lesions that have already developed in the otherwise normal breast-it causes apoptosis evasion and accelerated progression to cancer. The apoptosis evasion is due to the normally tightly controlled STAT5 signaling going astray-these precancerous cells activate STAT5 in response to pregnancy/lactation hormones and maintain STAT5 activation even during involution, thus preventing the apoptosis normally initiated by oncoprotein and involution. Short-term anti-STAT5 treatment of lactation-completed mice bearing early lesions eliminates the increased risk after a pregnancy. This chemoprevention strategy has important implications for preventing increased human breast cancer risk caused by pregnancy. DOI: http://dx.doi.org/10.7554/eLife.00996.001.

Ornaments of the earliest Upper Paleolithic: New insights from the Levant

PubMed Central

Kuhn, Steven L.; Stiner, Mary C.; Reese, David S.; Güleç, Erksin

2001-01-01

Two sites located on the northern Levantine coast, Üçağızlı Cave (Turkey) and Ksar 'Akil (Lebanon) have yielded numerous marine shell beads in association with early Upper Paleolithic stone tools. Accelerator mass spectrometry (AMS) radiocarbon dates indicate ages between 39,000 and 41,000 radiocarbon years (roughly 41,000–43,000 calendar years) for the oldest ornament-bearing levels in Üçağızlı Cave. Based on stratigraphic evidence, the earliest shell beads from Ksar 'Akil may be even older. These artifacts provide some of the earliest evidence for traditions of personal ornament manufacture by Upper Paleolithic humans in western Asia, comparable in age to similar objects from Eastern Europe and Africa. The new data show that the initial appearance of Upper Paleolithic ornament technologies was essentially simultaneous on three continents. The early appearance and proliferation of ornament technologies appears to have been contingent on variable demographic or social conditions. PMID:11390976

Electromagnetic Modeling of Human Body Using High Performance Computing

NASA Astrophysics Data System (ADS)

Ng, Cho-Kuen; Beall, Mark; Ge, Lixin; Kim, Sanghoek; Klaas, Ottmar; Poon, Ada

Realistic simulation of electromagnetic wave propagation in the actual human body can expedite the investigation of the phenomenon of harvesting implanted devices using wireless powering coupled from external sources. The parallel electromagnetics code suite ACE3P developed at SLAC National Accelerator Laboratory is based on the finite element method for high fidelity accelerator simulation, which can be enhanced to model electromagnetic wave propagation in the human body. Starting with a CAD model of a human phantom that is characterized by a number of tissues, a finite element mesh representing the complex geometries of the individual tissues is built for simulation. Employing an optimal power source with a specific pattern of field distribution, the propagation and focusing of electromagnetic waves in the phantom has been demonstrated. Substantial speedup of the simulation is achieved by using multiple compute cores on supercomputers.

Metabolic syndrome but not obesity measures are risk factors for accelerated age-related glomerular filtration rate decline in the general population.

PubMed

Stefansson, Vidar T N; Schei, Jørgen; Solbu, Marit D; Jenssen, Trond G; Melsom, Toralf; Eriksen, Bjørn O

2018-05-01

Rapid age-related glomerular filtration rate (GFR) decline increases the risk of end-stage renal disease, and a low GFR increases the risk of mortality and cardiovascular disease. High body mass index and the metabolic syndrome are well-known risk factors for patients with advanced chronic kidney disease, but their role in accelerating age-related GFR decline independent of cardiovascular disease, hypertension and diabetes is not adequately understood. We studied body mass index, waist circumference, waist-hip ratio and metabolic syndrome as risk factors for accelerated GFR decline in 1261 middle-aged people representative of the general population without diabetes, cardiovascular disease or kidney disease. GFR was measured as iohexol clearance at baseline and repeated after a median of 5.6 years. Metabolic syndrome was defined as fulfilling three out of five criteria, based on waist circumference, blood pressure, glucose, high-density lipoprotein cholesterol and triglycerides. The mean GFR decline rate was 0.95 ml/min/year. Neither the body mass index, waist circumference nor waist-hip ratio predicted statistically significant changes in age-related GFR decline, but individuals with baseline metabolic syndrome had a significant mean of 0.30 ml/min/year faster decline than individuals without metabolic syndrome in a multivariable adjusted linear regression model. This association was mainly driven by the triglyceride criterion of metabolic syndrome, which was associated with a significant 0.36 ml/min/year faster decline when analyzed separately. Results differed significantly when GFR was estimated using creatinine and/or cystatin C. Thus, metabolic syndrome, but not the body mass index, waist circumference or waist-hip ratio, is an independent risk factor for accelerated age-related GFR decline in the general population. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Ageing induced vascular smooth muscle cell senescence in atherosclerosis.

