WorldWideScience

Sample records for human accelerated aging

  1. Obesity accelerates epigenetic aging of human liver

    OpenAIRE

    Horvath, S; Erhart, W.; Brosch, M; Ammerpohl, O.; von Schonfels, W.; Ahrens, M.; Heits, N.; Bell, J.T.; Tsai, P.-C.; Spector, T D; Deloukas, P.; Siebert, R.; Sipos, B.; Becker, T.; Rocken, C.

    2014-01-01

    Because obese people are at an increased risk of many age-related diseases, it is a plausible hypothesis that obesity increases the biological age of some tissues and cell types. However, it has been difficult to detect such an accelerated aging effect because it is unclear how to measure tissue age. Here we use a recently developed biomarker of aging (known as “epigenetic clock”) to study the relationship between epigenetic age and obesity in several human tissues. We report an unexpectedly ...

  2. Obesity accelerates epigenetic aging of human liver.

    Science.gov (United States)

    Horvath, Steve; Erhart, Wiebke; Brosch, Mario; Ammerpohl, Ole; von Schönfels, Witigo; Ahrens, Markus; Heits, Nils; Bell, Jordana T; Tsai, Pei-Chien; Spector, Tim D; Deloukas, Panos; Siebert, Reiner; Sipos, Bence; Becker, Thomas; Röcken, Christoph; Schafmayer, Clemens; Hampe, Jochen

    2014-10-28

    Because of the dearth of biomarkers of aging, it has been difficult to test the hypothesis that obesity increases tissue age. Here we use a novel epigenetic biomarker of aging (referred to as an "epigenetic clock") to study the relationship between high body mass index (BMI) and the DNA methylation ages of human blood, liver, muscle, and adipose tissue. A significant correlation between BMI and epigenetic age acceleration could only be observed for liver (r = 0.42, P = 6.8 × 10(-4) in dataset 1 and r = 0.42, P = 1.2 × 10(-4) in dataset 2). On average, epigenetic age increased by 3.3 y for each 10 BMI units. The detected age acceleration in liver is not associated with the Nonalcoholic Fatty Liver Disease Activity Score or any of its component traits after adjustment for BMI. The 279 genes that are underexpressed in older liver samples are highly enriched (1.2 × 10(-9)) with nuclear mitochondrial genes that play a role in oxidative phosphorylation and electron transport. The epigenetic age acceleration, which is not reversible in the short term after rapid weight loss induced by bariatric surgery, may play a role in liver-related comorbidities of obesity, such as insulin resistance and liver cancer.

  3. Accelerated aging syndromes, are they relevant to normal human aging?

    Science.gov (United States)

    Dreesen, Oliver; Stewart, Colin L

    2011-09-01

    Hutchinson-Gilford Progeria (HGPS) and Werner syndromes are diseases that clinically resemble some aspects of accelerated aging. HGPS is caused by mutations in theLMNA gene resulting in post-translational processing defects that trigger Progeria in children. Werner syndrome, arising from mutations in the WRN helicase gene, causes premature aging in young adults. What are the molecular mechanism(s) underlying these disorders and what aspects of the diseases resemble physiological human aging? Much of what we know stems from the study of patient derived fibroblasts with both mutations resulting in increased DNA damage, primarily at telomeres. However, in vivo patients with Werner's develop arteriosclerosis, among other pathologies. In HGPS patients, including iPS derived cells from HGPS patients, as well as some mouse models for Progeria, vascular smooth muscle (VSM) appears to be among the most severely affected tissues. Defective Lamin processing, associated with DNA damage, is present in VSM from old individuals, indicating processing defects may be a factor in normal aging. Whether persistent DNA damage, particularly at telomeres, is the root cause for these pathologies remains to be established, since not all progeroid Lmna mutations result in DNA damage and genome instability.

  4. Acrylamide induces accelerated endothelial aging in a human cell model.

    Science.gov (United States)

    Sellier, Cyril; Boulanger, Eric; Maladry, François; Tessier, Frédéric J; Lorenzi, Rodrigo; Nevière, Rémi; Desreumaux, Pierre; Beuscart, Jean-Baptiste; Puisieux, François; Grossin, Nicolas

    2015-09-01

    Acrylamide (AAM) has been recently discovered in food as a Maillard reaction product. AAM and glycidamide (GA), its metabolite, have been described as probably carcinogenic to humans. It is widely established that senescence and carcinogenicity are closely related. In vitro, endothelial aging is characterized by replicative senescence in which primary cells in culture lose their ability to divide. Our objective was to assess the effects of AAM and GA on human endothelial cell senescence. Human umbilical vein endothelial cells (HUVECs) cultured in vitro were used as model. HUVECs were cultured over 3 months with AAM or GA (1, 10 or 100 μM) until growth arrest. To analyze senescence, β-galactosidase activity and telomere length of HUVECs were measured by cytometry and semi-quantitative PCR, respectively. At all tested concentrations, AAM or GA reduced cell population doubling compared to the control condition (p < 0.001). β-galactosidase activity in endothelial cells was increased when exposed to AAM (≥10 μM) or GA (≥1 μM) (p < 0.05). AAM (≥10 μM) or GA (100 μM) accelerated telomere shortening in HUVECs (p < 0.05). In conclusion, in vitro chronic exposure to AAM or GA at low concentrations induces accelerated senescence. This result suggests that an exposure to AAM might contribute to endothelial aging.

  5. Neurodegeneration in accelerated aging.

    Science.gov (United States)

    Scheibye-Knudsen, Moren

    2016-11-01

    The growing proportion of elderly people represents an increasing economic burden, not least because of age-associated diseases that pose a significant cost to the health service. Finding possible interventions to age-associated disorders therefore have wide ranging implications. A number of genetically defined accelerated aging diseases have been characterized that can aid in our understanding of aging. Interestingly, all these diseases are associated with defects in the maintenance of our genome. A subset of these disorders, Cockayne syndrome, Xeroderma pigmentosum group A and ataxia-telangiectasia, show neurological involvement reminiscent of what is seen in primary human mitochondrial diseases. Mitochondria are the power plants of the cells converting energy stored in oxygen, sugar, fat, and protein into ATP, the energetic currency of our body. Emerging evidence has linked this organelle to aging and finding mitochondrial dysfunction in accelerated aging disorders thereby strengthens the mitochondrial theory of aging. This theory states that an accumulation of damage to the mitochondria may underlie the process of aging. Indeed, it appears that some accelerated aging disorders that show neurodegeneration also have mitochondrial dysfunction. The mitochondrial alterations may be secondary to defects in nuclear DNA repair. Indeed, nuclear DNA damage may lead to increased energy consumption, alterations in mitochondrial ATP production and defects in mitochondrial recycling, a term called mitophagy. These changes may be caused by activation of poly-ADP-ribose-polymerase 1 (PARP1), an enzyme that responds to DNA damage. Upon activation PARP1 utilizes key metabolites that attenuate pathways that are normally protective for the cell. Notably, pharmacological inhibition of PARP1 or reconstitution of the metabolites rescues the changes caused by PARP1 hyperactivation and in many cases reverse the phenotypes associated with accelerated aging. This implies that modulation

  6. Atherosclerosis in ancient humans, accelerated aging syndromes and normal aging: is lamin a protein a common link?

    Science.gov (United States)

    Miyamoto, Michael I; Djabali, Karima; Gordon, Leslie B

    2014-06-01

    Imaging studies of ancient human mummies have demonstrated the presence of vascular calcification that is consistent with the presence of atherosclerosis. These findings have stimulated interest in the underlying biological processes that might impart to humans an inherent predisposition to the development of atherosclerosis. Clues to these processes may possibly be found in accelerated aging syndromes, such as Hutchinson-Gilford progeria syndrome (HGPS), an ultra-rare disorder characterized by premature aging phenotypes, including very aggressive forms of atherosclerosis, occurring in childhood. The genetic defect in HGPS eventuates in the production of a mutant form of the nuclear structural protein lamin A, called progerin, which is thought to interfere with normal nuclear functioning. Progerin appears to be expressed in vascular cells, resulting in vessel wall cell loss and replacement by fibrous tissue, reducing vessel compliance and promoting calcification, leading to the vascular dysfunction and atherosclerosis seen in HGPS. Interestingly, vascular progerin is detectable in lower levels, in an age-related manner, in the general population, providing the basis for further study of the potential role of abnormal forms of lamin A in the atherosclerotic process of normal aging.

  7. Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels.

    Science.gov (United States)

    Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F; Eszes, Marika; Faull, Richard L M; Curtis, Maurice A; Waldvogel, Henry J; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V; Coppola, Giovanni; Yang, X William

    2016-07-01

    Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=-0.41, p=5.5×10-8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels.

  8. From old organisms to new molecules: integrative biology and therapeutic targets in accelerated human ageing

    OpenAIRE

    Cox, L S; Faragher, R. G. A.

    2007-01-01

    Abstract. Understanding the basic biology of human ageing is a key milestone in attempting to ameliorate the deleterious consequences of old age. This is an urgent research priority given the global demographic shift towards an ageing population. Although some molecular pathways that have been proposed to contribute to ageing have been discovered using classical biochemistry and genetics, the complex, polygenic and stochastic nature of ageing is such that the process as a whole is not immedia...

  9. From old organisms to new molecules: integrative biology and therapeutic targets in accelerated human ageing.

    Science.gov (United States)

    Cox, L S; Faragher, R G A

    2007-10-01

    Understanding the basic biology of human ageing is a key milestone in attempting to ameliorate the deleterious consequences of old age. This is an urgent research priority given the global demographic shift towards an ageing population. Although some molecular pathways that have been proposed to contribute to ageing have been discovered using classical biochemistry and genetics, the complex, polygenic and stochastic nature of ageing is such that the process as a whole is not immediately amenable to biochemical analysis. Thus, attempts have been made to elucidate the causes of monogenic progeroid disorders that recapitulate some, if not all, features of normal ageing in the hope that this may contribute to our understanding of normal human ageing. Two canonical progeroid disorders are Werner's syndrome and Hutchinson-Gilford progeroid syndrome (also known as progeria). Because such disorders are essentially phenocopies of ageing, rather than ageing itself, advances made in understanding their pathogenesis must always be contextualised within theories proposed to help explain how the normal process operates. One such possible ageing mechanism is described by the cell senescence hypothesis of ageing. Here, we discuss this hypothesis and demonstrate that it provides a plausible explanation for many of the ageing phenotypes seen in Werner's syndrome and Hutchinson-Gilford progeriod syndrome. The recent exciting advances made in potential therapies for these two syndromes are also reviewed.

  10. IGBT accelerated aging data set.

    Data.gov (United States)

    National Aeronautics and Space Administration — Preliminary data from thermal overstress accelerated aging using the aging and characterization system. The data set contains aging data from 6 devices, one device...

  11. Accelerated Aging in Electrolytic Capacitors for Prognostics

    Data.gov (United States)

    National Aeronautics and Space Administration — 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...

  12. Accelerated epigenetic aging in Down syndrome

    OpenAIRE

    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 ...

  13. PETN Coarsening - Predictions from Accelerated Aging Data

    Energy Technology Data Exchange (ETDEWEB)

    Maiti, Amitesh [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Gee, Richard H. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2011-03-30

    Ensuring good ignition properties over long periods of time necessitates maintaining a good level of porosity in powders of initiator materials and preventing particle coarsening. To simulate porosity changes of such powder materials over long periods of time a common strategy is to perform accelerated aging experiments over shorter time spans at elevated temperatures. In this paper we examine historical accelerated-aging data on powders of Pentaerythritol Tetranitrate (PETN), an important energetic material, and make predictions for long-term aging under ambient conditions. Lastly, we develop an evaporation-condensation- based model to provide some mechanistic understanding of the coarsening process.

  14. Accelerated epigenetic aging in Down syndrome.

    Science.gov (United States)

    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

    2015-06-01

    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)).

  15. Is biological aging accelerated in drug addiction?

    Science.gov (United States)

    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.

  16. Pathology of Mouse Models of Accelerated Aging

    NARCIS (Netherlands)

    Harkema, L.; Youssef, S. A.; de Bruin, A.

    2016-01-01

    Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of geroscience, wh

  17. Pathology of Mouse Models of Accelerated Aging

    NARCIS (Netherlands)

    Harkema, L; Youssef, S A; de Bruin, A|info:eu-repo/dai/nl/304837261

    2016-01-01

    Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of "geroscience,"

  18. Pathology of Mouse Models of Accelerated Aging

    NARCIS (Netherlands)

    Harkema, L; Youssef, S A; de Bruin, A

    2016-01-01

    Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of "geroscience,"

  19. Accelerated Aging in Electrolytic Capacitors for Prognostics

    Science.gov (United States)

    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.

  20. Accelerated aging of polymer composite bridge materials

    Science.gov (United States)

    Carlson, Nancy M.; Blackwood, Larry G.; Torres, Lucinda L.; Rodriguez, Julio G.; Yoder, Timothy S.

    1999-05-01

    Accelerated aging research on samples of composite materials and candidate UV protective coatings is determining the effects of six environmental factors on material durability. Candidate fastener materials are being evaluated to determine corrosion rates and crevice corrosion effects at load-bearing joints. This work supports field testing of a 30-ft long, 18-ft wide polymer matrix composite (PMC) bridge at the Idaho National Engineering and Environmental Laboratory. Durability results and sensor data form test with live loads provide information required for determining the cost/benefit measures to use in life-cycle planning, determining a maintenance strategy, establishing applicable inspection techniques, and establishing guidelines, standards and acceptance criteria for PMC bridges for use in the transportation infrastructure.

  1. Accelerated Aging of Polymer Composite Bridge Materials

    Energy Technology Data Exchange (ETDEWEB)

    Carlson, Nancy Margaret; Blackwood, Larry Gene; Torres, Lucinda Laine; Rodriguez, Julio Gallardo; Yoder, Timothy Scott

    1999-03-01

    Accelerated aging research on samples of composite material and candidate ultraviolet (UV) protective coatings is determining the effects of six environmental factors on material durability. Candidate fastener materials are being evaluated to determine corrosion rates and crevice corrosion effects at load-bearing joints. This work supports field testing of a 30-ft long, 18-ft wide polymer matrix composite (PMC) bridge at the Idaho National Engineering and Environmental Laboratory (INEEL). Durability results and sensor data from tests with live loads provide information required for determining the cost/benefit measures to use in life-cycle planning, determining a maintenance strategy, establishing applicable inspection techniques, and establishing guidelines, standards, and acceptance criteria for PMC bridges for use in the transportation infrastructure.

  2. Premature and accelerated ageing: HIV or HAART?

    Directory of Open Access Journals (Sweden)

    Reuben Luke Smith

    2013-01-01

    Full Text Available Highly Active Anti-Retroviral Therapy (HAART has significantly increased life expectancy of the HIV-positive population. Nevertheless, the average lifespan of HIV patients remains shorter compared to uninfected individuals. Immunosenescence, a current explanation for this difference invokes heavily on viral stimulus despite HAART efficiency in viral suppression. We propose here that the premature and accelerated ageing of HIV patients can also be caused by adverse effects of antiretroviral drugs, specifically those that affect the mitochondria. The Nucleoside Reverse Transcriptase Inhibitor (NRTI antiretroviral drug class for instance, is known to cause depletion of mitochondrial DNA via inhibition of the mitochondrial specific DNA polymerase-ƴ. Besides NRTIs, other antiretroviral drug classes such as Protease Inhibitors also cause severe mitochondrial damage by increasing oxidative stress and diminishing mitochondrial function. We also discuss important areas for future research and argue in favour of the use of C. elegans as a novel model system for studying these effects.

  3. Kinematics of transition during human accelerated sprinting

    Directory of Open Access Journals (Sweden)

    Ryu Nagahara

    2014-07-01

    Full Text Available This study investigated kinematics of human accelerated sprinting through 50 m and examined whether there is transition and changes in acceleration strategies during the entire acceleration phase. Twelve male sprinters performed a 60-m sprint, during which step-to-step kinematics were captured using 60 infrared cameras. To detect the transition during the acceleration phase, the mean height of the whole-body centre of gravity (CG during the support phase was adopted as a measure. Detection methods found two transitions during the entire acceleration phase of maximal sprinting, and the acceleration phase could thus be divided into initial, middle, and final sections. Discriminable kinematic changes were found when the sprinters crossed the detected first transition—the foot contacting the ground in front of the CG, the knee-joint starting to flex during the support phase, terminating an increase in step frequency—and second transition—the termination of changes in body postures and the start of a slight decrease in the intensity of hip-joint movements, thus validating the employed methods. In each acceleration section, different contributions of lower-extremity segments to increase in the CG forward velocity—thigh and shank for the initial section, thigh, shank, and foot for the middle section, shank and foot for the final section—were verified, establishing different acceleration strategies during the entire acceleration phase. In conclusion, there are presumably two transitions during human maximal accelerated sprinting that divide the entire acceleration phase into three sections, and different acceleration strategies represented by the contributions of the segments for running speed are employed.

  4. Accelerated Aging Experiments for Capacitor Health Monitoring and Prognostics

    Data.gov (United States)

    National Aeronautics and Space Administration — This paper discusses experimental setups for health monitoring and prognostics of electrolytic capacitors under nominal operation and accelerated aging conditions....

  5. Biodemography of human ageing

    DEFF Research Database (Denmark)

    Vaupel, James W

    2010-01-01

    Human senescence has been delayed by a decade. This finding, documented in 1994 and bolstered since, is a fundamental discovery about the biology of human ageing, and one with profound implications for individuals, society and the economy. Remarkably, the rate of deterioration with age seems...... to be constant across individuals and over time: it seems that death is being delayed because people are reaching old age in better health. Research by demographers, epidemiologists and other biomedical researchers suggests that further progress is likely to be made in advancing the frontier of survival...... - and healthy survival - to even greater ages....

  6. Physical properties of maxillofacial elastomers under conditions of accelerated aging.

    Science.gov (United States)

    Yu, R; Koran, A; Craig, R G

    1980-06-01

    The stability of the physical properties of various commercially available maxillofacial prosthetic materials was evaluated with the use of an accelerated aging chamber. The tensile strength, maximum percent elongation, shear strength, tear energy, and Shore A hardness were determined before and after accelerated aging. Results indicate that silicone 44210, a RTV rubber, is a promising elastomer for maxillofacial application.

  7. Age-dependent decrease and alternative splicing of methionine synthase mRNA in human cerebral cortex and an accelerated decrease in autism.

    Directory of Open Access Journals (Sweden)

    Christina R Muratore

    Full Text Available The folate and vitamin B12-dependent enzyme methionine synthase (MS is highly sensitive to cellular oxidative status, and lower MS activity increases production of the antioxidant glutathione, while simultaneously decreasing more than 200 methylation reactions, broadly affecting metabolic activity. MS mRNA levels in postmortem human cortex from subjects across the lifespan were measured and a dramatic progressive biphasic decrease of more than 400-fold from 28 weeks of gestation to 84 years was observed. Further analysis revealed alternative splicing of MS mRNA, including deletion of folate-binding domain exons and age-dependent deletion of exons from the cap domain, which protects vitamin B12 (cobalamin from oxidation. Although three species of MS were evident at the protein level, corresponding to full-length and alternatively spliced mRNA transcripts, decreasing mRNA levels across the lifespan were not associated with significant changes in MS protein or methionine levels. MS mRNA levels were significantly lower in autistic subjects, especially at younger ages, and this decrease was replicated in cultured human neuronal cells by treatment with TNF-α, whose CSF levels are elevated in autism. These novel findings suggest that rather than serving as a housekeeping enzyme, MS has a broad and dynamic role in coordinating metabolism in the brain during development and aging. Factors adversely affecting MS activity, such as oxidative stress, can be a source of risk for neurological disorders across the lifespan via their impact on methylation reactions, including epigenetic regulation of gene expression.

  8. Transcranial electrical stimulation accelerates human sleep homeostasis.

    Directory of Open Access Journals (Sweden)

    Davide Reato

    Full Text Available The sleeping brain exhibits characteristic slow-wave activity which decays over the course of the night. This decay is thought to result from homeostatic synaptic downscaling. Transcranial electrical stimulation can entrain slow-wave oscillations (SWO in the human electro-encephalogram (EEG. A computational model of the underlying mechanism predicts that firing rates are predominantly increased during stimulation. Assuming that synaptic homeostasis is driven by average firing rates, we expected an acceleration of synaptic downscaling during stimulation, which is compensated by a reduced drive after stimulation. We show that 25 minutes of transcranial electrical stimulation, as predicted, reduced the decay of SWO in the remainder of the night. Anatomically accurate simulations of the field intensities on human cortex precisely matched the effect size in different EEG electrodes. Together these results suggest a mechanistic link between electrical stimulation and accelerated synaptic homeostasis in human sleep.

  9. An Epigenetic Clock Measures Accelerated Aging in Treated HIV Infection.

    Science.gov (United States)

    Boulias, Konstantinos; Lieberman, Judy; Greer, Eric Lieberman

    2016-04-21

    In this issue of Molecular Cell, Gross et al. (2016) find a CpG DNA methylation signature in blood cells of patients with chronic well-controlled HIV infection that correlates with accelerated aging.

  10. Effects of Horizontal Acceleration on Human Visual Acuity and Stereopsis

    Directory of Open Access Journals (Sweden)

    Chi-Ting Horng

    2015-01-01

    Full Text Available 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.

  11. Premature and accelerated aging: HIV or HAART?

    NARCIS (Netherlands)

    Smith, R.L.; de Boer, R.; Brul, S.; Budovskaya, Y.; van der Spek, H.

    2013-01-01

    Highly active antiretroviral therapy (HAART) has significantly increased life expectancy of the human immunodeficiency virus (HIV)-positive population. Nevertheless, the average lifespan of HIV-patients remains shorter compared to uninfected individuals. Immunosenescence, a current explanation for

  12. Accelerate Genomic Aging in Congenital Neutropenia

    Science.gov (United States)

    2015-08-01

    the Army position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704-0188...accumulate in HSCs as a function of age and likely accounts for the increased incidence of AML/MDS in the elderly . It follows, that conditions that...Introduction 1 2. Keywords 1 3. Accomplishments 1 4. Impact 4 5. Changes/Problems 4 6. Products 5 7. Participants & Other Collaborating Organizations 5 8

  13. Accelerated Aging with Electrical Overstress and Prognostics for Power MOSFETs

    Science.gov (United States)

    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

  14. Influence of Accelerated Aging on Detonation Performance of Explosives

    Institute of Scientific and Technical Information of China (English)

    GAO Da-yuan; HUA Cheng; WANG Xiang; HAN Yong

    2010-01-01

    To understand the aging effects on detonation performances of explosives, an accelerated aging mechanism and effect of explosives were analyzed. Based on the thermo-gravimetric (TG) curves of explosives under the heat rate of 5, 10 and 20 K·min-1, the thermal decomposition activation energy, pre-exponential factor, mechanism function and kinetic equation of the explosives were calculated by Ozawa's equation and decomposition extents. Then, according to the derived kinetic equation, the density, composition and heat of formation of GI-1, PBX-1 and PBX-2 explosive in different decompo-sition extents were calculated at accelerated aging temperatures of 70 ℃ and 75 ℃, respectively. Furthermore, the detona-tion parameters of GI-1, PBX-1 and PBX-2 explosives were found out by means of VLWR code. The results show that after accelerated aging, the density are decrease, the detonation velocity and pressure are all decreased slightly.

  15. Mechanisms of cardiovascular disease in accelerated aging syndromes.

    Science.gov (United States)

    Capell, Brian C; Collins, Francis S; Nabel, Elizabeth G

    2007-07-06

    In the past several years, remarkable progress has been made in the understanding of the mechanisms of premature aging. These rare, genetic conditions offer valuable insights into the normal aging process and the complex biology of cardiovascular disease. Many of these advances have been made in the most dramatic of these disorders, Hutchinson-Gilford progeria syndrome. Although characterized by features of normal aging such as alopecia, skin wrinkling, and osteoporosis, patients with Hutchinson-Gilford progeria syndrome are affected by accelerated, premature arteriosclerotic disease that leads to heart attacks and strokes at a mean age of 13 years. In this review, we highlight recent advances in the biology of premature aging uncovered in Hutchinson-Gilford progeria syndrome and other accelerated aging syndromes, advances that provide insight into the mechanisms of cardiovascular diseases ranging from atherosclerosis to arrhythmias.

  16. Many human accelerated regions are developmental enhancers.

    Science.gov (United States)

    Capra, John A; Erwin, Genevieve D; McKinsey, Gabriel; Rubenstein, John L R; Pollard, Katherine S

    2013-12-19

    The genetic changes underlying the dramatic differences in form and function between humans and other primates are largely unknown, although it is clear that gene regulatory changes play an important role. To identify regulatory sequences with potentially human-specific functions, we and others used comparative genomics to find non-coding regions conserved across mammals that have acquired many sequence changes in humans since divergence from chimpanzees. These regions are good candidates for performing human-specific regulatory functions. Here, we analysed the DNA sequence, evolutionary history, histone modifications, chromatin state and transcription factor (TF) binding sites of a combined set of 2649 non-coding human accelerated regions (ncHARs) and predicted that at least 30% of them function as developmental enhancers. We prioritized the predicted ncHAR enhancers using analysis of TF binding site gain and loss, along with the functional annotations and expression patterns of nearby genes. We then tested both the human and chimpanzee sequence for 29 ncHARs in transgenic mice, and found 24 novel developmental enhancers active in both species, 17 of which had very consistent patterns of activity in specific embryonic tissues. Of these ncHAR enhancers, five drove expression patterns suggestive of different activity for the human and chimpanzee sequence at embryonic day 11.5. The changes to human non-coding DNA in these ncHAR enhancers may modify the complex patterns of gene expression necessary for proper development in a human-specific manner and are thus promising candidates for understanding the genetic basis of human-specific biology.

  17. Accelerated thermal and radiative ageing of hydrogenated NBR for DRC

    Energy Technology Data Exchange (ETDEWEB)

    Mares, G. [EUROTEST S.A., Bucharest (Romania). Research, Equipment Testing, Industrial Engineering and Scientific Services; Notingher, P. [Univ. Politehnica, Bucharest (Romania). Faculty of Electrical Engineering

    1996-12-31

    The accelerated thermal and gamma radiation ageing of HNBR carbon black-T80 has been studied by measuring the residual deformation under constant deflection -- DRC, in air, using a relevant equation for the relaxation phenomena. The residual deformation under constant deflection during the process of accelerated ageing is increasing but the structure of polymer answers in the proper manner to the mechanical stress. The degradation equations were obtained, using Alfrey model for the relaxation polymer subject to compression and an Arrhenius dependence for the chemical reaction rate. The inverted relaxation time for the thermal degradation is depending on the chemical reaction rate and the dose rate of gamma radiation.

  18. [HIV infection as a cause of accelerated aging and frailty].

    Science.gov (United States)

    Jiménez, Zaida; Sánchez-Conde, Matilde; Brañas, Fátima

    2017-06-07

    The HIV-infected population is aging due to the success of combination antiretroviral therapy, which prolongs survival, as well as the growing number of newly diagnosed cases in adults 50 years old and over. HIV-infected individuals suffer from an accelerated aging due to the persistent and chronic activation of the immune system that leads to immune exhaustion and accelerated immunosenescence, even when on optimal immuno-virological control treatment. The clinical expression of the immunosenescence state is an increased prevalence of aging-related non-HIV associated comorbidities and a rising prevalence of frailty occurring earlier than in the general population. Thus, HIV-infected patients are biologically older than their chronological age, and they suffer from aging-related problems, such as frailty, which should be assessed. Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Toward GPGPU accelerated human electromechanical cardiac simulations.

    Science.gov (United States)

    Vigueras, Guillermo; Roy, Ishani; Cookson, Andrew; Lee, Jack; Smith, Nicolas; Nordsletten, David

    2014-01-01

    In this paper, we look at the acceleration of weakly coupled electromechanics using the graphics processing unit (GPU). Specifically, we port to the GPU a number of components of CHeart--a CPU-based finite element code developed for simulating multi-physics problems. On the basis of a criterion of computational cost, we implemented on the GPU the ODE and PDE solution steps for the electrophysiology problem and the Jacobian and residual evaluation for the mechanics problem. Performance of the GPU implementation is then compared with single core CPU (SC) execution as well as multi-core CPU (MC) computations with equivalent theoretical performance. Results show that for a human scale left ventricle mesh, GPU acceleration of the electrophysiology problem provided speedups of 164 × compared with SC and 5.5 times compared with MC for the solution of the ODE model. Speedup of up to 72 × compared with SC and 2.6 × compared with MC was also observed for the PDE solve. Using the same human geometry, the GPU implementation of mechanics residual/Jacobian computation provided speedups of up to 44 × compared with SC and 2.0 × compared with MC. © 2013 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons, Ltd.

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

    NARCIS (Netherlands)

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

    2016-01-01

    OBJECTIVE: 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

  1. Accelerated brain aging in schizophrenia : A longitudinal pattern recognition study

    NARCIS (Netherlands)

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

    2016-01-01

    OBJECTIVE: 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

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

    NARCIS (Netherlands)

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

    2016-01-01

    OBJECTIVE: 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

  3. Accelerated aging of GaAs concentrator solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Gregory, P.E.

    1982-04-01

    An accelerated aging study of AlGaAs/GaAs solar cells has been completed. The purpose of the study was to identify the possible degradation mechanisms of AlGaAs/GaAs solar cells in terrestrial applications. Thermal storage tests and accelerated AlGaAs corrosion studies were performed to provide an experimental basis for a statistical analysis of the estimated lifetime. Results of this study suggest that a properly designed and fabricated AlGaAs/GaAs solar cell can be mechanically rugged and environmentally stable with projected lifetimes exceeding 100 years.

  4. Accelerated aging of AP/HTPB propellants and the influence of various environmental aging conditions

    NARCIS (Netherlands)

    Keizers, H.L.J.

    1995-01-01

    Preliminary resuits on accelerated aging of lab-scale produced AP/HTPB propellant and propellants from dissectioned rocket motors are discussed, including aging logic, storage conditions, test techniques and resuits on mechanical, ballistic and safety testing. The mam aging effect observed was harde

  5. Accelerated aging of AP/HTPB propellants and the influence of various environmental aging conditions

    NARCIS (Netherlands)

    Keizers, H.L.J.

    1995-01-01

    Preliminary resuits on accelerated aging of lab-scale produced AP/HTPB propellant and propellants from dissectioned rocket motors are discussed, including aging logic, storage conditions, test techniques and resuits on mechanical, ballistic and safety testing. The mam aging effect observed was

  6. Cognitive deterioration in adult epilepsy: Does accelerated cognitive ageing exist?

    Science.gov (United States)

    Breuer, L E M; Boon, P; Bergmans, J W M; Mess, W H; Besseling, R M H; de Louw, A; Tijhuis, A G; Zinger, S; Bernas, A; Klooster, D C W; Aldenkamp, A P

    2016-05-01

    A long-standing concern has been whether epilepsy contributes to cognitive decline or so-called 'epileptic dementia'. Although global cognitive decline is generally reported in the context of chronic refractory epilepsy, it is largely unknown what percentage of patients is at risk for decline. This review is focused on the identification of risk factors and characterization of aberrant cognitive trajectories in epilepsy. Evidence is found that the cognitive trajectory of patients with epilepsy over time differs from processes of cognitive ageing in healthy people, especially in adulthood-onset epilepsy. Cognitive deterioration in these patients seems to develop in a 'second hit model' and occurs when epilepsy hits on a brain that is already vulnerable or vice versa when comorbid problems develop in a person with epilepsy. Processes of ageing may be accelerated due to loss of brain plasticity and cognitive reserve capacity for which we coin the term 'accelerated cognitive ageing'. We believe that the concept of accelerated cognitive ageing can be helpful in providing a framework understanding global cognitive deterioration in epilepsy.

  7. Are Anxiety Disorders Associated with Accelerated Aging? A Focus on Neuroprogression

    Directory of Open Access Journals (Sweden)

    Giampaolo Perna

    2016-01-01

    Full Text Available Anxiety disorders (AnxDs are highly prevalent throughout the lifespan, with detrimental effects on daily-life functioning, somatic health, and quality of life. An emerging perspective suggested that AnxDs may be associated with accelerated aging. In this paper, we explored the association between AnxDs and hallmarks of accelerated aging, with a specific focus on neuroprogression. We reviewed animal and human findings that suggest an overlap between processes of impaired neurogenesis, neurodegeneration, structural, functional, molecular, and cellular modifications in AnxDs, and aging. Although this research is at an early stage, our review suggests a link between anxiety and accelerated aging across multiple processes involved in neuroprogression. Brain structural and functional changes that accompany normal aging were more pronounced in subjects with AnxDs than in coevals without AnxDs, including reduced grey matter density, white matter alterations, impaired functional connectivity of large-scale brain networks, and poorer cognitive performance. Similarly, molecular correlates of brain aging, including telomere shortening, Aβ accumulation, and immune-inflammatory and oxidative/nitrosative stress, were overrepresented in anxious subjects. No conclusions about causality or directionality between anxiety and accelerated aging can be drawn. Potential mechanisms of this association, limitations of the current research, and implications for treatments and future studies are discussed.

  8. Accelerated aging and stabilization of radiation-vulcanized EPDM rubber

    Science.gov (United States)

    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.

  9. Accelerated Gray and White Matter Deterioration With Age in Schizophrenia.

    Science.gov (United States)

    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.

  10. ACCELERATED AGING AND ELECTRICAL CONDUCTIVITY TESTS IN CRAMBE SEEDS

    Directory of Open Access Journals (Sweden)

    Juliana Joice Pereira Lima

    2015-02-01

    Full Text Available The aim of this study was to adapt the methodology of the accelerated aging and electrical conductivity tests for determination of physiological potential in crambe seeds. Six seed lots of crambe (cv. FMS Brilhante were subjected to determination of moisture content, germination test, first count germination, emergence, and emergence speed index. For the accelerated aging test, the traditional methodology was used with water, and with a saturated potassium chloride and sodium chloride solution in three periods of exposure (24, 48, and 72 hours at 41°C; the electrical conductivity test was performed with four pre-soaking treatments (0, 2, 4, and 8 hours and four soaking periods (4, 8, 16, and 24 hours at 25°C. The accelerated aging test with water for 72 hours and the electrical conductivity test with 2 hours of pre-soaking and assessment after 16 hours were effective for classification of the crambe seed lots in regard to physiological quality.

  11. Can we delay the accelerated lung aging in COPD? Anti-aging molecules and interventions.

    Science.gov (United States)

    Papaioannou, Andriana I; Rossios, Christos; Kostikas, Konstantinos; Ito, Kazuhiro

    2013-02-01

    Chronic obstructive pulmonary disease (COPD) has been recently characterized as a disease of accelerated lung aging. The prevalence of COPD is age-dependent suggesting an intimate relationship between the pathogenesis of COPD and aging. Lung function decline, the hallmark feature of COPD evolution, is more prominent with increasing age and this decline is greater in smoking individuals. One of the major goals of COPD pharmacotherapy is the development of drugs that would be able to result in a decrease of the decline in lung function over years. However, till nowadays smoking cessation is the only known intervention which is able to decelerate lung function decline. Several mechanisms of aging, including oxidative stress, inflammation and telomere shortening have been shown to be implicated in COPD. Furthermore, numerous anti-aging molecules, including sirtuins and Nrf-2 are reduced, and pathways such as mTOR and genes such as Klotho have also been shown to be abnormal in the lungs of COPD patients. The above mechanisms have been associated with the accelerated lung aging in COPD patients. Numerous therapeutic interventions have been studied in an attempt to reverse accelerated lung aging, and some of them have already been tested in clinical trials. The aim of the present review is to summarize the mechanisms associated with the accelerated lung aging in COPD and to provide information about the possible therapeutic implications targeting those mechanisms.

  12. Electrochemical migration technique to accelerate ageing of cementitious materials

    Directory of Open Access Journals (Sweden)

    Abbas Z.

    2013-07-01

    Full Text Available Durability assessment of concrete structures for constructions in nuclear waste repositories requires long term service life predictions. As deposition of low and intermediate level radioactive waste (LILW takes up to 100 000 years, it is necessary to analyze the service life of cementitious materials in this time perspective. Using acceleration methods producing aged specimens would decrease the need of extrapolating short term data sets. Laboratory methods are therefore, needed for accelerating the ageing process without making any influencing distortion in the properties of the materials. This paper presents an electro-chemical migration method to increase the rate of calcium leaching from cementitious specimens. This method is developed based on the fact that major long term deterioration process of hardened cement paste in concrete structures for deposition of LILW is due to slow diffusion of calcium ions. In this method the cementitious specimen is placed in an electrochemical cell as a porous path way through which ions can migrate at a rate far higher than diffusion process. The electrical field is applied to the cell in a way to accelerate the ion migration without making destructions in the specimen’s micro and macroscopic properties. The anolyte and catholyte solutions are designed favoring dissolution of calcium hydroxide and compensating for the leached calcium ions with another ion like lithium.

  13. Electrochemical migration technique to accelerate ageing of cementitious materials

    Science.gov (United States)

    Babaahmadi, A.; Tang, L.; Abbas, Z.

    2013-07-01

    Durability assessment of concrete structures for constructions in nuclear waste repositories requires long term service life predictions. As deposition of low and intermediate level radioactive waste (LILW) takes up to 100 000 years, it is necessary to analyze the service life of cementitious materials in this time perspective. Using acceleration methods producing aged specimens would decrease the need of extrapolating short term data sets. Laboratory methods are therefore, needed for accelerating the ageing process without making any influencing distortion in the properties of the materials. This paper presents an electro-chemical migration method to increase the rate of calcium leaching from cementitious specimens. This method is developed based on the fact that major long term deterioration process of hardened cement paste in concrete structures for deposition of LILW is due to slow diffusion of calcium ions. In this method the cementitious specimen is placed in an electrochemical cell as a porous path way through which ions can migrate at a rate far higher than diffusion process. The electrical field is applied to the cell in a way to accelerate the ion migration without making destructions in the specimen's micro and macroscopic properties. The anolyte and catholyte solutions are designed favoring dissolution of calcium hydroxide and compensating for the leached calcium ions with another ion like lithium.

  14. Gouty arthritis in the human aging process

    Directory of Open Access Journals (Sweden)

    Juliana Secchi Batista

    2012-09-01

    Full Text Available The aging process has gained universal recognition and is occurring at an accelerated pace. Gout is a metabolic disorder in which an overproduction and / or decreased excretion of uric acid, leading to the deposition of crystals of sodium monourato joints and soft tissue. The present study was based on a literature review that aimed to analyze the incidence of gouty arthritis in the human aging process. To this end, we searched for articles indexed journals, books, among others, published in English and Portuguese, using the keywords "Human Aging", "Rheumatic Diseases", "Drop" and "Gouty Arthritis". The data obtained suggest that the prevalence of gout is higher in men, affecting oligo / polyarticular inflammatory symptoms with smaller and often with involvement of small joints of the hands also may be the coexistence of gout with other autoimmune diseases such as ankylosing spondylitis and rheumatoid arthritis, should be performed nutritional treatment and medication.

  15. Cerebrolysin Accelerates Metamorphosis and Attenuates Aging-Accelerating Effect of High Temperature in Drosophila Melanogaster.

    Science.gov (United States)

    Navrotskaya, V; Oxenkrug, G; Vorobyova, L; Sharma, H; Muresanu, D; Summergrad, P

    2014-10-01

    Cerebrolysin® (CBL) is a neuroprotective drug used for the treatment of neurodegenerative diseases. CBL's mechanisms of action remain unclear. Involvement of tryptophan (TRP)-kynurenine (KYN) pathway in neuroprotective effect of CBL might be suggested considering that modulation of KYN pathway of TRP metabolism by CBL, and protection against eclosion defect and prolongation of life span of Drosophila melanogaster with pharmacologically or genetically-induced down-regulation of TRP conversion into KYN. To investigate possible involvement of TRP-KYN pathway in mechanisms of neuroprotective effect of CBL, we evaluated CBL effects on metamorphosis and life span of Drosophila melanogaster maintained at 23 °C and 28 °C ambient temperature. CBL accelerated metamorphosis, exerted strong tendency (p = 0.04) to prolong life span in female but not in male flies, and attenuated aging-accelerating effect of high (28 °C) ambient temperature in both female and male flies. Further research of CBL effects on metamorphosis and resistance to aging-accelerating effect of high temperature might offer new insights in mechanisms of its neuroprotective action and expand its clinical applications.

  16. Accelerated Aging Experiments for Capacitor Health Monitoring and Prognostics

    Science.gov (United States)

    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.

  17. MORPHOLOGICAL CHANGES IN THE HIPPOCAMPUS OF RATS IN ACCELERATED AGING

    Directory of Open Access Journals (Sweden)

    K. Yu. Maksimova

    2014-01-01

    Full Text Available The aim of this work was the analysis of structural changes with age in the hippocampus of senescenceaccelerated OXYS rats when signs of accelerated brain aging are missing (age 14 days, developments (age 5 months, and active progresses (age 15 months. The study was performed on 15 OXYS rats and 15 Wistar rats (as a control. After dislocation, brains were dissected, fixed with 10% formalin, embedded in paraffin, and serially cut in coronal sections (5μm thickness. These sections were stained with Cresyl violet and examined with a photomicroscope (Carl Zeiss Axiostar plus, Germany. The total number of hippocampal pyramidal cells in the CA1, CA3 and the dentate gyrus regions were estimated in 14-dayold, 5and 15-month-old OXYS and Wistar rats (n = 5 on the 5 slices of each brain sections. The number of neurons with chromatolysis, hyperchromatic with darkly stained cytoplasm and shrunken neurons were calculated as degenerative neurons. The pictures obtained with the program Carl Zeiss Axio Vision 8.0 with increasing 10  100, determined the average area bodies and nuclei of neurons (mkm2. The significant structural changes of neurons in the CA1, CA3 and dentate gyrus regions of the hippocampus in OXYS rats at 5 month of age are revealed by light microscopy. This results indicates the early develop neurodegeneration in OXYS rats. The most pronounced morphological changes occur in the CA1 region of the hippocampus of OXYS rats and irreversible. The degenerative changes of neurons in the hippocampus increases by the age of 15 months. Morphometric analysis of the average area of bodies and the nuclei of hippocampal neurons in CA1, CA3 and the dentate gyrus regions of OXYS and Wistar rats at 14 days of age showed no significant interline differences. At 5 months of age in the CA1 region of the hippocampus of OXYS rats was determined a significantly lower average body size and nuclei of pyramidal neurons compared with Wistar rats. With age, these

  18. AGE IN NORMAL HUMAN PREGNANCY

    African Journals Online (AJOL)

    ABSTRACT. Normal human pregnancy (PREG) predisposes towards gestational age (GA) ... These results potently suggest that the HH changes observed in this study are of advantage to ... changes of physiological functions affecting all body.

  19. Repair mortars based on lime. Accelerated aging tests

    Directory of Open Access Journals (Sweden)

    Martínez-Ramírez, S.

    1995-06-01

    Full Text Available The behaviour under different accelerated aging tests (freeze/thaw and crystallization cycles of a new lime mortar with biocide properties destinated to monumental repair has been studied. New mortars (which have the biocide impregnated in a clay called sepiolite have a similar behaviour to lime mortars used as a reference. After the aging tests, the biocide properties of the mortars have been tried.

    Se ha estudiado el comportamiento frente a distintos ensayos de envejecimiento acelerado (ciclos de hielo/deshielo y cristalización de sales de un nuevo mortero de cal con propiedades biocidas, destinado a la reparación monumental. Se ha comprobado que los nuevos morteros (que llevan incorporado el biocida impregnado en una arcilla denominada sepiolita tienen un comportamiento muy similar a los morteros de cal utilizados como referencia. Tras los ensayos de envejecimiento se ha visto que las propiedades biocidas de los morteros se mantienen.

  20. Parasite infection accelerates age polyethism in young honey bees.

    Science.gov (United States)

    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.

  1. Ultraweak chemiluminescence of rice seeds during accelerated aging

    Science.gov (United States)

    Chen, Wenli; Xing, Da; He, Yonghong

    2002-04-01

    Ultraweak Chemiluminescence (UCL) studies of different aging degree of rice (Oryza sativa L.) seeds stored in a high temperature 40 degree(s)C and high relative humidity 90% environment (0 day, 8 days, 15 days, and 22 days) were carried out. We firstly observed that aging degree of rice seeds was positive correlation with ultraweak chemiluminescence during the early imbibition (0-1h). Addition of water to rice seeds stimulates ultraweak chemiluminescence, the intensity of which depends upon aging degree of seeds. The shorter the seed accelerated aging time was, the higher the intensity of the UCL in the early imbibition period, the lower hydrogen peroxide (H2O2) concentration of rice seeds, the higher percentage seed germination. The germination and superoxide dismutase (SOD) activity of dry rice seeds was obvious positive correlation with the intensity of UCL. While catalase (CAT) activity of rice seeds was determined. Mechanism of ultraweak chemiluminescence was discussed. It was concluded that the store time of rice seeds could be judged from their UCL characters during the early imbibition period, which might be a way to examine vigor of seeds.

  2. Desloratadine analysis: as a pharmaceutical preparation and after accelerating ageing

    Directory of Open Access Journals (Sweden)

    Bober Katarzyna

    2015-09-01

    Full Text Available Desloratadine is a biologically active compound that is not described in the Polish Pharmacopoeia IX, hence, its study is particular important. The aim of this work was to establish a procedure for desloratadine analysis by way of HPTLC in combination with densitometry, so as to be able to ascertain its presence and degree of presence within pharmaceutical preparations. In our work, a mixture of ethyl acetate, n-butanol, ammonia and methanol was used as the mobile phase. Moreover, HPTLC plates precoated with silica gel 60F254 were also employed. The proposed method was tested and subsequently validated. Spectrodensitometric analysis was then performed to determine the optimal wavelength for the quantitative determination (λ=276 nm, and following this, a quantitative analysis of desloratadine within certain pharmaceutical preparations was performed. Our research also took into consideration an analysis of the products of desloratadine decomposition that come about as a result of the accelerated aging of its solutions. The employed procedure for accelerating the aging of such desloratadine solutions consisted of heating these at 40℃ and then irradiating the solution surfaces with UV light. The changing color of these solutions after 2 hours of exposure served to indicate that degradation had occurred. Of note: as a result of irradiation with UV light, desloratadine content was seen to decrease with time, declining to almost zero after 30 hours. However, heating a solution of desloratadine alone did not induce a change in its content. Solutions of desloratadine that had previously undergone irradiation and heating were also analyzed to ascertain whether new substances were present. For this purpose, the GC-MS process was employed. As a result of this procedure, the spectrum of the solution after aging showed the presence of several new peaks that displayed retention several times larger and smaller than the normal desloratadine peak.

  3. Aging of organic materials around high-energy particle accelerators

    Science.gov (United States)

    Tavlet, Marc

    1997-08-01

    Around particle accelerators used for fundamental research on the basic structure of matter, materials and components are exposed to ionizing radiation caused by beam losses in the proton machines and by synchrotron radiation in the lepton machines. Furthermore, with the high-energy and high-intensity collisions produced from future colliders, radiation damage is also to be expected in particle-physics detectors. Therefore, for a safe and reliable operation, the radiation aging of most of the components has to be assessed prior to their selection. An extensive radiation-damage test program has been carried out at CERN for decades on a routine basis and many results have been published. The tests have mainly concentrated on magnet-coil insulations and cable-insulating materials; they are carried out in accordance with the IEC 544 standard which defines the mechanical tests to be performed and the methods of degradation evaluation. The mechanical tests are also used to assess the degradation of composite structural materials. Moreover, electrical properties of high-voltage insulations and optical properties of organic scintillators and wave guides have also been studied. Our long-term experience has pointed out many parameters to be taken into account for the estimate of the lifetime of components in the radiation environment of our accelerators. One of the main parameters is the dose-rate effect, but the influence of other parameters has sometimes to be taken into account.

  4. Parasite infection accelerates age polyethism in young honey bees

    DEFF Research Database (Denmark)

    Lecocq, Antoine; Jensen, Annette Bruun; Kryger, Per

    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...

  5. ACCELERATED AGEING EFFECTS ON CURCUBITEA PEPO SEED OIL

    Directory of Open Access Journals (Sweden)

    D. Mampouya A. H. W. Nakavoua

    2013-06-01

    Full Text Available Accelerated ageing of curcubitea pepo seed oil was followed by simulation of UV (light and ambiant oxygen actions held separately then simultaneously in order to know the effects of these parameters on this oil resistance to deterioraton. Nine withdrawals had undergone analyses by titrimetry supported by spectroscopic analyses notably MIR (Medium Infrared, DSC (Differential Scanning Calorimetry and also a gas chromatography for the composition in FA. This study has showed that pumpkin seed oil displays a weak resistance to UV which results among other in a decrease of unsaponifiable compounds. Its oxidization takes place very quickly in the presence of ambiant oxygen. However the accumulated action of the two factors weakens to the highest degree pumpkin seed oil and this results in polymerization. It has also enabled us to show the link between the formation of recticulations in the oil matrix and variations at the level of the molecular structure of pumpkin seed oil.

  6. Accelerated Aging System for Prognostics of Power Semiconductor Devices

    Science.gov (United States)

    Celaya, Jose R.; Vashchenko, Vladislav; Wysocki, Philip; Saha, Sankalita

    2010-01-01

    Prognostics is an engineering discipline that focuses on estimation of the health state of a component and the prediction of its remaining useful life (RUL) before failure. Health state estimation is based on actual conditions and it is fundamental for the prediction of RUL under anticipated future usage. Failure of electronic devices is of great concern as future aircraft will see an increase of electronics to drive and control safety-critical equipment throughout the aircraft. Therefore, development of prognostics solutions for electronics is of key importance. This paper presents an accelerated aging system for gate-controlled power transistors. This system allows for the understanding of the effects of failure mechanisms, and the identification of leading indicators of failure which are essential in the development of physics-based degradation models and RUL prediction. In particular, this system isolates electrical overstress from thermal overstress. Also, this system allows for a precise control of internal temperatures, enabling the exploration of intrinsic failure mechanisms not related to the device packaging. By controlling the temperature within safe operation levels of the device, accelerated aging is induced by electrical overstress only, avoiding the generation of thermal cycles. The temperature is controlled by active thermal-electric units. Several electrical and thermal signals are measured in-situ and recorded for further analysis in the identification of leading indicators of failures. This system, therefore, provides a unique capability in the exploration of different failure mechanisms and the identification of precursors of failure that can be used to provide a health management solution for electronic devices.

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

    Science.gov (United States)

    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

  8. Statistical analysis of data from accelerated ageing tests of PES UF membranes

    NARCIS (Netherlands)

    Zondervan, Edwin; Zwijnenburg, Arie; Roffel, Brian

    2007-01-01

    In this research, membrane life-time was evaluated by means of accelerated ageing experiments. A pressure pulse unit was used to perform the ageing experiments in an accelerated way. An experimental design has been set up and four ageing factors were varied at two levels. The four ageing factors stu

  9. Statistical analysis of data from accelerated ageing tests of PES UF membranes

    NARCIS (Netherlands)

    Zondervan, E.; Zwijnenburg, A.; Roffel, B.

    2007-01-01

    In this research, membrane life-time was evaluated by means of accelerated ageing experiments. A pressure pulse unit was used to perform the ageing experiments in an accelerated way. An experimental design has been set up and four ageing factors were varied at two levels. The four ageing factors

  10. Volatile profile of Madeira wines submitted to traditional accelerated ageing.

    Science.gov (United States)

    Pereira, Vanda; Cacho, Juan; Marques, José C

    2014-11-01

    The evolution of monovarietal fortified Madeira wines forced-aged by traditional thermal processing (estufagem) were studied in terms of volatiles. SPE extracts were analysed by GC-MS before and after heating at 45 °C for 3 months (standard) and at 70 °C for 1 month (overheating). One hundred and ninety volatile compounds were identified, 53 of which were only encountered in baked wines. Most chemical families increased after standard heating, especially furans and esters, up to 61 and 3-fold, respectively. On the contrary, alcohols, acetates and fatty acids decreased after heating. Varietal aromas, such as Malvasia's monoterpenic alcohols were not detected after baking. The accelerated ageing favoured the development of some volatiles previously reported as typical aromas of finest Madeira wines, particularly phenylacetaldeyde, β-damascenone and 5-ethoxymethylfurfural. Additionally, ethyl butyrate, ethyl 2-methylbutyrate, ethyl caproate, ethyl isovalerate, guaiacol, 5-hydroxymethylfurfural and γ-decalactone were also found as potential contributors to the global aroma of baked wines. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Effects of Accelerated Aging on Fiber Damage Thresholds

    Energy Technology Data Exchange (ETDEWEB)

    Setchell, R.E.

    1999-02-15

    internal defects. Damage characteristics obtained from fibers subjected to each of these aging environments were compared to results from fresh fibers tested under identical conditions. A surprising result was that internal damage was not observed in any of the tested fibers. Only breakdown at the fiber entrance face and catastrophic damage at both end faces were observed. Fiber end faces were not sealed during the accelerated aging environments, and thresholds at these faces were significantly lower in the aged fibers. However, most fibers transmitted relatively high pulse energies before damaging, and a large fraction never damaged before we reached the limits of our test laser. The absence of any observable affect on internal damage thresholds is encouraging, but the current results do not rule out the possibility that some other approach to accelerated aging could reveal a growth mechanism for internal defects.

  12. Comparison between accelerated thermo-hydro aged wood and naturally aged wood

    OpenAIRE

    Froidevaux, Julien; Volkmer, Thomas; Gril, Joseph; Fioravanti, Marco; Navi, Parviz

    2011-01-01

    The effects of aging in wood in term of physical, mechanical and chemical degradation has been studied first by Jiro Kohara [1] and more recently by Erhardt et al. [2-3] and Obataya [4]. It has been observed that similar degradation can be found in thermo-hydro (TH) treated wood [4]. The aim of this study is to compare the mechanical behavior of naturally aged and accelerate TH wood in the radial direction. A first pressure vessel with controllable temperature, oxygen pressure and relative hu...

  13. Arsenite exposure accelerates aging process regulated by the transcription factor DAF-16/FOXO in Caenorhabditis elegans.

    Science.gov (United States)

    Yu, Chan-Wei; How, Chun Ming; Liao, Vivian Hsiu-Chuan

    2016-05-01

    Arsenic is a known human carcinogen and high levels of arsenic contamination in food, soils, water, and air are of toxicology concerns. Nowadays, arsenic is still a contaminant of emerging interest, yet the effects of arsenic on aging process have received little attention. In this study, we investigated the effects and the underlying mechanisms of chronic arsenite exposure on the aging process in Caenorhabditis elegans. The results showed that prolonged arsenite exposure caused significantly decreased lifespan compared to non-exposed ones. In addition, arsenite exposure (100 μM) caused significant changes of age-dependent biomarkers, including a decrease of defecation frequency, accumulations of intestinal lipofuscin and lipid peroxidation in an age-dependent manner in C. elegans. Further evidence revealed that intracellular reactive oxygen species (ROS) level was significantly increased in an age-dependent manner upon 100 μM arsenite exposure. Moreover, the mRNA levels of transcriptional makers of aging (hsp-16.1, hsp-16.49, and hsp-70) were increased in aged worms under arsenite exposure (100 μM). Finally, we showed that daf-16 mutant worms were more sensitive to arsenite exposure (100 μM) on lifespan and failed to induce the expression of its target gene sod-3 in aged daf-16 mutant under arsenite exposure (100 μM). Our study demonstrated that chronic arsenite exposure resulted in accelerated aging process in C. elegans. The overproduction of intracellular ROS and the transcription factor DAF-16/FOXO play roles in mediating the accelerated aging process by arsenite exposure in C. elegans. This study implicates a potential ecotoxicological and health risk of arsenic in the environment.

  14. Comparative Assessment of Stabilised Polybutadiene Binder under Accelerated Ageing

    Directory of Open Access Journals (Sweden)

    Luiz Felipe Cannaval Sbegue

    2016-04-01

    Full Text Available Polybutadiene elastomers are versatile materials, being employed at several applications from rocket propellant binder to adhesives and sealants. The elastomers derived from hydroxyl-terminated polybutadiene are usually stabilised with antioxidants to prevent degradation. In this study, a comparative assessment among 2,2’-methylene-bis (4-methyl-6-tert-butylphenol (AO2246, 2,6-di-tert-butyl-4-methylphenol (BHT, p-phenylenediamine (pPDA, and triphenylphosphine (TPP regarding stabilisation of hydroxyl-terminated polybutadiene binder under accelerated ageing (six months at 65 °C was carried out. Evaluation of antioxidants effectiveness was examined through Oxidation Induction time, sol/gel extraction, swelling and mechanical testing, dynamic mechanical analysis, and mass variation measurement. AO2246 yielded the best performance, meanwhile BHT was poorly protective. TPP acted as prooxidant, causing a severe degradation of the binder, and pPDA was not manageable to be assessed due to the lower curing degree of the resulted polyurethane.

  15. Color stability of repaired composite submitted to accelerated artificial aging.

    Science.gov (United States)

    Souza, Ana Beatriz Silva; Silame, Francisca Daniele Jardilino; Alandia-Roman, Carla Cecilia; Cruvinel, Diogo Rodrigues; Garcia, Lucas da Fonseca Roberti; Pires-de-Souza, Fernanda de Carvalho Panzeri

    2012-01-01

    The aim of this study was to evaluate the color stability (ΔE) of nanoparticulate composite, with consideration for the type of surface treatment performed before repair. A Teflon matrix was used to fabricate 50 test specimens from composite. After initial color readout, the specimens were submitted to 100 hours of accelerated artificial aging (AAA). The samples were divided into five groups (n = 10), according to the surface treatment performed: sandblasting with aluminum oxide powder, phosphoric acid, and an adhesive system (Group 1); sandblasting with aluminum oxide powder, phosphoric acid, and a flowable composite (Group 2); abrasion with a diamond bur, phosphoric acid, and an adhesive system (Group 3); abrasion with a diamond bur, phosphoric acid, and a nanoparticulate composite (Group 4); and a control group (Group 5). After repair, a new color readout was taken, the test specimens were submitted to a new AAA cycle (300 hours), and the final color readout was taken. Comparison of the ΔE means (one-way ANOVA and Tukey tests, p 0.05) after 100 hours of AAA. After repair, Group 1 (4.61 ± 2.03) presented the highest color alteration with a statistically significant difference compared with the other groups (p color alteration in comparison with the other groups, with a statistically significant difference (p color alteration of the restorations over the course of time.

  16. Accelerated Aging during Chronic Oxidative Stress: A Role for PARP-1

    Directory of Open Access Journals (Sweden)

    Daniëlle M. P. H. J. Boesten

    2013-01-01

    Full Text Available Oxidative stress plays a major role in the pathophysiology of chronic inflammatory disease and it has also been linked to accelerated telomere shortening. Telomeres are specialized structures at the ends of linear chromosomes that protect these ends from degradation and fusion. Telomeres shorten with each cell division eventually leading to cellular senescence. Research has shown that poly(ADP-ribose polymerase-1 (PARP-1 and subtelomeric methylation play a role in telomere stability. We hypothesized that PARP-1 plays a role in accelerated aging in chronic inflammatory diseases due to its role as coactivator of NF-κb and AP-1. Therefore we evaluated the effect of chronic PARP-1 inhibition (by fisetin and minocycline in human fibroblasts (HF cultured under normal conditions and under conditions of chronic oxidative stress, induced by tert-butyl hydroperoxide (t-BHP. Results showed that PARP-1 inhibition under normal culturing conditions accelerated the rate of telomere shortening. However, under conditions of chronic oxidative stress, PARP-1 inhibition did not show accelerated telomere shortening. We also observed a strong correlation between telomere length and subtelomeric methylation status of HF cells. We conclude that chronic PARP-1 inhibition appears to be beneficial in conditions of chronic oxidative stress but may be detrimental under relatively normal conditions.

  17. Rapamycin suppresses brain aging in senescence-accelerated OXYS rats.

    Science.gov (United States)

    Kolosova, Nataliya G; Vitovtov, Anton O; Muraleva, Natalia A; Akulov, Andrey E; Stefanova, Natalia A; Blagosklonny, Mikhail V

    2013-06-01

    Cellular and organismal aging are driven in part by the MTOR (mechanistic target of rapamycin) pathway and rapamycin extends life span inC elegans, Drosophila and mice. Herein, we investigated effects of rapamycin on brain aging in OXYS rats. Previously we found, in OXYS rats, an early development of age-associated pathological phenotypes similar to several geriatric disorders in humans, including cerebral dysfunctions. Behavioral alterations as well as learning and memory deficits develop by 3 months. Here we show that rapamycin treatment (0.1 or 0.5 mg/kg as a food mixture daily from the age of 1.5 to 3.5 months) decreased anxiety and improved locomotor and exploratory behavior in OXYS rats. In untreated OXYS rats, MRI revealed an increase of the area of hippocampus, substantial hydrocephalus and 2-fold increased area of the lateral ventricles. Rapamycin treatment prevented these abnormalities, erasing the difference between OXYS and Wister rats (used as control). All untreated OXYS rats showed signs of neurodegeneration, manifested by loci of demyelination. Rapamycin decreased the percentage of animals with demyelination and the number of loci. Levels of Tau and phospho-Tau (T181) were increased in OXYS rats (compared with Wistar). Rapamycin significantly decreased Tau and inhibited its phosphorylation in the hippocampus of OXYS and Wistar rats. Importantly, rapamycin treatment caused a compensatory increase in levels of S6 and correspondingly levels of phospo-S6 in the frontal cortex, indicating that some downstream events were compensatory preserved, explaining the lack of toxicity. We conclude that rapamycin in low chronic doses can suppress brain aging.

  18. Accelerator human interface. 4. Object analysis by OMT technique

    Energy Technology Data Exchange (ETDEWEB)

    Abe, Isamu; Nakahara, Kazuo [National Lab. for High Energy Physics, Tsukuba, Ibaraki (Japan); Mutoh, Masakatsu; Shibasaki, Yoshinobu

    1995-07-01

    The analysis of the objects of various classes in accelerator domain was carried out by OMT technique, and its summary is reported. By changing the technique from the conventional procedural type to object-oriented type, and reconsidering accelerator control, it becomes possible to give large impact to the development of software and accelerator control. Also the importance of establishing fundamental object system and its outline are described. As to the original objects of accelerators, the change due to age is small as compared with computer environment. Accordingly, by extracting the standard objects as far as possible, and making the objects so as to be able to deal with control system and multi-platform progressing with age, the situation that control systems become out of date can be clearly solved. The establishment of optimal objects shows the possibility of presenting optimal control system, and object analysis brings about many merits. OMT was adopted here. Accelerator control domain is divided into device class and generic task class, and the latter is divided into operation, diagnosis, operation support, simulation, data base, indication system and maintenance classes. The abstracting of data and procedure, the succession between devices and the behavior of objects are described. (K.I.)

  19. Accelerated Aging of Intervertebral Discs in a Mouse Model of Progeria

    Science.gov (United States)

    Vo, Nam; Seo, Hyoung-Yeon; Robinson, Andria; Sowa, Gwendolyn; Bentley, Douglas; Taylor, Lauren; Studer, Rebecca; Usas, Arvydas; Huard, Johnny; Alber, Sean; Watkins, Simon C.; Lee, Joon; Coehlo, Paulo; Wang, Dong; Loppini, Mattia; Robbins, Paul D.; Niedernhofer, Laura J.; Kang, James

    2012-01-01

    Intervertebral disc degeneration (IDD) is a common and debilitating disorder that results in reduced flexibility of the spine, pain, and reduced mobility. Risk factors for IDD include age, genetic predisposition, injury, and other environmental factors such as smoking. Loss of proteoglycans (PGs) contributes to IDD with advancing age. Currently there is a lack of a model for rapid investigation of disc aging and evaluation of therapeutic interventions. Here we examined progression of disc aging in a murine model of a human progeroid syndrome caused by deficiency of the DNA repair endonuclease, ERCC1–XPF (Ercc1−/Δ mice). The ERCC1-deficient mice showed loss of disc height and degenerative structural changes in their vertebral bodies similar to those reported for old rodents. Compared to their wild-type littermates, Ercc1−/Δ mice also exhibit other age-related IDD characteristics, including premature loss of disc PG, reduced matrix PG synthesis, and enhanced apoptosis and cell senescence. Finally, the onset of age-associated disc pathologies was further accelerated in Ercc1−/Δ mice following chronic treatment with the chemotherapeutic agent mechlorethamine. These results demonstrate that Ercc1−/Δ mice represent an accurate and rapid model of disc aging and provide novel evidence that DNA damage negatively impacts PG synthesis. PMID:20973062

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  2. Towards Accelerated Aging Methodologies and Health Management of Power MOSFETs

    Data.gov (United States)

    National Aeronautics and Space Administration — Understanding aging mechanisms of electronic components is of extreme importance in the aerospace domain where they are part of numerous critical subsystems...

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

    Science.gov (United States)

    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.

  4. Chronic inflammation induces telomere dysfunction and accelerates ageing in mice

    NARCIS (Netherlands)

    Jurk, Diana; Wilson, Caroline; Passos, Joao F.; Oakley, Fiona; Correia-Melo, Clara; Greaves, Laura; Saretzki, Gabriele; Fox, Chris; Lawless, Conor; Anderson, Rhys; Hewitt, Graeme; Pender, Sylvia L. F.; Fullard, Nicola; Nelson, Glyn; Mann, Jelena; van de Sluis, Bart; Mann, Derek A.; von Zglinicki, Thomas

    2014-01-01

    Chronic inflammation is associated with normal and pathological ageing. Here we show that chronic, progressive low-grade inflammation induced by knockout of the nfkb1 subunit of the transcription factor NF-kappa B induces premature ageing in mice. We also show that these mice have reduced regenerati

  5. Chronic inflammation induces telomere dysfunction and accelerates ageing in mice

    NARCIS (Netherlands)

    Jurk, Diana; Wilson, Caroline; Passos, Joao F.; Oakley, Fiona; Correia-Melo, Clara; Greaves, Laura; Saretzki, Gabriele; Fox, Chris; Lawless, Conor; Anderson, Rhys; Hewitt, Graeme; Pender, Sylvia L. F.; Fullard, Nicola; Nelson, Glyn; Mann, Jelena; van de Sluis, Bart; Mann, Derek A.; von Zglinicki, Thomas

    2014-01-01

    Chronic inflammation is associated with normal and pathological ageing. Here we show that chronic, progressive low-grade inflammation induced by knockout of the nfkb1 subunit of the transcription factor NF-kappa B induces premature ageing in mice. We also show that these mice have reduced regenerati

  6. Lifetime sedentary living accelerates some aspects of secondary aging

    DEFF Research Database (Denmark)

    Booth, Frank W; Laye, Matthew J; Roberts, Michael D

    2011-01-01

    Lifetime physical inactivity interacts with secondary aging (i.e., aging caused by diseases and environmental factors) in three patterns of response. First, lifetime physical inactivity confers no apparent effects on a given set of physiological functions. Second, lifetime physical inactivity acc...

  7. Delayed and accelerated aging share common longevity assurance mechanisms

    NARCIS (Netherlands)

    Schumacher, B.; van der Pluijm, I.; Moorhouse, M.J.; Kosteas, T.; Robinson, A.R.; Suh, Y.; Breit, T.M.; van Steeg, H.; Niedernhofer, L.J.; van IJcken, W.; Bartke, A.; Spindler, S.R.; Hoeijmakers, J.H.J.; van der Horst, G.T.J.; Garinis, G.A.

    2008-01-01

    Mutant dwarf and calorie-restricted mice benefit from healthy aging and unusually long lifespan. In contrast, mouse models for DNA repair-deficient progeroid syndromes age and die prematurely. To identify mechanisms that regulate mammalian longevity, we quantified the parallels between the genome-wi

  8. Delayed and accelerated aging share common longevity assurance mechanisms

    NARCIS (Netherlands)

    Schumacher, B.; van der Pluijm, I.; Moorhouse, M.J.; Kosteas, T.; Robinson, A.R.; Suh, Y.; Breit, T.M.; van Steeg, H.; Niedernhofer, L.J.; van IJcken, W.; Bartke, A.; Spindler, S.R.; Hoeijmakers, J.H.J.; van der Horst, G.T.J.; Garinis, G.A.

    2008-01-01

    Mutant dwarf and calorie-restricted mice benefit from healthy aging and unusually long lifespan. In contrast, mouse models for DNA repair-deficient progeroid syndromes age and die prematurely. To identify mechanisms that regulate mammalian longevity, we quantified the parallels between the

  9. Color change of composite resins subjected to accelerated artificial aging

    Directory of Open Access Journals (Sweden)

    Denise Cremonezzi Tornavoi

    2013-01-01

    Conclusions: All composite resins presented unacceptable color changes after 382 h of aging and different composite resins with same hue, presented different colors before being subjected to the aging process (B2 and C2 and after (B2. It was also observed color difference within a group of the same composite resin and same hue.

  10. [Molecular mechanism of accelerating ageing by oxidative stress].

    Science.gov (United States)

    Yoshikawa, Toshikazu; Naito, Yuji

    2009-07-01

    Reactive oxygen species are important for many life sustaining processes of cells and tissues, but they can also induce cell damage and death. If their production and levels within cells are not effectively controlled, then the detrimental effects of oxidative stress can accumulate. Oxidative stress is widely thought to underpin many ageing processes, and the oxidative stress theory of ageing is one of the most widely acknowledged theories of ageing. As well as being the major source of reactive oxygen species, mitochondria are also a major site of oxidative damage. The purpose of this review is a concise and current review of the role of oxidative stress in ageing process. Emphasis is placed upon the roles of mitochondrial proton leak, the uncoupling proteins, and the anti-ageing effects of caloric restriction.

  11. Computational model of sustained acceleration effects on human cognitive performance.

    Science.gov (United States)

    McKinlly, Richard A; Gallimore, Jennie J

    2013-08-01

    Extreme acceleration maneuvers encountered in modern agile fighter aircraft can wreak havoc on human physiology, thereby significantly influencing cognitive task performance. As oxygen content declines under acceleration stress, the activity of high order cortical tissue reduces to ensure sufficient metabolic resources are available for critical life-sustaining autonomic functions. Consequently, cognitive abilities reliant on these affected areas suffer significant performance degradations. The goal was to develop and validate a model capable of predicting human cognitive performance under acceleration stress. Development began with creation of a proportional control cardiovascular model that produced predictions of several hemodynamic parameters, including eye-level blood pressure and regional cerebral oxygen saturation (rSo2). An algorithm was derived to relate changes in rSo2 within specific brain structures to performance on cognitive tasks that require engagement of different brain areas. Data from the "precision timing" experiment were then used to validate the model predicting cognitive performance as a function of G(z) profile. The following are value ranges. Results showed high agreement between the measured and predicted values for the rSo2 (correlation coefficient: 0.7483-0.8687; linear best-fit slope: 0.5760-0.9484; mean percent error: 0.75-3.33) and cognitive performance models (motion inference task--correlation coefficient: 0.7103-0.9451; linear best-fit slope: 0.7416-0.9144; mean percent error: 6.35-38.21; precision timing task--correlation coefficient: 0.6856-0.9726; linear best-fit slope: 0.5795-1.027; mean percent error: 6.30-17.28). The evidence suggests that the model is capable of accurately predicting cognitive performance of simplistic tasks under high acceleration stress.

  12. Effect of accelerated aging on translucency of monolithic zirconia

    Directory of Open Access Journals (Sweden)

    O. Abdelbary

    2016-12-01

    Conclusion: Thickness of zirconia has significant effect on translucency. Aging has significant effect on thinner sections of zirconia. More research is required on zirconia towards making the material more translucent for its potential use as esthetic monolithic restoration.

  13. Loss of caveolin-1 accelerates neurodegeneration and aging.

    Directory of Open Access Journals (Sweden)

    Brian P Head

    Full Text Available BACKGROUND: The aged brain exhibits a loss in gray matter and a decrease in spines and synaptic densities that may represent a sequela for neurodegenerative diseases such as Alzheimer's. Membrane/lipid rafts (MLR, discrete regions of the plasmalemma enriched in cholesterol, glycosphingolipids, and sphingomyelin, are essential for the development and stabilization of synapses. Caveolin-1 (Cav-1, a cholesterol binding protein organizes synaptic signaling components within MLR. It is unknown whether loss of synapses is dependent on an age-related loss of Cav-1 expression and whether this has implications for neurodegenerative diseases such as Alzheimer's disease. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed brains from young (Yg, 3-6 months, middle age (Md, 12 months, aged (Ag, >18 months, and young Cav-1 KO mice and show that localization of PSD-95, NR2A, NR2B, TrkBR, AMPAR, and Cav-1 to MLR is decreased in aged hippocampi. Young Cav-1 KO mice showed signs of premature neuronal aging and degeneration. Hippocampi synaptosomes from Cav-1 KO mice showed reduced PSD-95, NR2A, NR2B, and Cav-1, an inability to be protected against cerebral ischemia-reperfusion injury compared to young WT mice, increased Aβ, P-Tau, and astrogliosis, decreased cerebrovascular volume compared to young WT mice. As with aged hippocampi, Cav-1 KO brains showed significantly reduced synapses. Neuron-targeted re-expression of Cav-1 in Cav-1 KO neurons in vitro decreased Aβ expression. CONCLUSIONS: Therefore, Cav-1 represents a novel control point for healthy neuronal aging and loss of Cav-1 represents a non-mutational model for Alzheimer's disease.

  14. The challenges of human population ageing

    DEFF Research Database (Denmark)

    Sander, Miriam; Oxlund, Bjarke; Jespersen, Astrid;

    2015-01-01

    The 20th century saw an unprecedented increase in average human lifespan as well as a rapid decline in human fertility in many countries of the world. The accompanying worldwide change in demographics of human populations is linked to unanticipated and unprecedented economic, cultural, medical...... of Copenhagen (UCPH) and the Center for Healthy Ageing at UCPH, which took place on 20-21 June 2014 in Copenhagen, Denmark. Questions discussed here include the following: what is driving age-structural change in human populations? how can we create 'age-friendly' societies and promote 'ageing...

  15. Comparison of Degradation on Aluminum Reflectors for Solar Collectors due to Outdoor Exposure and Accelerated Aging

    Directory of Open Access Journals (Sweden)

    Johannes Wette

    2016-11-01

    Full Text Available Reflectors for concentrated solar thermal technologies need to withstand 20 or even 30 years of outdoor exposure without significant loss of solar specular reflectance. In order to test the durability of innovative reflectors within a shorter period of time, an accelerated aging methodology is required. The problem with accelerated testing is that poor correlation between laboratory and field test results has been achieved in the past. This is mainly because unrealistic degradation mechanisms are accelerated in the weathering chambers. In order to define a realistic testing procedure, a high number of accelerated aging tests have been performed on differently coated aluminum reflectors. The degradation mechanisms of the accelerated tests have been classified and systematically compared to samples that have been exposed at nine different exposure sites outdoors. Besides the standardized aging tests, innovative aging procedures have been developed in such way that the agreement to the degradation pattern observed outdoors is increased. Although degradation depends on materials and location, five generic degradation mechanisms were detected. Standardized tests only reproduced one or two of the five mechanisms detected outdoors. Additionally, several degradation effects that were not observed outdoors appeared. The innovative accelerated aging tests of artificially soiled samples were able to reproduce three of the five mechanisms observed outdoors, presenting a much more realistic overall degradation pattern.

  16. Recipient aging accelerates acquired transthyretin amyloidosis after domino liver transplantation.

    Science.gov (United States)

    Misumi, Yohei; Narita, Yasuko; Oshima, Toshinori; Ueda, Mitsuharu; Yamashita, Taro; Tasaki, Masayoshi; Obayashi, Konen; Isono, Kaori; Inomata, Yukihiro; Ando, Yukio

    2016-05-01

    Domino liver transplantation (DLT) with liver grafts from patients with hereditary transthyretin (TTR) amyloidosis has been performed throughout the world because of a severe liver graft shortage. Reports of acquired systemic TTR amyloidosis in domino liver recipients have been increasing; however, the precise pathogenesis and clinical course of acquired TTR amyloidosis remains unclear. We analyzed the relationship between the occurrence of acquired amyloidosis and clinical features in 22 consecutive domino liver donors with hereditary TTR amyloidosis (10 males and 12 females; mean age at DLT: 37.2 years; TTR mutations: V30M [n = 19], Y114C [n = 1], L55P [n = 1], and S50I [n = 1]) and 22 liver recipients (16 males and 6 females; mean age at DLT, 46.2 years). The mean times from DLT to amyloid first appearance and transplant recipient symptom onset were 8.2 years and 9.9 years, respectively. Kaplan-Meier analysis and quantification of the amyloid deposition revealed aging of recipients correlated with early de novo amyloid deposition. The sex of donors and recipients and the age, disease duration, and disease severity of donors had no significant effect on the latency of de novo amyloid deposition. In conclusion, our results demonstrate that recipient aging is associated with the early onset de novo amyloidosis. Because acquired amyloidosis will likely increase, careful follow-up for early amyloidosis detection and new treatments, including TTR stabilizers and gene-silencing therapies, are required. Liver Transplantation 22 656-664 2016 AASLD. © 2015 American Association for the Study of Liver Diseases.

  17. Analysis of Human Accelerated DNA Regions Using Archaic Hominin Genomes

    Science.gov (United States)

    Burbano, Hernán A.; Green, Richard E.; Maricic, Tomislav; Lalueza-Fox, Carles; de la Rasilla, Marco; Rosas, Antonio; Kelso, Janet; Pollard, Katherine S.; Lachmann, Michael; Pääbo, Svante

    2012-01-01

    Several previous comparisons of the human genome with other primate and vertebrate genomes identified genomic regions that are highly conserved in vertebrate evolution but fast-evolving on the human lineage. These human accelerated regions (HARs) may be regions of past adaptive evolution in humans. Alternatively, they may be the result of non-adaptive processes, such as biased gene conversion. We captured and sequenced DNA from a collection of previously published HARs using DNA from an Iberian Neandertal. Combining these new data with shotgun sequence from the Neandertal and Denisova draft genomes, we determine at least one archaic hominin allele for 84% of all positions within HARs. We find that 8% of HAR substitutions are not observed in the archaic hominins and are thus recent in the sense that the derived allele had not come to fixation in the common ancestor of modern humans and archaic hominins. Further, we find that recent substitutions in HARs tend to have come to fixation faster than substitutions elsewhere in the genome and that substitutions in HARs tend to cluster in time, consistent with an episodic rather than a clock-like process underlying HAR evolution. Our catalog of sequence changes in HARs will help prioritize them for functional studies of genomic elements potentially responsible for modern human adaptations. PMID:22412940

  18. Accelerated Telomere Shortening and Replicative Senescence in Human Fibroblasts Overexpressing Mutant and Wild Type Lamin A

    Science.gov (United States)

    Huang, Shurong; Risques, Rosa Ana; Martin, George M.; Rabinovitch, Peter S.; Oshima, Junko

    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. To 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 detectible 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. PMID:17870066

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

    NARCIS (Netherlands)

    W.P. Vermeij (Wilbert); M. Dollé (MartijnE.T.); E. Reiling (Erwin); D. Jaarsma (Dick); C. Payan-Gomez; C.R. Bombardieri (Cíntia R.); Wu, H.; A.J.M. Roks (Anton); S.M. Botter (Sander); B.C.J. van der Eerden (Bram); S.A. Youssef (Sameh Ahmed); R. Kuiper (Ruud); B. Nagarajah (Bhawani); C.T.M. van Oostrom (Conny); R.M.C. Brandt (Renata); S. Barnhoorn (Sander); S. Imholz (Sandra); J.L.A. Pennings (Jeroen L.A.); A. de Bruin (Alain); Gyenis, Á.; J. Pothof (Joris); J. Vijg (Jan); H. van Steeg (Harry); J.H.J. Hoeijmakers (Jan)

    2016-01-01

    textabstractMice deficient in the DNA excision-repair gene Ercc1 (Ercc1Δ/-) 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

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

    NARCIS (Netherlands)

    Vermeij, W. P.; Dolle, 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, A.; Pothof, J.; Vijg, J.; van Steeg, H.; Hoeijmakers, J. H. J.

    2016-01-01

    Mice deficient in the DNA excision-repair gene Ercc1 (Ercc1(Delta/-)) show numerous accelerated ageing features that limit their lifespan to 4-6 months(1-4). They also exhibit a 'survival response', which suppresses growth and enhances cellular maintenance. Such a response resembles the anti-ageing

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

    NARCIS (Netherlands)

    Vermeij, W P; Dollé, M E T; Reiling, E; Jaarsma, D|info:eu-repo/dai/nl/323051928; 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|info:eu-repo/dai/nl/305415042; Nagarajah, B; van Oostrom, C T; Brandt, R M C; Barnhoorn, S; Imholz, S; Pennings, J L A; de Bruin, A|info:eu-repo/dai/nl/304837261; Gyenis, Á; Pothof, J; Vijg, J; van Steeg, H; Hoeijmakers, J H J

    2016-01-01

    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

  2. Accelerated ageing in testing bricks used in the conservation of historic buildings

    Science.gov (United States)

    Pavlendová, Gabriela; Podoba, Rudolf; Baník, Ivan

    2014-11-01

    The effect of accelerated climate ageing on historical bricks in the laboratory is investigated in the paper. Differences in thermal properties are experimentally determined and studied before and after bricks exposure to climate ageing, which consists of 60 freeze-thaw cycles. For measuring thermal conductivity, diffusivity and specific heat, pulse method is used.

  3. Synaptic proteome changes in a DNA repair deficient Ercc1 mouse model of accelerated aging

    NARCIS (Netherlands)

    M.J. Végh (Marlene); M.C. de Waard (Monique); I. van der Pluijm (Ingrid); Y. Ridwan (Yanto); M.J.M. Sassen (Marion J.); P. van Nierop (Pim); R.C. van der Schors (Roel); K.W. Li (Ka Wan); J.H.J. Hoeijmakers (Jan); A.B. Smit (August); R.E. van Kesteren (Ronald)

    2012-01-01

    textabstractCognitive decline is one of the earliest hallmarks of both normal and pathological brain aging. Here we used Ercc1 mutant mice, which are impaired in multiple DNA repair systems and consequently show accelerated aging and progressive memory deficits, to identify changes in the levels of

  4. Why aging research? The moral imperative to retard human aging.

    Science.gov (United States)

    Farrelly, Colin

    2010-06-01

    The American philosopher John Rawls describes a fair system of social cooperation as one that is both rational and reasonable. Is it rational and reasonable for societies that (1) are vulnerable to diverse risks of morbidity (e.g., cancer, heart disease) and mortality and (2) are constrained by limited medical resources, to prioritize aging research? In this paper I make the case for answering "yes" on both accounts. Focusing on a plausible example of an applied gerontological intervention (i.e., an antiaging pharmaceutical), I argue that the goal of decelerating the rate of human aging would be a more effective strategy for extending the human health span than the current strategy of just tackling each specific disease of aging. Furthermore, the aspiration to retard human aging is also a reasonable aspiration, for the principle that underlies it (i.e., the duty to prevent harm) is one that no one could reasonably reject.

  5. Models of accelerated sarcopenia: critical pieces for solving the puzzle of age-related muscle atrophy.

    Science.gov (United States)

    Buford, Thomas W; Anton, Stephen D; Judge, Andrew R; Marzetti, Emanuele; Wohlgemuth, Stephanie E; Carter, Christy S; Leeuwenburgh, Christiaan; Pahor, Marco; Manini, Todd M

    2010-10-01

    Sarcopenia, the age-related loss of skeletal muscle mass, is a significant public health concern that continues to grow in relevance as the population ages. Certain conditions have the strong potential to coincide with sarcopenia to accelerate the progression of muscle atrophy in older adults. Among these conditions are co-morbid diseases common to older individuals such as cancer, kidney disease, diabetes, and peripheral artery disease. Furthermore, behaviors such as poor nutrition and physical inactivity are well-known to contribute to sarcopenia development. However, we argue that these behaviors are not inherent to the development of sarcopenia but rather accelerate its progression. In the present review, we discuss how these factors affect systemic and cellular mechanisms that contribute to skeletal muscle atrophy. In addition, we describe gaps in the literature concerning the role of these factors in accelerating sarcopenia progression. Elucidating biochemical pathways related to accelerated muscle atrophy may allow for improved discovery of therapeutic treatments related to sarcopenia.

  6. Ageing of the human hypothalamus.

    Science.gov (United States)

    Swaab, D F

    1995-01-01

    The various hypothalamic nuclei show very different patterns of change in ageing. These patterns are a basis for changes in biological rhythms, hormones, autonomous functions or behavior. The suprachiasmatic nucleus (SCN) coordinates circadian and circannual rhythms. A marked seasonal and circadian variation in the vasopressin (AVP) cell number of the SCN was observed in relation to the variation in photoperiod. During normal ageing, the circadian variation and number of AVP-expressing neurons in the SCN decreases. The sexually dimorphic nucleus (SDN), intermediate nucleus or INAH-1 is localized between the supraoptic and paraventricular nucleus (PVN). In adult men the SDN is twice as large as in adult women. In girls, the SDN shows a first period of decreasing cell numbers during prepubertal development, leading to sexual dimorphism. During ageing a decrease in cell number is found in both sexes. The cells of the supraoptic nucleus and PVN produce AVP or oxytocin and coexpress tyrosine hydroxylase. These nuclei are examples of neuron populations that seem to stay perfectly intact in ageing. Parvicellular corticotropin-releasing-hormone (CRH)-containing neurons are found throughout the PVN. CRH neurons in the PVN are activated in the course of ageing, as indicated by their increase in number and AVP coexpression. Part of the infundibular (or arcuate) nucleus, the subventricular nucleus, contains hypertrophic neurons in postmenopausal women. The hypertrophied neurons contain neurokinin-B (NKB), substance P and estrogen receptors and probably act on LHRH neurons as interneurons. The NKB neurons may also be involved in the initiation of menopausal flushes. The nucleus tuberalis lateralis might be involved in feeding behavior and metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. The challenges of human population ageing

    DEFF Research Database (Denmark)

    Sander, Miriam; Oxlund, Bjarke; Jespersen, Astrid

    2015-01-01

    The 20th century saw an unprecedented increase in average human lifespan as well as a rapid decline in human fertility in many countries of the world. The accompanying worldwide change in demographics of human populations is linked to unanticipated and unprecedented economic, cultural, medical...... of Copenhagen (UCPH) and the Center for Healthy Ageing at UCPH, which took place on 20-21 June 2014 in Copenhagen, Denmark. Questions discussed here include the following: what is driving age-structural change in human populations? how can we create 'age-friendly' societies and promote 'ageing......-in-community'? what tools will effectively promote social engagement and prevent social detachment among older individuals? is there a risk that further extension of human lifespan would be a greater burden to the individual and to society than is warranted by the potential benefit of longer life?...

  8. A stochastic model of randomly accelerated walkers for human mobility

    Science.gov (United States)

    Gallotti, Riccardo; Bazzani, Armando; Rambaldi, Sandro; Barthelemy, Marc

    2016-08-01

    Recent studies of human mobility largely focus on displacements patterns and power law fits of empirical long-tailed distributions of distances are usually associated to scale-free superdiffusive random walks called Lévy flights. However, drawing conclusions about a complex system from a fit, without any further knowledge of the underlying dynamics, might lead to erroneous interpretations. Here we show, on the basis of a data set describing the trajectories of 780,000 private vehicles in Italy, that the Lévy flight model cannot explain the behaviour of travel times and speeds. We therefore introduce a class of accelerated random walks, validated by empirical observations, where the velocity changes due to acceleration kicks at random times. Combining this mechanism with an exponentially decaying distribution of travel times leads to a short-tailed distribution of distances which could indeed be mistaken with a truncated power law. These results illustrate the limits of purely descriptive models and provide a mechanistic view of mobility.