PubMed

Uryga, Anna K; Bennett, Martin R

2016-04-15

Atherosclerosis is a disease of ageing in that its incidence and prevalence increase with age. However, atherosclerosis is also associated with biological ageing, manifest by a number of typical hallmarks of ageing in the atherosclerotic plaque. Thus, accelerated biological ageing may be superimposed on the effects of chronological ageing in atherosclerosis. Tissue ageing is seen in all cells that comprise the plaque, but particularly in vascular smooth muscle cells (VSMCs). Hallmarks of ageing include evidence of cell senescence, DNA damage (including telomere attrition), mitochondrial dysfunction, a pro-inflammatory secretory phenotype, defects in proteostasis, epigenetic changes, deregulated nutrient sensing, and exhaustion of progenitor cells. In this model, initial damage to DNA (genomic, telomeric, mitochondrial and epigenetic changes) results in a number of cellular responses (cellular senescence, deregulated nutrient sensing and defects in proteostasis). Ultimately, ongoing damage and attempts at repair by continued proliferation overwhelm reparative capacity, causing loss of specialised cell functions, cell death and inflammation. This review summarises the evidence for accelerated biological ageing in atherosclerosis, the functional consequences of cell ageing on cells comprising the plaque, and the causal role that VSMC senescence plays in atherogenesis. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

76 FR 56505 - Agency Information Collection (Application by Insured Terminally Ill Person for Accelerated...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-13

....Regulations.gov ; or to VA's OMB Desk Officer, OMB Human Resources and Housing Branch, New Executive Office...' Group Life Insurance (SGLI) or Veterans' Group Life Insurance (VGLI) prior to death. If the insured...' Group Life Insurance Accelerated Benefits Option application. The application must include a medical...

Adaptation to vestibular disorientation : V : Eye-Movement and subjective turning responses to two durations of angular acceleration.

DOT National Transportation Integrated Search

1967-05-01

Recordings of ocular nystagmus were obtained from a group of cats and a groups of human subjects to 4/sec2 angular accelerations of 8.4 sec and of 36 sec duration. Laternal canals and vertical canals were stimulated on seperate trails. Results showed...

Coupled aging effects in nanofiber-reinforced siloxane foams

DOE PAGES

Labouriau, Andrea; Robison, Tom; Geller, Drew Adam; ...

2018-01-11

Here, this study investigates the combined effects of ionizing radiation and thermal treatments on the aging of siloxane foams containing small amounts of carbon nanofibers. Our siloxane foams were exposed to accelerated aging conditions for more than two years, resulting in very low dose rates. In addition, foams were aged under compressive load to evaluate the strength of the porous microstructure. Samples were characterized by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), Mössbauer, mass spectroscopy, electron paramagnetic resonance spectroscopy (EPR), solvent swelling, imaging techniques, uniaxial compressive load testing and tearmore » testing. No significant changes in thermal stability or chemistry of the accelerated aged foam were observed, although gas evolution was detected. Changes in crystallization levels at low temperatures, microstructure, and mechanical properties were observed for foams with and without carbon nanofibers. In particular, foams aged under compressive load showed irreversible deformation of the porous microstructure. This study demonstrates that aging effects were enhanced when thermal and radiolysis were coupled together and that the addition of carbon nanofibers did not improve aging effects.« less