  9. Long-Term Flexural Behaviors of GFRP Reinforced Concrete Beams Exposed to Accelerated Aging Exposure Conditions

    Directory of Open Access Journals (Sweden)

    Yeonho Park

    2014-06-01

    Full Text Available This study investigates the impact of accelerated aging conditions on the long-term flexural behavior and ductility of reinforced concrete (RC members with glass fiber-reinforced polymer (GFRP bars (RC-GFRP specimen and steel bars (RC-steel specimen. A total of thirty six specimens were designed with different amounts of reinforcement with three types of reinforcing bars (i.e., helically wrapped GFRP, sand-coated surface GFRP and steel. Eighteen specimens were subjected to sustained loads and accelerated aging conditions (i.e., 47 °C and 80% relative humidity in a chamber. The flexural behavior of specimens under 300-day exposure was compared to that of the companion specimens without experiencing accelerated aging conditions. Results indicate that the accelerated aging conditions reduced flexural capacity in not only RC-steel, but also RC-GFRP specimens, with different rates of reduction. Different types of GFRP reinforcement exhibited different rates of degradation of the flexural capacity when embedded in concrete under the same exposure conditions. Several existing models were compared with experimental results for predicting the deflection and deformability index for specimens. Bischoff and Gross’s model exhibited an excellent prediction of the time-dependent deflections. Except for the deformability index proposed by Jaeger, there was no general trend related to the aging duration. This study recommends the need for further investigation on the prediction of the deformability index.

  10. Overexpression of eIF-5A2 in mice causes accelerated organismal aging by increasing chromosome instability

    Directory of Open Access Journals (Sweden)

    Chen Leilei

    2011-05-01

    Full Text Available Abstract Background Amplification of 3q26 is one of the most frequent genetic alterations in many human malignancies. Recently, we isolated a novel oncogene eIF-5A2 within the 3q26 region. Functional study has demonstrated the oncogenic role of eIF-5A2 in the initiation and progression of human cancers. In the present study, we aim to investigate the physiological and pathological effect of eIF-5A2 in an eIF-5A2 transgenic mouse model. Methods An eIF-5A2 transgenic mouse model was generated using human eIF-5A2 cDNA. The eIF-5A2 transgenic mice were characterized by histological and immunohistochemistry analyses. The aging phenotypes were further characterized by wound healing, bone X-ray imaging and calcification analysis. Mouse embryo fibroblasts (MEF were isolated to further investigate molecular mechanism of eIF-5A2 in aging. Results Instead of resulting in spontaneous tumor formation, overexpression of eIF-5A2 accelerated the aging process in adult transgenic mice. This included decreased growth rate and body weight, shortened life span, kyphosis, osteoporosis, delay of wound healing and ossification. Investigation of the correlation between cellular senescence and aging showed that cellular senescence is not required for the aging phenotypes in eIF-5A2 mice. Interestingly, we found that activation of eIF-5A2 repressed p19 level and therefore destabilized p53 in transgenic mouse embryo fibroblast (MEF cells. This subsequently allowed for the accumulation of chromosomal instability, such as errors in cell dividing during metaphase and anaphase. Additionally, a significantly increase in number of aneuploidy cells (p Conclusion These observations suggest that eIF-5A2 mouse models could accelerate organismal aging by increasing chromosome instability.

  11. Classifying Human Body Acceleration Patterns Using a Hierarchical Temporal Memory

    Science.gov (United States)

    Sassi, Federico; Ascari, Luca; Cagnoni, Stefano

    This paper introduces a novel approach to the detection of human body movements during daily life. With the sole use of one wearable wireless triaxial accelerometer attached to one's chest, this approach aims at classifying raw acceleration data robustly, to detect many common human behaviors without requiring any specific a-priori knowledge about movements. The proposed approach consists of feeding sensory data into a specifically trained Hierarchical Temporal Memory (HTM) to extract invariant spatial-temporal patterns that characterize different body movements. The HTM output is then classified using a Support Vector Machine (SVM) into different categories. The performance of this new HTM+SVM combination is compared with a single SVM using real-word data corresponding to movements like "standing", "walking", "jumping" and "falling", acquired from a group of different people. Experimental results show that the HTM+SVM approach can detect behaviors with very high accuracy and is more robust, with respect to noise, than a classifier based solely on SVMs.

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

    Science.gov (United States)

    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.

  13. The age of the universe, the Hubble constant, the accelerated expansion and the Hubble effect

    OpenAIRE

    Soares,Domingos

    2009-01-01

    The idea of an accelerating universe comes almost simultaneously with the determination of Hubble's constant by one of the Hubble Space Telescope Key Projects. The age of the universe dilemma is probably the link between these two issues. In an appendix, I claim that "Hubble's law" might yet to be investigated for its ultimate cause, and suggest the "Hubble effect" as the searched candidate.

  14. Accelerated aging and controlled deterioration for the determination of the physiological potential of onion seeds

    Directory of Open Access Journals (Sweden)

    Rodo Angelica Brod

    2003-01-01

    Full Text Available International research on vegetable seed vigor is not at the same level attained for grain crops species. This study was conducted to identify reliable procedures for the accelerated aging and controlled deterioration tests to rank onion (Allium cepa L. seed lots according to their physiological potential. Six seed lots of the cultivars Aurora and Petroline were evaluated in the laboratory for germination, first count, seedling vigor classification, traditional and saturated salt accelerated aging (41masculineC / 48 and 72 h, controlled deterioration (24% of water / 45masculineC / 24 h and seedling emergence tests. Seed moisture content after the saturated salt accelerated aging test was lower and uniform, which is considered an important advantage in comparison to the traditional procedure. The saturated salt accelerated aging (41masculineC / 48 and 72 h and controlled deterioration (moisture content adjusted to 24% / 45masculineC / 24 h tests were the best procedures to assess the physiological potential of onion seeds, and are indicated for use in quality control programs.

  15. Effect of accelerated aging of MSWI bottom ash on the leaching mechanisms of copper and molybdenum

    NARCIS (Netherlands)

    Dijkstra, J.J.; Zomeren, van A.; Meeussen, J.C.L.; Comans, R.N.J.

    2006-01-01

    The effect of accelerated aging of Municipal Solid Waste Incinerator (MSWI) bottom ash on the leaching of Cu and Mo was studied using a "multisurface" modeling approach, based on surface complexation to iron/aluminum (hydr) oxides, mineral dissolution/precipitation, and metal complexation by humic s

  16. The age of the universe, the Hubble constant, the accelerated expansion and the Hubble effect

    OpenAIRE

    Soares, Domingos

    2009-01-01

    The idea of an accelerating universe comes almost simultaneously with the determination of Hubble's constant by one of the Hubble Space Telescope Key Projects. The age of the universe dilemma is probably the link between these two issues. In an appendix, I claim that "Hubble's law" might yet to be investigated for its ultimate cause, and suggest the "Hubble effect" as the searched candidate.

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

    Science.gov (United States)

    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.

  18. Animal and human models to understand ageing.

    Science.gov (United States)

    Lees, Hayley; Walters, Hannah; Cox, Lynne S

    2016-11-01

    Human ageing is the gradual decline in organ and tissue function with increasing chronological time, leading eventually to loss of function and death. To study the processes involved over research-relevant timescales requires the use of accessible model systems that share significant similarities with humans. In this review, we assess the usefulness of various models, including unicellular yeasts, invertebrate worms and flies, mice and primates including humans, and highlight the benefits and possible drawbacks of each model system in its ability to illuminate human ageing mechanisms. We describe the strong evolutionary conservation of molecular pathways that govern cell responses to extracellular and intracellular signals and which are strongly implicated in ageing. Such pathways centre around insulin-like growth factor signalling and integration of stress and nutritional signals through mTOR kinase. The process of cellular senescence is evaluated as a possible underlying cause for many of the frailties and diseases of human ageing. Also considered is ageing arising from systemic changes that cannot be modelled in lower organisms and instead require studies either in small mammals or in primates. We also touch briefly on novel therapeutic options arising from a better understanding of the biology of ageing. Copyright © 2016. Published by Elsevier Ireland Ltd.

  19. Coffee Silverskin Extract Protects against Accelerated Aging Caused by Oxidative Agents

    Directory of Open Access Journals (Sweden)

    Amaia Iriondo-DeHond

    2016-06-01

    Full Text Available Nowadays, coffee beans are almost exclusively used for the preparation of the beverage. The sustainability of coffee production can be achieved introducing new applications for the valorization of coffee by-products. Coffee silverskin is the by-product generated during roasting, and because of its powerful antioxidant capacity, coffee silverskin aqueous extract (CSE may be used for other applications, such as antiaging cosmetics and dermaceutics. This study aims to contribute to the coffee sector’s sustainability through the application of CSE to preserve skin health. Preclinical data regarding the antiaging properties of CSE employing human keratinocytes and Caenorhabditis elegans are collected during the present study. Accelerated aging was induced by tert-butyl hydroperoxide (t-BOOH in HaCaT cells and by ultraviolet radiation C (UVC in C. elegans. Results suggest that the tested concentrations of coffee extracts were not cytotoxic, and CSE 1 mg/mL gave resistance to skin cells when oxidative damage was induced by t-BOOH. On the other hand, nematodes treated with CSE (1 mg/mL showed a significant increased longevity compared to those cultured on a standard diet. In conclusion, our results support the antiaging properties of the CSE and its great potential for improving skin health due to its antioxidant character associated with phenols among other bioactive compounds present in the botanical material.

  20. Influence of Different Types of Resin Luting Agents on Color Stability of Ceramic Laminate Veneers Subjected to Accelerated Artificial Aging

    OpenAIRE

    Silami,Francisca Daniele Jardilino; Tonani,Rafaella; Alandia-Román,Carla Cecilia; Pires-de-Souza, Fernanda de Carvalho Panzeri

    2016-01-01

    Abstract 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...

  1. Proteins induced by telomere dysfunction and DNA damage represent biomarkers of human aging and disease

    NARCIS (Netherlands)

    Jiang, Hong; Schiffer, Eric; Song, Zhangfa; Wang, Jianwei; Zürbig, Petra; Thedieck, Kathrin; Moes, Suzette; Bantel, Heike; Saal, Nadja; Jantos, Justyna; Brecht, Meiken; Jenö, Paul; Hall, Michael N; Hager, Klaus; Manns, Michael P; Hecker, Hartmut; Ganser, Arnold; Döhner, Konstanze; Bartke, Andrzej; Meissner, Christoph; Mischak, Harald; Ju, Zhenyu; Rudolph, K Lenhard

    2008-01-01

    Telomere dysfunction limits the proliferative capacity of human cells by activation of DNA damage responses, inducing senescence or apoptosis. In humans, telomere shortening occurs in the vast majority of tissues during aging, and telomere shortening is accelerated in chronic diseases that increase

  2. The challenges of human population ageing

    Science.gov (United States)

    Sander, Miriam; Oxlund, Bjarke; Jespersen, Astrid; Krasnik, Allan; Mortensen, Erik Lykke; Westendorp, Rudi Gerardus Johannes; Rasmussen, Lene Juel

    2015-01-01

    The 20th century saw an unprecedented increase in average human lifespan as well as a rapid decline in human fertility in many countries of the world. The accompanying worldwide change in demographics of human populations is linked to unanticipated and unprecedented economic, cultural, medical, social, public health and public policy challenges, whose full implications on a societal level are only just beginning to be fully appreciated. Some of these implications are discussed in this commentary, an outcome of Cultures of Health and Ageing, a conference co-sponsored by the University of Copenhagen (UCPH) and the Center for Healthy Ageing at UCPH, which took place on 20–21 June 2014 in Copenhagen, Denmark. Questions discussed here include the following: what is driving age-structural change in human populations? how can we create ‘age-friendly’ societies and promote ‘ageing-in-community’? what tools will effectively promote social engagement and prevent social detachment among older individuals? is there a risk that further extension of human lifespan would be a greater burden to the individual and to society than is warranted by the potential benefit of longer life? PMID:25452294

  3. Compatibility and accelerated aging study for Li(Si)/FeS/sub 2 thermally activated batteries

    Science.gov (United States)

    Mead, J. W.; Searcy, J. Q.; Neiswander, P. N.; Poole, R. L.

    1983-12-01

    Thermally activated batteries using the lithium (silicon) iron disulfide (Li(Si)/FeS2) electrochemical system are used in weapons having a required storage life of 25 years and high reliability. A review of known data revealed no information on the compatibility of Li(Si)/FeS2 with the organic materials used in the system. The compatibility question is studied. Accelerated-aging data on pairs of materials were produced. In addition, a group of production batteries was aged and tested. Three aging temperatures were used during the one-year study. Gas analyses, electrical tests and mechanical tests were compared for control and aged samples. Two results, the depletion of oxygen and an increase in hydrogen in the compatibility and accelerated-aging samples, stimulated additional studies. No unexpected or significant changes were observed in the electrical or mechanical properties of the organic materials. Calorific output and chloride ion content of heat pellets indicated no degradation with aging. Ignition sensitivity and burn rate measurements suggested no heat pellet degradation. Oxygen content in aged lithium (silicon) anodes remained within acceptable limits. Single-cell tests and battery test results showed no degradation with aging.

  4. Down syndrome as a model of DNA polymerase beta haploinsufficiency and accelerated aging.

    Science.gov (United States)

    Patterson, David; Cabelof, Diane C

    2012-04-01

    Down syndrome is a condition of intellectual disability characterized by accelerated aging. As with other aging syndromes, evidence accumulated over the past several decades points to a DNA repair defect inherent in Down syndrome. This evidence has led us to suggest that Down syndrome results in reduced DNA base excision repair (BER) capacity, and that this contributes to the genomic instability and the aging phenotype of Down syndrome. We propose important roles for microRNA and/or folate metabolism and oxidative stress in the dysregulation of BER in Down syndrome. Further, we suggest these pathways are involved in the leukemogenesis of Down syndrome. We have reviewed the role of BER in the processing of oxidative stress, and the impact of folate depletion on BER capacity. Further, we have reviewed the role that loss of BER, specifically DNA polymerase beta, plays in accelerating the rate of aging. Like that seen in the DNA polymerase beta heterozygous mouse, the aging phenotype of Down syndrome is subtle, unlike the aging phenotypes seen in the classical progeroid syndromes and mouse models of aging. As such, Down syndrome may provide a model for elucidating some of the basic mechanisms of aging.

  5. Heroin abuse accelerates biological aging: a novel insight from telomerase and brain imaging interaction.

    Science.gov (United States)

    Cheng, G L F; Zeng, H; Leung, M-K; Zhang, H-J; Lau, B W M; Liu, Y-P; Liu, G-X; Sham, P C; Chan, C C H; So, K-F; Lee, T M C

    2013-05-21

    Heroin abuse and natural aging exert common influences on immunological cell functioning. This observation led to a recent and untested idea that aging may be accelerated in abusers of heroin. We examined this claim by testing whether heroin use is associated with premature aging at both cellular and brain system levels. A group of abstinent heroin users (n=33) and matched healthy controls (n=30) were recruited and measured on various biological indicators of aging. These measures included peripheral blood telomerase activity, which reflects cellular aging, and both structural and functional measures of brain magnetic resonance imaging. We found that heroin users were characterized by significantly low telomerase activity (0.21 vs 1.78; 88% reduction; t(61)=6.96, Pbrain region implicated in aging. Using the PFC location identified from the structural analyses as a 'seed' region, it was further revealed that telomerase activity interacted with heroin use to impact age-sensitive brain functional networks (AlphaSim corrected Pbrain system and behavioral measures in the context of substance abuse. The present finding that heroin abuse is associated with accelerated aging at both cellular and brain system levels is novel and forms a unique contribution to our knowledge in how the biological processes of drug abusers may be disrupted.

  6. Human folate metabolism using 14C-accelerator mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Clifford, A. J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Arjomand, A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Duecker, S. R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Johnson, H. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Schneider, P. D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Zulim, R. A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Bucholz, B. A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Vogel, J. S. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    1999-03-25

    Folate is a water soluble vitamin required for optimal health, growth and development. It occurs naturally in various states of oxidation of the pteridine ring and with varying lengths to its glutamate chain. Folates function as one-carbon donors through methyl transferase catalyzed reactions. Low-folate diets, especially by those with suboptimal methyltransferase activity, are associated with increased risk of neural tube birth defects in children, hyperhomocysteinemic heart disease, and cancer in adults. Rapidly dividing (neoplastic) cells have a high folate need for DNA synthesis. Chemical analogs of folate (antifolates) that interfere with folate metabolism are used as therapeutic agents in cancer treatment. Although much is known about folate chemistry, metabolism of this vitamin in vivo in humans is not well understood. Since folate levels in blood and tissues are very low and methods to measure them are inadequate, the few previous studies that have examined folate metabolism used large doses of radiolabeled folic acid in patients with Hodgkin's disease and cancer (Butterworth et al. 1969, Krumdieck et al. 1978). A subsequent protocol using deuterated folic acid was also insufficiently sensitive to trace a physiologic folate dose (Stites et al. 1997). Accelerator mass spectrometry (AMS) is an emerging bioanalytical tool that overcomes the limitations of traditional mass spectrometry and of decay counting of long lived radioisotopes (Vogel et al. 1995). AMS can detect attomolar concentrations of 14 C in milligram-sized samples enabling in vivo radiotracer studies in healthy humans. We used AMS to study the metabolism of a physiologic 80 nmol oral dose of 14 C-folic acid (1/6 US RDA) by measuring the 14 C-folate levels in serial plasma, urine and feces samples taken over a 150-day period after dosing a healthy adult volunteer.

  7. Heme oxygenase-1 accelerates tumor angiogenesis of human pancreatic cancer.

    Science.gov (United States)

    Sunamura, Makoto; Duda, Dan G; Ghattas, Maivel H; Lozonschi, Lucian; Motoi, Fuyuhiko; Yamauchi, Jun-Ichiro; Matsuno, Seiki; Shibahara, Shigeki; Abraham, Nader G

    2003-01-01

    Angiogenesis is necessary for the continued growth of solid tumors, invasion and metastasis. Several studies clearly showed that heme oxygenase-1 (HO-1) plays an important role in angiogenesis. In this study, we used the vital microscope system, transparent skinfold model, lung colonization model and transduced pancreatic cancer cell line (Panc-1)/human heme oxygenase-1 (hHO-1) cells, to precisely analyze, for the first time, the effect of hHO-1 gene on tumor growth, angiogenesis and metastasis. Our results revealed that HO-1 stimulates angiogenesis of pancreatic carcinoma in severe combined immune deficient mice. Overexpression of human hHO-1 after its retroviral transfer into Panc-1 cells did not interfere with tumor growth in vitro. While in vivo the development of tumors was accelerated upon transfection with hHO-1. On the other hand, inhibition of heme oxygenase (HO) activity by stannous mesoporphyrin was able transiently to delay tumor growth in a dose dependent manner. Tumor angiogenesis was markedly increased in Panc-1/hHO-1 compared to mock transfected and wild type. Lectin staining and Ki-67 proliferation index confirmed these results. In addition hHO-1 stimulated in vitro tumor angiogenesis and increased endothelial cell survival. In a lung colonization model, overexpression of hHO-1 increased the occurrence of metastasis, while inhibition of HO activity by stannous mesoporphyrin completely inhibited the occurrence of metastasis. In conclusion, overexpression of HO-1 genes potentiates pancreatic cancer aggressiveness, by increasing tumor growth, angiogenesis and metastasis and that the inhibition of the HO system may be of useful benefit for the future treatment of the disease.

  8. Mitochondrial theory of aging in human age-related sarcopenia.

    Science.gov (United States)

    Parise, Gianni; De Lisio, Michael

    2010-01-01

    Understanding age-related sarcopenia and, more importantly, devising counterstrategies require an intimate knowledge of the underlying mechanism(s) of sarcopenia. The mitochondrial theory of aging (MTA) has been a leading theory on aging for the last decade; however, there is relatively little information from human tissue to support or rebut the involvement of the MTA in aging skeletal muscle. It is believed that mitochondria may contribute to sarcopenia in a stochastic fashion where regions of fibers containing dysfunctional mitochondria are forced to atrophy. Resistance exercise, a known hypertrophic stimulus, has been shown to improve the mitochondrial phenotype of aged skeletal muscle. Furthermore, activation of skeletal muscle stem cells by resistance exercise may attenuate sarcopenia in two ways. First by inducing nuclear addition to postmitotic fibers, and, second, by increasing the proportion of functional mitochondria donated by muscle stem cells in a process termed 'gene shifting'. In this chapter we review the evidence supporting the MTA, the potential to attenuate the MTA with a known hypertrophic stimuli and explore the role of muscle stem cells in gene shifting to determine the connection between mitochondrial dysfunction and age-related sarcopenia. Copyright © 2010 S. Karger AG, Basel.

  9. Telomere length in subjects with schizophrenia, their unaffected siblings and healthy controls: Evidence of accelerated aging.

    Science.gov (United States)

    Czepielewski, Leticia Sanguinetti; Massuda, Raffael; Panizzutti, Bruna; da Rosa, Eduarda Dias; de Lucena, David; Macêdo, Danielle; Grun, Lucas Kich; Barbé-Tuana, Florencia María; Gama, Clarissa Severino

    2016-07-01

    Schizophrenia (SZ) is associated with broad burden. The clinical manifestations of SZ are related to pathophysiological alterations similar to what is seen in normal aging. Our aim was to evaluate the differences in telomere length (TL), a biomarker of cellular aging, in subjects with SZ (n=36), unaffected siblings (SB, n=36) and healthy controls (HC, n=47). SZ had shorter TL compared to HC, but no difference was found in SB comparing to SZ. These findings indicate that a pathological accelerated aging profile could be present in the course of SZ and further studies are needed to confirm TL as potential endophenotype, especially in at risk populations.

  10. Compatibility and accelerated aging study for Li(Si)/FeS2 thermally activated batteries

    Science.gov (United States)

    Mead, J. W.; Searcy, J. Q.; Neiswander, P. A.; Poole, R. L.

    Thermally activated batteries using Li(Si)/FeS2 for use in systems which require a storage life of 25 years and high reliability are examined. All of the materials in the system, both organic and inorganic are incorporated except the heat paper and electric match are studied. No compatibility or aging problems are indicated. The following results are reported: oxygen vanishes from the overgas in containers that were accelerated aged; hydrogen increases sharply in the overgas initially but generally decreases as aging progresses. No unexpected or significant changes were observed in the volume resistivity, glass transition temperature, or shear modulus or organic materials.

  11. The role of oxidative and nitrosative stress in accelerated aging and major depressive disorder.

    Science.gov (United States)

    Maurya, Pawan Kumar; Noto, Cristiano; Rizzo, Lucas B; Rios, Adiel C; Nunes, Sandra O V; Barbosa, Décio Sabbatini; Sethi, Sumit; Zeni, Maiara; Mansur, Rodrigo B; Maes, Michael; Brietzke, Elisa

    2016-02-01

    Major depressive disorder (MDD) affects millions of individuals and is highly comorbid with many age associated diseases such as diabetes mellitus, immune-inflammatory dysregulation and cardiovascular diseases. Oxidative/nitrosative stress plays a fundamental role in aging, as well as in the pathogenesis of neurodegenerative/neuropsychiatric disorders including MDD. In this review, we critically review the evidence for an involvement of oxidative/nitrosative stress in acceleration of aging process in MDD. There are evidence of the association between MDD and changes in molecular mechanisms involved in aging. There is a significant association between telomere length, enzymatic antioxidant activities (SOD, CAT, GPx), glutathione (GSH), lipid peroxidation (MDA), nuclear factor κB, inflammatory cytokines with MDD. Major depression also is characterized by significantly lower concentration of antioxidants (zinc, coenzyme Q10, PON1). Since, aging and MDD share a common biological base in their pathophysiology, the potential therapeutic use of antioxidants and anti-aging molecules in MDD could be promising.

  12. Acceleration of cardiovascular-biological age by amphetamine exposure is a power function of chronological age

    Science.gov (United States)

    Norman, Amanda; Hulse, Gary Kenneth

    2017-01-01

    Background Amphetamine abuse is becoming more widespread internationally. The possibility that its many cardiovascular complications are associated with a prematurely aged cardiovascular system, and indeed biological organism systemically, has not been addressed. Methods Radial arterial pulse tonometry was performed using the SphygmoCor system (Sydney). 55 amphetamine exposed patients were compared with 107 tobacco smokers, 483 non-smokers and 68 methadone patients (total=713 patients) from 2006 to 2011. A cardiovascular-biological age (VA) was determined. Results The age of the patient groups was 30.03±0.51–40.45±1.15 years. This was controlled for with linear regression. The sex ratio was the same in all groups. 94% of amphetamine exposed patients had used amphetamine in the previous week. When the (log) VA was regressed against the chronological age (CA) and a substance-type group in both cross-sectional and longitudinal models, models quadratic in CA were superior to linear models (both pamphetamine exposure persisted after adjustment for all known cardiovascular risk factors (pamphetamines is associated with an advancement of cardiovascular-organismal age both over age and over time, and is robust to adjustment. That this is associated with power functions of age implies a feed-forward positively reinforcing exacerbation of the underlying ageing process. PMID:28243315

  13. Reduced quality and accelerated follicle loss with female reproductive aging - does decline in theca dehydroepiandrosterone (DHEA) underlie the problem?

    Science.gov (United States)

    Ford, Judith H

    2013-12-13

    Infertility, spontaneous abortion and conception of trisomic offspring increase exponentially with age in mammals but in women there is an apparent acceleration in the rate from about age 37. The problems mostly commonly occur when the ovarian pool of follicles is depleted to a critical level with age but are also found in low follicular reserve of other etiologies. Since recent clinical studies have indicated that dehydroepiandrosterone (DHEA) supplementation may reverse the problem of oocyte quality, this review of the literature was undertaken in an attempt to find an explanation of why this is effective? In affected ovaries, oxygenation of follicular fluid is low, ultrastructural disturbances especially of mitochondria, occur in granulosa cells and oocytes, and considerable disturbances of meiosis occur. There is, however, no evidence to date that primordial follicles are compromised. In females with normal fertility, pre-antral ovarian theca cells respond to stimulation by inhibin B to provide androgen-based support for the developing follicle. With depletion of follicle numbers, inhibin B is reduced with consequent reduction in theca DHEA. Theca cells are the sole ovarian site of synthesis of DHEA, which is both a precursor of androstenedione and an essential ligand for peroxisome proliferator-activated receptor alpha (PPARα), the key promoter of genes affecting fatty acid metabolism and fat transport and genes critical to mitochondrial function. As well as inducing a plethora of deleterious changes in follicular cytoplasmic structure and function, the omega 9 palmitate/oleate ratio is increased by lowered activity of PPARα. This provides conditions for increased ceramide synthesis and follicular loss through ceramide-induced apoptosis is accelerated. In humans critical theca DHEA synthesis occurs at about 70 days prior to ovulation thus effective supplementation needs to be undertaken about four months prior to intended conception; timing which is also

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

    Directory of Open Access Journals (Sweden)

    Giulio Valenti

    Full Text Available 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.

  15. Contemporary views on human aging and longevity

    Directory of Open Access Journals (Sweden)

    Chmielewski Piotr

    2016-06-01

    Full Text Available Aging is currently stimulating intense interest of both researchers and the general public. In developed countries, the average life expectancy has increased by roughly 30 years within the last century, and human senescence has been delayed by around a decade. Although aging is arguably the most familiar aspect of human biology, its proximate and ultimate causes have not been elucidated fully and understood yet. Nowadays there are two main approaches to the ultimate causes of aging. These are deterministic and stochastic models. The proximate theories constitute a distinct group of explanations. They focus on mechanistic causes of aging. In this view, there is no reason to believe that there is only one biological mechanism responsible for aging. The aging process is highly complex and results from an accumulation of random molecular damage. Currently, the disposable soma theory (DST, proposed by Thomas Kirkwood, is the most influential and coherent line of reasoning in biogerontology. This model does not postulate any particular mechanism underpinning somatic defense. Therefore, it is compatible with various models, including mechanistic and evolutionary explanations. Recently, however, an interesting theory of hyper-function of mTOR as a more direct cause of aging has been formulated by Mikhail Blagosklonny, offering an entirely different approach to numerous problems and paradoxes in current biogerontology. In this view, aging is quasi-programmed, which means that it is an aimless continuation of developmental growth. This mTOR-centric model allows the prediction of completely new relationships. The aim of this article is to present and compare the views of both parties in the dispute, based on the results of some recent experimental studies, and the contemporary knowledge of selected major aspects of human aging and longevity

  16. Models of Accelerated Sarcopenia: Critical Pieces for Solving the Puzzle of Age-Related Muscle Atrophy

    Science.gov (United States)

    Buford, Thomas W.; Anton, Stephen D.; Judge, Andrew R.; Marzetti, Emanuele; Wohlgemuth, Stephanie E; Carter, Christy S.; Leeuwenburgh, Christiaan; Pahor, Marco; Manini, Todd M.

    2013-01-01

    Sarcopenia, the age-related loss of skeletal muscle mass, is a significant public health concern that continues to grow in relevance as the population ages. Certain conditions have the strong potential to coincide with sarcopenia to accelerate the progression of muscle atrophy in older adults. Among these conditions are co-morbid diseases common to older individuals such as cancer, kidney disease, diabetes, and peripheral artery disease. Furthermore, behaviors such as poor nutrition and physical inactivity are well-known to contribute to sarcopenia development. However, we argue that these behaviors are not inherent to the development of sarcopenia but rather accelerate its progression. In the present review, we discuss how these factors affect systemic and cellular mechanisms that contribute to skeletal muscle atrophy. In addition, we describe gaps in the literature concerning the role of these factors in accelerating sarcopenia progression. Elucidating biochemical pathways related to accelerated muscle atrophy may allow for improved discovery of therapeutic treatments related to sarcopenia. PMID:20438881

  17. Hypotension during endotoxemia in aged humans

    DEFF Research Database (Denmark)

    Krabbe, Karen Suarez; Kemp, Helle Bruunsgaard; Qvist, Jesper

    2001-01-01

    BACKGROUND: and objective The aim of this study was to determine possible age-associated differences in human blood pressure regulation during an immunological challenge in healthy subjects. METHODS: Eight healthy young volunteers (median age 24 yr) and nine healthy elderly volunteers (median age....... Increased plasma epinephrine concentrations were found 2-3 h after endotoxin administration in both groups. Five hours after the endotoxin challenge, the epinephrine concentration had returned to control values in the elderly group only, in spite of decreased blood pressure. CONCLUSION: In conclusion...

  18. Gamma radiation and magnetic field mediated delay in effect of accelerated ageing of soybean.

    Science.gov (United States)

    Kumar, Mahesh; Singh, Bhupinder; Ahuja, Sumedha; Dahuja, Anil; Anand, Anjali

    2015-08-01

    Soybean seeds were exposed to gamma radiation (0.5, 1, 3 and 5 kGy), static magnetic field (50, 100 and 200 mT) and a combination of gamma radiation and magnetic energy (0.5 kGy + 200 mT and 5 kGy + 50 mT) and stored at room temperature for six months. These seeds were later subjected to accelerated ageing treatment at 42 °C temperature and 95-100 % relative humidity and were compared for various physical and biochemical characteristics between the untreated and the energized treatments. Energy treatment protected the quality of stored seeds in terms of its protein and oil content . Accelerated aging conditions, however, affected the oil and protein quantity and quality of seed negatively. Antioxidant enzymes exhibited a decline in their activity during aging while the LOX activity, which reflects the rate of lipid peroxidation, in general, increased during the aging. Gamma irradiated (3 and 5 kGy) and magnetic field treated seeds (100 and 200 mT) maintained a higher catalase and ascorbate peroxidase activity which may help in efficient scavenging of deleterious free radical produced during the aging. Aging caused peroxidative changes to lipids, which could be contributed to the loss of oil quality. Among the electromagnetic energy treatments, a dose of 1-5 kGy of gamma and 100 mT, 200 mT magnetic field effectively slowed the rate of biochemical degradation and loss of cellular integrity in seeds stored under conditions of accelerated aging and thus, protected the deterioration of seed quality. Energy combination treatments did not yield any additional protection advantage.

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

    Science.gov (United States)

    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.

  20. Effect of Mn doping on electrical properties and accelerated ageing behaviours of ternary ZVM varistors

    Indian Academy of Sciences (India)

    C-W Nahm

    2011-12-01

    The electrical properties and d.c. accelerated ageing behaviour of ZVM (Zn–V–Mn) ceramics were investigated with different valences and contents of Mn. The incorporation of Mn into the ZV ceramics was found to restrict the abnormal grain growth of ZnO. The nonlinear properties and stability against the d.c. accelerated ageing stress are significantly affected by different valences and contents of Mn. The high valence of Mn (Mn4+) in the ZVM ceramics resulted in better nonlinear properties than low valence of Mn (Mn2.66+). Furthermore, an increase in doping level of MnO2 greatly improved its nonlinear properties. The ZVM ceramics doped with 2 mol% MnO2 exhibited not only a high nonlinearity, in which the nonlinear coefficient is 27 and the leakage current density is 0.042 mA/cm2, but also a good stability, in which % 1\\ mA = –2.1%, % = –25.9% for the d.c. accelerated ageing stress of 0.85 1\\ mA/85°C/24 h.

  1. DNA methylation and healthy human aging.

    Science.gov (United States)

    Jones, Meaghan J; Goodman, Sarah J; Kobor, Michael S

    2015-12-01

    The process of aging results in a host of changes at the cellular and molecular levels, which include senescence, telomere shortening, and changes in gene expression. Epigenetic patterns also change over the lifespan, suggesting that epigenetic changes may constitute an important component of the aging process. The epigenetic mark that has been most highly studied is DNA methylation, the presence of methyl groups at CpG dinucleotides. These dinucleotides are often located near gene promoters and associate with gene expression levels. Early studies indicated that global levels of DNA methylation increase over the first few years of life and then decrease beginning in late adulthood. Recently, with the advent of microarray and next-generation sequencing technologies, increases in variability of DNA methylation with age have been observed, and a number of site-specific patterns have been identified. It has also been shown that certain CpG sites are highly associated with age, to the extent that prediction models using a small number of these sites can accurately predict the chronological age of the donor. Together, these observations point to the existence of two phenomena that both contribute to age-related DNA methylation changes: epigenetic drift and the epigenetic clock. In this review, we focus on healthy human aging throughout the lifetime and discuss the dynamics of DNA methylation as well as how interactions between the genome, environment, and the epigenome influence aging rates. We also discuss the impact of determining 'epigenetic age' for human health and outline some important caveats to existing and future studies.

  2. The human ocular torsion position response during yaw angular acceleration.

    Science.gov (United States)

    Smith, S T; Curthoys, I S; Moore, S T

    1995-07-01

    Recent results by Wearne [(1993) Ph.D. thesis] using the scleral search-coil method of measuring eye position indicate that changes in ocular torsion position (OTP) occur during yaw angular acceleration about an earth vertical axis. The present set of experiments, using an image processing method of eye movement measurement free from the possible confound of search coil slippage, demonstrates the generality and repeatability of this phenomenon and examines its possible causes. The change in torsion position is not a linear vestibulo-ocular reflex (LVOR) response to interaural linear acceleration stimulation of the otoliths, but rather the effect is dependent on the characteristics of the angular acceleration stimulus, commencing at the onset and decaying at the offset of the angular acceleration. In the experiments reported here, the magnitude of the angular acceleration stimulus was varied and the torsion position response showed corresponding variations. We consider that the change in torsion position observed during angular acceleration is most likely to be due to activity of the semicircular canals.

  3. Accelerated features of age-related bone loss in zmpste24 metalloproteinase-deficient mice.

    Science.gov (United States)

    Rivas, Daniel; Li, Wei; Akter, Rahima; Henderson, Janet E; Duque, Gustavo

    2009-10-01

    Age-related bone loss is associated with changes in bone cellularity, which include marrow fat infiltration and decreasing levels of osteoblastogenesis. The mechanisms that explain these changes remain unclear. Although nuclear lamina alterations occur in premature aging syndromes that include changes in body fat and severe osteoporosis, the role of proteins of the nuclear lamina in age-related bone loss remains unknown. Using the Zmpste24-null progeroid mice (Zmpste24(-/-)), which exhibit nuclear lamina defects and accumulate unprocessed prelamin A, we identified several alterations in bone cellularity in vivo. We found that defective prelamin A processing induced accelerated features of age-related bone loss including lower osteoblast and osteocyte numbers and higher levels of marrow adipogenesis. In summary, processing of prelamin A could become a new approach to regulate osteoblastogenesis and bone turnover and thus for the prevention and treatment of senile osteoporosis.

  4. Proposition of an Accelerated Ageing Method for Natural Fibre/Polylactic Acid Composite

    Science.gov (United States)

    Zandvliet, Clio; Bandyopadhyay, N. R.; Ray, Dipa

    2015-10-01

    Natural fibre composite based on polylactic acid (PLA) composite is of special interest because it is entirely from renewable resources and biodegradable. Some samples of jute/PLA composite and PLA alone made 6 years ago and kept in tropical climate on a shelf shows too fast ageing degradation. In this work, an accelerated ageing method for natural fibres/PLA composite is proposed and tested. Experiment was carried out with jute and flax fibre/PLA composite. The method was compared with the standard ISO 1037-06a. The residual flexural strength after ageing test was compared with the one of common wood-based panels and of real aged samples prepared 6 years ago.

  5. Service Lifetime Estimation of EPDM Rubber Based on Accelerated Aging Tests

    Science.gov (United States)

    Liu, Jie; Li, Xiangbo; Xu, Likun; He, Tao

    2017-02-01

    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.

  6. Beneficial effects of melatonin on cardiological alterations in a murine model of accelerated aging.

    Science.gov (United States)

    Forman, Katherine; Vara, Elena; García, Cruz; Kireev, Roman; Cuesta, Sara; Acuña-Castroviejo, Darío; Tresguerres, J A F

    2010-10-01

    This study investigated the effect of aging-related parameters such as inflammation, oxidative stress and cell death in the heart in an animal model of accelerated senescence and analyzed the effects of chronic administration of melatonin on these markers. Thirty male mice of senescence-accelerated prone (SAMP8) and 30 senescence-accelerated-resistant mice (SAMR1) at 2 and 10 months of age were used. Animals were divided into eight experimental groups, four from each strain: two young control groups, two old untreated control groups, and four melatonin-treated groups. Melatonin was provided at two different dosages (1 and 10 mg/kg/day) in the drinking water. After 30 days of treatment, the expression of inflammatory mediators (tumor necrosis factor-alpha, interleukin 1 and 10, NFkBp50 and NFkBp52), apoptosis markers (BAD, BAX and Bcl2) and parameters related to oxidative stress (heme oxygenases 1 and 2, endothelial and inducible nitric oxide synthases) were determined in the heart by real-time reverse transcription polymerase chain reaction (RT-PCR). Inflammation, as well as, oxidative stress and apoptosis markers was increased in old SAMP8 males, when compared to its young controls. SAMR1 mice showed significantly lower basal levels of the measured parameters and smaller increases with age or no increases at all. After treatment with melatonin, these age-altered parameters were partially reversed, especially in SAMP8 mice. The results suggest that oxidative stress and inflammation increase with aging and that chronic treatment with melatonin, a potent antioxidant, reduces these parameters. The effects were more marked in the SAMP8 animals. © 2010 The Authors. Journal of Pineal Research © 2010 John Wiley & Sons A/S.

  7. Non-thermal emissions from outer magnetospheric accelerators of middle-aged pulsars

    CERN Document Server

    Takata, J

    2008-01-01

    We discuss $\\gamma$-ray emissions from the outer gap accelerators of middle-aged pulsars for part of the series of our studies. A two-dimensional electrodynamic model is used to solve the distribution of accelerating electric fields with electron and positron pair creation and radiation processes in the magnetic meridional plane. We compute the curvature radiation and the synchrotron radiation by solving the evolution of the Lorentz factor and the pitch angle. The calculated spectra are compared with observed phase-averaged spectra. We also use a three-dimensional geometrical model to discuss the pulse profiles. We argue that the outer gap of middle-aged pulsars occupies the whole region between the last-open field lines and the critical magnetic field lines, which are perpendicular to the rotational axis at the light cylinder. We assume that there is no outer gap accelerator inside the light cylinder between the rotational axis and the critical magnetic field lines. For the Geminga pulsar, we demonstrate tha...

  8. Time dependent diffusive shock acceleration and its application to middle aged supernova remnants

    CERN Document Server

    Tang, Xiaping

    2016-01-01

    Recent gamma-ray observations show that middle aged supernova remnants (SNRs) interacting with molecular clouds (MCs) can be sources of both GeV and TeV emission. Based on the MC association, two scenarios have been proposed to explain the observed gamma-ray emission. In one, energetic cosmic ray (CR) particles escape from the SNR and then illuminate nearby MCs, producing gamma-ray emission, while the other involves direct interaction between the SNR and MC. In the direct interaction scenario, re-acceleration of pre-existing CRs in the ambient medium is investigated while particles injected from the thermal pool are neglected in view of the slow shock speeds in middle aged SNRs. However, standard diffusive shock acceleration (DSA) theory produces a steady state particle spectrum that is too flat compared to observations, which suggests that the high energy part of the observed spectrum has not yet reached a steady state. We derive a time dependent DSA solution in the test particle limit for re-acceleration of...

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

    Directory of Open Access Journals (Sweden)

    Herman Mansur

    2009-05-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  11. Effects of different polishing methods on color stability of resin composites after accelerated aging.

    Science.gov (United States)

    Sirin Karaarslan, Emine; Bulbul, Mehmet; Yildiz, Esma; Secilmis, Asli; Sari, Fatih; Usumez, Aslihan

    2013-01-01

    The purpose of this study was to evaluate the effect of polishing procedures on the color stability of different types of composites after aging. Forty disk-shaped specimens (Ø10×2 mm) were prepared for each composite resin type (an ormocer, a packable, a nanohybrid, and a microhybrid) for a total of 160 specimens. Each composite group was divided into four subgroups according to polishing method (n=10): control (no finishing and polishing), polishing disk, polishing wheel, and glaze material. Color parameters (L*, a*, and b*) and surface roughness were measured before and after accelerated aging. Of the polishing methods, glazed specimens showed the lowest color change (∆E*), ∆L*, and ∆b* values (p<0.05). Of the composite resins, the microhybrid composite showed the lowest ∆E* value, whereas the ormocer showed the highest (p<0.05). For all composite types, the surface roughness of their control groups decreased after aging (p<0.05). In conclusion, all composite resins showed color changes after accelerated aging, with the use of glaze material resulting in the lowest color change.

  12. Applying the LLTM for the determination of children’s cognitive age-acceleration function

    Directory of Open Access Journals (Sweden)

    Klaus D. Kubinger

    2011-06-01

    Full Text Available The paper uses Item Response Theory (IRT for modeling and hypothesis testing children’s cogni-tive age-acceleration function – within calibration and standardization of some intelligence test. For this, basically Fischer’s Linear logistic test model (LLTM; Fischer, 1973, 2005 is applied. How-ever, instead of originally decomposing the item difficulty parameters of the Rasch model into certain hypothesized elementary parameters, we now suggest to decompose the person parameter alike. That is, there is a decomposition into a testee’s basic ability parameter and an age-leveled effect due to the developmental stage of the age-group in question. For convenience, we only inter-change testees and items in order to facilitate parameter estimation and model test – of course, the Rasch model is totally symmetric as concerns testees and items. By doing so, all findings in the context of LLTM apply; in particular, pertinent program packages are at our disposal. In order to examine the suggested approach’s feasibility, an empirical example is given. An Analogy test with eight items administered to more than 300 testees aged between 6 and 16, was analyzed. As a matter of fact, the logistic acceleration function proved to fit the data well and best.