Coupled aging effects in nanofiber-reinforced siloxane foams

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

Labouriau, Andrea; Robison, Tom; Geller, Drew Adam

Here, this study investigates the combined effects of ionizing radiation and thermal treatments on the aging of siloxane foams containing small amounts of carbon nanofibers. Our siloxane foams were exposed to accelerated aging conditions for more than two years, resulting in very low dose rates. In addition, foams were aged under compressive load to evaluate the strength of the porous microstructure. Samples were characterized by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), Mössbauer, mass spectroscopy, electron paramagnetic resonance spectroscopy (EPR), solvent swelling, imaging techniques, uniaxial compressive load testing and tearmore » testing. No significant changes in thermal stability or chemistry of the accelerated aged foam were observed, although gas evolution was detected. Changes in crystallization levels at low temperatures, microstructure, and mechanical properties were observed for foams with and without carbon nanofibers. In particular, foams aged under compressive load showed irreversible deformation of the porous microstructure. This study demonstrates that aging effects were enhanced when thermal and radiolysis were coupled together and that the addition of carbon nanofibers did not improve aging effects.« less

Antigraviceptive neck muscle responses to "moving up and moving down" in human.

PubMed

Aoki, M; Han, X Y; Yamada, H; Muto, T; Satake, H; Ito, Y; Matsunami, K

2000-07-01

The responses of neck muscle to sudden transit from one 'g' to hyper 'g', work to support the head and remain the relative position of head on trunk as common observed: i.e. in sudden acceleration or deceleration by car or ejection of pilot from aircraft. Accordingly it is highly possible that the neck muscle responses to moving up may be important to prevent the neck injury due to sudden linear acceleration such as moving up against gravity. However little is known about the evaluation of mechanism of this reflex. Therefore the present study was conducted with two aims. The first aim was to investigate the neck muscle responses to vertical linear acceleration bv 0.4 g produced with an electro-hydraulic servo-system. We chose the vertical linear acceleration because it activates mainly sacculus, from which afferents have been demonstrated to be connected directly to sternocleidomastoid muscle in animals and human. The second aim was to determine whether there is a difference of neck muscle response to moving down and moving up.

Antigraviceptive neck muscle responses to "moving up and moving down" in human

NASA Technical Reports Server (NTRS)

Aoki, M.; Han, X. Y.; Yamada, H.; Muto, T.; Satake, H.; Ito, Y.; Matsunami, K.

2000-01-01

The responses of neck muscle to sudden transit from one 'g' to hyper 'g', work to support the head and remain the relative position of head on trunk as common observed: i.e. in sudden acceleration or deceleration by car or ejection of pilot from aircraft. Accordingly it is highly possible that the neck muscle responses to moving up may be important to prevent the neck injury due to sudden linear acceleration such as moving up against gravity. However little is known about the evaluation of mechanism of this reflex. Therefore the present study was conducted with two aims. The first aim was to investigate the neck muscle responses to vertical linear acceleration bv 0.4 g produced with an electro-hydraulic servo-system. We chose the vertical linear acceleration because it activates mainly sacculus, from which afferents have been demonstrated to be connected directly to sternocleidomastoid muscle in animals and human. The second aim was to determine whether there is a difference of neck muscle response to moving down and moving up.

Bacteroidaceae in Thromboembolic Disease: Effects of Cell Wall Components on Blood Coagulation In Vivo and In Vitro

PubMed Central

Bjornson, H. S.; Hill, E. O.

1973-01-01

The effects of Bacteroides sp., Fusobacterium mortiferum, Bacteroides fragilis, and Sphaerophorus necrophorus on various parameters of blood coagulation in vivo and in vitro were determined and compared to the coagulation effects of Escherichia coli and Salmonella minnesota, wild type and R595. Intravenous injection of washed cells, culture filtrate, lipopolysaccharide, or lipid A of the anaerobic gram-negative microorganisms into mice resulted in acceleration of coagulation. Lipopolysaccharide and lipid A of the anaerobic microorganisms had no apparent effect on circulating platelets in mice or rabbits and did not cause aggregation of human platelets in vitro. Washed cells, lipopolysaccharide, and lipid A of Bacteroides sp. and F. mortiferum also significantly accelerated the clotting time of recalcified platelet poor normal human plasma and C6-deficient rabbit plasma. Lipid A, but not lipopolysaccharide, of E. coli and washed cells of S. minnesota R595 accelerated coagulation by a similar mechanism. These results indicated that Bacteroides sp. and F. mortiferum can accelerate blood coagulation in vivo and in vitro by a mechanism which does not involve platelets or terminal components of complement. PMID:4594118

Combined small-molecule inhibition accelerates the derivation of functional, early-born, cortical neurons from human pluripotent stem cells