  13. Effect of energy density on color stability in dental resin composites under accelerated aging.

    Science.gov (United States)

    Zamarripa, Eliezer; Ancona, Adriana L; D'Accorso, Norma B; Macchi, Ricardo L; Abate, Pablo F

    2008-01-01

    The effects of the energy density that is used for polymerization on properties of dental resin composites are well known. However, few studies relate color stability to this factor. The aim of this study was to assess color changes (deltaE*), in vitro, in terms of accelerated aging under UV exposure of specimens prepared with different energy densities. Four commercial dental resin composites were included in the study. Thirty six specimens were prepared for each one of them, following the procedure established by ISO 4049 Standard, and assigned to three groups: A (3.75 J/cm2), B (9 J/cm2), C (24 J/cm2). Each group was further subdivided into four subgroups: 1 (no aging), 2 (500 hours aging), 3 (1000 hours aging) and 4 (1500 hours aging). The results were analyzed by means of ANOVA and Tukey's test (alpha = 0.05) to determine the effect of the factors. Correlation was performed in order to determine the possible relationship among variables. Energy density is not a significant factor in color stability. However aging is directly proportional to color changes. deltaE* depends on filler size; hybrid material presented deltaE* of 2.1(0.5), 2.4(0.6) and 3.3(0.3) at 500, 1000 and 1500 hours of accelerated aging respectively, and nanofilled material showed deltaE* of 3.0(0.6), 4.5(1.2) and 5.9(0.6) at the same times respectively. It can be concluded that deltaE* does not depend on energy density; however other factors are involved in color change. Further studies in this area are warranted.

  14. Two-Step Acceleration Model of Cosmic Rays at Middle-Aged SNR

    CERN Document Server

    Inoue, Tsuyoshi; Inutsuka, Shu-ichiro

    2010-01-01

    Recent gamma-ray observations of middle-aged supernova remnants revealed a mysterious broken power-law spectrum. Using three-dimensional magnetohydrodynamics simulations, we show that the interaction between a supernova blast wave and interstellar clouds formed by thermal instability generates multiple reflected shocks. The typical Mach numbers of the reflected shocks are shown to be M ~ 2 depending on the density contrast between the diffuse intercloud gas and clouds. These secondary shocks can further energize cosmic-ray particles originally accelerated at the blast-wave shock. This "two-step" acceleration scenario reproduces the observed gamma-ray spectrum and predicts the high-energy spectral index ranging approximately from 3 to 4.

  15. Biomarkers related to aging in human populations.

    Science.gov (United States)

    Crimmins, Eileen; Vasunilashorn, Sarinnapha; Kim, Jung Ki; Alley, Dawn

    2008-01-01

    Biomarkers are increasingly employed in empirical studies of human populations to understand physiological processes that change with age, diseases whose onset appears linked to age, and the aging process itself. In this chapter, we describe some of the most commonly used biomarkers in population aging research, including their collection, associations with other markers, and relationships to health outcomes. We discuss biomarkers of the cardiovascular system, metabolic processes, inflammation, activity in the hypothalamic-pituitary axis (HPA) and sympathetic nervous system (SNS), and organ functioning (including kidney, lung, and heart). In addition, we note that markers of functioning of the central nervous system and genetic markers are now becoming part of population measurement. Where possible, we detail interrelationships between these markers by providing correlations between high risk levels of each marker from three population-based surveys: the National Health and Nutrition Examination Survey (NHANES) III, NHANES 1999-2002, and the MacArthur Study of Successful Aging. NHANES III is used instead of NHANES 1999-2002 when specific markers of interest are available only in NHANES III and when we examine the relationship of biomarkers to mortality which is only known for NHANES III. We also describe summary measures combining biomarkers across systems. Finally, we examine associations between individual markers and mortality and provide information about biomarkers of growing interest for future research in population aging and health.

  16. Age changes in human bone: an overview

    Energy Technology Data Exchange (ETDEWEB)

    Sharpe, W.D.

    1977-12-03

    The human skeleton steadily changes structure and mass during life because of a variety of internal and external factors. Extracellular substance and bone cells get old, characteristic structural remodeling occurs with age and these age-related changes are important in the discrimination between pathological and physiological changes. Perhaps 20 percent of the bone mass is lost between the fourth and the ninth decades, osteoblasts function less efficiently and gradual loss of bone substance is enhanced by delayed mineralization of an increased surface area of thin and relatively less active osteoid seams. After the fifth decade, osteoclasia and the number of Howship's lacunae increase, and with age, the number of large osteolytic osteocytes increases as the number of small osteocytes declines and empty osteocyte lacunae become more common. The result is greater liability to fracture and diminished healing or replacement of injured bone.

  17. The Age of Human Cerebral Cortex Neurons

    Energy Technology Data Exchange (ETDEWEB)

    Bhardwaj, R D; Curtis, M A; Spalding, K L; Buchholz, B A; Fink, D; Bjork-Eriksson, T; Nordborg, C; Gage, F H; Druid, H; Eriksson, P S; Frisen, J

    2006-04-06

    The traditional static view of the adult mammalian brain has been challenged by the realization of continuous generation of neurons from stem cells. Based mainly on studies in experimental animals, adult neurogenesis may contribute to recovery after brain insults and decreased neurogenesis has been implicated in the pathogenesis of neurological and psychiatric diseases in man. The extent of neurogenesis in the adult human brain has, however, been difficult to establish. We have taken advantage of the integration of {sup 14}C, generated by nuclear bomb tests during the Cold War, in DNA to establish the age of neurons in the major areas of the human cerebral cortex. Together with the analysis of the cortex from patients who received BrdU, which integrates in the DNA of dividing cells, our results demonstrate that whereas non-neuronal cells turn over, neurons in the human cerebral cortex are not generated postnatally at detectable levels, but are as old as the individual.

  18. Anticedants and natural prevention of environmental toxicants induced accelerated aging of skin.

    Science.gov (United States)

    Tanuja Yadav; Mishra, Shivangi; Das, Shefali; Aggarwal, Shikha; Rani, Vibha

    2015-01-01

    Skin is frequently exposed to a variety of environmental and chemical agents that accelerate ageing. External stress such as UV radiations (UVR) and environmental pollutants majorly deteriorate the skin morphology, by activating certain intrinsic factors such as Reactive Oxygen Species (ROS) which trigger the activation of Matrix Metalloproteinases (MMPs) and inflammatory responses hence damaging the extracellular matrix (ECM) components. To counter this, an exogenous supply of anti-oxidants, is required since the endogenous anti-oxidant system cannot alone suffice the need. Bio-prospecting of natural resources for anti-oxidants has hence been intensified. Immense research is being carried out to identify potential plants with potent anti-oxidant activity against skin ageing. This review summarizes the major factors responsible for premature skin ageing and the plants being targeted to lessen the impact of those.

  19. Accelerated aging of melon seeds Envelhecimento acelerado em sementes de melão

    Directory of Open Access Journals (Sweden)

    Salvador Barros Torres

    2003-02-01

    Full Text Available Accelerated aging is one of the most useful tests used for the evaluation of seed vigor but it is seldomly used to test melon (Cucumis melo L. seeds. The objective this research was to compare different procedures of the accelerated aging test to evaluate the physiological quality of melon seeds and the efficiency of using saturated salt solution for the control of water uptake by seeds. Five seed lots each of the hybrids AF-646 and AF-682 were tested for germination, seedling emergence, traditional accelerated aging (periods 0f 48, 72 and 96 hours, at 38 or 41°C and salt saturated accelerated aging. The accelerated aging test (traditional procedure and with salt solution for 72h and 96h, at 38 or 41°C was sensitive to detect differences in the physiological quality of the seeds. It was also observed that the seed water content after salt saturated accelerated aging was lower and more uniform, thus presenting advantagens in relation to the traditional procedure.O teste de envelhecimento acelerado é um dos mais utilizados para a avaliação do potencial fisiológico das sementes de várias espécies. Entretanto, estudos com sementes de melão ainda são escassos. Avaliou-se procedimentos para a condução do teste de envelhecimento acelerado para avaliação do potencial fisiológico de sementes de melão (Cucumis melo L., incluindo o uso de solução saturada de sal em substituição à água. Cinco lotes de sementes, dos híbridos AF-646 e AF-682, foram submetidos aos testes de germinação, emergência de plântulas em casa de vegetação e envelhecimento acelerado (períodos de 48, 72 ou 96 horas, a 38 ou 41°C, com e sem o uso de solução saturada de NaCl. O teste de envelhecimento acelerado (procedimento tradicional e com solução salina, conduzido com períodos de exposição de 72h e 96h a 38 ou 41°C, apresentou sensibilidade suficiente para detectar diferenças no potencial fisiológico de lotes de sementes de melão. A utiliza

  20. Investigations of Accelerated Climate Aged Wood Substrates by Fourier Transform Infrared Material Characterization

    Directory of Open Access Journals (Sweden)

    Bjørn Petter Jelle

    2012-01-01

    Full Text Available Fourier transform infrared (FTIR material characterization by applying the attenuated total reflectance (ATR experimental technique represents a powerful measurement tool. The ATR technique may be applied on both solid state materials, liquids and gases with none or only minor sample preparations, also including materials which are nontransparent to infrared radiation. This facilitation is made possible by pressing the sample directly onto various crystals, for example, diamond, with high refractive indices, in a special reflectance setup. Materials undergoing ageing processes by natural and accelerated climate exposure, decomposition and formation of chemical bonds and products, may be studied in an ATR-FTIR analysis. In this work, the ATR-FTIR technique is utilized to detect changes in selected wood building material substrates subjected to accelerated climate exposure conditions. Changes in specific FTIR absorbance peaks are designated to different wood deterioration processes. One aim is by ATR-FTIR analysis to be able to quantitatively determine the length of the wood ageing time before priming/treatment. Climate parameters like temperature (including freezing/thawing, relative air humidity, wind driven rain amount, solar and/or ultraviolet radiation, and exposure duration may be controlled in different climate ageing apparatuses. Both impregnated and raw wood samples have been employed in the experimental investigations.

  1. Evaluating Period of Accelerated Skeletal Maturation in Gujarati Children between Ages 8+ and 14+ Years

    Directory of Open Access Journals (Sweden)

    Amarjit Singh Bhatia

    2012-01-01

    Aims and objective: In the present study, an attempt was made to assess the level of skeletal maturation and period of accelerated growth in 70 boys and 70 girls between the ages (8+ and (14+ years using CVMS index. Materials and methods: Lateral cephalogram of 140 individuals were selected, i.e. 70 girls and 70 boys, each of age group from 8+ to 14+ years. It is observed that CVMS index used is highly significant for this purpose. It is observed that this index is highly effective for this purpose. Conclusion: Females′ vertebrae mature earlier than males at each stage. The maturation rate is not constant between the various stages and period of accelerated growth is experienced at different ages and levels in males and females. Need arises to confirm that early maturation in females is not because of their smaller sized vertebra. Further, the time duration recorded between the two subsequent stages is different not because the changes required to be done by nature is different. Longitudinal growth studies of the jaws proper are desired to be conducted for this purpose.

  2. Envelhecimento acelerado em sementes de alface Accelerated aging in lettuce seeds

    Directory of Open Access Journals (Sweden)

    Rafael Marani Barbosa

    2011-11-01

    Full Text Available Objetivou-se adequar a metodologia do teste de envelhecimento acelerado para avaliação do potencial fisiológico de sementes de quatro lotes dos genótipos de alface 'Babá de verão', 'Tainá' e 'Vera', aplicando-se o método tradicional e com o uso de solução saturada de NaCl. Para tal, as sementes foram submetidas à determinação do teor de água, testes de germinação e vigor (primeira contagem, condutividade elétrica, emergência em bandeja, índice de velocidade de emergência incluindo o teste de envelhecimento acelerado, conduzido nos períodos de 24, 48, e 72 horas, a 41°C com e sem solução saturada de NaCl. O experimento foi conduzido em delineamento inteiramente casualizado com quatro repetições. Os procedimentos tradicional e com o uso da solução saturada de NaCl por 72 horas foram sensíveis em estratificar os lotes em níveis de vigor, além de estarem de acordo com os demais testes utilizados. Portanto, o envelhecimento acelerado de sementes de alface deve ser feito utilizando o período de 72 horas, podendo ser realizado tanto pelo método tradicional quanto pelo método da solução saturada de NaCl.The objective was to adapt the methodology of the accelerated aging test to evaluate the physiological potential of seeds of four lots of lettuce genotypes 'Babá de verão', 'Tainá' and 'Vera' applying the traditional method and using a saturated NaCl solution. So, the seeds were subjected to determination of water content, seed germination and vigor (first count, electrical conductivity, speed emergency index, emergency tray including the accelerated aging test conducted in periods of 24, 48, 72 hours at 41°C with and without saturated solution of NaCl. The experiment was conducted in a randomized design with four replications. The accelerated aging traditional and saturated solution of NaCl by 72h was more sensitive to stratify the lots in vigor levels. Therefore, accelerated aging of seeds of lettuce should be

  3. Psychiatric Disorders, Morbidity, and Mortality: Tracing Mechanistic Pathways to Accelerated Aging.

    Science.gov (United States)

    Kiecolt-Glaser, Janice K; Wilson, Stephanie J

    2016-09-01

    A meta-analysis published in this issue of Psychosomatic Medicine provides convincing evidence that certain psychiatric populations have shorter telomeres than nonpsychiatric controls, in accord with the strong evidence linking psychiatric disorders with premature mortality. After addressing the clinical significance of shorter telomeres, this editorial describes mechanistic pathways that lead to telomere shortening. Additionally, two other novel methods for measuring biological markers of accelerated aging are briefly discussed: DNA methylation and cellular senescence based on p16. These innovative approaches could be used to confirm and extend our understanding of psychiatric patients' increased health and mortality risks.

  4. Acceleration of age-associated methylation patterns in HIV-1-infected adults.

    Directory of Open Access Journals (Sweden)

    Tammy M Rickabaugh

    Full Text Available Patients with treated HIV-1-infection experience earlier occurrence of aging-associated diseases, raising speculation that HIV-1-infection, or antiretroviral treatment, may accelerate aging. We recently described an age-related co-methylation module comprised of hundreds of CpGs; however, it is unknown whether aging and HIV-1-infection exert negative health effects through similar, or disparate, mechanisms. We investigated whether HIV-1-infection would induce age-associated methylation changes. We evaluated DNA methylation levels at >450,000 CpG sites in peripheral blood mononuclear cells (PBMC of young (20-35 and older (36-56 adults in two separate groups of participants. Each age group for each data set consisted of 12 HIV-1-infected and 12 age-matched HIV-1-uninfected samples for a total of 96 samples. The effects of age and HIV-1 infection on methylation at each CpG revealed a strong correlation of 0.49, p<1 x 10(-200 and 0.47, p<1 x 10(-200. Weighted gene correlation network analysis (WGCNA identified 17 co-methylation modules; module 3 (ME3 was significantly correlated with age (cor=0.70 and HIV-1 status (cor=0.31. Older HIV-1+ individuals had a greater number of hypermethylated CpGs across ME3 (p=0.015. In a multivariate model, ME3 was significantly associated with age and HIV status (Data set 1: βage=0.007088, p=2.08 x 10(-9; βHIV=0.099574, p=0.0011; Data set 2: βage=0.008762, p=1.27 x 10(-5; βHIV=0.128649, p=0.0001. Using this model, we estimate that HIV-1 infection accelerates age-related methylation by approximately 13.7 years in data set 1 and 14.7 years in data set 2. The genes related to CpGs in ME3 are enriched for polycomb group target genes known to be involved in cell renewal and aging. The overlap between ME3 and an aging methylation module found in solid tissues is also highly significant (Fisher-exact p=5.6 x 10(-6, odds ratio=1.91. These data demonstrate that HIV-1 infection is associated with methylation patterns that

  5. Effect of accelerated environmental aging on tensile properties of oil palm/jute hybrid composites

    Science.gov (United States)

    Jawaid, M.; Saba, N.; Alothman, O.; Paridah, M. T.

    2016-11-01

    Recently natural fibre based hybrid composites are receiving growing consideration due to environmental and biodegradability properties. In order to look behaviour of hybrid composites in outdoor applications, its environmental degradation properties such as UV accelerated weathering properties need to analyze. In this study oil palm empty fruit bunch (EFB) and jute fibres reinforced hybrid composites, pure EFB, pure jute and epoxy composites were fabricated through hand lay-up techniques. Hybrid composites with different layering pattern (EFB/jute/EFB and Jute/EFB/jute) while maintaining 40 wt. % total fibre loading were fabricates to compared with EFB and jute composites. Effect of UV accelerated environmental aging on tensile properties of epoxy, pure EFB, pure jute, and hybrid composites were assessed and evaluate under UV exposure. Tensile samples of all composites were subjected to accelerated weathering for 100h, at temperature (75°C), relative humidity (35%), Light (125 W/m2), and water spray off. Obtained results indicated that there is reduction in tensile strength, modulus and elongation at break values of hybrid and pure composites due to degradation of lignin and fibre-matrix interfacial bonding.

  6. Wet climate and transportation routes accelerate spread of human plague

    Science.gov (United States)

    Xu, Lei; Stige, Leif Chr.; Kausrud, Kyrre Linné; Ben Ari, Tamara; Wang, Shuchun; Fang, Xiye; Schmid, Boris V.; Liu, Qiyong; Stenseth, Nils Chr.; Zhang, Zhibin

    2014-01-01

    Currently, large-scale transmissions of infectious diseases are becoming more closely associated with accelerated globalization and climate change, but quantitative analyses are still rare. By using an extensive dataset consisting of date and location of cases for the third plague pandemic from 1772 to 1964 in China and a novel method (nearest neighbour approach) which deals with both short- and long-distance transmissions, we found the presence of major roads, rivers and coastline accelerated the spread of plague and shaped the transmission patterns. We found that plague spread velocity was positively associated with wet conditions (measured by an index of drought and flood events) in China, probably due to flood-driven transmission by people or rodents. Our study provides new insights on transmission patterns and possible mechanisms behind variability in transmission speed, with implications for prevention and control measures. The methodology may also be applicable to studies of disease dynamics or species movement in other systems. PMID:24523275

  7. Bitter taste receptor polymorphisms and human aging.

    Directory of Open Access Journals (Sweden)

    Daniele Campa

    Full Text Available Several studies have shown that genetic factors account for 25% of the variation in human life span. On the basis of published molecular, genetic and epidemiological data, we hypothesized that genetic polymorphisms of taste receptors, which modulate food preferences but are also expressed in a number of organs and regulate food absorption processing and metabolism, could modulate the aging process. Using a tagging approach, we investigated the possible associations between longevity and the common genetic variation at the three bitter taste receptor gene clusters on chromosomes 5, 7 and 12 in a population of 941 individuals ranging in age from 20 to 106 years from the South of Italy. We found that one polymorphism, rs978739, situated 212 bp upstream of the TAS2R16 gene, shows a statistically significant association (p = 0.001 with longevity. In particular, the frequency of A/A homozygotes increases gradually from 35% in subjects aged 20 to 70 up to 55% in centenarians. These data provide suggestive evidence on the possible correlation between human longevity and taste genetics.

  8. Chronological ageing of human hair keratin fibres.

    Science.gov (United States)

    Thibaut, S; de Becker, E; Bernard, B A; Huart, M; Fiat, F; Baghdadli, N; Luengo, G S; Leroy, F; Angevin, P; Kermoal, A M; Muller, S; Peron, M; Provot, G; Kravtchenko, S; Saint-Léger, D; Desbois, G; Gauchet, L; Nowbuth, K; Galliano, A; Kempf, J Y; Silberzan, I

    2010-12-01

    Examination of very long hair (length > 2.4 m) using a large range of evaluation methods including physical, chemical, biochemical and microscopic techniques has enabled to attain a detailed understanding of natural ageing of human hair keratin fibres. Scrutinizing hair that has undergone little or no oxidative aggression--because of the absence of action of chemical agents such as bleaching or dyeing--from the root to the tip shows the deterioration process, which gradually takes place from the outside to the inside of the hair shaft: first, a progressive abrasion of the cuticle, whilst the cortex structure remains unaltered, is evidenced along a length of roughly 1 m onwards together with constant shine, hydrophobicity and friction characteristics. Further along the fibre, a significant damage to cuticle scales occurs, which correlates well with ceramides and 18-Methyl Eicosanoic Acid (18-MEA) decline, and progressive decrease in keratin-associated protein content. Most physical descriptors of mechanical and optical properties decay significantly. This detailed description of natural ageing of human hair fibres by a fine analysis of hair components and physical parameters in relationship with cosmetic characteristics provides a time-dependent 'damage scale' of human hair, which may help in designing new targeted hair care formulations.

  9. Melatonin can improve insulin resistance and aging-induced pancreas alterations in senescence-accelerated prone male mice (SAMP8)

    OpenAIRE

    Cuesta, Sara; Kireev, Roman; García, Cruz; Rancan, Lisa; Vara, Elena; Jesús A. F. Tresguerres

    2012-01-01

    The aim of the present study was to investigate the effect of aging on several parameters related to glucose homeostasis and insulin resistance in pancreas and how melatonin administration could affect these parameters. Pancreas samples were obtained from two types of male mice models: senescence-accelerated prone (SAMP8) and senescence-accelerated-resistant mice (SAMR1). Insulin levels in plasma were increased with aging in both SAMP8 and SAMR1 mice, whereas insulin content in pancreas was d...

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

    Science.gov (United States)

    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.

  11. Presbyopia - a maverick of human aging.

    Science.gov (United States)

    Pierścionek, B K; Weale, R A

    1995-01-01

    The aim of this study was to examine the extent to which the age-related variations of properties of the human lens may be able to account for presbyopia. Dimensionless linear regressions were calculated for age-related biological functions with special reference to ocular and lenticular ones. Their intercepts on the x-(age-)axis are compared, and their distribution is analyzed. An analysis was made of the effect of the growth of the lens on the relation between its shape and the proximal zonular anchorages on the one hand and the age-related variation of the angle between the zonule and the equatorial plane of the lens. The lens is not unusual in seeming to have evolved in support of a life-span of about 120 years. Presbyopia, however, fails to fit into the general picture and this is hypothesized to result from lenticular growth and a combination of factors which are not all governed by senescence. The potential involvement of the root of the iris throws an interesting light on the apparently worldwide variation of the condition.

  12. Investigations into the Degradation of PTFE Surface Properties by Accelerated Aging Tests

    Directory of Open Access Journals (Sweden)

    C. Fragassa

    2016-06-01

    Full Text Available This paper describes an accelerate aging procedure used for investigating the surface alteration of PTFE gaskets commercialized by two alternative producers. These gaskets are installed in modern process plants where tires moulds are cleaned inside a multistage ultrasonic process. The surface of gaskets degrades inexplicably under ordinary operative conditions after a relatively short period. Even if these gaskets are exposed to a combination of ultrasonic waves, temperature, humidity and acid attack, the PTFE properties of resistance nominally exclude the possibility of severe erosion phenomena as highlighted during the real utilization. A possible explanation could be represented by the presence of unexpected chemical compounds emerging from the disaggregation of highly reacting elements from the tire composition. In particular, it is believed that the unpredicted combination of fluorides and chlorides could explain the violent chemical attack highlighted on steel tanks and on their gaskets. But no evidence exists. Thus, the experimental characterization of PTFE properties has to follow an appropriate accelerated aging, aiming at actuating the specific mechanics of wearing as in industrial use.

  13. Validation of accelerated ageing of Thales rotary Stirling cryocoolers for the estimation of MTTF

    Science.gov (United States)

    Seguineau, C.,; Cauquil, J.-M.; Martin, J.-Y.; Benschop, T.

    2016-05-01

    The cooled IR detectors are used in a wide range of applications. Most of the time, the cryocoolers are one of the components dimensioning the lifetime of the system. The current market needs tend to reliability figures higher than 15,000hrs in "standard conditions". Field returns are hardly useable mostly because of the uncertain environmental conditions of use, or the differences in user profiles. A previous paper explains how Thales Cryogenics has developed an approach based on accelerated ageing and statistical analysis [1]. The aim of the current paper is to compare results obtained on accelerated ageing on one side, and on the other side, specific field returns where the conditions of use are well known. The comparison between prediction and effective failure rate is discussed. Moreover, a specific focus is done on how some new applications of cryocoolers (continuous operation at a specific temperature) can increase the MTTF. Some assumptions are also exposed on how the failure modes, effects and criticality analysis evolves for continuous operation at a specific temperature and compared to experimental data.

  14. Macrophage Response to UHMWPE Submitted to Accelerated Ageing in Hydrogen Peroxide

    Science.gov (United States)

    Rocha, Magda F.G.; Mansur, Alexandra A.P.; Martins, Camila P.S.; Barbosa-Stancioli, Edel F.; Mansur, Herman S.

    2010-01-01

    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 properties to extend the longevity of knee prostheses. The present study investigated the accelerated ageing of UHMWPE in hydrogen peroxide highly oxidative chemical environment. The sliced samples of UHMWPE were oxidized in a hydrogen peroxide solution for 120 days with their total level of oxidation (Iox) characterized by Fourier Transformed Infrared Spectroscopy (FTIR). The potential inflammatory response, cell viability and biocompatibility of such oxidized UHMWPE systems were assessed by a novel biological in vitro assay based on the secretion of nitric oxide (NO) by activated murine macrophages with gamma interferon (IFN-γ) cytokine and lipopolysaccharide (LPS). Furthermore, macrophage morphologies in contact with UHMWPE oxidized surfaces were analyzed by cell spreading-adhesion procedure using scanning electron microscopy (SEM). The results have given significant evidence that the longer the period of accelerated aging of UHMWPE the higher was the macrophage inflammatory equivalent response based on NO secretion analysis. PMID:20721321

  15. Analysis of Samples Treated by Resistance Test Method Exposed to Accelerated Aging

    Directory of Open Access Journals (Sweden)

    Irena Bates

    2015-09-01

    Full Text Available Global awareness that packaging has to be fully adequate and of high quality, is gradually increasing. That is why printing inks and substrates, which have no detrimental effect on packed products, should be considered a compulsory precondition for food and tobacco packaging. Printing inks that have been developed in the recent years, especially for food and tobacco packaging, have low-odour and low migration into the printing substrate during the drying process. Their migration into the printing substrate is within the acceptable limits and has no detrimental effect in terms of food safety. Another extremely important element of prints in high quality food and tobacco packaging is their stability, as they have to be resistant to liquids and chemicals, which are a part of packed product. The selection of an appropriate printing substrate is also extremely relevant, since the interaction of substrate with printing inks should have zero effect on the packed product and should not change the physical appearance of packaging. This paper presents the results of analysing the stability of laboratory samples printed with low-migration inks, observed immediately after the printing (unaged and two treatments of accelerated aging. The accelerated aging of prints was conducted in order to simulate conditions in which food and tobacco packaging can be found due to the prolonged indoors storage. The stability of prints was analysed based on optical characteristics by observing the prints’ relative reflectance curves.

  16. The signaling pathways by which the Fas/FasL system accelerates oocyte aging.

    Science.gov (United States)

    Zhu, Jiang; Lin, Fei-Hu; Zhang, Jie; Lin, Juan; Li, Hong; Li, You-Wei; Tan, Xiu-Wen; Tan, Jing-He

    2016-02-01

    In spite of great efforts, the mechanisms for postovulatory oocyte aging are not fully understood. Although our previous work showed that the FasL/Fas signaling facilitated oocyte aging, the intra-oocyte signaling pathways are unknown. Furthermore, the mechanisms by which oxidative stress facilitates oocyte aging and the causal relationship between Ca2+ rises and caspase-3 activation and between the cell cycle and apoptosis during oocyte aging need detailed investigations. Our aim was to address these issues by studying the intra-oocyte signaling pathways for Fas/FasL to accelerate oocyte aging. The results indicated that sFasL released by cumulus cells activated Fas on the oocyte by increasing reactive oxygen species via activating NADPH oxidase. The activated Fas triggered Ca2+ release from the endoplasmic reticulum by activating phospholipase C-γ pathway and cytochrome c pathway. The cytoplasmic Ca2+ rises activated calcium/calmodulin-dependent protein kinase II (CaMKII) and caspase-3. While activated CaMKII increased oocyte susceptibility to activation by inactivating maturation-promoting factor (MPF) through cyclin B degradation, the activated caspase-3 facilitated further Ca2+releasing that activates more caspase-3 leading to oocyte fragmentation. Furthermore, caspase-3 activation and fragmentation were prevented in oocytes with a high MPF activity, suggesting that an oocyte must be in interphase to undergo apoptosis.

  17. TECHNOLOGY AND INNOVATION IN HUMAN ACTIVITY OF THE INFORMATION AGE: INFORMATION CHALLENGES AND TECHNOLOGIES

    Directory of Open Access Journals (Sweden)

    Oleksandr Yu. Burov

    2015-10-01

    Full Text Available It is discussed the role of technology development, especially in connection with social transformation and transition of humanity to the era of information/knowledge, analyzed the trend accelerating technological change and its relation to civil and military changes in society. It is emphasized the fundamental novelty of the information age, namely the transition of mankind from the production of material products mainly to intangible (information, knowledge, human cognitive processes. It is emphasized that ICT gain not only growing importance, but become a driving force of human civilization. The basic features of education in the information age, including ICT educational purpose out technology for distance education are described.

  18. [Analysis of human tissue samples for volatile fire accelerants].

    Science.gov (United States)

    Treibs, Rudolf

    2014-01-01

    In police investigations of fires, the cause of a fire and the fire debris analysis regarding traces of fire accelerants are important aspects for forensic scientists. Established analytical procedures were recently applied to the remains of fire victims. When examining lung tissue samples, vapors inhaled from volatile ignitable liquids could be identified and differentiated from products of pyrolysis caused by the fire. In addition to the medico-legal results this evidence allowed to draw conclusions as to whether the fire victim was still alive when the fire started.

  19. Can agricultural fungicides accelerate the discovery of human antifungal drugs?

    Science.gov (United States)

    Myung, Kyung; Klittich, Carla J R

    2015-01-01

    Twelve drugs from four chemical classes are currently available for treatment of systemic fungal infections in humans. By contrast, more than 100 structurally distinct compounds from over 30 chemical classes have been developed as agricultural fungicides, and these fungicides target many modes of action not represented among human antifungal drugs. In this article we introduce the diverse aspects of agricultural fungicides and compare them with human antifungal drugs. We propose that the information gained from the development of agricultural fungicides can be applied to the discovery of new mechanisms of action and new antifungal agents for the management of human fungal infections.

  20. Recognizing Age-Separated Face Images: Humans and Machines

    OpenAIRE

    Daksha Yadav; Richa Singh; Mayank Vatsa; Afzel Noore

    2014-01-01

    Humans utilize facial appearance, gender, expression, aging pattern, and other ancillary information to recognize individuals. It is interesting to observe how humans perceive facial age. Analyzing these properties can help in understanding the phenomenon of facial aging and incorporating the findings can help in designing effective algorithms. Such a study has two components - facial age estimation and age-separated face recognition. Age estimation involves predicting the age of an individua...

  1. Bisphenol A exposure accelerated the aging process in the nematode Caenorhabditis elegans.

    Science.gov (United States)

    Tan, Ling; Wang, Shunchang; Wang, Yun; He, Mei; Liu, Dahai

    2015-06-01

    Bisphenol A (BPA) is a well-known environmental estrogenic disruptor that causes adverse effects. Recent studies have found that chronic exposure to BPA is associated with a high incidence of several age-related diseases. Aging is characterized by progressive function decline, which affects quality of life. However, the effects of BPA on the aging process are largely unknown. In the present study, by using the nematode Caenorhabditis elegans as a model, we investigated the influence of BPA exposure on the aging process. The decrease in body length, fecundity, and population size and the increased egg laying defection suggested that BPA exposure resulted in fitness loss and reproduction aging in this animal. Lifetime exposure of worms to BPA shortened the lifespan in a dose-dependant manner. Moreover, prolonged BPA exposure resulted in age-related behavior degeneration and the accumulation of lipofuscin and lipid peroxide products. The expression of mitochondria-specific HSP-6 and endoplasmic reticulum (ER)-related HSP-70 exhibited hormetic decrease. The expression of ER-related HSP-4 decreased significantly while HSP-16.2 showed a dose-dependent increase. The decreased expression of GCS-1 and GST-4 implicated the reduced antioxidant ability under BPA exposure, and the increase in SOD-3 expression might be caused by elevated levels of reactive oxygen species (ROS) production. Finally, BPA exposure increased the generation of hydrogen peroxide-related ROS and superoxide anions. Our results suggest that BPA exposure resulted in an accelerated aging process in C. elegans mediated by the induction of oxidative stress.

  2. Melatonin and aging: prospects for human treatment.

    Science.gov (United States)

    Bubenik, G A; Konturek, S J

    2011-02-01

    Human life span, with or without modern medicine is around 85-95 years. All living creatures have their inner clock that measures their daily (circadian) and their seasonal (circannual) time. These time changes are mediated by the alteration of levels of melatonin, an evolutionary ancient hormone, which is produced in many body tissues, including the pineal gland, retina and the gastrointestinal tract (GIT). Light is blocking the production of melatonin in the pineal gland, darkness is stimulating it. So, the diurnal changes of light intensity of melatonin, provide a "daily clock" and the seasonal changes provide a "seasonal clock". Finally, the reduction of melatonin observed with aging, may indicate the presence of an "age clock". Melatonin is a strong antioxidant (often it is called scavenger of free radicals), which protects the body from the effects of noxious compounds. Therefore it was hypothesized that the reduction of melatonin levels with age contributes to the aging process. So far, the only remedy to extend the life span was a 40% reduction in caloric intake, which prolonged the life in mice, rats, dogs and monkeys by 30-50%. A large group of people imitate these experiments performed on animals, but the results of these experiments will not be known for several decades. How is being hungry prolonging the life span? There is a connection between caloric reduction and melatonin levels in GIT. Several experiments indicate that fasting in animals substantially increased their production of GIT melatonin. Therefore, instead of being permanently hungry, a prolongation of human life could be achieved by a replacement melatonin therapy. A daily intake of melatonin before bed time might achieve the same effect as fasting e.g. an increase of body melatonin levels, which will protect the individual from the ravages of old age. That includes Parkinson's disease and Alzheimer's disease. There is a large group of people taking melatonin daily who believe that

  3. Aging, human immunodeficiency virus, and bone health

    Directory of Open Access Journals (Sweden)

    Kim C Mansky

    2010-09-01

    Full Text Available Kim C ManskyDivision of Orthodontics, Department of Developmental and Surgical Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN, USAAbstract: Highly active antiretroviral therapy (HAART has had a profound impact on improving the long-term prognosis for individuals infected with human immunodeficiency virus (HIV. HAART has been available for close to two decades, and now a significant number of patients with access to HAART are over the age of 50 years. Many clinical studies have indicated that HIV infection, as well as components of HAART, can increase the risk in these individuals to a variety of noninfectious complications, including a risk to bone health. There is a significant need for detailed mechanistic analysis of the aging, HIV-infected population regarding the risk of HIV infection and therapy in order to maintain bone health. Insights from basic mechanistic studies will help to shed light on the role of HIV infection and the components of HAART that impact bone health, and will help in identifying preventative countermeasures, particularly for individuals 50 years of age and older.Keywords: osteopenia, osteomalacia, osteoporosis, bisphosphonates, tenofovir, osteoimmunology

  4. The immune system in the aging human.

    Science.gov (United States)

    Rymkiewicz, Paulina Dominika; Heng, Yi Xiong; Vasudev, Anusha; Larbi, Anis

    2012-09-01

    With the improvement of medical care and hygienic conditions, there has been a tremendous increment in human lifespan. However, many of the elderly (>65 years) display chronic illnesses, and a majority requires frequent and longer hospitalization. The robustness of the immune system to eliminate or control infections is often eroded with advancing age. Nevertheless, some elderly individuals do cope better than others. The origin of these inter-individual differences may come from genetic, lifestyle conditions (nutrition, socio-economic parameters), as well as the type, number and recurrence of pathogens encountered during life. The theory we are supporting is that chronic infections, through life, will induce profound changes in the immune system probably due to unbalanced inflammatory profiles. Persistent viruses such a cytomegalovirus are not eliminated and are a driven force to immune exhaustion. Because of their age, elderly individuals may have seen more of these chronic stimulators and have experienced more reactivation episodes ultimately leading to shrinkage of their repertoire and overall immune robustness. This review integrates updates on immunity with advancing age and its impact on associated clinical conditions.

  5. Transcriptomic insights into human brain evolution: acceleration, neutrality, heterochrony.

    Science.gov (United States)

    Somel, Mehmet; Rohlfs, Rori; Liu, Xiling

    2014-12-01

    Primate brain transcriptome comparisons within the last 12 years have yielded interesting but contradictory observations on how the transcriptome evolves, and its adaptive role in human cognitive evolution. Since the human-chimpanzee common ancestor, the human prefrontal cortex transcriptome seems to have evolved more than that of the chimpanzee. But at the same time, most expression differences among species, especially those observed in adults, appear as consequences of neutral evolution at cis-regulatory sites. Adaptive expression changes in the human brain may be rare events involving timing shifts, or heterochrony, in specific neurodevelopmental processes. Disentangling adaptive and neutral expression changes, and associating these with human-specific features of the brain require improved methods, comparisons across more species, and further work on comparative development.

  6. Accelerated Age-Dependent Hippocampal Volume Loss in Parkinson Disease With Mild Cognitive Impairment.

    Science.gov (United States)

    Schneider, Christine B; Donix, Markus; Linse, Katharina; Werner, Annett; Fauser, Mareike; Klingelhoefer, Lisa; Löhle, Matthias; von Kummer, Rüdiger; Reichmann, Heinz; Storch, Alexander

    2017-09-01

    Patients with Parkinson disease are at high risk of developing dementia. During the course of the disease, a substantial number of patients will experience a cognitive decline, indicating the dynamics of the underlying neuropathology. Magnetic resonance imaging (MRI) has become increasingly useful for identifying structural characteristics in radiological brain anatomy existing prior to clinical symptoms. Whether these changes reflect pathology, whether they are aging related, or both often remains unclear. We hypothesized that aging-associated brain structural changes would be more pronounced in the hippocampal region among patients with Parkinson disease having mild cognitive deficits relative to cognitively unimpaired patients. Using MRI, we investigated 30 cognitively healthy patients with Parkinson disease and 33 patients with nondemented Parkinson disease having mild cognitive impairment. All participants underwent structural MRI scanning and extensive clinical and neuropsychological assessments. Irrespective of the study participants' cognitive status, older age was associated with reduced cortical thickness in various neocortical regions. Having mild cognitive impairment was not associated with an increased rate of cortical thinning or volume loss in these regions, except in the hippocampus bilaterally. Patients with Parkinson disease having mild cognitive impairment show an accelerated age-dependent hippocampal volume loss when compared with cognitively healthy patients with Parkinson disease. This may indicate pathological processes in a key region for memory functioning in patients with Parkinson disease at risk of developing dementia. Structural MRI of the hippocampal region could potentially contribute to identifying patients who should receive early treatment aimed at delaying the clinical onset of dementia.

  7. Model of human aging: Recent findings on Werner’s and Hutchinson-Gilford progeria syndromes

    Directory of Open Access Journals (Sweden)

    Shian-ling Ding

    2008-09-01

    Full Text Available Shian-ling Ding1, Chen-Yang Shen2,3,41Department of Nursing, Kang-Ning Junior College of Medical Care and Management, Taipei, Taiwan; 2Institute of Biomedical Sciences, and 3Life Science Library, Academia Sinica, Taipei, Taiwan; 4Graduate Institute of Environmental Science, China Medical University, Taichong, TaiwanAbstract: The molecular mechanisms involved in human aging are complicated. Two progeria syndromes, Werner’s syndrome (WS and Hutchinson-Gilford progeria syndrome (HGPS, characterized by clinical features mimicking physiological aging at an early age, provide insights into the mechanisms of natural aging. Based on recent findings on WS and HGPS, we suggest a model of human aging. Human aging can be triggered by two main mechanisms, telomere shortening and DNA damage. In telomere-dependent aging, telomere shortening and dysfunction may lead to DNA damage responses which induce cellular senescence. In DNA damage-initiated aging, DNA damage accumulates, along with DNA repair deficiencies, resulting in genomic instability and accelerated cellular senescence. In addition, aging due to both mechanisms (DNA damage and telomere shortening is strongly dependent on p53 status. These two mechanisms can also act cooperatively to increase the overall level of genomic instability, triggering the onset of human aging phenotypes.Keywords: human aging, Hutchinson-Gilford Progeria syndrome, Werner syndrome

  8. AGE WISE HISTOMORPHOLOGICAL CHANGES IN HUMAN LIVER

    Directory of Open Access Journals (Sweden)

    Tribeni

    2015-11-01

    Full Text Available CONTEXT: Hepato cellular carcinoma (HCC results in between 2.5 lakhs to 1million deaths globally per annum. Liver transplantation nowadays is a well accepted treatment option for end-stage liver disease and acute liver failure. AIMS: Keeping this concept in view, a study was conducted in the Guwahati Zone of Northeast India, to compare the histomorphological features of the human liver in different age groups. SETTING AND DESIGN: Apparently healthy livers were obtained from 21 subjects on whom medicolegal post-mortems had been performed. Their ages varied from newborn to 90 years. Subjects were divided into 3 groups. 7 specimens were taken from each group. (1 Pediatric (2 Adult (3 Old age. METHODS AND MATERIALS: In all the above age groups, immediately after removal of the livers, they were washed in normal saline, dried with blotting paper and weighed in an electronic weighing machine. Sections of liver were fixed, processed, cut and stained with Harris Haematoxylin and Eosin stain. RESULTS: The liver loses weight from 50 years onwards. There appears to be racial and environmental differences in the change in liver weight in old age. Autopsy studies show a diminution of nearly 46% in liver weight between the 3rd and 10th decades of life. The liver decreases in size with age. The hepatocytes are radially disposed in the liver lobule. They are piled up, forming a layer one cell thick (except in young children in a fashion similar to the bricks of a wall. These plates are directed from the periphery of the lobule to its centre and anastomose freely forming a complex labyrinthine and sponge-like structure. CONCLUSIONS: From the findings in the present study it can be concluded that: 1. Nowadays, the measurement of liver volume has gained practical use in relation to liver transplantation. 2. We have compared the histomorphology of adult liver with a child. The findings in both the groups are very similar. This feature is important, since in

  9. A stochastic model of randomly accelerated walkers for human mobility

    National Research Council Canada - National Science Library

    Gallotti, Riccardo; Bazzani, Armando; Rambaldi, Sandro; Barthelemy, Marc

    2016-01-01

    Recent studies of human mobility largely focus on displacements patterns and power law fits of empirical long-tailed distributions of distances are usually associated to scale-free superdiffusive random walks called Lévy flights...

  10. Relative time course of degeneration of different cochlear structures in the CD/1 mouse model of accelerated aging.

    Science.gov (United States)

    Mahendrasingam, Shanthini; Macdonald, Jamie A; Furness, David N

    2011-08-01

    Presbycusis (age-related hearing loss) can result from various cochlear pathologies. We have studied the time course of degeneration in a mouse that shows accelerated presbycusis, the CD/1 mouse, as a possible model to investigate stem-cell strategies to prevent or ameliorate presbycusic changes. CD/1 mice from 0 to 72 weeks old were examined by light and electron microscopy. Early pathological changes were detected in basal turn spiral ligament fibrocytes and spiral ganglion, but the latter was variable as both satellite cells and neurons were normal in some cochleae. Light microscopic counts in the spiral ligament of 20-week-old mice revealed that of the five main types (types I-V), only type V fibrocytes showed no reduction in numbers compared with 3-week-old animals, and type IV showed the greatest losses. However, all types of fibrocyte showed subtle damage when examined using electron microscopy, in the form of swollen mitochondria, as early as 2 weeks. The extent of mitochondrial damage showed a degree of correspondence with the light microscopic pattern of fibrocyte loss in that types III and IV fibrocytes had the most abnormal mitochondria and type V the least, especially at early stages. By 10-15 weeks, ultrastructural features of fibrocyte damage were similar to longer term changes reported in gerbils. Stria vascularis, spiral ganglion and hair cells showed few consistent early signs of damage but became increasingly affected, lagging behind the fibrocyte damage. Our data suggest that fibrocyte pathology may precede other presbycusic changes; breakdown of homeostatic mechanisms to which they contribute may cause the subsequent degeneration of the hair cells. Overall, there were many similarities to presbycusic changes in other rodents and humans. Therefore, the features of accelerated aging in this mouse make it a suitable model for rapidly assessing possible strategies to prevent or ameliorate presbycusic changes.

  11. Age-Infusion Approach to Derive Injury Risk Curves for Dummies from Human Cadaver Tests

    Science.gov (United States)

    Yoganandan, Narayan; Banerjee, Anjishnu; Pintar, Frank A.

    2015-01-01

    Injury criteria and risk curves are needed for anthropomorphic test devices (dummies) to assess injuries for improving human safety. The present state of knowledge is based on using injury outcomes and biomechanical metrics from post-mortem human subject (PMHS) and mechanical records from dummy tests. Data from these models are combined to develop dummy injury assessment risk curves (IARCs)/dummy injury assessment risk values (IARVs). This simple substitution approach involves duplicating dummy metrics for PMHS tested under similar conditions and pairing with PMHS injury outcomes. It does not directly account for the age of each specimen tested in the PMHS group. Current substitution methods for injury risk assessments use age as a covariate and dummy metrics (e.g., accelerations) are not modified so that age can be directly included in the model. The age-infusion methodology presented in this perspective article accommodates for an annual rate factor that modifies the dummy injury risk assessment responses to account for the age of the PMHS that the injury data were based on. The annual rate factor is determined using human injury risk curves. The dummy metrics are modulated based on individual PMHS age and rate factor, thus “infusing” age into the dummy data. Using PMHS injuries and accelerations from side-impact experiments, matched-pair dummy tests, and logistic regression techniques, the methodology demonstrates the process of age-infusion to derive the IARCs and IARVs. PMID:26697422

  12. Age-Infusion Approach to Derive Injury Risk Curves for Dummies from Human Cadaver Tests.

    Science.gov (United States)

    Yoganandan, Narayan; Banerjee, Anjishnu; Pintar, Frank A

    2015-01-01

    Injury criteria and risk curves are needed for anthropomorphic test devices (dummies) to assess injuries for improving human safety. The present state of knowledge is based on using injury outcomes and biomechanical metrics from post-mortem human subject (PMHS) and mechanical records from dummy tests. Data from these models are combined to develop dummy injury assessment risk curves (IARCs)/dummy injury assessment risk values (IARVs). This simple substitution approach involves duplicating dummy metrics for PMHS tested under similar conditions and pairing with PMHS injury outcomes. It does not directly account for the age of each specimen tested in the PMHS group. Current substitution methods for injury risk assessments use age as a covariate and dummy metrics (e.g., accelerations) are not modified so that age can be directly included in the model. The age-infusion methodology presented in this perspective article accommodates for an annual rate factor that modifies the dummy injury risk assessment responses to account for the age of the PMHS that the injury data were based on. The annual rate factor is determined using human injury risk curves. The dummy metrics are modulated based on individual PMHS age and rate factor, thus "infusing" age into the dummy data. Using PMHS injuries and accelerations from side-impact experiments, matched-pair dummy tests, and logistic regression techniques, the methodology demonstrates the process of age-infusion to derive the IARCs and IARVs.

  13. Age infusion approach to derive injury assessment risk curves for dummies from human cadaver tests

    Directory of Open Access Journals (Sweden)

    Narayan eYoganandan

    2015-12-01

    Full Text Available Injury criteria and risk curves are needed for anthropomorphic test devices (dummies to assess injuries for improving human safety. The present state of knowledge is based on using injury outcomes and biomechanical metrics from post-mortem human subject (PMHS and mechanical records from dummy tests. Data from these models are combined to develop dummy injury assessment risk curves/values (IARCs and IARVs. This simple substitution approach involves duplicating dummy metrics for PMHS tested under similar conditions and pairing with PMHS injury outcomes. It does not account for the age of each specimen tested in the PMHS group. Current substitution methods for injury risk assessments use age as a covariate and dummy metrics (e.g., accelerations are not modified so that age can be directly included in the model. The age-infusion methodology presented in this perspective article accommodates for an annual rate factor that modifies the dummy injury risk assessment responses to account for the age of the PMHS that the injury data was based on. The annual rate factor is determined using human injury risk curves. The dummy metrics are modulated based on individual PMHS age and rate factor, thus infusing age into the dummy data. Using PMHS injuries and accelerations from side-impact experiments, matched-pair dummy tests and logistic regression techniques, the methodology demonstrates the process of age-infusion to derive the IARCs and IARVs.

  14. Evaluation of oxidative behavior of polyolefin geosynthetics utilizing accelerated aging tests based on temperature and pressure

    Science.gov (United States)

    Li, Mengjia

    Polyolefin geosynthetics are susceptible to oxidation, which eventually leads to the reduction in their engineering properties. In the application of polyolefin geosynthetics, a major issue is an estimate of the materials durability (i.e. service lifetime) under various aging conditions. Antioxidant packages are added to the polyolefin products to extend the induction time, during which antioxidants are gradually depleted and polymer oxidation reactions are prevented. In this PhD study, an improved laboratory accelerating aging method under elevated and high pressure environments was applied to evaluate the combined effect of temperature and pressure on the depletion of the antioxidants and the oxidation of polymers. Four types of commercial polyolefn geosynthetic materials selected for aging tests included HDPE geogrid, polypropylene woven and nonwoven geotextiles. A total of 33 different temperature/pressure aging conditions were used, with the incubation duration up to 24 months. The applied oven temperature ranged from 35°C to 105°C and the partial oxygen pressure ranged from 0.005 MPa to 6.3 MPa. Using the Oxidative Induction Time (OIT) test, the antioxidant depletion, which is correlated to the decrease of the OIT value, was found to follow apparent first-order decay. The OIT data also showed that, the antioxidant depletion rate increased with temperature according to the Arrhenius equation, while under constant temperatures, the rate increased exponentially with the partial pressure of oxygen. A modified Arrhenius model was developed to fit the antioxidant depletion rate as a function of temperature and pressure and to predict the antioxidant lifetime under various field conditions. This study has developed new temperature/pressure incubation aging test method with lifetime prediction models. Using this new technique, the antioxidant lifetime prediction results are close to regular temperature aging data while the aging duration can be reduced considerably

  15. Theory of SEI Formation in Rechargeable Batteries: Capacity Fade, Accelerated Aging and Lifetime Prediction

    CERN Document Server

    Pinson, Matthew B

    2012-01-01

    Cycle life is critically important in applications of rechargeable batteries, but lifetime prediction is mostly based on empirical trends, rather than mathematical models. In practical lithium-ion batteries, capacity fade occurs over thousands of cycles, limited by slow electrochemical processes, such as the formation of a solid-electrolyte interphase (SEI) in the negative electrode, which compete with reversible lithium intercalation. Focusing on SEI growth as the canonical degradation mechanism, we show that a simple single-particle model can accurately explain experimentally observed capacity fade in commercial cells with graphite anodes, and predict future fade based on limited accelerated aging data for short times and elevated temperatures. The theory is extended to porous electrodes, predicting that SEI growth is essentially homogeneous throughout the electrode, even at high rates. The lifetime distribution for a sample of batteries is found to be consistent with Gaussian statistics, as predicted by th...

  16. Evaluation of Experimental Parameters in the Accelerated Aging of Closed-Cell Foam Insulation

    Energy Technology Data Exchange (ETDEWEB)

    Stovall, Therese K [ORNL; Vanderlan, Michael [ORNL; Atchley, Jerald Allen [ORNL

    2012-12-01

    The thermal conductivity of many closed-cell foam insulation products changes over time as production gases diffuse out of the cell matrix and atmospheric gases diffuse into the cells. Thin slicing has been shown to be an effective means of accelerating this process in such a way as to produce meaningful results. Efforts to produce a more prescriptive version of the ASTM C1303 standard test method led to the ruggedness test described here. This test program included the aging of full size insulation specimens for time periods of five years for direct comparison to the predicted results. Experimental parameters under investigation include: slice thickness, slice origin (at the surface or from the core of the slab), thin slice stack composition, product facings, original product thickness, product density, and product type. The test protocol has been completed and this report provides a detailed evaluation of the impact of the test parameters on the accuracy of the 5-year thermal conductivity prediction.

  17. Accelerated increase and relative decrease in subjective age and changes in attitudes toward own aging over a 4-year period: results from the Health and Retirement Study.

    Science.gov (United States)

    Bodner, Ehud; Ayalon, Liat; Avidor, Sharon; Palgi, Yuval

    2017-03-01

    The passage of time may force people to adjust their subjective age in response to changes in their attitudes toward own aging (ATOA). Although positive associations have been found between well-being and both positive ATOA and younger subjective age, the relationships between changes in these measures have not been examined yet. We expected (1) a decrease in positive ATOA to be associated with an accelerated increase in subjective age and (2) an increase in positive ATOA to be associated with a relative decrease in subjective age. Participants were individuals and their spouses, aged 50 and over, recruited by the Health and Retirement Study, who provided responses to a question concerning one's subjective age in 2008 and 2012 (n = 4174). A change in subjective age over the two waves was regarded as (1) an accelerated increase if it was greater than 5 years (36.2 % of the sample); (2) a relative decrease (39.1 %), if it was less than the 3 years; (3) no change if it did not comply with criteria 1 or 2 (24.7 %). A decrease in positive ATOA over the two waves resulted in an accelerated increase in subjective age, and an increase resulted in a relative decrease in subjective age. Older age and more physical impairments and depressive symptoms in 2012 compared with 2008 were associated with an accelerated increase in subjective age. Our findings emphasize the consequences ATOA might have on subjective age experiences, and the need to improve them.

  18. Accelerated cell aging in female APOE-ε4 carriers: implications for hormone therapy use.

    Directory of Open Access Journals (Sweden)

    Emily G Jacobs

    Full Text Available Apolipoprotein-ε4 (APOE-ε4 is a major genetic risk factor for cognitive decline, Alzheimer's disease (AD and early mortality. An accelerated rate of biological aging could contribute to this increased risk. Here, we determined whether APOE-ε4 status impacts leukocyte telomere length (TL and the rate of cellular senescence in healthy mid-life women and, further, whether hormone replacement therapy (HT modifies this association. Post-menopausal women (N = 63, Mean age = 57.7, all HT users for at least one year, were enrolled in a randomized longitudinal study. Half of the participants (N = 32 remained on their HT regimen and half (N = 31 went off HT for approximately two years (Mean  = 1.93 years. Participants included 24 APOE-ε4 carriers and 39 non-carrier controls. Leukocyte TL was measured at baseline and the end of year 2 using quantitative polymerase chain reaction. Logistic regression analysis indicated that the odds of an APOE-ε4 carrier exhibiting telomere shortening (versus maintenance/growth over the 2-year study were more than 6 (OR  = 6.26, 95% CI  = 1.02, 38.49 times higher than a non-carrier, adjusting for established risk factors and potential confounds. Despite the high-functioning, healthy mid-life status of study participants, APOE-ε4 carriers had marked telomere attrition during the 2-year study window, the equivalent of approximately one decade of additional aging compared to non-carriers. Further analyses revealed a modulatory effect of hormone therapy on the association between APOE status and telomere attrition. APOE-ε4 carriers who went off their HT regimen exhibited TL shortening, as predicted for the at-risk population. APOE-ε4 carriers who remained on HT, however, did not exhibit comparable signs of cell aging. The opposite pattern was found in non-carriers. The results suggest that hormone use might buffer against accelerated cell aging in mid-life women at risk for dementia

  19. Comparative Study on Accelerated Thermal Ageing of Vegetable Insulating Oil-paperboard and Mineral Oil-paperboard

    Science.gov (United States)

    Zhou, Zhu-Jun; Hu, Ting; Cheng, Lin; Tian, Kai; Yang, Jun; Wang, Xuan; Fang, Fu-Xin; Kong, Hai-Yang; Qian, Hang

    2016-05-01

    To comparatively study the insulation ageing life of vegetable insulating oil-paperboard and mineral oil-paperboard, we conducted accelerated thermal ageing experiments at 170°C. Then according to the temperature rise of vegetable insulating oil transformer, we conducted accelerated thermal ageing experiments at 150°C for vegetable insulating oil-paperboard and at 140°C for mineral oil-paperboard. The appearance, polymerization degree, and SEM microstructure of the paperboard after different ageing experiments were comparative analyzed. The results show that after the oil-paperboard system is accelerated ageing for 1 000 h at 170°C, that is equivalent to 20 years natural ageing, the structure of paperboard in vegetable insulating oil is damaged severely, which indicates that the lifetime of transformer are in the late stage; while the structure of paperboard in mineral oil maintain complete, and the polymerization degree is still above 500, which indicate that the lifetime of transformer are in the middle stage. The accelerated ageing rate of the vegetable insulating oil-paperboard system at 150°C is slower than that of the mineral oil-paperboard system, which indicates that the lifetime of the vegetable insulating oil-paperboard is longer than that of the mineral oil-paperboard.

  20. Effects of Operating Temperatures and Accelerated Environmental Ageing on the Mechanical Properties of a Glass-Vinylester Composite

    Science.gov (United States)

    Klasztorny, M.; Nycz, D. B.; Romanowski, R. K.; Gotowicki, P.; Kiczko, A.; Rudnik, D.

    2017-07-01

    Experimental identification of the mechanical properties of a selected glass-vinylester structural composite is developed, performed, and analysed taking into account accelerated environmental ageing and three operating temperatures (-20, 20, and 55°C) corresponding to the operating temperature range for composite footbridges in the Central Europe. The main constituents of the composite fabricated using infusion technology are a bidirectional balanced stitched E-glass fabric and a flame retardant, vinylester resin. After homogenization, the composite reinforced with one fabric forms a single lamina and is modeled as a linear elastic-brittle orthotropic material. Full sets of material constants were identified for the initial and aged composites at the selected operating temperatures. The accelerated environmental ageing of the composite was performed on 4-layer symmetric laminate platelets protected with a 300-mm-thick gelcoat layer, using an ageing chamber and a relevant ageing programme. A comparative analysis was carried out in order to determine the effects of operating temperature and accelerated environmental ageing on the material constants of the GFRP composite. It is found that the composite tested can be modeled as a linear elastic-brittle orthotropic material to the level of 20% of its strength in each strength test. The impact of the accelerated environmental ageing and operating temperature in the range from -20 to 55°C on the elastic/strength/ultimate strain constants of the selected E-glass/vinylester composite can be significant and different for individual constants.

  1. Influence of acceleration voltage on scanning electron microscopy of human blood platelets.

    Science.gov (United States)

    Pretorius, E

    2010-03-01

    Scanning electron microscopy (SEM) is used to view a variety of surface structures, molecules, or nanoparticles of different materials, ranging from metals, dental and medical instruments, and chemistry (e.g. polymer analysis) to biological material. Traditionally, the operating conditions of the SEM are very important in the material sciences, particularly the acceleration voltage. However, in biological sciences, it is not typically seen as an important parameter. Acceleration voltage allows electrons to penetrate the sample; thus, the higher the acceleration voltage the more penetration into the sample will occur. As a result, ultrastructural information from deeper layers will interfere with the actual surface morphology that is seen. Therefore, ultimately, if acceleration voltage is lower, a better quality of the surface molecules and structures will be produced. However, in biological sciences, this is an area that is not well-documented. Typically, acceleration voltages of between 5 and 20 kV are used. This manuscript investigates the influence of acceleration voltages ranging from 5 kV to as low as 300 V, by studying surface ultrastructure of a human platelet aggregate. It is concluded that, especially at higher magnifications, much more surface detail is visible in biological samples when using an acceleration voltage between 2 kV and 300 V.

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

    Science.gov (United States)

    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

  3. Age effect on fatigue-induced limb acceleration as a consequence of high-level sustained submaximal contraction.

    Science.gov (United States)

    Huang, Chien-Ting; Huang, Chien-Chun; Young, Ming-Shing; Hwang, Ing-Shiou

    2007-08-01

    In reference to electromyographic measurement, the study was conducted to reassess differences in the behavior of fatigue-related neuromuscular function between young and elderly humans with limb acceleration (LA). Fourteen young and fourteen elderly subjects performed sustained index abduction at 75% of their maximal voluntary contractions (MVC) until task failure. Measures of neuromuscular function, including temporal/spectral features of muscle activity of the first dorsal interosseous (FDI) and LA of the index and hand, were monitored. The results showed a manifest fatigue-induced increase in LA of the index in the elderly group, but not in the young group. In contrast, only the young group developed a significant increase in amplitude of the electromyography (EMG) until task failure. Spectral analyses of LA in the index reflected marked age-dependent reorganization following muscle fatigue, with a greater reduction of relative spectral amplitude of LA in the range of 20-40 Hz, but a lesser reduction in coherence between EMG and LA in the elderly group. In line with fatigue-associated restructuring of LA, the mechanical coupling of the metacarpophalangeal joint was more severely undermined in the elderly group than in the young group. The present study manifested an age-related difference in the relative contributions of neural versus mechanical factors to muscle fatigue. Subsequent to a high-level sustained submaximal isometric contraction, a predominant mechanical failure of the musculotendon complex in the elderly was featured with LA, whereas EMG measurement characterized prevailing impairment of neuromuscular propagation in the young.

  4. Modular knowledge systems accelerate human migration in asymmetric random environments.

    Science.gov (United States)

    Wang, Dong; Deem, Michael W

    2016-12-01

    Migration is a key mechanism for expansion of communities. In spatially heterogeneous environments, rapidly gaining knowledge about the local environment is key to the evolutionary success of a migrating population. For historical human migration, environmental heterogeneity was naturally asymmetric in the north-south (NS) and east-west (EW) directions. We here consider the human migration process in the Americas, modelled as random, asymmetric, modularly correlated environments. Knowledge about the environments determines the fitness of each individual. We present a phase diagram for asymmetry of migration as a function of carrying capacity and fitness threshold. We find that the speed of migration is proportional to the inverse complement of the spatial environmental gradient, and in particular, we find that NS migration rates are lower than EW migration rates when the environmental gradient is higher in the NS direction. Communication of knowledge between individuals can help to spread beneficial knowledge within the population. The speed of migration increases when communication transmits pieces of knowledge that contribute in a modular way to the fitness of individuals. The results for the dependence of migration rate on asymmetry and modularity are consistent with existing archaeological observations. The results for asymmetry of genetic divergence are consistent with patterns of human gene flow. © 2016 The Author(s).

  5. The anorexia of aging in humans.

    Science.gov (United States)

    Hays, Nicholas P; Roberts, Susan B

    2006-06-30

    Energy intake is reduced in older individuals, with several lines of evidence suggesting that both physiological impairment of food intake regulation and non-physiological mechanisms are important. Non-physiological causes of the anorexia of aging include social (e.g. poverty, isolation), psychological (e.g. depression, dementia), medical (e.g. edentulism, dysphagia), and pharmacological factors. Physiological factors include changes in taste and smell, diminished sensory-specific satiety, delayed gastric emptying, altered digestion-related hormone secretion and hormonal responsiveness, as well as food intake-related regulatory impairments for which specific mechanisms remain largely unknown. Studies in healthy elderly individuals have shown that men who consume diets over several weeks providing either too few or too many calories relative to dietary energy needs subsequently do not compensate for the resulting energy deficit or surplus when provided an ad libitum diet. Healthy elders have also been shown to be less hungry at meal initiation and to become more rapidly satiated during a standard meal compared to younger adults. Studies in animal models are required to investigate potential mechanisms underlying these observations, while human studies should focus on examining the potential consequences of this phenomenon and practical therapeutic strategies for the maintenance of appropriate energy intake with increasing age. In light of this need, we have recently demonstrated that low reported hunger assessed using a simple questionnaire predicts unintentional weight loss in a sample of healthy older women, and thus may provide a clinically useful tool for identifying older individuals at risk for undesirable weight change and therefore at high priority for intervention.

  6. Accelerated fat cell aging links oxidative stress and insulin resistance in adipocytes

    Indian Academy of Sciences (India)

    Finny Monickaraj; Sankaramoorthy Aravind; Pichamoorthy Nandhini; Paramasivam Prabu; Chandrakumar Sathishkumar; Viswanathan Mohan; Muthuswamy Balasubramanyam

    2013-03-01

    Telomere shortening is emerging as a biological indicator of accelerated aging and aging-related diseases including type 2 diabetes. While telomere length measurements were largely done in white blood cells, there is lack of studies on telomere length in relation to oxidative stress in target tissues affected in diabetes. Therefore, the aim of this study is to induct oxidative stress in adipocytes and to test whether these adipocytes exhibit shortened telomeres, senescence and functional impairment. 3T3-L1 adipocytes were subjected to oxidative stress and senescence induction by a variety of means for 2 weeks (exogenous application of H2O2, glucose oxidase, asymmetric dimethylarginine (ADMA) and glucose oscillations). Cells were probed for reactive oxygen species generation (ROS), DNA damage, mRNA and protein expression of senescent and pro-inflammatory markers, telomere length and glucose uptake. Compared to untreated cells, both ROS generation and DNA damage were significantly higher in cells subjected to oxidative stress and senescence. Adipocytes subjected to oxidative stress also showed shortened telomeres and increased mRNA and protein expression of p53, p21, TNF and IL-6. Senescent cells were also characterized by decreased levels of adiponectin and impaired glucose uptake. Briefly, adipocytes under oxidative stress exhibited increased ROS generation, DNA damage, shortened telomeres and switched to senescent/pro-inflammatory phenotype with impaired glucose uptake.

  7. Accelerating Neuronal Aging in In Vitro Model Brain Disorders: a Focus on Reactive Oxygen Species

    Directory of Open Access Journals (Sweden)

    Priscila Britto Campos

    2014-10-01

    Full Text Available In this review, we discuss insights gained through the use of stem cell preparations regarding the modeling of neurological diseases, the need for aging neurons derived from pluripotent stem cells to further advance the study of late-onset adult neurological diseases, and the extent to which mechanisms linked to the mismanagement of ROS. The context of these issues can be revealed using the three disease states of Parkinson’s (PD, Alzheimer’s (AD, and schizophrenia, as considerable insights have been gained into these conditions through the use of stem cells in terms of disease etiologies and the role of oxidative stress. The latter subject is a primary area of interest of our group. After discussing the molecular models of accelerated aging, we highlight the role of ROS for the three diseases explored here. Importantly, we do not seek to provide an extensive account of all genetic mutations for each of the three disorders discussed in this review, but we aim instead to provide a conceptual framework that could maximize the gains from merging the approaches of stem cell microsystems and the study of oxidative stress in disease in order to optimize therapeutics and determine new molecular targets against oxidative stress that spare stem cell proliferation and development.

  8. Accelerated aging of solid lubricants for the W76-1 TSL : effects of polymer outgassing.

    Energy Technology Data Exchange (ETDEWEB)

    Dugger, Michael Thomas; Wallace, William O.; Huffman, Elizabeth M.

    2006-09-01

    The behavior of MoS{sub 2} lubricants intended for the W76-1 TSL was evaluated after 17 and 82 thermal cycles, each lasting seven days and including a low temperature of -35 C and a high temperature of 93 C, in a sealed container containing organic materials. The MoS{sub 2} was applied by tumbling with MoS{sub 2} powder and steel pins (harperized), or by spraying with a resin binder (AS Mix). Surface composition measurements indicated an uptake of carbon and silicon on the lubricant surfaces after aging. Oxidation of the MoS{sub 2} on harperized coupons, where enough MoS{sub 2} was present at the surface to result in significant Mo and S concentrations, was found to be minimal for the thermal cycles in an atmosphere of primarily nitrogen. Bare steel surfaces showed a reduction in friction for exposed coupons compared to control coupons stored in nitrogen, at least for the initial cycles of sliding until the adsorbed contaminants were worn away. Lubricated surfaces showed no more than a ten percent increase in steady-state friction coefficient after exposure. Initial coefficient of friction was up to 250 percent higher than steady-state for AS Mix films on H950 coupons after 82 thermal cycles. However, the friction coefficient exhibited by lubricated coupons was never greater than 0.25, and more often less than 0.15, even after the accelerated aging exposures.

  9. Color stability of modern composites subjected to different periods of accelerated artificial aging.

    Science.gov (United States)

    Drubi-Filho, Brahim; Garcia, Lucas da Fonseca Roberti; Cruvinel, Diogo Rodrigues; Sousa, Ana Beatriz Silva; Pires-de-Souza, Fernanda de Carvalho Panzeri

    2012-01-01

    The aim of this study was to evaluate the color stability of composites subjected to different periods of accelerated artificial aging (AAA). A polytetrafluorethylene matrix (10 x 2 mm) was used to fabricate 24 test specimens of three different composites (n=8): Tetric Ceram (Ivoclar/Vivadent); Filtek P90 and Z250 (3M ESPE), shade A3. After light activation for 20 s (FlashLite 1401), polishing and initial color readout (Spectrophotometer PCB 687; BYK Gardner), the test specimens were subjected to AAA (C-UV; Comexim), in 8-h cycles: 4 h exposure to UV-B rays at 50°C and 4 h condensation at 50°C. At the end of each cycle, color readouts were taken and the test ended when the mean value of ΔE attained a level ≥3.30. Tetric Ceram presented alteration in ΔE equal to 3.33 in the first aging cycle. For Filtek P90 and Z250, two (ΔE=3.60) and four (ΔE=3.42) AAA cycles were necessary. After each cycle, there was a reduction of luminosity in all the samples (ΔL). It was concluded that a short period of AAA was sufficient to promote clinically unacceptable color alteration in composites, and that this alteration was material-dependent.

  10. Immune responses accelerate ageing: proof-of-principle in an insect model.

    Directory of Open Access Journals (Sweden)

    E Rhiannon Pursall

    Full Text Available The pathology of many of the world's most important infectious diseases is caused by the immune response. Additionally age-related disease is often attributed to inflammatory responses. Consequently a reduction in infections and hence inflammation early in life has been hypothesized to explain the rise in lifespan in industrialized societies. Here we demonstrate experimentally for the first time that eliciting an immune response early in life accelerates ageing. We use the beetle Tenebrio molitor as an inflammation model. We provide a proof of principle for the effects of early infection on morbidity late in life and demonstrate a long-lasting cost of immunopathology. Along with presenting a proof-of-principle study, we discuss a mechanism for the apparently counter-adaptive persistence of immunopathology in natural populations. If immunopathology from early immune response only becomes costly later in life, natural selection on reducing self-harm would be relaxed, which could explain the presence of immune self-harm in nature.

  11. Accelerated aging tests of radiation damaged lasers and photodiodes for the CMS tracker optical links

    CERN Document Server

    Gill, K; Batten, J; Cervelli, G; Grabit, R; Jensen, F; Troska, Jan K; Vasey, F

    1999-01-01

    The combined effects of radiation damage and accelerated ageing in COTS lasers and p-i-n photodiodes are presented. Large numbers of these devices are employed in future High Energy Physics experiments and it is vital that these devices are confirmed to be sufficiently robust in terms of both radiation resistance and reliability. Forty 1310 nm InGaAsP edge-emitting lasers (20 irradiated) and 30 InGaAs p- i-n photodiodes (19 irradiated) were aged for 4000 hours at 80 degrees C with periodic measurements made of laser threshold and efficiency, in addition to p-i-n leakage current and photocurrent. There were no sudden failures and there was very little wearout- related degradation in either unirradiated or irradiated sample groups. The results suggest that the tested devices have a sufficiently long lifetime to operate for at least 10 years inside the Compact Muon Solenoid experiment despite being exposed to a harsh radiation environment. (13 refs).

  12. Accelerating epistasis analysis in human genetics with consumer graphics hardware

    Directory of Open Access Journals (Sweden)

    Cancare Fabio

    2009-07-01

    Full Text Available Abstract Background Human geneticists are now capable of measuring more than one million DNA sequence variations from across the human genome. The new challenge is to develop computationally feasible methods capable of analyzing these data for associations with common human disease, particularly in the context of epistasis. Epistasis describes the situation where multiple genes interact in a complex non-linear manner to determine an individual's disease risk and is thought to be ubiquitous for common diseases. Multifactor Dimensionality Reduction (MDR is an algorithm capable of detecting epistasis. An exhaustive analysis with MDR is often computationally expensive, particularly for high order interactions. This challenge has previously been met with parallel computation and expensive hardware. The option we examine here exploits commodity hardware designed for computer graphics. In modern computers Graphics Processing Units (GPUs have more memory bandwidth and computational capability than Central Processing Units (CPUs and are well suited to this problem. Advances in the video game industry have led to an economy of scale creating a situation where these powerful components are readily available at very low cost. Here we implement and evaluate the performance of the MDR algorithm on GPUs. Of primary interest are the time required for an epistasis analysis and the price to performance ratio of available solutions. Findings We found that using MDR on GPUs consistently increased performance per machine over both a feature rich Java software package and a C++ cluster implementation. The performance of a GPU workstation running a GPU implementation reduces computation time by a factor of 160 compared to an 8-core workstation running the Java implementation on CPUs. This GPU workstation performs similarly to 150 cores running an optimized C++ implementation on a Beowulf cluster. Furthermore this GPU system provides extremely cost effective

  13. Color stability after accelerated aging of two silicones, pigmented or not, for use in facial prostheses

    Directory of Open Access Journals (Sweden)

    Daniela Nardi Mancuso

    2009-06-01

    Full Text Available One of the greatest challenges faced by buccomaxillofacial prosthetists is to reproduce the patient's exact skin color and provide adequate esthetics. To reach this objective, professionals must use materials with easy characterization and that maintain color over long periods of time. The objective of this study was, thus, to evaluate the color stability of two types of silicones, Silastic 732 and Silastic MDX4-4210. Twenty-four test specimens were made from each type of silicone and were divided into a colorless group and groups intrinsically pigmented with ceramics, cosmetics or iron oxide. The specimens were submitted to an accelerated system of aging for non-metallic materials. Readings were carried out initially and after periods corresponding to 163, 351, 692 and 1,000 hours of aging, using a reflection spectrophotometer analysis, and color alterations were calculated by the CIE L*a*b* system. The data were submitted to variance analysis and Tukey's test at a 5% level of probability. The results demonstrated that, irrespective of the period of time analyzed, all the materials underwent some type of chromatic alteration (ΔE > 0. The test specimens made with Silastic 732 and MDX4-4210, without pigmentation, presented the lowest color alteration values after 1,000 hours of aging. Of the pigments, ceramic presented the lowest color alteration values and cosmetic powder presented the highest values. Thus, it may be concluded that the materials without the incorporation of pigments presented similar color alteration values, and did not differ statistically. The cosmetic powder used in this study was the pigment that most altered the color of the test specimens.

  14. Circadian disruption induced by light-at-night accelerates aging and promotes tumorigenesis in young but not in old rats

    Science.gov (United States)

    Vinogradova, Irina A.; Anisimov, Vladimir N.; Bukalev, Andrey V.; Ilyukha, Viktor A.; Khizhkin, Evgeniy A.; Lotosh, Tatiana A.; Semenchenko, Anna V.; Zabezhinski, Mark A.

    2010-01-01

    We evaluated the effect of exposure to constant light started at the age of 1 month and at the age of 14 months on the survival, life span, tumorigenesis and age-related dynamics of antioxidant enzymes activity in various organs in comparison to the rats maintained at the standard (12:12 light/dark) light/dark regimen. We found that exposure to constant light started at the age of 1 month accelerated spontaneous tumorigenesis and shortened life span both in male and female rats as compared to the standard regimen. At the same time, the exposure to constant light started at the age of 14 months failed to influence survival of male and female rats. While delaying tumors in males, constant light accelerated tumors in females. We conclude that circadian disruption induced by light-at-night started at the age of 1 month accelerates aging and promotes tumorigenesis in rats, however failed affect survival when started at the age of 14 months. PMID:20354269

  15. Positive selection, relaxation, and acceleration in the evolution of the human and chimp genome.

    Directory of Open Access Journals (Sweden)

    Leonardo Arbiza

    2006-04-01

    Full Text Available For years evolutionary biologists have been interested in searching for the genetic bases underlying humanness. Recent efforts at a large or a complete genomic scale have been conducted to search for positively selected genes in human and in chimp. However, recently developed methods allowing for a more sensitive and controlled approach in the detection of positive selection can be employed. Here, using 13,198 genes, we have deduced the sets of genes involved in rate acceleration, positive selection, and relaxation of selective constraints in human, in chimp, and in their ancestral lineage since the divergence from murids. Significant deviations from the strict molecular clock were observed in 469 human and in 651 chimp genes. The more stringent branch-site test of positive selection detected 108 human and 577 chimp positively selected genes. An important proportion of the positively selected genes did not show a significant acceleration in rates, and similarly, many of the accelerated genes did not show significant signals of positive selection. Functional differentiation of genes under rate acceleration, positive selection, and relaxation was not statistically significant between human and chimp with the exception of terms related to G-protein coupled receptors and sensory perception. Both of these were over-represented under relaxation in human in relation to chimp. Comparing differences between derived and ancestral lineages, a more conspicuous change in trends seems to have favored positive selection in the human lineage. Since most of the positively selected genes are different under the same functional categories between these species, we suggest that the individual roles of the alternative positively selected genes may be an important factor underlying biological differences between these species.

  16. The Effect of Priming on Germination and Enzyme Activity of Sesame (Sesamum indicum L. Seeds After Accelerated Aging

    Directory of Open Access Journals (Sweden)

    Tabatabaei S. A.

    2013-11-01

    Full Text Available Maximum germination percentage achieves immediately after harvesting and gradually de#creases with storage time. Aging is one of the key factors in plant yield loss especially in vegetables. Seed aging is the main problem of seed storage. Application of accelerated aging treatment is used to assess seed vigor and quality. Seed priming enhances seed germination performance after aging. An experiment was conduct in order to investigate the activity of catalase and ascorbate peroxidase during accelerated aging and repair during priming treatment of sesame (Sesamum indicum L. seeds. In order to improve germination characteristics in aged seeds with seed priming. Our result showed that seed priming treatments significantly (p≤ 0.01 affected, germination percentage, germination Index and normal seedling percentage after aging (0, 3 and 6 days. Increasing aging duration resulted higher reduction in germination characteristics. Priming with gibberelic acid (GA increased germination characteristics of seed aged. The highest germination percentage, germination index, normal seedling percentage and enzyme activity were achieved in control conditions (0 day of aging. Also antioxidant activity of aged seeds increased after seed priming.

  17. The effect of the accelerated aging on the mechanical properties of the PMMA denture base materials modified with itaconates

    Directory of Open Access Journals (Sweden)

    Spasojević Pavle M.

    2011-01-01

    Full Text Available This study evaluated the effect of accelerated ageing on the tensile strength, elongation at break, hardness and Charpy impact strength in commercial PMMA denture base material modified with di-methyl itaconate (DMI and di-n-butyl itaconate (DBI. The samples were prepared by modifying commercial formulation by addition of itaconates in the amounts of 2.5, 5, 7.5 and 10% by weight. After polymerization samples were characterized by FT-IR and DSC analysis while residual monomer content was determined by HPLC-UV. Accelerated ageing was performed at 70°C in water for periods of 7, 15 and 30 days. Tensile measurements were performed using Instron testing machine while the hardness of the polymerized samples was measured by Shore D method. The addition of itaconate significantly reduces the residual MMA. Even at the small amounts of added itaconates (2.5% the residual MMA content was reduced by 50%. The increase of itaconate content in the system leads to the decrease of residual MMA. It has been found that the addition of di-n-alkyl itaconates decreases the tensile strength, hardness and Charpy impact strength and increases elongation at break. Samples modified with DMI had higher values of tensile strength, hardness and Charpy impact strength compared to the ones modified with DBI. This is explained by the fact that DBI has longer side chain compared to DMI. After accelerated ageing during a 30 days period the tensile strength decreased for all the investigated samples. The addition of DMI had no effect on the material ageing and the values for the tensile strength of all of the investigated samples decreased around 20%, while for the samples modified with DBI, the increase of the amount of DBI in the polymerized material leads to the higher decrease of the tensile strength after the complete accelerated ageing period od 30 days, aulthough after the first seven days of the accelerated ageing the values of hardness have increased for all of the

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

    Science.gov (United States)

    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.

  19. Biological psychological and social determinants of old age: Bio-psycho-social aspects of human aging

    Directory of Open Access Journals (Sweden)

    Małgorzata Dziechciaż

    2014-11-01

    Full Text Available Biological psychological and social determinants of old age: Bio-psycho-social aspects of human aging. The aging of humans is a physiological and dynamic process ongoing with time. In accordance with most gerontologists’ assertions it starts in the fourth decade of life and leads to death. The process of human aging is complex and individualized, occurs in the biological, psychological and social sphere. Biological aging is characterized by progressive age-changes in metabolism and physicochemical properties of cells, leading to impaired self-regulation, regeneration, and to structural changes and functional tissues and organs. It is a natural and irreversible process which can run as successful aging, typical or pathological. Biological changes that occur with age in the human body affect mood, attitude to the environment, physical condition and social activity, and designate the place of seniors in the family and society. Psychical ageing refers to human awareness and his adaptability to the ageing process. Among adaptation attitudes we can differentiate: constructive, dependence, hostile towards others and towards self attitudes. With progressed age, difficulties with adjustment to the new situation are increasing, adverse changes in the cognitive and intellectual sphere take place, perception process involutes, perceived sensations and information received is lowered, and thinking processes change. Social ageing is limited to the role of an old person is culturally conditioned and may change as customs change. Social ageing refers to how a human being perceives the ageing process and how society sees it.

  20. Microstructure and mechanical properties of composite resins subjected to accelerated artificial aging.

    Science.gov (United States)

    dos Reis, Andréa Cândido; de Castro, Denise Tornavoi; Schiavon, Marco Antônio; da Silva, Leandro Jardel; Agnelli, José Augusto Marcondes

    2013-01-01

    The aim of this study was to investigate the influence of accelerated artificial aging (AAA) on the microstructure and mechanical properties of the Filtek Z250, Filtek Supreme, 4 Seasons, Herculite, P60, Tetric Ceram, Charisma and Filtek Z100. composite resins. The composites were characterized by Fourier-transform Infrared spectroscopy (FTIR) and thermal analyses (Differential Scanning Calorimetry - DSC and Thermogravimetry - TG). The microstructure of the materials was examined by scanning electron microscopy. Surface hardness and compressive strength data of the resins were recorded and the mean values were analyzed statistically by ANOVA and Tukey's test (α=0.05). The results showed significant differences among the commercial brands for surface hardness (F=86.74, psurface hardness: F=0.39, p=0.53; compressive strength: F=2.82, p=0.09) of any of the composite resins. FTIR, DSC and TG analyses showed that resin polymerization was complete, and there were no differences between the spectra and thermal curve profiles of the materials obtained before and after AAA. TG confirmed the absence of volatile compounds and evidenced good thermal stability up to 200 °C, and similar amounts of residues were found in all resins evaluated before and after AAA. The AAA treatment did not significantly affect resin surface. Therefore, regardless of the resin brand, AAA did not influence the microstructure or the mechanical properties.

  1. Sox4 Links Tumor Suppression to Accelerated Aging in Mice by Modulating Stem Cell Activation

    Directory of Open Access Journals (Sweden)

    Miguel Foronda

    2014-07-01

    Full Text Available Sox4 expression is restricted in mammals to embryonic structures and some adult tissues, such as lymphoid organs, pancreas, intestine, and skin. During embryogenesis, Sox4 regulates mesenchymal and neural progenitor survival, as well as lymphocyte and myeloid differentiation, and contributes to pancreas, bone, and heart development. Aberrant Sox4 expression is linked to malignant transformation and metastasis in several types of cancer. To understand the role of Sox4 in the adult organism, we first generated mice with reduced whole-body Sox4 expression. These mice display accelerated aging and reduced cancer incidence. To specifically address a role for Sox4 in adult stem cells, we conditionally deleted Sox4 (Sox4cKO in stratified epithelia. Sox4cKO mice show increased skin stem cell quiescence and resistance to chemical carcinogenesis concomitantly with downregulation of cell cycle, DNA repair, and activated hair follicle stem cell pathways. Altogether, these findings highlight the importance of Sox4 in regulating adult tissue homeostasis and cancer.

  2. Polyphenols, Antioxidant Potential and Color of Fortified Wines during Accelerated Ageing: The Madeira Wine Case Study

    Directory of Open Access Journals (Sweden)

    José C. Marques

    2013-03-01

    Full Text Available Polyphenols, antioxidant potential and color of three types of fortified Madeira wines were evaluated during the accelerated ageing, named as estufagem. The traditional estufagem process was set to 45 °C for 3 months. Overheating conditions, 1 month at 70 °C, were also examined. Total polyphenols (TP, total monomeric anthocyanins (TMA and total flavonoids (TF were assessed by spectrophotometric methods, while individual polyphenols and furans were simultaneously determined by HPLC-DAD. Antioxidant potential (AP was estimated by ABTS, DPPH and FRAP assays, while color was evaluated by Glories and CIELab. Traditional estufagem decreased the TP and AP up to 20% and 26%, respectively, with final values similar to other wines. TMA of the Madeira wines from red grapes decreased during estufagem. Six hydroxybenzoic acids, three hydroxycinnamic acids, one stilbene, three flavonols and three flavan-3-ols were found in these wines. The prominent phenolics were hydroxycinnamates and hydroxybenzoates, even after estufagem. Most polyphenols decreased, with the exception of caffeic, ferulic, p-coumaric, gallic and syringic acids. Finally, both chromatic systems revealed that all wines tended to similar chromatic characteristics after estufagem. The study suggests that estufagem can be applied without high impact on polyphenols and antioxidant potential of these fortified wines.

  3. Imbibitions, energy test and accelerated ageing in primed and non-primed seeds of Peltophorum dubium

    Institute of Scientific and Technical Information of China (English)

    LILei-hong; ZHANGWan-li; ZUYuan-gang; SONIAPerez

    2005-01-01

    Peltophorum dubium seeds were set to imbibe with four treatments, soaked with solution Captan 0.2% under 10and 27℃,PEG 6000 -1.0 MPa under 10 and 27℃. For each treatment there were four replicates with 40 seeds incubated in 9-cm Petri dishes with double filter paper moistened with testing solution. The imbibition curves showed that the final weight increase were from 70% to 150% in the treatments when imbibition entered a lag phase. Seeds were tested for effects on germination of five treatments: control group (nonprimed), primed with PEG6000 -1.0 MPa at 10 and 27℃, primed with Captan 0.2% at 10 and 27℃. For each treatment, there were three sub-treatments: seeds were soaked in distilled water for 12, 24 and 36h before the energy test. Germination percentages of nonprimed seeds and primed in PEG 27℃ soaked in distilled water during 12 h were the highest, reaching 100%. The lowest germination percentage occurred primed seeds with PEG6000 27℃ and soaked in distilled water during 36 h, which was only 52%. Germination mean time of primed seeds in PEG at 10℃, soaked 24 h was 1.08 days, mean time of primed seeds in PEG at 27℃ soaked 12 h was 2.42 days. Accelerated ageing results showed low or no germination after ageing 72 h. Control group had a higher germination percentage and seeds were more resistant to deterioration than those in primed groups, both in Petri dish (27℃) and vermiculate (room temperature).