PubMed Central

Qi, Yuchen; Zhang, Xin-Jun; Renier, Nicolas; Wu, Zhuhao; Atkin, Talia; Sun, Ziyi; Ozair, M. Zeeshan; Tchieu, Jason; Zimmer, Bastian; Fattahi, Faranak; Ganat, Yosif; Azevedo, Ricardo; Zeltner, Nadja; Brivanlou, Ali H.; Karayiorgou, Maria; Gogos, Joseph; Tomishima, Mark; Tessier-Lavigne, Marc; Shi, Song-Hai; Studer, Lorenz

2017-01-01

Considerable progress has been made in converting human pluripotent stem cells (hPSCs) into functional neurons. However, the protracted timing of human neuron specification and functional maturation remains a key challenge that hampers the routine application of hPSC-derived lineages in disease modeling and regenerative medicine. Using a combinatorial small-molecule screen, we previously identified conditions for the rapid differentiation of hPSCs into peripheral sensory neurons. Here we generalize the approach to central nervous system (CNS) fates by developing a small-molecule approach for accelerated induction of early-born cortical neurons. Combinatorial application of 6 pathway inhibitors induces post-mitotic cortical neurons with functional electrophysiological properties by day 16 of differentiation, in the absence of glial cell co-culture. The resulting neurons, transplanted at 8 days of differentiation into the postnatal mouse cortex, are functional and establish long-distance projections, as shown using iDISCO whole brain imaging. Accelerated differentiation into cortical neuron fates should facilitate hPSC-based strategies for disease modeling and cell therapy in CNS disorders. PMID:28112759

Identification of capacitive MEMS accelerometer structure parameters for human body dynamics measurements.

PubMed

Benevicius, Vincas; Ostasevicius, Vytautas; Gaidys, Rimvydas

2013-08-22

Due to their small size, low weight, low cost and low energy consumption, MEMS accelerometers have achieved great commercial success in recent decades. The aim of this research work is to identify a MEMS accelerometer structure for human body dynamics measurements. Photogrammetry was used in order to measure possible maximum accelerations of human body parts and the bandwidth of the digital acceleration signal. As the primary structure the capacitive accelerometer configuration is chosen in such a way that sensing part measures on all three axes as it is 3D accelerometer and sensitivity on each axis is equal. Hill climbing optimization was used to find the structure parameters. Proof-mass displacements were simulated for all the acceleration range that was given by the optimization problem constraints. The final model was constructed in Comsol Multiphysics. Eigenfrequencies were calculated and model's response was found, when vibration stand displacement data was fed into the model as the base excitation law. Model output comparison with experimental data was conducted for all excitation frequencies used during the experiments.

Effect of mouthwash and accelerated aging on the color stability of esthetic restorative materials.

PubMed

Lee, Y K; El Zawahry, M; Noaman, K M; Powers, J M

2000-06-01

To evaluate the color stability of esthetic restorative materials after immersion in mouthwashes and accelerated aging. Compomers and resin-based composites (RBC) were measured at baseline and repeatedly after immersion in three kinds of mouthwash (Listerine, Peridex, Rembrandt Age Defying) for 24 hrs and 7 days, and after aging for 150 kJ/m2. Color was measured according to CIE L*a*b* color scale on a reflection spectrophotometer. After immersion for 7 days, the mouthwash groups did not produce significantly higher color changes than the distilled water group, except with some mouthwashes used with Tetric-Ceram. After immersion for 7 days and aging for 150 kJ/m2, the mouthwash groups did not produce significantly higher color changes than the distilled water group. Aging in weathering chamber produced color change (deltaE*) of 1.1-3.9, which was mainly influenced by the material. With some exceptions, the color changes from immersion of the RBCs and compomers in mouthwashes were not perceptible (deltaE*<3.3).

Premature aging-related peripheral neuropathy in a mouse model of progeria.