  4. Recognizing age-separated face images: humans and machines.

    Science.gov (United States)

    Yadav, Daksha; Singh, Richa; Vatsa, Mayank; Noore, Afzel

    2014-01-01

    Humans utilize facial appearance, gender, expression, aging pattern, and other ancillary information to recognize individuals. It is interesting to observe how humans perceive facial age. Analyzing these properties can help in understanding the phenomenon of facial aging and incorporating the findings can help in designing effective algorithms. Such a study has two components--facial age estimation and age-separated face recognition. Age estimation involves predicting the age of an individual given his/her facial image. On the other hand, age-separated face recognition consists of recognizing an individual given his/her age-separated images. In this research, we investigate which facial cues are utilized by humans for estimating the age of people belonging to various age groups along with analyzing the effect of one's gender, age, and ethnicity on age estimation skills. We also analyze how various facial regions such as binocular and mouth regions influence age estimation and recognition capabilities. Finally, we propose an age-invariant face recognition algorithm that incorporates the knowledge learned from these observations. Key observations of our research are: (1) the age group of newborns and toddlers is easiest to estimate, (2) gender and ethnicity do not affect the judgment of age group estimation, (3) face as a global feature, is essential to achieve good performance in age-separated face recognition, and (4) the proposed algorithm yields improved recognition performance compared to existing algorithms and also outperforms a commercial system in the young image as probe scenario.

  5. Recognizing age-separated face images: humans and machines.

    Directory of Open Access Journals (Sweden)

    Daksha Yadav

    Full Text Available Humans utilize facial appearance, gender, expression, aging pattern, and other ancillary information to recognize individuals. It is interesting to observe how humans perceive facial age. Analyzing these properties can help in understanding the phenomenon of facial aging and incorporating the findings can help in designing effective algorithms. Such a study has two components--facial age estimation and age-separated face recognition. Age estimation involves predicting the age of an individual given his/her facial image. On the other hand, age-separated face recognition consists of recognizing an individual given his/her age-separated images. In this research, we investigate which facial cues are utilized by humans for estimating the age of people belonging to various age groups along with analyzing the effect of one's gender, age, and ethnicity on age estimation skills. We also analyze how various facial regions such as binocular and mouth regions influence age estimation and recognition capabilities. Finally, we propose an age-invariant face recognition algorithm that incorporates the knowledge learned from these observations. Key observations of our research are: (1 the age group of newborns and toddlers is easiest to estimate, (2 gender and ethnicity do not affect the judgment of age group estimation, (3 face as a global feature, is essential to achieve good performance in age-separated face recognition, and (4 the proposed algorithm yields improved recognition performance compared to existing algorithms and also outperforms a commercial system in the young image as probe scenario.

  6. Accelerated evolution of the pituitary adenylate cyclase-activating polypeptide precursor gene during human origin

    DEFF Research Database (Denmark)

    Wang, Yin-Qiu; Qian, Ya-Ping; Yang, Su

    2005-01-01

    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. Udgivelsesdato: 2005-Jun...

  7. Gene expression and DNA repair in progeroid syndromes and human aging.

    Science.gov (United States)

    Kyng, Kasper J; Bohr, Vilhelm A

    2005-11-01

    Human progeroid syndromes are caused by mutations in single genes accelerating some but not all features of normal aging. Most progeroid disorders are linked to defects in genome maintenance, and while it remains unknown if similar processes underlie normal and premature aging, they provide useful models for the study of aging. Altered transcription is speculated to play a causative role in aging, and is involved in the pathology of most if not all progeroid syndromes. Previous studies demonstrate that there is a similar pattern of gene expression changes in primary cells from old and Werner syndrome compared to young suggesting a presence of common cellular aging mechanisms in old and progeria. Here we review the role of transcription in progeroid syndromes and discuss the implications of similar transcription aberrations in normal and premature aging.

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

    Science.gov (United States)

    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.

  9. Influence of Different Types of Resin Luting Agents on Color Stability of Ceramic Laminate Veneers Subjected to Accelerated Artificial Aging.

    Science.gov (United States)

    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 (pveneers 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 (pcements. The changes in self-adhesive cement do not depend on restoration thickness.

  10. Molecular aging and rejuvenation of human muscle stem cells

    DEFF Research Database (Denmark)

    Carlson, Morgan E; Suetta, Charlotte; Conboy, Michael J

    2009-01-01

    Very little remains known about the regulation of human organ stem cells (in general, and during the aging process), and most previous data were collected in short-lived rodents. We examined whether stem cell aging in rodents could be extrapolated to genetically and environmentally variable humans....... Our findings establish key evolutionarily conserved mechanisms of human stem cell aging. We find that satellite cells are maintained in aged human skeletal muscle, but fail to activate in response to muscle attrition, due to diminished activation of Notch compounded by elevated transforming growth...... factor beta (TGF-beta)/phospho Smad3 (pSmad3). Furthermore, this work reveals that mitogen-activated protein kinase (MAPK)/phosphate extracellular signal-regulated kinase (pERK) signalling declines in human muscle with age, and is important for activating Notch in human muscle stem cells. This molecular...

  11. Genome-wide approaches to understanding human ageing

    Directory of Open Access Journals (Sweden)

    Kaeberlein Matt

    2006-06-01

    Full Text Available Abstract The use of genomic technologies in biogerontology has the potential to greatly enhance our understanding of human ageing. High-throughput screens for alleles correlated with survival in long-lived people have uncovered novel genes involved in age-associated disease. Genome-wide longevity studies in simple eukaryotes are identifying evolutionarily conserved pathways that determine longevity. It is hoped that validation of these 'public' aspects of ageing in mice, along with analyses of variation in candidate human ageing genes, will provide targets for future interventions to slow the ageing process and retard the onset of age-associated pathologies.

  12. Effects of accelerated aging upon the lipid composition of seeds from two soft wheat varieties from Morocco

    Energy Technology Data Exchange (ETDEWEB)

    Ouzouline, M.; Tahani, N.; Demandre, C.; El Amrani, A.; Benhassaine-Kesri, G.; Serghini Caid, H.

    2009-07-01

    The lipid composition of the seeds from two soft wheat varieties (Triticum aestivum, cv. Marchouche and Mahdia) were analyzed before and after accelerated aging. Eight days of accelerated aging resulted in a total inhibition of seed germ inability as well as a decrease in their total and especially unsaturated fatty acid contents. Oleic and linoleic acid contents decreased particularly in the phosphatidylcholine of the seeds from both varieties. The proportion of polar lipids also decreased after aging as compared to neutral lipids: a 5.8% and 7.2% decrease in polar lipids was e observed in Mahdia and Marchouche cultivars, respectively. In the neutral lipids of the seeds from the Marchouche variety, the percentage of free fatty acids increased whereas the triacylglycerols decreased. After aging, the fatty acid compositions of all lipid classes were modified in the same manner as total fatty acid compositions. Among polar lipids, phospholipid proportions were particularly small, especially the phosphatidylcholine percentages with an 18.1% and 19.1% decrease in Mahdia and Marchouche varieties, respectively. In contrast, MGDG percentages increased, especially in the seeds from the Marchouche variety. A 15.5% increase was noticed when compared with seeds which were not aged. At the same time, the DGDG percentage showed a 16.6% decrease after accelerated aging of the seeds from the Marchouche variety. From these results we concluded that the lipid content decrease observed in seeds after accelerated aging could be linked to a loss in the germination and vigor of wheat seeds. (Author) 38 refs.

  13. The Gestational Age Pattern of Human Mortality

    DEFF Research Database (Denmark)

    Schöley, Jonas

    I present a lifetable by gestational age from week 23 until week 100 after the last menstrual period of the mother. The lifetable shows the pre-natal, peri-natal and post-natal mortality levels for US fetus/infants conceived in the year 2009. The observed age pattern of the force of mortality...

  14. Effect of dietary, social, and lifestyle determinants of accelerated aging and its common clinical presentation: A survey study.

    Science.gov (United States)

    Samarakoon, S M S; Chandola, H M; Ravishankar, B

    2011-07-01

    Aging is unavoidable and natural phenomenon of life. Modern gerontologists are realizing the fact that aging is a disease, which Ayurveda had accepted as natural disease since long. Rate of aging is determined by one's biological, social, lifestyle, and psychological conditions and adversity of which leads to accelerated form of aging (Akalaja jara or premature aging). The aim of this study is to identify potential factors that may accelerate aging in the context of dietry factors, lifestyle and mental makeup. The 120 diagnosed subjects of premature-ageing of 30-60 years were randomly selected in the survey study. Premature ageing was common among females (75.83%), in 30-40 age group (70%), 86.67% were married, had secondary level of education (36.66%), house-views (61.67%), belongs top middle class (58.33%) and engaged in occupations that dominating physical labour (88.33%). The maximum patients are constipated (60%), had mandagni (80%), vata-kapha prakriti (48.33%), rajasika prakriti (58.33%), madhyama vyayama shakti (73.33%), and madhyama jarana shakti (85.83%). Collectively, 43.33% patients were above normal BMI. The more patients had anushna (38.33%) and vishamasana dietary pattern (25.83%), consumed Lavana (88.33%) and Amla rasa (78.33%) in excess on regular basis. Some patients had addicted to tobacco (11.67%) and beetle chewing (5.83%). The maximum patients had no any exercise (79.17%) and specific hobby (79.17%) in their leisure times. Analyzing Hamilton Anxiety and Depression Rating Scales revealed that 39.80%, 37.86%, 33.98%, 24.27% and 18.44% patients had insomnia, depression, tension, GIT symptoms and anxious mood respectively. These data suggest that certain social, dietary and lifestyle factors contribute towards accelerated ageing among young individuals.

  15. Confocal Raman study of aging process in diabetes mellitus human voluntaries

    Science.gov (United States)

    Pereira, Liliane; Téllez Soto, Claudio Alberto; dos Santos, Laurita; Ali, Syed Mohammed; Fávero, Priscila Pereira; Martin, Airton A.

    2015-06-01

    Accumulation of AGEs [Advanced Glycation End - products] occurs slowly during the human aging process. However, its formation is accelerated in the presence of diabetes mellitus. In this paper, we perform a noninvasive analysis of glycation effect on human skin by in vivo confocal Raman spectroscopy. This technique uses a laser of 785 nm as excitation source and, by the inelastic scattering of light, it is possible to obtain information about the biochemical composition of the skin. Our aim in this work was to characterize the aging process resulting from the glycation process in a group of 10 Health Elderly Women (HEW) and 10 Diabetic Elderly Women (DEW). The Raman data were collected from the dermis at a depth of 70-130 microns. Through the theory of functional density (DFT) the bands positions of hydroxyproline, proline and AGEs (pentosidine and glucosepane) were calculated by using Gaussian 0.9 software. A molecular interpretation of changes in type I collagen was performed by the changes in the vibrational modes of the proline (P) and hydroxyproline (HP). The data analysis shows that the aging effects caused by glycation of proteins degrades type I collagen differently and leads to accelerated aging process.

  16. Myths of Human Sexuality in the Aging.

    Science.gov (United States)

    Andrus, Charles E.

    Human sexuality is discussed in terms of misconceptions about its function and the changing sexual needs of older adults. A review of history indicates that human sexuality has traditionally been connected with ideas of purity and strict importance of procreation. Judaeo-Christian ethics and the doctrine of Saint Augustine illustrate these…

  17. Poor maternal nutrition and accelerated postnatal growth induces an accelerated aging phenotype and oxidative stress in skeletal muscle of male rats

    Science.gov (United States)

    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

  18. Poor maternal nutrition and accelerated postnatal growth induces an accelerated aging phenotype and oxidative stress in skeletal muscle of male rats

    Directory of Open Access Journals (Sweden)

    Jane L. Tarry-Adkins

    2016-10-01

    Full Text Available ‘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

  19. Structural Basis for Accelerated Cleavage of Bovine Pancreatic Trypsin Inhibitor (BPTI) by Human Mesotrypsin

    Energy Technology Data Exchange (ETDEWEB)

    Salameh,M.; Soares, A.; Hockla, A.; Radisky, E.

    2008-01-01

    Human mesotrypsin is an isoform of trypsin that displays unusual resistance to polypeptide trypsin inhibitors and has been observed to cleave several such inhibitors as substrates. Whereas substitution of arginine for the highly conserved glycine 193 in the trypsin active site has been implicated as a critical factor in the inhibitor resistance of mesotrypsin, how this substitution leads to accelerated inhibitor cleavage is not clear. Bovine pancreatic trypsin inhibitor (BPTI) forms an extremely stable and cleavage-resistant complex with trypsin, and thus provides a rigorous challenge of mesotrypsin catalytic activity toward polypeptide inhibitors. Here, we report kinetic constants for mesotrypsin and the highly homologous (but inhibitor sensitive) human cationic trypsin, describing inhibition by, and cleavage of BPTI, as well as crystal structures of the mesotrypsin-BPTI and human cationic trypsin-BPTI complexes. We find that mesotrypsin cleaves BPTI with a rate constant accelerated 350-fold over that of human cationic trypsin and 150,000-fold over that of bovine trypsin. From the crystal structures, we see that small conformational adjustments limited to several side chains enable mesotrypsin-BPTI complex formation, surmounting the predicted steric clash introduced by Arg-193. Our results show that the mesotrypsin-BPTI interface favors catalysis through (a) electrostatic repulsion between the closely spaced mesotrypsin Arg-193 and BPTI Arg-17, and (b) elimination of two hydrogen bonds between the enzyme and the amine leaving group portion of BPTI. Our model predicts that these deleterious interactions accelerate leaving group dissociation and deacylation.

  20. The gestational age pattern of human mortality

    DEFF Research Database (Denmark)

    Schöley, Jonas; Vaupel, James W.; Jacobsen, Rune

    of a "birth hump" peaking week 38. The absolute rate of decline slows down over age. The observed gestational age pattern of the force of mortality is consistent with three hypotheses concerning the causes for ontogenescense: 1) Adaptation: as the organism growths it becomes more resilient towards death, 2......) transitional timing: the transition of birth is a stressful event and momentarily increases the force of mortality, 3) mortality selection: The frailest die first, resulting in the mean force of mortality to decline with age. In order to quantify the relative importance of these three processes I fit a three...

  1. The Gestational Age Pattern of Human Mortality

    DEFF Research Database (Denmark)

    Schöley, Jonas; Vaupel, James W.; Jacobsen, Rune

    of a "birth hump" peaking week 38. The absolute rate of decline slows down over age. The observed gestational age pattern of the force of mortality is consistent with three hypotheses concerning the causes for ontogenescense: 1) Adaptation: as the organism growths it becomes more resilient towards death, 2......) transitional timing: the transition of birth is a stressful event and momentarily increases the force of mortality, 3) mortality selection: The frailest die first, resulting in the mean force of mortality to decline with age. In order to quantify the relative importance of these three processes I fit a three...

  2. Exposure to omega-3 fatty acids at early age accelerate bone growth and improve bone quality.

    Science.gov (United States)

    Koren, Netta; Simsa-Maziel, Stav; Shahar, Ron; Schwartz, Betty; Monsonego-Ornan, Efrat

    2014-06-01

    Omega-3 fatty acids (FAs) are essential nutritional components that must be obtained from foods. Increasing evidence validate that omega-3 FAs are beneficial for bone health, and several mechanisms have been suggested to mediate their effects on bone, including alterations in calcium absorption and urinary calcium loss, prostaglandin synthesis, lipid oxidation, osteoblast formation and inhibition of osteoclastogenesis. However, to date, there is scant information regarding the effect of omega-3 FAs on the developing skeleton during the rapid growth phase. In this study we aim to evaluate the effect of exposure to high levels of omega-3 FAs on bone development and quality during prenatal and early postnatal period. For this purpose, we used the fat-1 transgenic mice that have the ability to convert omega-6 to omega-3 fatty acids and the ATDC5 chondrogenic cell line as models. We show that exposure to high concentrations of omega-3 FAs at a young age accelerates bone growth through alterations of the growth plate, associated with increased chondrocyte proliferation and differentiation. We further propose that those effects are mediated by the receptors G-protein coupled receptor 120 (GPR120) and hepatic nuclear factor 4α, which are expressed by chondrocytes in culture. Additionally, using a combined study on the structural and mechanical bone parameters, we show that high omega-3 levels contribute to superior trabecular and cortical structure, as well as to stiffer bones and improved bone quality. Most interestingly, the fat-1 model allowed us to demonstrate the role of maternal high omega-3 concentration on bone growth during the gestation and postnatal period. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Hypothalamic leptin gene therapy reduces body weight without accelerating age-related bone loss.

    Science.gov (United States)

    Turner, Russell T; Dube, Michael; Branscum, Adam J; Wong, Carmen P; Olson, Dawn A; Zhong, Xiaoying; Kweh, Mercedes F; Larkin, Iske V; Wronski, Thomas J; Rosen, Clifford J; Kalra, Satya P; Iwaniec, Urszula T

    2015-12-01

    Excessive weight gain in adults is associated with a variety of negative health outcomes. Unfortunately, dieting, exercise, and pharmacological interventions have had limited long-term success in weight control and can result in detrimental side effects, including accelerating age-related cancellous bone loss. We investigated the efficacy of using hypothalamic leptin gene therapy as an alternative method for reducing weight in skeletally-mature (9 months old) female rats and determined the impact of leptin-induced weight loss on bone mass, density, and microarchitecture, and serum biomarkers of bone turnover (CTx and osteocalcin). Rats were implanted with cannulae in the 3rd ventricle of the hypothalamus and injected with either recombinant adeno-associated virus encoding the gene for rat leptin (rAAV-Leptin, n=7) or a control vector encoding green fluorescent protein (rAAV-GFP, n=10) and sacrificed 18 weeks later. A baseline control group (n=7) was sacrificed at vector administration. rAAV-Leptin-treated rats lost weight (-4±2%) while rAAV-GFP-treated rats gained weight (14±2%) during the study. At study termination, rAAV-Leptin-treated rats weighed 17% less than rAAV-GFP-treated rats and had lower abdominal white adipose tissue weight (-80%), serum leptin (-77%), and serum IGF1 (-34%). Cancellous bone volume fraction in distal femur metaphysis and epiphysis, and in lumbar vertebra tended to be lower (PLeptin and rAAV-GFP rats. In summary, rAAV-Leptin-treated rats maintained a lower body weight compared to baseline and rAAV-GFP-treated rats with minimal effects on bone mass, density, microarchitecture, or biochemical markers of bone turnover.

  4. Human neurologic function and the aging process.

    Science.gov (United States)

    Potvin, A R; Syndulko, K; Tourtellotte, W W; Lemmon, J A; Potvin, J H

    1980-01-01

    Sixty-one normal men whose ages ranged from 20 to 80 years were evaluated on two occasions by means of a comprehensive series of 128 instrumented tests of neurologic function. The tests measured cognition, vision, strength, steadiness, reactions, speed, coordination, fatigue, gait, station, sensations, and tasks of daily living. The reliability of each test measured was determined, and any measure found unreliable (r less than or equal to 0.41) was not further analyzed. Significant age-related linear decreases were found for almost all neurologic functions. The declines over the age span varied from less than 10 percent to more than 90 percent for different functions. For the upper extremities, the largest declines (greater than 50 percent) were in hand-force steadiness, speed of hand-arm movements, and vibration sense; for the lower extremities, the largest declines were in one-legged balance with eyes closed and in vibration sense. For 13 of 14 tests in which significant dominant body-side effects were found, larger re-testing 7-10 days later, the subjects improved their scores by more than 5 percent on only 17 tests, 9 of which concerned the activities of daily living. No significant differential learning effects were found across age groups. The results point to the importance of developing a data bank on age-based neurologic function so that therapeutic effects can be evaluated in terms of age- and sex-matched normal functioning.

  5. Rapid evaluation of the durability of cortical neural implants using accelerated aging with reactive oxygen species

    Science.gov (United States)

    Takmakov, Pavel; Ruda, Kiersten; Phillips, K Scott; Isayeva, Irada S; Krauthamer, Victor; Welle, Cristin G

    2017-01-01

    Objective A challenge for implementing high bandwidth cortical brain–machine interface devices in patients is the limited functional lifespan of implanted recording electrodes. Development of implant technology currently requires extensive non-clinical testing to demonstrate device performance. However, testing the durability of the implants in vivo is time-consuming and expensive. Validated in vitro methodologies may reduce the need for extensive testing in animal models. Approach Here we describe an in vitro platform for rapid evaluation of implant stability. We designed a reactive accelerated aging (RAA) protocol that employs elevated temperature and reactive oxygen species (ROS) to create a harsh aging environment. Commercially available microelectrode arrays (MEAs) were placed in a solution of hydrogen peroxide at 87 °C for a period of 7 days. We monitored changes to the implants with scanning electron microscopy and broad spectrum electrochemical impedance spectroscopy (1 Hz–1 MHz) and correlated the physical changes with impedance data to identify markers associated with implant failure. Main results RAA produced a diverse range of effects on the structural integrity and electrochemical properties of electrodes. Temperature and ROS appeared to have different effects on structural elements, with increased temperature causing insulation loss from the electrode microwires, and ROS concentration correlating with tungsten metal dissolution. All array types experienced impedance declines, consistent with published literature showing chronic (>30 days) declines in array impedance in vivo. Impedance change was greatest at frequencies <10 Hz, and smallest at frequencies 1 kHz and above. Though electrode performance is traditionally characterized by impedance at 1 kHz, our results indicate that an impedance change at 1 kHz is not a reliable predictive marker of implant degradation or failure. Significance ROS, which are known to be present in vivo, can create

  6. Biological psychological and social determinants of old age: bio-psycho-social aspects of human aging.

    Science.gov (United States)

    Dziechciaż, Małgorzata; Filip, Rafał

    2014-01-01

    The aging of humans is a physiological and dynamic process ongoing with time. In accordance with most gerontologists' assertions it starts in the fourth decade of life and leads to death. The process of human aging is complex and individualized, occurs in the biological, psychological and social sphere. Biological aging is characterized by progressive age-changes in metabolism and physicochemical properties of cells, leading to impaired self-regulation, regeneration, and to structural changes and functional tissues and organs. It is a natural and irreversible process which can run as successful aging, typical or pathological. Biological changes that occur with age in the human body affect mood, attitude to the environment, physical condition and social activity, and designate the place of seniors in the family and society. Psychical ageing refers to human awareness and his adaptability to the ageing process. Among adaptation attitudes we can differentiate: constructive, dependence, hostile towards others and towards self attitudes. With progressed age, difficulties with adjustment to the new situation are increasing, adverse changes in the cognitive and intellectual sphere take place, perception process involutes, perceived sensations and information received is lowered, and thinking processes change. Social ageing is limited to the role of an old person is culturally conditioned and may change as customs change. Social ageing refers to how a human being perceives the ageing process and how society sees it.

  7. Human Growth Hormone (HGH): Does It Slow Aging?

    Science.gov (United States)

    Healthy Lifestyle Healthy aging Human growth hormone is described by some as the key to slowing the aging process. Before you sign up, get the facts. ... stave off some of the changes linked to aging, such as decreased muscle and bone mass. If ...

  8. A Model of Human Orientation and Self Motion Perception during Body Acceleration: The Orientation Modeling System

    Science.gov (United States)

    2016-09-28

    Aviation accident investigators often conduct qualitative perceptual analyses of mishaps when spatial disorientation is inferred as a cause. We have...developed a quantitative perceptual model of human spatial orientation and have employed it to evaluate data from a variety of acceleration situations, in...Research and Material Command (USAMRMC; In-House Laboratory Independent Research), Small Business Innovative Research program (PEO Aviation), and the

  9. Behavior of human horizontal vestibulo-ocular reflex in response to high-acceleration stimuli

    Science.gov (United States)

    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).

  10. The age pattern of human capital and regional productivity

    OpenAIRE

    Hirte, Georg; Brunow, Stephan

    2008-01-01

    We explore the impact of the age structure of human capital on average regional productivity by applying a spatial econometric analysis based on an augmented Lucas-type production function. We also apply a new definition of regional human capital focusing on its availability. The estimates provide evidence that there are age specific human capital effects in Germany and that a temporary increase in regional productivity could occur during the demographic transition. Furthermore, it becomes cl...

  11. Effects of different surface treatments and accelerated artificial aging on the bond strength of composite resin repairs

    Directory of Open Access Journals (Sweden)

    Marco Aurélio Veiga de Melo

    2011-12-01

    Full Text Available 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.

  12. Test of a device for accelerated ageing of polymeric material in high concentrated sunlight at the DLR solar furnace

    Energy Technology Data Exchange (ETDEWEB)

    Witzke, A.; Neumann, A.; Kaluza, J. [German Aerospace Center (DLR), Solar Energy Technology, Cologne (Germany); Demuth, M.; Ritterskamp, P. [Max-Planck-Inst. fuer Strahlenchemie, Muelheim a.d.R. (Germany)

    2001-07-01

    Within this study the design and first tests of a device for accelerated ageing with high concentrated sunlight have been described. Firstly, the device was designed for testing samples of lacquer for the car industry. It is based on two points: first, the photochemical effect that the ageing of polymers is mainly initiated by the UV solar radiation and, second, on the idea to accelerate the ageing process by increasing the UV radiation dose. Therefore the concentrated sunlight at the DLR Solar Furnace is filtered by a cold-mirror that reflects the radiation with a wavelength below 450 nm onto the samples. The samples are fixed in a chamber where they can simultaneously be wetted by a spraying device. The first tests show that this device enables us to radiate the relevant samples with a high UV radiation intensity without overheating them. During one day irradiation at the DLR Solar Furnace in March 2001 we reach an UV radiation dose which is about sixteen times higher than the dose after 24 hours irradiation in common used weathering devices. Further tests at the DLR Solar Furnace have to examine in what way this increased radiation dose leads to a high accelerated ageing of the polymeric material. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Mancuso Daniela

    2009-01-01

    Full Text Available Objectives: 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. Materials and Methods: 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. Results: 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.

  14. Chronomics, human time estimation, and aging

    Directory of Open Access Journals (Sweden)

    Franz Halberg

    2008-12-01

    Full Text Available Franz Halberg, Robert B Sothern, Germaine Cornélissen, Jerzy Czaplicki1Halberg Chronobiology Center, University of Minnesota, Minneapolis, MN, USA; 1Institut de Pharmacologie et de Biologie Structurale CNRS, Université Paul Sabatier, Toulouse, FranceBackground: Circadian rhythm stage affects many outcomes, including those of mental aging.Methods: Estimations of 1 minute ∼5 times/day for a year, 25 years apart, by a healthy male biomedical scientist (RBS, are analyzed by the extended cosinor.Results: Cycles of a half-week, a week, ∼30 days, a half-year and a year, in self-assessed 1-minute estimation by RBS between 25 and 60 years of age in health, are mapped for the first time, compared and opposite effects are found. For RBS at 60 vs at 25 years of age, it takes less time in the morning around 10:30 (P < 0.001, but not in the evening around 19:30 (P = 0.956, to estimate 1 minute.Discussion: During the intervening decades, the time of estimating 1 minute differed greatly, dependent on circadian stage, being a linear decrease in the morning and increase in the evening, the latter modulated by a ∼33.6-year cycle.Conclusion: Circadian and infradian rhythm mapping is essential for a scrutiny of effects of aging. A ∼30-day and a circannual component apparent at 25 years of age are not found later; cycles longer than a year are detected. Rhythm stages await tests as markers for timing therapy in disease.Keywords: circadian rhythm, mental function, time estimation

  15. Aging of the Human Vestibular System

    Science.gov (United States)

    Zalewski, Christopher K.

    2015-01-01

    Aging affects every sensory system in the body, including the vestibular system. Although its impact is often difficult to quantify, the deleterious impact of aging on the vestibular system is serious both medically and economically. The deterioration of the vestibular sensory end organs has been known since the 1970s; however, the measurable impact from these anatomical changes remains elusive. Tests of vestibular function either fall short in their ability to quantify such anatomical deterioration, or they are insensitive to the associated physiologic decline and/or central compensatory mechanisms that accompany the vestibular aging process. When compared with healthy younger individuals, a paucity of subtle differences in test results has been reported in the healthy older population, and those differences are often observed only in response to nontraditional and/or more robust stimuli. In addition, the reported differences are often clinically insignificant insomuch that the recorded physiologic responses from the elderly often fall within the wide normative response ranges identified for normal healthy adults. The damaging economic impact of such vestibular sensory decline manifests itself in an exponential increase in geriatric dizziness and a subsequent higher prevalence of injurious falls. An estimated $10 to $20 billion dollar annual cost has been reported to be associated with falls-related injuries and is the sixth leading cause of death in the elderly population, with a 20% mortality rate. With an estimated 115% increase in the geriatric population over 65 years of age by the year 2050, the number of balanced-disordered patients with a declining vestibular system is certain to reach near epidemic proportions. An understanding of the effects of age on the vestibular system is imperative if clinicians are to better manage elderly patients with balance disorders, dizziness, and vestibular disease. PMID:27516717

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

    Science.gov (United States)

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

    2016-05-19

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

  17. Gene expression in the aging human brain: an overview.

    Science.gov (United States)

    Mohan, Adith; Mather, Karen A; Thalamuthu, Anbupalam; Baune, Bernhard T; Sachdev, Perminder S

    2016-03-01

    The review aims to provide a summary of recent developments in the study of gene expression in the aging human brain. Profiling differentially expressed genes or 'transcripts' in the human brain over the course of normal aging has provided valuable insights into the biological pathways that appear activated or suppressed in late life. Genes mediating neuroinflammation and immune system activation in particular, show significant age-related upregulation creating a state of vulnerability to neurodegenerative and neuropsychiatric disease in the aging brain. Cellular ionic dyshomeostasis and age-related decline in a host of molecular influences on synaptic efficacy may underlie neurocognitive decline in later life. Critically, these investigations have also shed light on the mobilization of protective genetic responses within the aging human brain that help determine health and disease trajectories in older age. There is growing interest in the study of pre and posttranscriptional regulators of gene expression, and the role of noncoding RNAs in particular, as mediators of the phenotypic diversity that characterizes human brain aging. Gene expression studies in healthy brain aging offer an opportunity to unravel the intricately regulated cellular underpinnings of neurocognitive aging as well as disease risk and resiliency in late life. In doing so, new avenues for early intervention in age-related neurodegenerative disease could be investigated with potentially significant implications for the development of disease-modifying therapies.

  18. Proteomics and aging : studying the influence of aging on endothelial cells and human plasma

    NARCIS (Netherlands)

    Eman, M.R.

    2007-01-01

    In general, human aging is considered one of the most complex and less-well understood process in biology. In this thesis the possibilities of proteomics technology in the field of aging were explored. The complexity of the aging process was supposed to accompanied by relatively subtle proteome vari

  19. Reward motivation accelerates the onset of neural novelty signals in humans to 85 milliseconds.

    Science.gov (United States)

    Bunzeck, Nico; Doeller, Christian F; Fuentemilla, Lluis; Dolan, Raymond J; Duzel, Emrah

    2009-08-11

    The neural responses that distinguish novel from familiar items in recognition memory tasks are remarkably fast in both humans and nonhuman primates. In humans, the earliest onsets of neural novelty effects emerge at about approximately 150-200 ms after stimulus onset. However, in recognition memory studies with nonhuman primates, novelty effects can arise at as early as 70-80 ms. Here, we address the possibility that this large species difference in onset latencies is caused experimentally by the necessity of using reward reinforcement to motivate the detection of novel or familiar items in nonhuman primates but not in humans. Via magnetoencephalography in humans, we show in two experiments that the onset of neural novelty signals is accelerated from approximately 200 ms to approximately 85 ms if correct recognition memory for either novel or familiar items is rewarded. Importantly, this acceleration is independent of whether the detection of the novel or the familiar scenes is rewarded. Furthermore, this early novelty effect contributed to memory retrieval because neural reward responses, which were contingent upon novelty detection, followed approximately 100 ms later. Thus, under the contextual influence of reward motivation, behaviorally relevant novelty signals emerge much faster than previously held possible in humans.

  20. Lifestyle-induced metabolic inflexibility and accelerated ageing syndrome: insulin resistance, friend or foe?

    Directory of Open Access Journals (Sweden)

    Bell Jimmy D

    2009-04-01

    that as oxidative stress determines functional longevity, a rather more descriptive term for the metabolic syndrome is the 'lifestyle-induced metabolic inflexibility and accelerated ageing syndrome'. Ultimately, thriftiness is good for us as long as we have hormetic stimuli; unfortunately, mankind is attempting to remove all hormetic (stressful stimuli from his environment.

  1. ACCELERATED THERMAL AGEING OF ACRYLIC COPOLYMERS, CYCLOHEXANONE-BASED AND UREA-ALDEHYDE RESINS USED IN PAINTINGS CONSERVATION

    OpenAIRE

    Farmakalidis, Helen Velonika; Douvas, Antonios M.; Karatasios, Ioannis; Sotiropoulou, Sophia; Boyatzis, Stamatis; Argitis, Panagiotis; Chryssoulakis, Yannis; Kilikoglou, Vassilis

    2016-01-01

    The monitoring of performance characteristics of resins was always an issue for the conservation community, since the stability of the art objects depends on the service life of conservation materials used. Among the resins commonly applied in the field of paintings conservation, four of the most popular ones, Paraloid B72, Primal AC33 (acrylic polymers), Ketone Resin N (cyclohexanone) and Laropal A81 (ureaaldehyde) were selected to be comparatively studied under accelerated ageing conditions...

  2. Klotho is a serum factor related to human aging

    Institute of Scientific and Technical Information of China (English)

    肖能明; 张焱明; 郑权; 顾军

    2004-01-01

    Background Does klotho (KL) protein exist in human serum, and is there any correlation between KL protein in serum with human aging? In order to answer those questions, we identified KL protein in human serum and established the correlation between KL protein in human serum and aging.Methods We prepared a polyclonal antibody against human KL protein that was able to recognize the C-terminal of human secreted KL protein. Western blot and enzyme-linked immunosorbent assay (ELISA) were used to identify KL protein in human serum.Results In Western blot, the antibody specifically recognized a 60-kD KL protein in both human and mice serum. The population aged from 0 to 91 years screened by ELISA revealed that the level of serum KL declined while age increased, though each individual level was variable and that the trend of decreasing in serum KL had no difference in sex.Conclusion Our data suggest that KL is a serum factor related to human aging.

  3. Climate change in the age of humans

    Science.gov (United States)

    J. Curt. Stager

    2014-01-01

    The Anthropocene epoch presents a mix of old and new challenges for the world’s forests. Climatic instability has typified most of the Cenozoic Era but today’s situation is unique due to the presence of billions of humans on the planet. The potential rate and magnitude of future warming driven by continued fossil fuel combustion could be unprecedented during the last...

  4. Influence of Workforce Ageing on Human Capital Formation

    OpenAIRE

    Stonawski, M.

    2008-01-01

    This paper addresses the question of how workforce ageing influences human capital formation, human capital deterioration, and future productivity growth. The method presented in this paper focuses on the magnitude of human capital that has been accumulated in an individual. It takes into consideration education, acquiring knowledge and experience, knowledge becoming obsolete or forgotten, as well as the impact of health. The estimated human capital curve (based on the net effect of the vario...

  5. Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Vaziri, H.; Uchida, I.; Lan Wei; Harley, C.B. (McMaster Univ., Hamilton, Ontario (Canada)); Schaechter, F.; Cohen, D. (Centre d' Etude du Polymorphisme Humain, Paris (France)); Xiaoming Zhu; Effros, R. (Univ. of California, Los Angeles (United States))

    1993-04-01

    The telomere hypothesis of cellular aging proposes that loss of telomeric DNA (TTAGGG) from human chromosomes may ultimately cause cell-cycle exit during replicative senescence. Since lymphocytes have a limited replicative capacity and since blood cells were previously shown to lose telomeric DNA during aging in vivo, the authors wished to determine (a) whether accelerated telomere loss is associated with the premature immunosenescence of lymphocytes in individuals with Down syndrome (DS) and (b) whether telomeric DNA is also lost during aging of lymphocytes in vitro. To investigate the effects of aging and trisomy 21 on telomere loss in vivo, genomic DNA was isolated from peripheral blood lymphocytes of 140 individuals (age 0--107 years), including 21 DS patients (age 0--45 years). Digestion with restriction enzymes HinfI and RsaI generated terminal restriction fragments (TRFs), which were detected by Southern analysis using a telomere-specific probe ([sup 32]P-(C[sub 3]TA[sub 2])[sub 3]). The rate of telomere loss was calculated from the decrease in mean TRF length, as a function of donor age. DS patients showed a significantly higher rate of telomere loss with donor age (133 [+-] 15 bp/year) compared with age-matched controls (41 [+-] 7.7 bp/year) (P < .0005), suggesting that accelerated telomere loss is a biomarker of premature immunosenescence of DS patients and that it may play a role in this process. Telomere loss during aging in vitro was calculated for lymphocytes from four normal individuals, grown in culture for 10--30 population doublings. The rate of telomere loss was [approximately]120 bp/cell doubling, comparable to that seen in other somatic cells. Moreover, telomere lengths of lymphocytes from centenarians and from older DS patients were similar to those of senescent lymphocytes in culture, which suggests that replicative senescence could partially account for aging of the immune system in DS patients and in elderly individuals. 31 refs., 3 figs.

  6. A preliminary study of the composition of commercial oil, acrylic and vinyl paints and their behaviour after accelerated ageing conditions

    Directory of Open Access Journals (Sweden)

    Francesca Caterina Izzo

    2014-12-01

    Full Text Available This study is part of a research project dealing with the establishment of monitoring and damage prevention plans for contemporary artworks. For this purpose, some commercial paints, among the most currently used by young artists, were selected: Winton oil paint (Winsor & Newton, UK, Heavy Body acrylic paint (Liquitex, USA and Flashe vinyl paint (Lefranc & Bourgeois, France. The paints were subjected to different treatments of accelerated ageing, the results indicating different behaviour in relation both to the type of binders and pigments present in the different formulations. In particular, it was observed that ageing produced by ozone plays an important role in the stability of the oil paints, above all in those containing organic azo pigments. Thermal ageing, as expected, influences the stability of all the commercial paints examined, with the formation of alteration products and visible changes in the paint films. Ageing produced by moisture clearly affects the synthetic polymer-based paints, particularly evident in the changes in mass. In all cases, the accelerated ageing treatments produced chromatic variations, more evidently for the oil paints containing organic pigment.

  7. Elevation of cartilage AGEs does not accelerate initiation of canine experimental osteoarthritis upon mild surgical damage

    NARCIS (Netherlands)

    Vos, P.A.J.M.; Degroot, J.; Barten-Van Rijbroek, A.D.; Zuurmond, A.-M.; Bijlsma, J.W.J.; Mastbergen, S.C.; Lafeber, F.P.J.G.

    2012-01-01

    Osteoarthritis is a highly prevalent disease, age being the main risk factor. The age-related accumulation of advanced-glycation-endproducts (AGEs) adversely affects the mechanical and biochemical properties of cartilage. The hypothesis that accumulation of cartilage AGEs in combination with surgica

  8. Can Social Instability, Food Deprivation and Food Inequality Accelerate Neuronal Aging?

    Directory of Open Access Journals (Sweden)

    Shahnaz Mojarab

    2012-07-01

    Full Text Available Based on both animal and human studies, inequality in food intake and social instability has adverse effects on the health of individuals and the community. However, it is not known whether social instability, food deprivation and food inequality affect neuronal death and premature aging in young animals. To address this question, the effects of these adverse situations, histopathological changes in hippocampal pyramidal cells and aging process were investigated.Forty eight New Zeeland white male rabbits were divided into six groups and all of them were housed in similar conditions, with 2 animals per cage in a temperature-controlled colony room under light–dark cycle . All experimental animals were fed on standard rabbit commercial pellets and different social situations such as food deprivation, inequality in food intake, and unstable social status were applied to experimental groups during eight weeks. Afterward, lipofuscin accumulation and apoptosis, as main markers of aging, were compared to the control group by Long Ziehl Nelseen staining and the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL reaction assay to reveal the rate of lipofuscin pigment accumulation and TUNEL-reactive apoptotic bodies in the hippocampal pyramidal cells. Serum cortisol level was also measured. Inequality in social situation raised chronic stress (i.e. food deprivation, social inequality and instability and caused significant changes in lipofuscin accumulation in hippocampal pyramidal cells in comparison to the control group (p<0.005 . The results also showed a significant increase in the ratio of apoptotic to normal cells in all of the stressed groups compared to the control group (p<0.05. Moreover, application of the social inequality and stresses alone or together modulated levels of cortisol in the experimental group. These findings suggest that food deprivation, inequality and social instability enhance the susceptibility of hippocampal

  9. Human age estimation framework using different facial parts

    OpenAIRE

    Mohamed Y. El Dib; Hoda M. Onsi

    2011-01-01

    Human age estimation from facial images has a wide range of real-world applications in human computer interaction (HCI). In this paper, we use the bio-inspired features (BIF) to analyze different facial parts: (a) eye wrinkles, (b) whole internal face (without forehead area) and (c) whole face (with forehead area) using different feature shape points. The analysis shows that eye wrinkles which cover 30% of the facial area contain the most important aging features compared to internal face and...

  10. A current genetic and epigenetic view on human aging mechanisms.

    Science.gov (United States)

    Ostojić, Sala; Pereza, Nina; Kapović, Miljenko

    2009-06-01

    The process of aging is one of the most complex and intriguing biological phenomenons. Aging is a genetically regulated process in which the organism's maximum lifespan potential is pre-determined, while the rate of aging is influenced by environmental factors and lifestyle. Considering the complexity of mechanisms involved in the regulation of aging process, up to this date there isn't a major, unifying theory which could explain them. As genetic/epigenetic and environmental factors both inevitably influence the aging process, here we present a review on the genetic and epigenetic regulation of the most important molecular and cellular mechanisms involved in the process of aging. Based on the studies on oxidative stress, metabolism, genome stability, epigenetic modifications and cellular senescence in animal models and humans, we give an overview of key genetic and molecular pathways related to aging. As most of genetic manipulations which influence the aging process also affect reproduction, we discuss aging in humans as a post-reproductive genetically determined process. After the age of reproductive success, aging continously progresses which clinically coincides with the onset of most chronic diseases, cancers and dementions. As evolution shapes the genomes for reproductive success and not for post-reproductive survival, aging could be defined as a protective mechanism which ensures the preservation and progress of species through the modification, trasmission and improvement of genetic material.

  11. Accelerator mass spectrometry for human biochemistry: The practice and the potential

    Science.gov (United States)

    Vogel, John S.

    2000-10-01

    Isotopic labels are a primary tool for tracing chemicals in natural systems. Accelerator mass spectrometry (AMS) quantifies long-lived isotopes that can be used in safe, sensitive and precise biochemical research with human participants. AMS could reduce the use of animals in biochemical research and remove the uncertain extrapolations from animal models to humans. Animal data seldom represent the sort of variability expected in a human population. People, knowingly or not, routinely expose themselves to radiation risks much greater than AMS-based biochemical research that traces μg/kg doses of chemicals containing tens of nCi of 14C for as long as 7 months. AMS is applied to research in toxicology, pharmacology and nutrition.

  12. Epigenetic Mechanisms of the Aging Human Retina

    Science.gov (United States)

    Pennington, Katie L.; DeAngelis, Margaret M.

    2015-01-01

    Degenerative retinal diseases, such as glaucoma, age-related macular degeneration, and diabetic retinopathy, have complex etiologies with environmental, genetic, and epigenetic contributions to disease pathology. Much effort has gone into elucidating both the genetic and the environmental risk factors for these retinal diseases. However, little is known about how these genetic and environmental risk factors bring about molecular changes that lead to pathology. Epigenetic mechanisms have received extensive attention of late for their promise of bridging the gap between environmental exposures and disease development via their influence on gene expression. Recent studies have identified epigenetic changes that associate with the incidence and/or progression of each of these retinal diseases. Therefore, these epigenetic modifications may be involved in the underlying pathological mechanisms leading to blindness. Further genome-wide epigenetic studies that incorporate well-characterized tissue samples, consider challenges similar to those relevant to gene expression studies, and combine the genome-wide epigenetic data with genome-wide genetic and expression data to identify additional potentially causative agents of disease are needed. Such studies will allow researchers to create much-needed therapeutics to prevent and/or intervene in disease progression. Improved therapeutics will greatly enhance the quality of life and reduce the burden of disease management for millions of patients living with these potentially blinding conditions. PMID:26966390

  13. Computational biology in human aging : an omics data integration approach

    NARCIS (Netherlands)

    Akker, Erik Ben van den

    2015-01-01

    Throughout this thesis, human aging and its relation to health are studied in the context of two parallel though complementary lines of research: biomarkers and genetics. The search for informative biomarkers of aging focuses on easy accessible and quantifiable substances of the body that can be u

  14. Age-correlated gene expression in normal and neurodegenerative human brain tissues.

    Directory of Open Access Journals (Sweden)

    Kajia Cao

    Full Text Available BACKGROUND: Human brain aging has received special attention in part because of the elevated risks of neurodegenerative disorders such as Alzheimer's disease in seniors. Recent technological advances enable us to investigate whether similar mechanisms underlie aging and neurodegeneration, by quantifying the similarities and differences in their genome-wide gene expression profiles. PRINCIPAL FINDINGS: We have developed a computational method for assessing an individual's "physiological brain age" by comparing global mRNA expression datasets across a range of normal human brain samples. Application of this method to brains samples from select regions in two diseases--Alzheimer's disease (AD, superior frontal gyrus, frontotemporal lobar degeneration (FTLD, in rostral aspect of frontal cortex ∼BA10--showed that while control cohorts exhibited no significant difference between physiological and chronological ages, FTLD and AD exhibited prematurely aged expression profiles. CONCLUSIONS: This study establishes a quantitative scale for measuring premature aging in neurodegenerative disease cohorts, and it identifies specific physiological mechanisms common to aging and some forms of neurodegeneration. In addition, accelerated expression profiles associated with AD and FTLD suggest some common mechanisms underlying the risk of developing these diseases.

  15. Evolution of the microstructure of unmodified and polymer modified asphalt binders with aging in an accelerated weathering tester.

    Science.gov (United States)

    Menapace, Ilaria; Masad, Eyad

    2016-09-01

    This paper presents findings on the evolution of the surface microstructure of two asphalt binders, one unmodified and one polymer modified, directly exposed to aging agents with increasing durations. The aging is performed using an accelerated weathering tester, where ultraviolet radiation, oxygen and an increased temperature are applied to the asphalt binder surface. Ultraviolet and dark cycles, which simulated the succession of day and night, alternated during the aging process, and also the temperature varied, which corresponded to typical summer day and night temperatures registered in the state of Qatar. Direct aging of an exposed binder surface is more effective in showing microstructural modifications than previously applied protocols, which involved the heat treatment of binders previously aged with standardized methods. With the new protocol, any molecular rearrangements in the binder surface after aging induced by the heat treatment is prevented. Optical photos show the rippling and degradation of the binder surface due to aging. Microstructure images obtained by means of atomic force microscopy show gradual alteration of the surface due to aging. The original relatively flat microstructure was substituted with a profoundly different microstructure, which significantly protrudes from the surface, and is characterized by various shapes, such as rods, round structures and finally 'flower' or 'leaf' structures.

  16. Deficiency in Poly(ADP-ribose) Polymerase-1 (PARP-1) Accelerates Aging and Spontaneous Carcinogenesis in Mice

    Science.gov (United States)

    Piskunova, Tatiana S.; Yurova, Maria N.; Ovsyannikov, Anton I.; Semenchenko, Anna V.; Zabezhinski, Mark A.; Popovich, Irina G.; Wang, Zhao-Qi; Anisimov, Vladimir N.

    2008-01-01

    Genetic and biochemical studies have shown that PARP-1 and poly(ADP-ribosyl)ation play an important role in DNA repair, genomic stability, cell death, inflammation, telomere maintenance, and suppressing tumorigenesis, suggesting that the homeostasis of poly(ADP-ribosyl)ation and PARP-1 may also play an important role in aging. Here we show that PARP-1−/− mice exhibit a reduction of life span and a significant increase of population aging rate. Analysis of noninvasive parameters, including body weight gain, body temperature, estrous function, behavior, and a number of biochemical indices suggests the acceleration of biological aging in PARP-1−/− mice. The incidence of spontaneous tumors in both PARP-1−/− and PARP-1+/+ groups is similar; however, malignant tumors including uterine tumors, lung adenocarcinomas and hepatocellular carcinomas, develop at a significantly higher frequency in PARP-1−/− mice than PARP-1+/+ mice (72% and 49%, resp.; P < .05). In addition, spontaneous tumors appear earlier in PARP-1−/− mice compared to the wild type group. Histopathological studies revealed a wide spectrum of tumors in uterus, ovaries, liver, lungs, mammary gland, soft tissues, and lymphoid organs in both groups of the mice. These results demonstrate that inactivation of DNA repair gene PARP-1 in mice leads to acceleration of aging, shortened life span, and increased spontaneous carcinogenesis. PMID:19415146

  17. Deficiency in Poly(ADP-ribose Polymerase-1 (PARP-1 Accelerates Aging and Spontaneous Carcinogenesis in Mice

    Directory of Open Access Journals (Sweden)

    Tatiana S. Piskunova

    2008-01-01

    Full Text Available Genetic and biochemical studies have shown that PARP-1 and poly(ADP-ribosylation play an important role in DNA repair, genomic stability, cell death, inflammation, telomere maintenance, and suppressing tumorigenesis, suggesting that the homeostasis of poly(ADP-ribosylation and PARP-1 may also play an important role in aging. Here we show that PARP-1−/− mice exhibit a reduction of life span and a significant increase of population aging rate. Analysis of noninvasive parameters, including body weight gain, body temperature, estrous function, behavior, and a number of biochemical indices suggests the acceleration of biological aging in PARP-1−/− mice. The incidence of spontaneous tumors in both PARP-1−/− and PARP-1+/+ groups is similar; however, malignant tumors including uterine tumors, lung adenocarcinomas and hepatocellular carcinomas, develop at a significantly higher frequency in PARP-1−/− mice than PARP-1+/+ mice (72% and 49%, resp.; < .05. In addition, spontaneous tumors appear earlier in PARP-1−/− mice compared to the wild type group. Histopathological studies revealed a wide spectrum of tumors in uterus, ovaries, liver, lungs, mammary gland, soft tissues, and lymphoid organs in both groups of the mice. These results demonstrate that inactivation of DNA repair gene PARP-1 in mice leads to acceleration of aging, shortened life span, and increased spontaneous carcinogenesis.

  18. Uniquely Human Self-Control Begins at School Age

    Science.gov (United States)

    Herrmann, Esther; Misch, Antonia; Hernandez-Lloreda, Victoria; Tomasello, Michael

    2015-01-01

    Human beings have remarkable skills of self-control, but the evolutionary origins of these skills are unknown. Here we compare children at 3 and 6 years of age with one of humans' two nearest relatives, chimpanzees, on a battery of reactivity and self-control tasks. Three-year-old children and chimpanzees were very similar in their abilities to…

  19. Uniquely Human Self-Control Begins at School Age

    Science.gov (United States)

    Herrmann, Esther; Misch, Antonia; Hernandez-Lloreda, Victoria; Tomasello, Michael

    2015-01-01

    Human beings have remarkable skills of self-control, but the evolutionary origins of these skills are unknown. Here we compare children at 3 and 6 years of age with one of humans' two nearest relatives, chimpanzees, on a battery of reactivity and self-control tasks. Three-year-old children and chimpanzees were very similar in their abilities to…

  20. Characterizing healthy samples for studies of human cognitive aging

    OpenAIRE

    Geldmacher, David S.; Levin, Bonnie E.; Wright, Clinton B.

    2012-01-01

    Characterizing the cognitive declines associated with aging, and differentiating them from the effects of disease in older adults, are important goals for human neuroscience researchers. This is also an issue of public health urgency in countries with rapidly aging populations. Progress toward understanding cognitive aging is complicated by numerous factors. Researchers interested in cognitive changes in healthy older adults need to consider these complexities when they design and interpre...

  1. Chronologic versus Biologic Aging of the Human Choroid

    OpenAIRE

    Christian Albrecht May

    2013-01-01

    Several aspects of chronologic and biologic aging in the human choroid are reviewed from the literature. They often reveal methodological problems for age-dependent changes of the following parameters: choroidal thickness, choroidal pigmentation, choroidal vasculature and blood flow, and choroidal innervation. On reinterpreting some data of studies concerning Bruch’s membrane, changes observed at different age points seem more likely to be nonlinear. Concluding from the data presented so far,...

  2. Accelerated evolution of the ASPM gene controlling brain size begins prior to human brain expansion.

    Directory of Open Access Journals (Sweden)

    Natalay Kouprina

    2004-05-01

    Full Text Available Primary microcephaly (MCPH is a neurodevelopmental disorder characterized by global reduction in cerebral cortical volume. The microcephalic brain has a volume comparable to that of early hominids, raising the possibility that some MCPH genes may have been evolutionary targets in the expansion of the cerebral cortex in mammals and especially primates. Mutations in ASPM, which encodes the human homologue of a fly protein essential for spindle function, are the most common known cause of MCPH. Here we have isolated large genomic clones containing the complete ASPM gene, including promoter regions and introns, from chimpanzee, gorilla, orangutan, and rhesus macaque by transformation-associated recombination cloning in yeast. We have sequenced these clones and show that whereas much of the sequence of ASPM is substantially conserved among primates, specific segments are subject to high Ka/Ks ratios (nonsynonymous/synonymous DNA changes consistent with strong positive selection for evolutionary change. The ASPM gene sequence shows accelerated evolution in the African hominoid clade, and this precedes hominid brain expansion by several million years. Gorilla and human lineages show particularly accelerated evolution in the IQ domain of ASPM. Moreover, ASPM regions under positive selection in primates are also the most highly diverged regions between primates and nonprimate mammals. We report the first direct application of TAR cloning technology to the study of human evolution. Our data suggest that evolutionary selection of specific segments of the ASPM sequence strongly relates to differences in cerebral cortical size.

  3. Accelerated Thermal Ageing of Polypropylene Fibres under High Oxygen pressure In Aqueous Media : Methodological Aspects

    OpenAIRE

    Richaud, E.; Farcas, F.; FAYOLLE, B.; Audouin, L.; VERDU, J.

    2005-01-01

    Polypropylene materials are currently used in civil engineering, for example for soils reinforcement or concrete protection in tunnels. The expected lifetime (100 years) makes accelerated tests necessary in order to evaluate durability. These one are traditionally performed in ventilated ovens at high temperature (110°C-130°C). This approach is nonetheless very questionable for many reasons (stabilizers efficiency and degradation mechanism changes with temperature) so a new test is now under ...

  4. Priming of microglia in a DNA-repair deficient model of accelerated aging

    NARCIS (Netherlands)

    Raj, Divya D. A.; Jaarsma, Dick; Holtman, Inge R.; Olah, Marta; Ferreira, Filipa M.; Schaafsma, Wandert; Brouwer, Nieske; Meijer, Michel M.; de Waard, Monique C.; van der Pluijm, Ingrid; Brandt, Renata; Kreft, Karim L.; Laman, Jon D.; de Haan, Gerald; Biber, Knut P. H.; Hoeijmakers, Jan H. J.; Eggen, Bart J. L.; Boddeke, Hendrikus W. G. M.

    2014-01-01

    Aging is associated with reduced function, degenerative changes, and increased neuroinflammation of the central nervous system (CNS). Increasing evidence suggests that changes in microglia cells contribute to the age-related deterioration of the CNS. The most prominent age-related change of microgli

  5. Priming of microglia in a DNA-repair deficient model of accelerated aging

    NARCIS (Netherlands)

    Raj, Divya D. A.; Jaarsma, Dick; Holtman, Inge R.; Olah, Marta; Ferreira, Filipa M.; Schaafsma, Wandert; Brouwer, Nieske; Meijer, Michel M.; de Waard, Monique C.; van der Pluijm, Ingrid; Brandt, Renata; Kreft, Karim L.; Laman, Jon D.; de Haan, Gerald; Biber, Knut P. H.; Hoeijmakers, Jan H. J.; Eggen, Bart J. L.; Boddeke, Hendrikus W. G. M.

    2014-01-01

    Aging is associated with reduced function, degenerative changes, and increased neuroinflammation of the central nervous system (CNS). Increasing evidence suggests that changes in microglia cells contribute to the age-related deterioration of the CNS. The most prominent age-related change of microgli

  6. Age-dependent recombination rates in human pedigrees.

    Directory of Open Access Journals (Sweden)

    Julie Hussin

    2011-09-01

    Full Text Available In humans, chromosome-number abnormalities have been associated with altered recombination and increased maternal age. Therefore, age-related effects on recombination are of major importance, especially in relation to the mechanisms involved in human trisomies. Here, we examine the relationship between maternal age and recombination rate in humans. We localized crossovers at high resolution by using over 600,000 markers genotyped in a panel of 69 French-Canadian pedigrees, revealing recombination events in 195 maternal meioses. Overall, we observed the general patterns of variation in fine-scale recombination rates previously reported in humans. However, we make the first observation of a significant decrease in recombination rates with advancing maternal age in humans, likely driven by chromosome-specific effects. The effect appears to be localized in the middle section of chromosomal arms and near subtelomeric regions. We postulate that, for some chromosomes, protection against non-disjunction provided by recombination becomes less efficient with advancing maternal age, which can be partly responsible for the higher rates of aneuploidy in older women. We propose a model that reconciles our findings with reported associations between maternal age and recombination in cases of trisomies.

  7. Identification of the imprinted KLF14 transcription factor undergoing human-specific accelerated evolution.

    Science.gov (United States)

    Parker-Katiraee, Layla; Carson, Andrew R; Yamada, Takahiro; Arnaud, Philippe; Feil, Robert; Abu-Amero, Sayeda N; Moore, Gudrun E; Kaneda, Masahiro; Perry, George H; Stone, Anne C; Lee, Charles; Meguro-Horike, Makiko; Sasaki, Hiroyuki; Kobayashi, Keiko; Nakabayashi, Kazuhiko; Scherer, Stephen W

    2007-05-04

    Imprinted genes are expressed in a parent-of-origin manner and are located in clusters throughout the genome. Aberrations in the expression of imprinted genes on human Chromosome 7 have been suggested to play a role in the etiologies of Russell-Silver Syndrome and autism. We describe the imprinting of KLF14, an intronless member of the Krüppel-like family of transcription factors located at Chromosome 7q32. We show that it has monoallelic maternal expression in all embryonic and extra-embryonic tissues studied, in both human and mouse. We examine epigenetic modifications in the KLF14 CpG island in both species and find this region to be hypomethylated. In addition, we perform chromatin immunoprecipitation and find that the murine Klf14 CpG island lacks allele-specific histone modifications. Despite the absence of these defining features, our analysis of Klf14 in offspring from DNA methyltransferase 3a conditional knockout mice reveals that the gene's expression is dependent upon a maternally methylated region. Due to the intronless nature of Klf14 and its homology to Klf16, we suggest that the gene is an ancient retrotransposed copy of Klf16. By sequence analysis of numerous species, we place the timing of this event after the divergence of Marsupialia, yet prior to the divergence of the Xenarthra superclade. We identify a large number of sequence variants in KLF14 and, using several measures of diversity, we determine that there is greater variability in the human lineage with a significantly increased number of nonsynonymous changes, suggesting human-specific accelerated evolution. Thus, KLF14 may be the first example of an imprinted transcript undergoing accelerated evolution in the human lineage.

  8. Identification of the imprinted KLF14 transcription factor undergoing human-specific accelerated evolution.

    Directory of Open Access Journals (Sweden)

    Layla Parker-Katiraee

    2007-05-01

    Full Text Available Imprinted genes are expressed in a parent-of-origin manner and are located in clusters throughout the genome. Aberrations in the expression of imprinted genes on human Chromosome 7 have been suggested to play a role in the etiologies of Russell-Silver Syndrome and autism. We describe the imprinting of KLF14, an intronless member of the Krüppel-like family of transcription factors located at Chromosome 7q32. We show that it has monoallelic maternal expression in all embryonic and extra-embryonic tissues studied, in both human and mouse. We examine epigenetic modifications in the KLF14 CpG island in both species and find this region to be hypomethylated. In addition, we perform chromatin immunoprecipitation and find that the murine Klf14 CpG island lacks allele-specific histone modifications. Despite the absence of these defining features, our analysis of Klf14 in offspring from DNA methyltransferase 3a conditional knockout mice reveals that the gene's expression is dependent upon a maternally methylated region. Due to the intronless nature of Klf14 and its homology to Klf16, we suggest that the gene is an ancient retrotransposed copy of Klf16. By sequence analysis of numerous species, we place the timing of this event after the divergence of Marsupialia, yet prior to the divergence of the Xenarthra superclade. We identify a large number of sequence variants in KLF14 and, using several measures of diversity, we determine that there is greater variability in the human lineage with a significantly increased number of nonsynonymous changes, suggesting human-specific accelerated evolution. Thus, KLF14 may be the first example of an imprinted transcript undergoing accelerated evolution in the human lineage.

  9. Role of Age-Associated Alterations of the Dermal Extracellular Matrix Microenvironment in Human Skin Aging

    OpenAIRE

    Quan, Taihao; Fisher, Gary J.

    2015-01-01

    Human skin is largely composed of a collagen-rich connective tissue, which provides structural and functional support. The collagen-rich connective tissue is produced, organized, and maintained by dermal fibroblasts. During aging, dermal collagen fibrils undergo progressive loss and fragmentation, leading to thin and structurally weakened skin. Age-related alterations of collagen fibrils impairs skin structure and function and creates a tissue microenvironment that promotes age-related skin d...

  10. Development of a lifetime prediction model for lithium-ion batteries based on extended accelerated aging test data

    Science.gov (United States)

    Ecker, Madeleine; Gerschler, Jochen B.; Vogel, Jan; Käbitz, Stefan; Hust, Friedrich; Dechent, Philipp; Sauer, Dirk Uwe

    2012-10-01

    Battery lifetime prognosis is a key requirement for successful market introduction of electric and hybrid vehicles. This work aims at the development of a lifetime prediction approach based on an aging model for lithium-ion batteries. A multivariable analysis of a detailed series of accelerated lifetime experiments representing typical operating conditions in hybrid electric vehicle is presented. The impact of temperature and state of charge on impedance rise and capacity loss is quantified. The investigations are based on a high-power NMC/graphite lithium-ion battery with good cycle lifetime. The resulting mathematical functions are physically motivated by the occurring aging effects and are used for the parameterization of a semi-empirical aging model. An impedance-based electric-thermal model is coupled to the aging model to simulate the dynamic interaction between aging of the battery and the thermal as well as electric behavior. Based on these models different drive cycles and management strategies can be analyzed with regard to their impact on lifetime. It is an important tool for vehicle designers and for the implementation of business models. A key contribution of the paper is the parameterization of the aging model by experimental data, while aging simulation in the literature usually lacks a robust empirical foundation.

  11. Age estimation based on aspartic acid racemization in human sclera.

    Science.gov (United States)

    Klumb, Karolin; Matzenauer, Christian; Reckert, Alexandra; Lehmann, Klaus; Ritz-Timme, Stefanie

    2016-01-01

    Age estimation based on racemization of aspartic acid residues (AAR) in permanent proteins has been established in forensic medicine for years. While dentine is the tissue of choice for this molecular method of age estimation, teeth are not always available which leads to the need to identify other suitable tissues. We examined the suitability of total tissue samples of human sclera for the estimation of age at death. Sixty-five samples of scleral tissue were analyzed. The samples were hydrolyzed and after derivatization, the extent of aspartic acid racemization was determined by gas chromatography. The degree of AAR increased with age. In samples from younger individuals, the correlation of age and D-aspartic acid content was closer than in samples from older individuals. The age-dependent racemization in total tissue samples proves that permanent or at least long-living proteins are present in scleral tissue. The correlation of AAR in human sclera and age at death is close enough to serve as basis for age estimation. However, the precision of age estimation by this method is lower than that of age estimation based on the analysis of dentine which is due to molecular inhomogeneities of total tissue samples of sclera. Nevertheless, the approach may serve as a valuable alternative or addition in exceptional cases.

  12. Melatonin can improve insulin resistance and aging-induced pancreas alterations in senescence-accelerated prone male mice (SAMP8).

    Science.gov (United States)

    Cuesta, Sara; Kireev, Roman; García, Cruz; Rancan, Lisa; Vara, Elena; Tresguerres, Jesús A F

    2013-06-01

    The aim of the present study was to investigate the effect of aging on several parameters related to glucose homeostasis and insulin resistance in pancreas and how melatonin administration could affect these parameters. Pancreas samples were obtained from two types of male mice models: senescence-accelerated prone (SAMP8) and senescence-accelerated-resistant mice (SAMR1). Insulin levels in plasma were increased with aging in both SAMP8 and SAMR1 mice, whereas insulin content in pancreas was decreased with aging in SAMP8 and increased in SAMR1 mice. Expressions of glucagon and GLUT2 messenger RNAs (mRNAs) were increased with aging in SAMP8 mice, and no differences were observed in somatostatin and insulin mRNA expressions. Furthermore, aging decreased also the expressions of Pdx-1, FoxO 1, FoxO 3A and Sirt1 in pancreatic SAMP8 samples. Pdx-1 was decreased in SAMR1 mice, but no differences were observed in the rest of parameters on these mice strains. Treatment with melatonin was able to decrease plasma insulin levels and to increase its pancreatic content in SAMP8 mice. In SAMR1, insulin pancreatic content and plasma levels were decreased. HOMA-IR was decreased with melatonin treatment in both strains of animals. On the other hand, in SAMP8 mice, treatment decreased the expression of glucagon, GLUT2, somatostatin and insulin mRNA. Furthermore, it was also able to increase the expression of Sirt1, Pdx-1 and FoxO 3A. According to these results, aging is associated with significant alterations in the relative expression of pancreatic genes associated to glucose metabolism. This has been especially observed in SAMP8 mice. Melatonin administration was able to improve pancreatic function in old SAMP8 mice and to reduce HOMA-IR improving their insulin physiology and glucose metabolism.

  13. Influence of age, irradiation and humanization on NSG mouse phenotypes

    Directory of Open Access Journals (Sweden)

    Jaclyn S. Knibbe-Hollinger

    2015-10-01

    Full Text Available Humanized mice are frequently utilized in bench to bedside therapeutic tests to combat human infectious, cancerous and degenerative diseases. For the fields of hematology-oncology, regenerative medicine, and infectious diseases, the immune deficient mice have been used commonly in basic research efforts. Obstacles in true translational efforts abound, as the relationship between mouse and human cells in disease pathogenesis and therapeutic studies requires lengthy investigations. The interplay between human immunity and mouse biology proves ever more complicated when aging, irradiation, and human immune reconstitution are considered. All can affect a range of biochemical and behavioral functions. To such ends, we show age- and irradiation-dependent influences for the development of macrocytic hyper chromic anemia, myelodysplasia, blood protein reductions and body composition changes. Humanization contributes to hematologic abnormalities. Home cage behavior revealed day and dark cycle locomotion also influenced by human cell reconstitutions. Significant age-related day-to-day variability in movement, feeding and drinking behaviors were observed. We posit that this data serves to enable researchers to better design translational studies in this rapidly emerging field of mouse humanization.

  14. Electrical properties of human skin as aging biomarkers.

    Science.gov (United States)

    Simić-Krstić, Jovana B; Kalauzi, Aleksandar J; Ribar, Srdjan N; Matija, Lidija R; Misevic, Gradimir N

    2014-09-01

    A non-invasive bioimpedance spectroscopy (BIS) and Cole-Cole impedance model parameters (R0, R∞, τ and α) were used to analyze electrical properties of intact and stripped human skin for both gender subjects divided into younger and older age groups. R0, R∞ and τ significantly increased while α significantly decreased with age in stripped skin for both genders (pCole-Cole parameters were age dependent with specific differences observed for genders and intact and stripped skin layers. Therefore, Cole-Cole parameters, obtained by non-invasive BIS measurements, are a new type of age dependent biomarkers.

  15. Cognitive training during infancy and adolescence accelerates adult associative learning: critical impact of age, stimulus contingency and training intensity.

    Science.gov (United States)

    Gruss, Michael; Abraham, Andreas; Schäble, Sandra; Becker, Susann; Braun, Katharina

    2010-10-01

    A growing body of evidence supports the hypothesis that juvenile cognitive training shapes neural networks and behavior, and thereby determines the adult's capacity for learning and memory. In particular, we have shown that infant rats, even though they do not develop an active avoidance strategy in a two-way active avoidance task, show as adults accelerated learning in the same learning task. This indicates that a memory trace was formed in the infant rats, which most likely is recruited during adult training. To identify the learning conditions, which are essential prerequisites to form this memory trace in infancy or adolescence, we investigated the critical impact of: (i) age, (ii) CS-UCS contingency, and (iii) pre-training intensity on this facilitating effect. We observed: (i) an age-dependent improvement of avoidance learning, (ii) that the beneficial impact of infant or adolescent pre-training on adult learning increases with the age at pre-training, (iii) that CS-UCS contingency during infant pre-training was most efficient to accelerate adult learning, (iv) that pre-training intensity (i.e. number of pre-training trials) was positively correlated with the pre-training induced acceleration of adult learning, and (v) that infant rats, compared to adolescent rats, need a higher training intensity to show learning improvement as adults. These results indicate that infant rats develop a goal-oriented escape strategy, which during adult training is replaced by an avoidance strategy, facilitated by the recruitment of the CS-UCS association, which has been learned during infant training. Based on these results the future challenge will be to identify the specific contribution of prefronto-limbic circuits in infant and adult learning in relation to their functional maturation. Copyright © 2010 Elsevier Inc. All rights reserved.

  16. Nutrition modulation of human aging: The calorie restriction paradigm.

    Science.gov (United States)

    Das, Sai Krupa; Balasubramanian, Priya; Weerasekara, Yasoma K

    2017-11-05

    Globally, the aging population is growing rapidly, creating an urgent need to attenuate age-related health conditions, including metabolic disease and disability. A promising strategy for healthy aging based on consistently positive results from studies with a variety of species, including non-human primates (NHP), is calorie restriction (CR), or the restriction of energy intake while maintaining intake of essential nutrients. The burgeoning evidence for this approach in humans is reviewed and the major study to date to address this question, CALERIE (Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy), is described. CALERIE findings indicate the feasibility of CR in non-obese humans, confirm observations in NHP, and are consistent with improvements in disease risk reduction and potential anti-aging effects. Finally, the mechanisms of CR in humans are reviewed which sums up the fact that evolutionarily conserved mechanisms mediate the anti-aging effects of CR. Overall, the prospect for further research in both NHP and humans is highly encouraging. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Accelerated cellular senescence phenotype of GAPDH-depleted human lung carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Phadke, Manali; Krynetskaia, Natalia [Temple University School of Pharmacy, Philadelphia, PA 19140 (United States); Mishra, Anurag [Jayne Haines Center for Pharmacogenomics, Temple University School of Pharmacy, Philadelphia, PA 19140 (United States); Krynetskiy, Evgeny, E-mail: ekrynets@temple.edu [Temple University School of Pharmacy, Philadelphia, PA 19140 (United States); Jayne Haines Center for Pharmacogenomics, Temple University School of Pharmacy, Philadelphia, PA 19140 (United States)

    2011-07-29

    Highlights: {yields} We examined the effect of glyceraldehyde 3-phosphate (GAPDH) depletion on proliferation of human carcinoma A549 cells. {yields} GAPDH depletion induces accelerated senescence in tumor cells via AMPK network, in the absence of DNA damage. {yields} Metabolic and genetic rescue experiments indicate that GAPDH has regulatory functions linking energy metabolism and cell cycle. {yields} Induction of senescence in LKB1-deficient lung cancer cells via GAPDH depletion suggests a novel strategy to control tumor cell proliferation. -- Abstract: Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a pivotal glycolytic enzyme, and a signaling molecule which acts at the interface between stress factors and the cellular apoptotic machinery. Earlier, we found that knockdown of GAPDH in human carcinoma cell lines resulted in cell proliferation arrest and chemoresistance to S phase-specific cytotoxic agents. To elucidate the mechanism by which GAPDH depletion arrests cell proliferation, we examined the effect of GAPDH knockdown on human carcinoma cells A549. Our results show that GAPDH-depleted cells establish senescence phenotype, as revealed by proliferation arrest, changes in morphology, SA-{beta}-galactosidase staining, and more than 2-fold up-regulation of senescence-associated genes DEC1 and GLB1. Accelerated senescence following GAPDH depletion results from compromised glycolysis and energy crisis leading to the sustained AMPK activation via phosphorylation of {alpha} subunit at Thr172. Our findings demonstrate that GAPDH depletion switches human tumor cells to senescent phenotype via AMPK network, in the absence of DNA damage. Rescue experiments using metabolic and genetic models confirmed that GAPDH has important regulatory functions linking the energy metabolism and the cell cycle networks. Induction of senescence in LKB1-deficient non-small cell lung cancer cells via GAPDH depletion suggests a novel strategy to control tumor cell proliferation.

  18. Chronic vitamin C deficiency does not accelerate oxidative stress in ageing brains of guinea pigs

    DEFF Research Database (Denmark)

    Tveden-Nyborg, Pernille; Hasselholt, Stine; Miyashita, Namiyo

    2012-01-01

      Increased oxidative stress in the brain has consistently been implied in ageing and in several degenerative brain disorders. Acting as a pivotal antioxidant in the brain, vitamin C is preferentially retained during deficiency and may play an essential role in neuroprotection during ageing. Thus...

  19. Evidence of accelerated ageing in clinical drug addiction from immune, hepatic and metabolic biomarkers

    Directory of Open Access Journals (Sweden)

    Reece Albert

    2007-09-01

    Full Text Available Abstract Background Drug addiction is associated with significant disease and death, but its impact on the ageing process has not been considered. The recent demonstration that many of the items available in routine clinical pathology have applicability as biomarkers of the ageing process implies that routine clinical laboratory parameters would be useful as an initial investigation of this possibility. Methods 12,093 clinical laboratory results 1995–2006 were reviewed. To make the age ranges of the medical and addicted groups comparable the age range was restricted to 15–45 years. Results 739 drug addicted (DA and 5834 general medical (GM age matched blood samples were compared. Significant elevation of immune parameters was noted in the C-reactive protein, erythrocyte sedimentation rate, total lymphocyte count, serum globulins and the globulin:albumin ratio (P Conclusion These data demonstrate for the first time that addiction is associated with an altered profile of common biomarkers of ageing raising the possibility that the ageing process may be altered in this group. Infective and immune processes may be centrally involved. They suggest that addiction forms an interesting model to further examine the contribution of immune suppression and hyperstimulation to the ageing process.

  20. Inflammaging (inflammation + aging): A driving force for human aging based on an evolutionarily antagonistic pleiotropy theory?

    Science.gov (United States)

    Goto, Makoto

    2008-12-01

    Aging, and especially human aging, can be explained by the emerging concept of parainflammation-driven inflammaging, i.e. a combination of inflammation and aging. Inflammaging posits that aging either physiologically or pathologically can be driven by the pro-inflammatory cytokines and substances produced by the innate immune system. Animals must maintain homeostasis as they age despite incessant attack from both intrinsic and extrinsic stimuli/antigens. These potentially harmful pro-inflammatory signals at a later stage of life may act antagonistically to the beneficial role they had in an earlier stage of life, like serving as developmental engines for body system formation. The concept of inflammaging is based on an antagonistic pleiotropy theory programmed during evolution. Clinical trials including caloric restriction, sirtuin activators, and p38 MAPK inhibitors against both pathological aging such as metabolic syndrome, diabetes mellitus, rheumatoid arthritis, and Werner syndrome and physiological aging have been proposed.

  1. Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells

    DEFF Research Database (Denmark)

    Dokkedahl, Karin Stenderup; Justesen, Jeannette; Clausen, Christian

    2003-01-01

    donors were able to form similar amounts of mineralized matrix in vitro and of normal lamellar bone in vivo. In adipogenic medium similar numbers of adipocytes formed in cultures of young and old donors. In conclusion, aging is associated with decreased proliferative capacity of osteoprogenitor cells......Age-related decrease in bone formation is well described. However, the cellular causes are not known. Thus, we have established cultures of bone marrow stromal cells (MSC) from young (aged 18-29 years, n = 6) and old (aged 68-81 years, n = 5) donors. MSC were serially passaged until reaching......, suggesting that decreased osteoblastic cell number, and not function, leads to age-related decrease in bone formation....

  2. Effect of weaning age on hair sheep lamb and ewe production traits in an accelerated lambing system in the tropics.

    Science.gov (United States)

    Godfrey, R W; Weis, A J

    2016-03-01

    This study was designed to evaluate the impact of weaning age on lamb and ewe productivity in an accelerated lambing system. St. Croix White (STX) and Dorper × St. Croix White (DRPX) lambs were assigned at birth based on breed, gender, and litter size to be weaned at 63 (Early-1; 106 lambs and 68 ewes) or 90 d of age (Late-1; 99 lambs and 60 ewes) in Exp.1 or at 63 (Early-2; 77 lambs and 57 ewes) or 120 d of age (Late-2; 75 lambs and 56 ewes) in Exp. 2. After weaning, lambs were weighed weekly and fed a concentrate ration (2% BW·lamb·d) while grazing guinea grass pastures. In Exp. 1, weaning weight was greater ( 0.06) between Early-2 and Late-2 lambs (5.1 ± 0.2 vs. 5.6 ± 0.3 kg, respectively). In Exp. 1 and 2, ewe BW at breeding and lambing and weaning and lambing rate were not different among weaning ages of lambs ( > 0.17). The Early-1 ewes exhibited estrus earlier than Late-1 ewes (10.9 ± 0.9 vs. 13.9 ± 1.0 d, respectively) but there was no difference ( > 0.63) between Early-2 and Late-2 ewes. Weaning hair lambs at 90 or 120 d of age can be done in an accelerated lambing system with no detrimental effect on lamb or ewe productivity. Late weaning resulted in a decreased number of days that lambs received high-cost, imported feed without a reduction in growth, resulting in savings of US$6 to $15 per lamb.

  3. Analysis of tetragonal to monoclinic phase transformation caused by accelerated artificial aging and the effects of microstructure in stabilized zirconia

    Science.gov (United States)

    Lucas, Thomas J.

    This investigation addresses the issue that yttria stabilized zirconia is being used as a dental biomaterial without substantial evidence of its long-term viability. Furthermore, stabilized zirconia (SZ) undergoes low temperature degradation (LTD), which can lead to roughening of the surface. A rougher exterior can lead to increased wear of the antagonist in the oral environment. Despite the LTD concerns, SZ is now widely used in restorative dentistry, including full contour crowns. A comparison of aging methods to determine the role of artificial aging on inducing the transformation has not been extensively studied. Therefore, simulations of the transformation process were investigated by comparing different methods of accelerated aging. The rejected null hypothesis is that the temperature of aging treatment will not affect the time required to cause measurable monoclinic transformation of yttria stabilized zirconia. The transformation of SZ starts at the surface and progresses inward; however, it is unclear whether the progression is constant for different aging conditions. This investigation analyzed the depth of transformation as a function of aging conditions for stabilized zirconia in the top 5-6 mum from the surface. The rejected null hypothesis is that the transformation amount is constant throughout the first six micrometers from the surface. The effects of grain size on the amount of monoclinic transformation were also investigated. This study aimed to determine if the grain size of partially stabilized zirconia affects the amount of monoclinic transformation, surface roughness, and property degradation due to aging. The rejected null hypothesis is that the grain size will not affect the amount of monoclinic transformation, thus have no effect on surface roughening or property degradation. The final part of this study addresses the wear of enamel when opposing zirconia by observing how grain size and aging affected the wear rate of an enamel antagonist

  4. Network model of human aging: Frailty limits and information measures

    Science.gov (United States)

    Farrell, Spencer G.; Mitnitski, Arnold B.; Rockwood, Kenneth; Rutenberg, Andrew D.

    2016-11-01

    Aging is associated with the accumulation of damage throughout a persons life. Individual health can be assessed by the Frailty Index (FI). The FI is calculated simply as the proportion f of accumulated age-related deficits relative to the total, leading to a theoretical maximum of f ≤1 . Observational studies have generally reported a much more stringent bound, with f ≤fmaxcomputationally accelerated network model that also allows us to tune the scale-free network exponent α . The network exponent α significantly affects the growth of mortality rates with age. However, we are only able to recover fmax by also introducing a deficit sensitivity parameter 1 -q , which is equivalent to a false-negative rate q . Our value of q =0.3 is comparable to finite sensitivities of age-related deficits with respect to mortality that are often reported in the literature. In light of nonzero q , we use mutual information I to provide a nonparametric measure of the predictive value of the FI with respect to individual mortality. We find that I is only modestly degraded by q topology of aging populations.

  5. Age and gender specific biokinetic model for strontium in humans

    Energy Technology Data Exchange (ETDEWEB)

    Shagina, N. B.; Tolstykh, E. I.; Degteva, M. O.; Anspaugh, L. R.; Napier, Bruce A.

    2015-03-01

    A biokinetic model for strontium in humans is necessary for quantification of internal doses due to strontium radioisotopes. The ICRP-recommended biokinetic model for strontium has limitation for use in a population study, because it is not gender specific and does not cover all age ranges. The extensive Techa River data set on 90Sr in humans (tens of thousands of measurements) is a unique source of data on long-term strontium retention for men and women of all ages at intake. These, as well as published data, were used for evaluation of age- and gender-specific parameters for a new compartment biokinetic model for strontium (Sr-AGe model). The Sr-AGe model has similar structure as the ICRP model for the alkaline earth elements. The following parameters were mainly reevaluated: gastro-intestinal absorption and parameters related to the processes of bone formation and resorption defining calcium and strontium transfers in skeletal compartments. The Sr-AGe model satisfactorily describes available data sets on strontium retention for different kinds of intake (dietary and intravenous) at different ages (0–80 years old) and demonstrates good agreement with data sets for different ethnic groups. The Sr-AGe model can be used for dose assessment in epidemiological studies of general population exposed to ingested strontium radioisotopes.

  6. Leukocyte Telomere Length in Young Adults Born Preterm: Support for Accelerated Biological Ageing.

    Directory of Open Access Journals (Sweden)

    Carolina C J Smeets

    Full Text Available Subjects born preterm have an increased risk for age-associated diseases, such as cardiovascular disease in later life, but the underlying causes are largely unknown. Shorter leukocyte telomere length (LTL, a marker of biological age, is associated with increased risk of cardiovascular disease.To compare LTL between subjects born preterm and at term and to assess if LTL is associated with other putative cardiovascular risk factors at young adult age.We measured mean LTL in 470 young adults. LTL was measured using a quantitative PCR assay and expressed as T/S ratio. We analyzed the influence of gestational age on LTL and compared LTL between subjects born preterm (n = 186 and at term (n = 284. Additionally, we analyzed the correlation between LTL and potential risk factors of cardiovascular disease.Gestational age was positively associated with LTL (r = 0.11, p = 0.02. Subjects born preterm had shorter LTL (mean (SD T/S ratio = 3.12 (0.44 than subjects born at term (mean (SD T/S ratio = 3.25 (0.46, p = 0.003. The difference remained significant after adjustment for gender and size at birth (p = 0.001. There was no association of LTL with any one of the putative risk factors analyzed.Young adults born preterm have shorter LTL than young adults born at term. Although we found no correlation between LTL and risk for CVD at this young adult age, this biological ageing indicator may contribute to CVD and other adult onset diseases at a later age in those born preterm.

  7. Do glutathione levels decline in aging human brain?

    Science.gov (United States)

    Tong, Junchao; Fitzmaurice, Paul S; Moszczynska, Anna; Mattina, Katie; Ang, Lee-Cyn; Boileau, Isabelle; Furukawa, Yoshiaki; Sailasuta, Napapon; Kish, Stephen J

    2016-04-01

    For the past 60 years a major theory of "aging" is that age-related damage is largely caused by excessive uncompensated oxidative stress. The ubiquitous tripeptide glutathione is a major antioxidant defense mechanism against reactive free radicals and has also served as a marker of changes in oxidative stress. Some (albeit conflicting) animal data suggest a loss of glutathione in brain senescence, which might compromise the ability of the aging brain to meet the demands of oxidative stress. Our objective was to establish whether advancing age is associated with glutathione deficiency in human brain. We measured reduced glutathione (GSH) levels in multiple regions of autopsied brain of normal subjects (n=74) aged one day to 99 years. Brain GSH levels during the infancy/teenage years were generally similar to those in the oldest examined adult group (76-99 years). During adulthood (23-99 years) GSH levels remained either stable (occipital cortex) or increased (caudate nucleus, frontal and cerebellar cortices). To the extent that GSH levels represent glutathione antioxidant capacity, our postmortem data suggest that human brain aging is not associated with declining glutathione status. We suggest that aged healthy human brains can maintain antioxidant capacity related to glutathione and that an age-related increase in GSH levels in some brain regions might possibly be a compensatory response to increased oxidative stress. Since our findings, although suggestive, suffer from the generic limitations of all postmortem brain studies, we also suggest the need for "replication" investigations employing the new (1)H MRS imaging procedures in living human brain. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Modulation of the phenolic composition and colour of red wines subjected to accelerated ageing by controlling process variables.

    Science.gov (United States)

    González-Sáiz, J M; Esteban-Díez, I; Rodríguez-Tecedor, S; Pérez-Del-Notario, N; Arenzana-Rámila, I; Pizarro, C

    2014-12-15

    The aim of the present work was to evaluate the effect of the main factors conditioning accelerated ageing processes (oxygen dose, chip dose, wood origin, toasting degree and maceration time) on the phenolic and chromatic profiles of red wines by using a multivariate strategy based on experimental design methodology. The results obtained revealed that the concentrations of monomeric anthocyanins and flavan-3-ols could be modified through the application of particular experimental conditions. This fact was particularly remarkable since changes in phenolic profile were closely linked to changes observed in chromatic parameters. The main strength of this study lies in the possibility of using its conclusions as a basis to make wines with specific colour properties based on quality criteria. To our knowledge, the influence of such a large number of alternative ageing parameters on wine phenolic composition and chromatic attributes has not been studied previously using a comprehensive experimental design methodology. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Modelling of degradation processes in creep resistant steels through accelerated creep tests after long-term isothermal ageing

    Energy Technology Data Exchange (ETDEWEB)

    Sklenicka, V.; Kucharova, K.; Svoboda, M.; Kroupa, A.; Kloc, L. [Academy of Sciences of the Czech Republic, Brno (Czech Republic). Inst. of Physics of Materials; Cmakal, J. [UJP PRAHA a.s., Praha-Zbraslav (Czech Republic)

    2010-07-01

    Creep behaviour and degradation of creep properties of creep resistant materials are phenomena of major practical relevance, often limiting the lives of components and structures designed to operate for long periods under stress at elevated and/or high temperatures. Since life expectancy is, in reality, based on the ability of the material to retain its high-temperature creep strength for the projected designed life, methods of creep properties assessment based on microstructural evolution in the material during creep rather than simple parametric extrapolation of short-term creep tests are necessary. In this paper we will try to further clarify the creep-strength degradation of selected advanced creep resistant steels. In order to accelerate some microstructural changes and thus to simulate degradation processes in long-term service, isothermal ageing at 650 C for 10 000 h was applied to P91 and P23 steels in their as-received states. The accelerated tensile creep tests were performed at temperature 600 C in argon atmosphere on all steels both in the as-received state and after long-term isothermal ageing, in an effort to obtain a more complete description of the role of microstructural stability in high temperature creep of these steels. Creep tests were followed by microstructural investigations by means of both transmission and scanning electron microscopy and by the thermodynamic calculations. The applicability of the accelerated creep tests was verified by the theoretical modelling of the phase equilibria at different temperatures. It is suggested that under restructed oxidation due to argon atmosphere microstructural instability is the main detrimental process in the long-term degradation of the creep rupture strength of these steels. (orig.)