PubMed

Goss, James R; Stolz, Donna Beer; Robinson, Andria Rasile; Zhang, Mingdi; Arbujas, Norma; Robbins, Paul D; Glorioso, Joseph C; Niedernhofer, Laura J

2011-08-01

Peripheral neuropathy is a common aging-related degenerative disorder that interferes with daily activities and leads to increased risk of falls and injury in the elderly. The etiology of most aging-related peripheral neuropathy is unknown. Inherited defects in several genome maintenance mechanisms cause tissue-specific accelerated aging, including neurodegeneration. We tested the hypothesis that a murine model of XFE progeroid syndrome, caused by reduced expression of ERCC1-XPF DNA repair endonuclease, develops peripheral neuropathy. Nerve conduction studies revealed normal nerve function in young adult (8 week) Ercc1(-/Δ) mice, but significant abnormalities in 20 week-old animals. Morphologic and ultrastructural analysis of the sciatic nerve from mutant mice revealed significant alterations at 20 but not 8 weeks of age. We conclude that Ercc1(-/Δ) mice have accelerated spontaneous peripheral neurodegeneration that mimics aging-related disease. This provides strong evidence that DNA damage can drive peripheral neuropathy and offers a rapid and novel model to test therapies. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Microstructural modifications induced by accelerated aging and lipid absorption in remelted and annealed UHMWPEs for total hip arthroplasty

PubMed Central

Puppulin, Leonardo; Zhu, Wenliang; Sugano, Nobuhiko

2014-01-01

Three types of commercially available ultra-high molecular weight polyethylene (UHMWPE) acetabular cups currently used in total hip arthroplasty have been studied by means of Raman micro-spectroscopy to unfold the microstructural modification induced by the oxidative degradation after accelerated aging with and without lipid absorption. The three investigated materials were produced by three different manufacturing procedures, as follows: irradiation followed by remelting, one-step irradiation followed by annealing, 3-step irradiation and annealing. Clear microstructural differences were observed in terms of phase contents (i.e. amorphous, crystalline and intermediate phase fraction). The three-step annealed material showed the highest crystallinity fraction in the bulk, while the remelted polyethylene is clearly characterized by the lowest content of crystalline phase and the highest content of amorphous phase. After accelerated aging either with or without lipids, the amount of amorphous phase decreased in all the samples as a consequence of the oxidation-induced recrystallization. The most remarkable variations of phase contents were detected in the remelted and in the single-step annealed materials. The presence of lipids triggered oxidative degradation especially in the remelted polyethylene. Such experimental evidence might be explained by the highest amount of amorphous phase in which lipids can be absorbed prior to accelerated aging. The results of these spectroscopic characterizations help to rationalize the complex effect of different irradiation and post-irradiation treatments on the UHMWPE microstructure and gives useful information on how significantly any single step of the manufacturing procedures might affect the oxidative degradation of the polymer. PMID:25179830

Loss of circadian clock accelerates aging in neurodegeneration-prone mutants.

PubMed

Krishnan, Natraj; Rakshit, Kuntol; Chow, Eileen S; Wentzell, Jill S; Kretzschmar, Doris; Giebultowicz, Jadwiga M

2012-03-01

Circadian clocks generate rhythms in molecular, cellular, physiological, and behavioral processes. Recent studies suggest that disruption of the clock mechanism accelerates organismal senescence and age-related pathologies in mammals. Impaired circadian rhythms are observed in many neurological diseases; however, it is not clear whether loss of rhythms is the cause or result of neurodegeneration, or both. To address this important question, we examined the effects of circadian disruption in Drosophila melanogaster mutants that display clock-unrelated neurodegenerative phenotypes. We combined a null mutation in the clock gene period (per(01)) that abolishes circadian rhythms, with a hypomorphic mutation in the carbonyl reductase gene sniffer (sni(1)), which displays oxidative stress induced neurodegeneration. We report that disruption of circadian rhythms in sni(1) mutants significantly reduces their lifespan compared to single mutants. Shortened lifespan in double mutants was coupled with accelerated neuronal degeneration evidenced by vacuolization in the adult brain. In addition, per(01)sni(1) flies showed drastically impaired vertical mobility and increased accumulation of carbonylated proteins compared to age-matched single mutant flies. Loss of per function does not affect sni mRNA expression, suggesting that these genes act via independent pathways producing additive effects. Finally, we show that per(01) mutation accelerates the onset of brain pathologies when combined with neurodegeneration-prone mutation in another gene, swiss cheese (sws(1)), which does not operate through the oxidative stress pathway. Taken together, our data suggest that the period gene may be causally involved in neuroprotective pathways in aging Drosophila. Copyright © 2011 Elsevier Inc. All rights reserved.