  10. Towards A Model-Based Prognostics Methodology for Electrolytic Capacitors: A Case Study Based on Electrical Overstress Accelerated Aging

    Science.gov (United States)

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

    2012-01-01

    A remaining useful life prediction methodology for electrolytic capacitors is presented. This methodology is based on the Kalman filter framework and an empirical degradation model. Electrolytic capacitors are used in several applications ranging from power supplies on critical avionics equipment to power drivers for electro-mechanical actuators. These devices are known for their comparatively low reliability and given their criticality in electronics subsystems they are a good candidate for component level prognostics and health management. Prognostics provides a way to assess remaining useful life of a capacitor based on its current state of health and its anticipated future usage and operational conditions. We present here also, experimental results of an accelerated aging test under electrical stresses. The data obtained in this test form the basis for a remaining life prediction algorithm where a model of the degradation process is suggested. This preliminary remaining life prediction algorithm serves as a demonstration of how prognostics methodologies could be used for electrolytic capacitors. In addition, the use degradation progression data from accelerated aging, provides an avenue for validation of applications of the Kalman filter based prognostics methods typically used for remaining useful life predictions in other applications.

  11. Accelerated Aging of BKC 44306-10 Rigid Polyurethane Foam: FT-IR Spectroscopy, Dimensional Analysis, and Micro Computed Tomography

    Energy Technology Data Exchange (ETDEWEB)

    Gilbertson, Robert D. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Patterson, Brian M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Smith, Zachary [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2014-01-02

    An accelerated aging study of BKC 44306-10 rigid polyurethane foam was carried out. Foam samples were aged in a nitrogen atmosphere at three different temperatures: 50 °C, 65 °C, and 80 °C. Foam samples were periodically removed from the aging canisters at 1, 3, 6, 9, 12, and 15 month intervals when FT-IR spectroscopy, dimensional analysis, and mechanical testing experiments were performed. Micro Computed Tomography imaging was also employed to study the morphology of the foams. Over the course of the aging study the foams the decreased in size by a magnitude of 0.001 inches per inch of foam. Micro CT showed the heterogeneous nature of the foam structure likely resulting from flow effects during the molding process. The effect of aging on the compression and tensile strength of the foam was minor and no cause for concern. FT-IR spectroscopy was used to follow the foam chemistry. However, it was difficult to draw definitive conclusions about the changes in chemical nature of the materials due to large variability throughout the samples.

  12. The telomere attrition rate is not accelerated in women born small for gestational age: A birth cohort study.

    Science.gov (United States)

    de Melo, Anderson Sanches; Reis, Rosana Maria Dos; Calado, Rodrigo T; de Carvalho Cavalli, Ricardo; Bettiol, Heloisa; Cardoso, Viviane Cunha; Ferriani, Rui Alberto; Barbieri, Marco Antonio; Vieira, Carolina Sales

    2017-02-05

    Physiologically, a reduction in telomere length (LTL) occurs with aging, but epigenetic changes may accelerate telomere shortening and also facilitate the onset of oxidative/inflammatory stress and the development of clinical/metabolic comorbidities in life spam. Although individuals born small for gestational age (SGA) may be related to those epigenetic changes, the assessment of LTL in individuals born SGA has yielded conflicting results (only cross-sectional studies) and has not been carried out in longitudinal studies. We performed a birth cohort study to evaluate the rate of telomere erosion in women born SGA in comparison to women born appropriate for gestational age (AGA) assessed at two different time points during the third decade of life. In our research, born SGA or AGA showed no difference in LTL shortening during a period of five years in the third decade of life. Our finding may have implications for understanding the natural history of diseases in lifespan because the same women (under the influence of similar environmental factors) may be accessed in different phases of life. Thus, the analysis of the present cohort population at a more advanced age may reveal a dynamics of telomere shortening different from here and its possible relation with onset of age-related diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Reduction in podocyte SIRT1 accelerates kidney injury in aging mice.

    Science.gov (United States)

    Chuang, Peter Y; Cai, Weijing; Li, Xuezhu; Fang, Lu; Xu, Jin; Yacoub, Rabi; He, John Cijiang; Lee, Kyung

    2017-09-01

    Both the incidence and prevalence of chronic kidney disease are increasing in the elderly population. Although aging is known to induce kidney injury, the underlying molecular mechanisms remain unclear. Sirtuin 1 (Sirt1), a longevity gene, is known to protect kidney cell injury from various cellular stresses. In previous studies, we showed that the podocyte-specific loss of Sirt1 aggravates diabetic kidney injury. However, the role of Sirt1 in aging-induced podocyte injury is not known. Therefore, in this study we sought to determine the effects of podocyte-specific reduction of Sirt1 in age-induced kidney injury. We employed the inducible podocyte-specific Sirt1 knockdown mice that express shRNA against Sirt1 (Pod-Sirt1(RNAi)) and control mice that express shRNA for luciferase (Pod-Luci(RNAi)). We found that reduction of podocyte Sirt1 led to aggravated aging-induced glomerulosclerosis and albuminuria. In addition, urinary level of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative stress, was markedly increased in aged Pod-Sirt1(RNAi) mice compared with aged Pod-Luci(RNAi) mice. Although podocyte-specific markers decreased in aged mice compared with the young controls, the decrease was further exacerbated in aged Pod-Sirt1(RNAi) compared with Pod-Luci(RNAi) mice. Interestingly, expression of cellular senescence markers was significantly higher in the glomeruli of Pod-Sirt1(RNAi) mice than Pod-Luci(RNAi) mice, suggesting that cellular senescence may contribute to podocyte loss in aging kidneys. Finally, we confirmed that Pod-Sirt1(RNAi) glomeruli were associated with reduced activation of the transcription factors peroxisome proliferator-activated receptor (PPAR)-α coactivador-1 (PGC1α)/PPARγ, forkhead box O (FOXO)3, FOXO4, and p65 NF-κB, through SIRT1-mediated deacetylation. Together, our data suggest that SIRT1 may be a potential therapeutic target to treat patients with aging-related kidney disease.

  14. Effects of accelerated aging upon the lipid composition of seeds from two soft wheat varieties from Morocco

    Directory of Open Access Journals (Sweden)

    Serghini Caid, H.

    2009-09-01

    Full Text Available The lipid composition of the seeds from two soft wheat varieties (Triticum aestivum, cv. Marchouche and Mahdia were analyzed before and after accelerated aging. Eight days of accelerated aging resulted in a total inhibition of seed germinability as well as a decrease in their total and especially unsaturated fatty acid contents. Oleic and linoleic acid contents decreased particularly in the phosphatidylcholine of the seeds from both varieties. The proportion of polar lipids also decreased after aging as compared to neutral lipids: a 5.8% and 7.2% decrease in polar lipids was e observed in Mahdia and Marchouche cultivars, respectively. In the neutral lipids of the seeds from the Marchouche variety, the percentage of free fatty acids increased whereas the triacylglycerols decreased. After aging, the fatty acid compositions of all lipid classes were modified in the same manner as total fatty acid compositions. Among polar lipids, phospholipid proportions were particularly small, especially the phosphatidylcholine percentages with an 18.1% and 19.1% decrease in Mahdia and Marchouche varieties, respectively. In contrast, MGDG percentages increased, especially in the seeds from the Marchouche variety. A 15.5% increase was noticed when compared with seeds which were not aged. At the same time, the DGDG percentage showed a 16.6% decrease after accelerated aging of the seeds from the Marchouche variety. From these results we concluded that the lipid content decrease observed in seeds after accelerated aging could be linked to a loss in the germination and vigor of wheat seeds.La composición lipídica de semillas de dos variedades de trigo blando (Triticum aestivum, cv. Marchouche and Mahdia fueron analizadas antes y después del envejecimiento acelerado. Ocho días de envejecimiento acelerado provoco una inhibición total de la geminabilidad, así como un descenso en el contenido total de ácidos grasos, en especial de los ácidos grasos insaturados

  15. Lipofuscin Granules in the Epileptic Human Temporal Neocortex with Age.

    Science.gov (United States)

    Merlo, Suélen; Nakayama, Ana Beatriz S; Brusco, Janaina; Rossi, Marcos A; Carlotti, Carlos G; Moreira, Jorge E

    2015-01-01

    Lipofuscin granules (LGs), the "age pigments", are autofluorescent cell products from lysosomes that diverge in number and size among brain regions. Human temporal cortex from 20- to 55-year-old epileptic subjects were studied with the fat soluble dye Sudan Black, under confocal and electron microscopy. Ultrastructural analysis showed that with age LGs increase in area, but not in number. Proportionally to the LGs area, the electron lucid portion increases and the electron dense reduces over time. The robust increase in lipid components is possibly due to modifications in the neuronal metabolism with age in physiological and pathological conditions.

  16. Role of Age-Associated Alterations of the Dermal Extracellular Matrix Microenvironment in Human Skin Aging

    Science.gov (United States)

    Quan, Taihao; Fisher, Gary J

    2015-01-01

    Human skin is largely composed of a collagen-rich connective tissue, which provides structural and functional support. The collagen-rich connective tissue is produced, organized, and maintained by dermal fibroblasts. During aging, dermal collagen fibrils undergo progressive loss and fragmentation, leading to thin and structurally weakened skin. Age-related alterations of collagen fibrils impairs skin structure and function and creates a tissue microenvironment that promotes age-related skin diseases, such as delayed wound healing and skin cancer development. This review describes cellular mechanisms that give rise to self-perpetuating, collagen fibril fragmentation that creates an age-associated dermal microenvironment (AADM), which contributes to decline of human skin function. PMID:25660807

  17. Responses to rotating linear acceleration vectors considered in relation to a model of the otolith organs. [human oculomotor response to transverse acceleration stress

    Science.gov (United States)

    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.

  18. The Human Right to Leisure in Old Age: Reinforcement of the Rights of an Aging Population.

    Science.gov (United States)

    Karev, Iris; Doron, Israel Issi

    2017-01-01

    The right to leisure is recognized as a human right under the 1948 United Nations Universal Declaration of Human Rights. The actual meaning and material content of this human right is subject to debate. The aim of this study is to examine the extent and the context to which this human right is specifically recognized with regard to older persons. Methodologically, this study textually analyzed 17 different international older persons' human rights documents. The findings reveal that in the majority of these documents there is no reference to the right to leisure. In the remaining documents, the right to leisure is mostly referred to indirectly or in a narrow legal construction. These findings support the notion that despite the growing body of knowledge regarding the importance of meaningful leisure in old age-and its empowering and anti-ageist nature-this knowledge has not transformed into a legal human rights discourse.

  19. Studies on the Effect of Accelerated Thermal Aging on Electrical and Physicochemical Properties of XLPE Cable

    Institute of Scientific and Technical Information of China (English)

    KIM Chon-ung; JIN Zhi-jian; JIANG Ping-kai; ZHU Zi-shu; LIU Fei; KIM Ui-chon

    2007-01-01

    The degradation of crosslinked polyethylene (XLPE) cable insulation during service, such as thermo-oxidation and water treeing may lead to a premature electrical breakdown of the XLPE insulation cables. Therefore,it is necessary to optimize the period of replacement to evenly distribute the replacement cost by ascertaining the deterioration degree. Estimation of the aging degree is at present the most important task for diagnosis of the residual lifetime of the power cable insulation. This paper presents a study on the changes in the dielectric properties of the thermally aged XLPE cables in the frequency range from 0.07~10 MHz. Based on electrical and physicochemical characterization, some new "dactylograms" for the thermally aged XLPE cable insulation have been proposed.

  20. Elastin aging and lipid oxidation products in human aorta

    Directory of Open Access Journals (Sweden)

    Kamelija Zarkovic

    2015-04-01

    Full Text Available Vascular aging is associated with structural and functional modifications of the arteries, and by an increase in arterial wall thickening in the intima and the media, mainly resulting from structural modifications of the extracellular matrix (ECM components. Among the factors known to accumulate with aging, advanced lipid peroxidation end products (ALEs are a hallmark of oxidative stress-associated diseases such as atherosclerosis. Aldehydes generated from the peroxidation of polyunsaturated fatty acids (PUFA, (4-hydroxynonenal, malondialdehyde, acrolein, form adducts on cellular proteins, leading to a progressive protein dysfunction with consequences in the pathophysiology of vascular aging. The contribution of these aldehydes to ECM modification is not known. This study was carried out to investigate whether aldehyde-adducts are detected in the intima and media in human aorta, whether their level is increased in vascular aging, and whether elastin fibers are a target of aldehyde-adduct formation. Immunohistological and confocal immunofluorescence studies indicate that 4-HNE-histidine-adducts accumulate in an age-related manner in the intima, media and adventitia layers of human aortas, and are mainly expressed in smooth muscle cells. In contrast, even if the structure of elastin fiber is strongly altered in the aged vessels, our results show that elastin is not or very poorly modified by 4-HNE. These data indicate a complex role for lipid peroxidation and in particular for 4-HNE in elastin homeostasis, in the vascular wall remodeling during aging and atherosclerosis development.

  1. Relationship between Human Aging Muscle and Oxidative System Pathway

    Directory of Open Access Journals (Sweden)

    Enrico Doria

    2012-01-01

    Full Text Available Ageing is a complex process that in muscle is usually associated with a decrease in mass, strength, and velocity of contraction. One of the most striking effects of ageing on muscle is known as sarcopenia. This inevitable biological process is characterized by a general decline in the physiological and biochemical functions of the major systems. At the cellular level, aging is caused by a progressive decline in mitochondrial function that results in the accumulation of reactive oxygen species (ROS generated by the addition of a single electron to the oxygen molecule. The aging process is characterized by an imbalance between an increase in the production of reactive oxygen species in the organism and the antioxidant defences as a whole. The goal of this review is to examine the results of existing studies on oxidative stress in aging human skeletal muscles, taking into account different physiological factors (sex, fibre composition, muscle type, and function.

  2. Age-related changes in mucins from human whole saliva.

    Science.gov (United States)

    Denny, P C; Denny, P A; Klauser, D K; Hong, S H; Navazesh, M; Tabak, L A

    1991-10-01

    The predominant mucins in human whole saliva, MG1 and MG2, serve to protect and to lubricate the oral cavity. In this study, both unstimulated and stimulated whole salivas were collected from two groups of subjects: young (18-35 years of age) and aged (65-83 years of age). The subjects were in apparent good health. Saliva samples from each subject were analyzed by SDS-PAGE. The gels were stained with Stains-all, and both MG1 and MG2 were quantitated by video-image densitometry. The protocol gave reproducible values for each mucin. The stimulated and unstimulated salivas from aged subjects showed significant reductions in concentrations of both MG1 and MG2, as quantitated in mucin dye-binding units. Possible associations of these reductions with the aging process are discussed.

  3. Antiaging Effect of Metformin on Brain in Naturally Aged and Accelerated Senescence Model of Rat.

    Science.gov (United States)

    Garg, Geetika; Singh, Sandeep; Singh, Abhishek Kumar; Rizvi, Syed Ibrahim

    2017-01-09

    Metformin, a biguanide, is a widely used antidiabetic drug, which inhibits gluconeogenesis and is used to treat hyperglycemia in type 2 diabetes. Through activation of AMPK (AMP-activated protein kinase) pathway, metformin also mimics caloric restriction health benefits. Aging causes substantial molecular to morphological changes in brain, the brain cells being more susceptible toward oxidative stress mediated damages due to the presence of high lipid content and higher oxygen consumption. Wistar rats (naturally aged and d-galactose induced rat model) were supplemented with metformin (300 mg/kg b.w. orally) for 6 weeks. The biomarkers of oxidative stress such as antioxidant capacity (ferric reducing antioxidant potential [FRAP]), malondialdehyde (MDA), reduced glutathione (GSH), protein carbonyl (PCO), reactive oxygen species (ROS), acetylcholinesterase (AChE) activity, and nitric oxide (NO) were measured in brain tissues of control and experimental groups. The results indicate that metformin treatment augmented the levels of FRAP and GSH in naturally aged, and d-gal induced aging model groups compared to the respective controls. In contrast, metformin treated groups exhibited significant reduction in MDA, PCO, ROS, and NO levels and a significant increase in AChE activity in induced aging rats. The administration of d-galactose upregulated the expression of sirtuin-2, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) and downregulated the expression of Beclin-1. Metformin supplementation downregulated the d-galactose induced expressions of sirtuin-2, IL-6, and TNF-α expression, whereas upregulated the Beclin-1 expression. Our data confirm that metformin restores the antioxidant status and improves healthy brain aging through the activation of autophagy and reduction in inflammation.

  4. Cellular and molecular effects for mutation induction in normal human cells irradiated with accelerated neon ions.

    Science.gov (United States)

    Suzuki, Masao; Tsuruoka, Chizuru; Kanai, Tatsuaki; Kato, Takeshi; Yatagai, Fumio; Watanabe, Masami

    2006-02-22

    We investigated the linear energy transfer (LET) dependence of mutation induction on the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus in normal human fibroblast-like cells irradiated with accelerated neon-ion beams. The cells were irradiated with neon-ion beams at various LETs ranging from 63 to 335 keV/microm. Neon-ion beams were accelerated by the Riken Ring Cyclotron at the Institute of Physical and Chemical Research in Japan. Mutation induction at the HPRT locus was detected to measure 6-thioguanine-resistant clones. The mutation spectrum of the deletion pattern of exons of mutants was analyzed using the multiplex polymerase chain reaction (PCR). The dose-response curves increased steeply up to 0.5 Gy and leveled off or decreased between 0.5 and 1.0 Gy, compared to the response to (137)Cs gamma-rays. The mutation frequency increased up to 105 keV/microm and then there was a downward trend with increasing LET values. The deletion pattern of exons was non-specific. About 75-100% of the mutants produced using LETs ranging from 63 to 335 keV/mum showed all or partial deletions of exons, while among gamma-ray-induced mutants 30% showed no deletions, 30% partial deletions and 40% complete deletions. These results suggested that the dose-response curves of neon-ion-induced mutations were dependent upon LET values, but the deletion pattern of DNA was not.

  5. Loss of caspase-2 accelerates age-dependent alterations in mitochondrial production of reactive oxygen species

    OpenAIRE

    Lopez-Cruzan, Marisa; Herman, Brian

    2013-01-01

    Mitochondria are known to be a major source and target of oxidative stress. Oxidative stress increases during aging and is suggested to underlie in part the aging process. We have previously documented an increase in endogenous caspase-2 (casp2) activity in hepatocytes obtained from old (28 months) vs. young mice (5 months). More recently, we have shown that casp2 is activated by oxidative stress and is critical for mitochondrial oxidative stress-induced apoptosis. Since casp2 appears integra...

  6. Human Aging Is a Metabolome-related Matter of Gender.

    Science.gov (United States)

    Jové, Mariona; Maté, Ianire; Naudí, Alba; Mota-Martorell, Natalia; Portero-Otín, Manuel; De la Fuente, Mónica; Pamplona, Reinald

    2016-05-01

    A molecular description of the mechanisms by which aging is produced is still very limited. Here, we have determined the plasma metabolite profile by using high-throughput metabolome profiling technologies of 150 healthy humans ranging from 30 to 100 years of age. Using a nontargeted approach, we detected 2,678 metabolite species in plasma, and the multivariate analyses separated perfectly two groups indicating a specific signature for each gender. In addition, there is a set of gender-shared metabolites, which change significantly during aging with a similar tendency. Among the identified molecules, we found vitamin D2-related compound, phosphoserine (40:5), monoacylglyceride (22:1), diacylglyceride (33:2), and resolvin D6, all of them decreasing with the aging process. Finally, we found three molecules that directly correlate with age and seven that inversely correlate with age, independently of gender. Among the identified molecules (6 of 10 according to exact mass and retention time), we found a proteolytic product (l-γ-glutamyl-l-leucine), which increased with age. On the contrary, a hydroxyl fatty acid (25-hydroxy-hexacosanoic), a polyunsaturated fatty acid (eicosapentaenoic acid), two phospholipids (phosphocholine [42:9]and phosphoserine [42:3]) and a prostaglandin (15-keto-prostaglandin F2α) decreased with aging. These results suggest that lipid species and their metabolism are closely linked to the aging process.

  7. Accelerating regional atrophy rates in the progression from normal aging to Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Sluimer, Jasper D. [VU University Medical Centre, Department of Diagnostic Radiology, Amsterdam (Netherlands); VU University Medical Centre, Alzheimer Centre, Amsterdam (Netherlands); VU University Medical Centre, Image Analysis Centre, Amsterdam (Netherlands); VU University Medical Centre, Department of Diagnostic Radiology and Alzheimer Centre, PO Box 7057, Amsterdam (Netherlands); Flier, Wiesje M. van der; Scheltens, Philip [VU University Medical Centre, Alzheimer Centre, Amsterdam (Netherlands); VU University Medical Centre, Department of Neurology, Amsterdam (Netherlands); Karas, Giorgos B.; Barkhof, Frederik [VU University Medical Centre, Department of Diagnostic Radiology, Amsterdam (Netherlands); VU University Medical Centre, Alzheimer Centre, Amsterdam (Netherlands); VU University Medical Centre, Image Analysis Centre, Amsterdam (Netherlands); Schijndel, Ronald van [VU University Medical Centre, Image Analysis Centre, Amsterdam (Netherlands); VU University Medical Centre, Department of Informatics, Amsterdam (Netherlands); Barnes, Josephine; Boyes, Richard G. [UCL, Institute of Neurology, Dementia Research Centre, London (United Kingdom); Cover, Keith S. [VU University Medical Centre, Department of Physics and Medical Technology, Amsterdam (Netherlands); Olabarriaga, Silvia D. [University of Amsterdam, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, Amsterdam (Netherlands); Fox, Nick C. [VU University Medical Centre, Department of Neurology, Amsterdam (Netherlands); UCL, Institute of Neurology, Dementia Research Centre, London (United Kingdom); Vrenken, Hugo [VU University Medical Centre, Alzheimer Centre, Amsterdam (Netherlands); VU University Medical Centre, Image Analysis Centre, Amsterdam (Netherlands); VU University Medical Centre, Department of Physics and Medical Technology, Amsterdam (Netherlands)

    2009-12-15

    We investigated progression of atrophy in vivo, in Alzheimer's disease (AD), and mild cognitive impairment (MCI). We included 64 patients with AD, 44 with MCI and 34 controls with serial MRI examinations (interval 1.8 {+-} 0.7 years). A nonlinear registration algorithm (fluid) was used to calculate atrophy rates in six regions: frontal, medial temporal, temporal (extramedial), parietal, occipital lobes and insular cortex. In MCI, the highest atrophy rate was observed in the medial temporal lobe, comparable with AD. AD patients showed even higher atrophy rates in the extramedial temporal lobe. Additionally, atrophy rates in frontal, parietal and occipital lobes were increased. Cox proportional hazard models showed that all regional atrophy rates predicted conversion to AD. Hazard ratios varied between 2.6 (95% confidence interval (CI) = 1.1-6.2) for occipital atrophy and 15.8 (95% CI = 3.5-71.8) for medial temporal lobe atrophy. In conclusion, atrophy spreads through the brain with development of AD. MCI is marked by temporal lobe atrophy. In AD, atrophy rate in the extramedial temporal lobe was even higher. Moreover, atrophy rates also accelerated in parietal, frontal, insular and occipital lobes. Finally, in nondemented elderly, medial temporal lobe atrophy was most predictive of progression to AD, demonstrating the involvement of this region in the development of AD. (orig.)

  8. Age variations in the properties of human tibial trabecular bone

    DEFF Research Database (Denmark)

    Ding, Ming; Dalstra, M; Danielsen, CC;

    1997-01-01

    We tested in compression specimens of human proximal tibial trabecular bone from 31 normal donors aged from 16 to 83 years and determined the mechanical properties, density and mineral and collagen content. Young's modulus and ultimate stress were highest between 40 and 50 years, whereas ultimate...

  9. Variations in Human Capital Investment Activity by Age.

    Science.gov (United States)

    Simpson, Patricia A.; Greller, Martin M.; Stroh, Linda K.

    2002-01-01

    Late-career workers (ages 50-65) were more likely to participate in credentialing programs, targeted job-related courses, and on-the-job computer training than younger adults and received similar employer support. However, participation might be a consequence of support received. Human capital investment thus is more complex than conventional…

  10. The theory of bipolar disorder as an illness of accelerated aging: implications for clinical care and research.

    Science.gov (United States)

    Rizzo, Lucas Bortolotto; Costa, Leonardo Gazzi; Mansur, Rodrigo B; Swardfager, Walter; Belangero, Síntia Iole; Grassi-Oliveira, Rodrigo; McIntyre, Roger S; Bauer, Moisés E; Brietzke, Elisa

    2014-05-01

    Bipolar Disorder (BD) has been conceptualized as both a cyclic and a progressive disorder. Mechanisms involved in neuroprogression in BD remain largely unknown although several non-mutually exclusive models have been proposed as explanatory frameworks. In the present paper, we propose that the pathophysiological changes observed in BD (e.g. brain structural alterations, cognitive deficits, oxidative stress imbalance, amyloid metabolism, immunological deregulation, immunosenescence, neurotrophic deficiencies and telomere shortening) converge on a model of accelerated aging (AA). Aging can be understood as a multidimensional process involving physical, neuropsychological, and social changes, which can be highly variable between individuals. Determinants of successful aging (e.g environmental and genetic factors), may also confer differential vulnerability to components of BD pathophysiology and contribute to the clinical presentation of BD. Herein we discuss how the understanding of aging and senescence can contribute to the search for new and promising molecular targets to explain and ameliorate neuroprogression in BD. We also present the strengths and limitations of this concept.

  11. Iron overload accelerates bone loss in healthy postmenopausal women and middle-aged men: a 3-year retrospective longitudinal study.

    Science.gov (United States)

    Kim, Beom-Jun; Ahn, Seong Hee; Bae, Sung Jin; Kim, Eun Hee; Lee, Seung-Hun; Kim, Hong-Kyu; Choe, Jae Won; Koh, Jung-Min; Kim, Ghi Su

    2012-11-01

    Despite extensive experimental and animal evidence about the detrimental effects of iron and its overload on bone metabolism, there have been no clinical studies relating iron stores to bone loss, especially in nonpathologic conditions. In the present study, we performed a large longitudinal study to evaluate serum ferritin concentrations in relation to annualized changes in bone mineral density (BMD) in healthy Koreans. A total of 1729 subjects (940 postmenopausal women and 789 middle-aged men) aged 40 years or older who had undergone comprehensive routine health examinations with an average 3 years of follow-up were enrolled. BMD in proximal femur sites (ie, the total femur, femur neck, and trochanter) was measured with dual-energy X-ray absorptiometry using the same equipment at baseline and follow-up. The mean age of women and men in this study was 55.8 ± 6.0 years and 55.5 ± 7.8 years, respectively, and serum ferritin levels were significantly higher in men than in women (p men. After adjustment for potential confounders, the rates of bone loss in all proximal femur sites in both genders were significantly accelerated in a dose-response fashion across increasing ferritin quartile categories (p for trend = 0.043 to <0.001). Consistently, compared with subjects in the lowest ferritin quartile category, those in the third and/or highest ferritin quartile category showed significantly faster bone loss in the total femur and femur neck in both genders (p = 0.023 to <0.001). In conclusion, these data provide the first clinical evidence that increased total body iron stores could be an independent risk factor for accelerated bone loss, even in healthy populations.

  12. Target disruption of ribosomal protein pNO40 accelerates aging and impairs osteogenic differentiation of mesenchymal stem cells.

    Science.gov (United States)

    Lin, Yen-Ming; Wu, Chih-Ching; Chang, Yu-Chen; Wu, Chu-Han; Ho, Hsien Li; Hu, Ji Wei; Chang, Ren-Chi; Wang, Chung-Ta; Ouyang, Pin

    2016-01-22

    pNO40/PS1D, a novel nucleolar protein, has been characterized as a core protein of eukaryotic 60S ribosome and at least two splicing forms of pNO40 mRNAs with alternative starting sites have been identified. Through production of knockout (ko) mice with either exon 2 (△E2), exon 4 (△E4) or △E2+E4 targeted disruption we identified a cryptic splicing product occurring in the ko tissues examined which in general cannot be observed in regular RT-PCR detection of wild-type (wt) animals. Among ko animals, △E4 null embryos exhibited prominent senescence-associated β-galactosidase (SA-β-gal) staining, a marker for senescent cells, in notochord, forelimbs and heart while bone marrow-derived mesenchymal stem cells (MSCs) from △E4 null mice developed accelerated aging and osteogenic differentiation defects compared to those from wt and other isoform mutant mice. Examination of the causal relationship between pNO40 deficiency and MSC-accelerated aging revealed △E4 null disruption in MSCs elicits high levels of ROS and elevated expression levels of p16 and Rb but not p53. Further analysis with iTraq identified CYP1B1, a component of the cytochrome p450 system, as a potential molecule mediating ROS generation in pNO40 deficient MSCs. We herein established a mouse model of MSC aging through pNO40-targeted depletion and demonstrated the effects of loss of pNO40 on bone homeostasis.

  13. Frataxin Accelerates [2Fe-2S] Cluster Formation on the Human Fe–S Assembly Complex

    Science.gov (United States)

    Fox, Nicholas G.; Das, Deepika; Chakrabarti, Mrinmoy; Lindahl, Paul A.; Barondeau, David P.

    2015-01-01

    Iron–sulfur (Fe–S) clusters function as protein cofactors for a wide variety of critical cellular reactions. In human mitochondria, a core Fe–S assembly complex [called SDUF and composed of NFS1, ISD11, ISCU2, and frataxin (FXN) proteins] synthesizes Fe–S clusters from iron, cysteine sulfur, and reducing equivalents and then transfers these intact clusters to target proteins. In vitro assays have relied on reducing the complexity of this complicated Fe–S assembly process by using surrogate electron donor molecules and monitoring simplified reactions. Recent studies have concluded that FXN promotes the synthesis of [4Fe-4S] clusters on the mammalian Fe–S assembly complex. Here the kinetics of Fe–S synthesis reactions were determined using different electron donation systems and by monitoring the products with circular dichroism and absorbance spectroscopies. We discovered that common surrogate electron donor molecules intercepted Fe–S cluster intermediates and formed high-molecular weight species (HMWS). The HMWS are associated with iron, sulfide, and thiol-containing proteins and have properties of a heterogeneous solubilized mineral with spectroscopic properties remarkably reminiscent of those of [4Fe-4S] clusters. In contrast, reactions using physiological reagents revealed that FXN accelerates the formation of [2Fe-2S] clusters rather than [4Fe-4S] clusters as previously reported. In the preceding paper [Fox, N. G., et al. (2015) Biochemistry 54, DOI: 10.1021/bi5014485], [2Fe-2S] intermediates on the SDUF complex were shown to readily transfer to uncomplexed ISCU2 or apo acceptor proteins, depending on the reaction conditions. Our results indicate that FXN accelerates a rate-limiting sulfur transfer step in the synthesis of [2Fe-2S] clusters on the human Fe–S assembly complex. PMID:26016518

  14. Theobromine Upregulates Osteogenesis by Human Mesenchymal Stem Cells In Vitro and Accelerates Bone Development in Rats.

    Science.gov (United States)

    Clough, Bret H; Ylostalo, Joni; Browder, Elizabeth; McNeill, Eoin P; Bartosh, Thomas J; Rawls, H Ralph; Nakamoto, Tetsuo; Gregory, Carl A

    2017-03-01

    Theobromine (THB) is one of the major xanthine-like alkaloids found in cacao plant and a variety of other foodstuffs such as tea leaves, guarana and cola nuts. Historically, THB and its derivatives have been utilized to treat cardiac and circulatory disorders, drug-induced nephrotoxicity, proteinuria and as an immune-modulator. Our previous work demonstrated that THB has the capacity to improve the formation of hydroxyl-apatite during tooth development, suggesting that it may also enhance skeletal development. With its excellent safety profile and resistance to pharmacokinetic elimination, we reasoned that it might be an excellent natural osteoanabolic supplement during pregnancy, lactation and early postnatal growth. To determine whether THB had an effect on human osteoprogenitors, we subjected primary human bone marrow mesenchymal stem cells (hMSCs) to osteogenic assays after exposure to THB in vitro and observed that THB exposure increased the rate of osteogenesis and mineralization by hMSCs. Moreover, THB exposure resulted in a list of upregulated mRNA transcripts that best matched an osteogenic tissue expression signature as compared to other tissue expression signatures archived in several databases. To determine whether oral administration of THB resulted in improved skeletal growth, we provided pregnant rats with chow supplemented with THB during pregnancy and lactation. After weaning, offspring received THB continuously until postnatal day 50 (approximately 10 mg kg(-1) day(-1)). Administration of THB resulted in neonates with larger bones, and 50-day-old offspring accumulated greater body mass, longer and thicker femora and superior tibial trabecular parameters. The accelerated growth did not adversely affect the strength and resilience of the bones. These results indicate that THB increases the osteogenic potential of bone marrow osteoprogenitors, and dietary supplementation of a safe dose of THB to expectant mothers and during the postnatal period

  15. Human fibrocyte-derived exosomes accelerate wound healing in genetically diabetic mice

    Energy Technology Data Exchange (ETDEWEB)

    Geiger, Adolf, E-mail: ageiger@dreirosen-pharma.com; Walker, Audrey, E-mail: awalker@dreirosen-pharma.com; Nissen, Erwin, E-mail: enissen@dreirosen-pharma.com

    2015-11-13

    Diabetic ulcers represent a substantial societal and healthcare burden worldwide and scarcely respond to current treatment strategies. This study was addressed to evaluate the therapeutic potential of exosomes secreted by human circulating fibrocytes, a population of mesenchymal progenitors involved in normal wound healing via paracrine signaling. The exosomes released from cells sequentially stimulated with platelet-derived growth factor-BB and transforming growth factor-β1, in the presence of fibroblast growth factor 2, did not show potential immunogenicity. These exosomes exhibited in-vitro proangiogenic properties, activated diabetic dermal fibroblasts, induced the migration and proliferation of diabetic keratinocytes, and accelerated wound closure in diabetic mice in vivo. Important components of the exosomal cargo were heat shock protein-90α, total and activated signal transducer and activator of transcription 3, proangiogenic (miR-126, miR-130a, miR-132) and anti-inflammatory (miR124a, miR-125b) microRNAs, and a microRNA regulating collagen deposition (miR-21). This proof-of-concept study demonstrates the feasibility of the use of fibrocytes-derived exosomes for the treatment of diabetic ulcers. - Highlights: • Fibrocytes have shown potent wound healing properties in vitro and in vivo. • Their clinical use is precluded by low numbers and antigen-presenting function. • We isolated exosomes with no immunogenicity potential from human fibrocytes. • Their cargo included microRNAs and proteins that are known healing promoters. • They accelerated wound closure in diabetic mice in a dose-dependent manner.

  16. Use of Accelerator Mass Spectrometry in Human Health and Molecular Toxicology.

    Science.gov (United States)

    Enright, Heather A; Malfatti, Michael A; Zimmermann, Maike; Ognibene, Ted; Henderson, Paul; Turteltaub, Kenneth W

    2016-12-19

    Accelerator mass spectrometry (AMS) has been adopted as a powerful bioanalytical method for human studies in the areas of pharmacology and toxicology. The exquisite sensitivity (10(-18) mol) of AMS has facilitated studies of toxins and drugs at environmentally and physiologically relevant concentrations in humans. Such studies include risk assessment of environmental toxicants, drug candidate selection, absolute bioavailability determination, and more recently, assessment of drug-target binding as a biomarker of response to chemotherapy. Combining AMS with complementary capabilities such as high performance liquid chromatography (HPLC) can maximize data within a single experiment and provide additional insight when assessing drugs and toxins, such as metabolic profiling. Recent advances in the AMS technology at Lawrence Livermore National Laboratory have allowed for direct coupling of AMS with complementary capabilities such as HPLC via a liquid sample moving wire interface, offering greater sensitivity compared to that of graphite-based analysis, therefore enabling the use of lower (14)C and chemical doses, which are imperative for clinical testing. The aim of this review is to highlight the recent efforts in human studies using AMS, including technological advancements and discussion of the continued promise of AMS for innovative clinical based research.

  17. Response of sensitive human ataxia and resistant T-1 cell lines to accelerated heavy ions

    Energy Technology Data Exchange (ETDEWEB)

    Tobias, C.A.; Blakely, E.A.; Chang, P.Y.; Lommel, L.; Roots, R.

    1983-07-01

    The radiation dose responses of fibroblast from a patient with Ataxia telangiectasis (AT-2SF) and an established line of human T-1 cells were studied. Nearly monoenergetic accelerated neon and argon ions were used at the Berkeley Bevalac with various residual range values. The LET of the particles varied from 30 keV/..mu..m to over 1000 keV/..mu..m. All Ataxia survival curves were exponential functions of the dose. Their radiosensitivity reached peak values at 100 to 200 keV/..mu..m. Human T-1 cells have effective sublethal damage repair as has been evidenced by split dose experiments, and they are much more resistant to low LET than to high LET radiation. The repair-misrepair model has been used to interpret these results. We have obtained mathematical expressions that describe the cross sections and inactivation coefficients for both human cell lines as a function of the LET and the type of particle used. The results suggest either that high-LET particles induce a greater number of radiolesions per track or that heavy-ions at high LET induce lesions that kill cells more effectively and that are different from those produced at low LET. We assume that the lesions induced in T-1 and Ataxia cells are qualitatively similar and that each cell line attempts to repair these lesions. The result in most irradiated Ataxia cells, however, is either lethal misrepair or incomplete repair leading to cell death. 63 references, 10 figures, 1 table.

  18. Inhibition of FGF signaling accelerates neural crest cell differentiation of human pluripotent stem cells.

    Science.gov (United States)

    Jaroonwitchawan, Thiranut; Muangchan, Pattamon; Noisa, Parinya

    2016-12-02

    Neural crest (NC) is a transient population, arising during embryonic development and capable of differentiating into various somatic cells. The defects of neural crest development leads to neurocristopathy. Several signaling pathways were revealed their significance in NC cell specification. Fibroblast growth factor (FGF) is recognized as an important signaling during NC development, for instance Xenopus and avian; however, its contributions in human species are remained elusive. Here we used human pluripotent stem cells (hPSCs) to investigate the consequences of FGF inhibition during NC cell differentiation. The specific-FGF receptor inhibitor, SU5402, was used in this investigation. The inhibition of FGF did not found to affect the proliferation or death of hPSC-derived NC cells, but promoted hPSCs to commit NC cell fate. NC-specific genes, including PAX3, SLUG, and TWIST1, were highly upregulated, while hPSC genes, such as OCT4, and E-CAD, rapidly reduced upon FGF signaling blockage. Noteworthy, TFAP-2α, a marker of migratory NC cells, abundantly presented in SU5402-induced cells. This accelerated NC cell differentiation could be due to the activation of Notch signaling upon the blockage of ERK1/2 phosphorylation, since NICD was increased by SU5402. Altogether, this study proposed the contributions of FGF signaling in controlling human NC cell differentiation from hPSCs, the crosstalk between FGF and Notch, and might imply to the influences of FGF signaling in neurocristophatic diseases.

  19. Human age estimation framework using different facial parts

    Directory of Open Access Journals (Sweden)

    Mohamed Y. El Dib

    2011-03-01

    Full Text Available Human age estimation from facial images has a wide range of real-world applications in human computer interaction (HCI. In this paper, we use the bio-inspired features (BIF to analyze different facial parts: (a eye wrinkles, (b whole internal face (without forehead area and (c whole face (with forehead area using different feature shape points. The analysis shows that eye wrinkles which cover 30% of the facial area contain the most important aging features compared to internal face and whole face. Furthermore, more extensive experiments are made on FG-NET database by increasing the number of missing pictures in older age groups using MORPH database to enhance the results.

  20. A direct PCR approach to accelerate analyses of human-associated microbial communities.

    Directory of Open Access Journals (Sweden)

    Gilberto E Flores

    Full Text Available Since the composition of the human microbiome is highly variable both within and between individuals, researchers are increasingly reliant on high-throughput molecular approaches to identify linkages between the composition of these communities and human health. While new sequencing technologies have made it increasingly feasible to analyze large numbers of human-associated samples, the extraction of DNA from samples often remains a bottleneck in the process. Here we tested a direct PCR approach using the Extract-N-Amp Plant PCR Kit to accelerate the 16S rRNA gene-based analyses of human-associated bacterial communities, directly comparing this method to a more commonly-used approach whereby DNA is first extracted and purified from samples using a series of steps prior to PCR amplification. We used both approaches on replicate samples collected from each of five body habitats (tongue surface, feces, forehead skin, underarm skin, and forearm skin from four individuals. With the exception of the tongue samples, there were few significant differences in the estimates of taxon richness or phylogenetic diversity obtained using the two approaches. Perhaps more importantly, there were no significant differences between the methods in their ability resolve body habitat differences or inter-individual differences in bacterial community composition and the estimates of the relative abundances of individual taxa were nearly identical with the two methods. Overall, the two methods gave very similar results and the direct PCR approach is clearly advantageous for many studies exploring the diversity and composition of human-associated bacterial communities given that large numbers of samples can be processed far more quickly and efficiently.

  1. Interventions to Slow Aging in Humans: Are We Ready?

    Science.gov (United States)

    Longo, Valter D; Antebi, Adam; Bartke, Andrzej; Barzilai, Nir; Brown-Borg, Holly M; Caruso, Calogero; Curiel, Tyler J; de Cabo, Rafael; Franceschi, Claudio; Gems, David; Ingram, Donald K; Johnson, Thomas E; Kennedy, Brian K; Kenyon, Cynthia; Klein, Samuel; Kopchick, John J; Lepperdinger, Guenter; Madeo, Frank; Mirisola, Mario G; Mitchell, James R; Passarino, Giuseppe; Rudolph, Karl L; Sedivy, John M; Shadel, Gerald S; Sinclair, David A; Spindler, Stephen R; Suh, Yousin; Vijg, Jan; Vinciguerra, Manlio; Fontana, Luigi

    2015-08-01

    The workshop entitled 'Interventions to Slow Aging in Humans: Are We Ready?' was held in Erice, Italy, on October 8-13, 2013, to bring together leading experts in the biology and genetics of aging and obtain a consensus related to the discovery and development of safe interventions to slow aging and increase healthy lifespan in humans. There was consensus that there is sufficient evidence that aging interventions will delay and prevent disease onset for many chronic conditions of adult and old age. Essential pathways have been identified, and behavioral, dietary, and pharmacologic approaches have emerged. Although many gene targets and drugs were discussed and there was not complete consensus about all interventions, the participants selected a subset of the most promising strategies that could be tested in humans for their effects on healthspan. These were: (i) dietary interventions mimicking chronic dietary restriction (periodic fasting mimicking diets, protein restriction, etc.); (ii) drugs that inhibit the growth hormone/IGF-I axis; (iii) drugs that inhibit the mTOR-S6K pathway; or (iv) drugs that activate AMPK or specific sirtuins. These choices were based in part on consistent evidence for the pro-longevity effects and ability of these interventions to prevent or delay multiple age-related diseases and improve healthspan in simple model organisms and rodents and their potential to be safe and effective in extending human healthspan. The authors of this manuscript were speakers and discussants invited to the workshop. The following summary highlights the major points addressed and the conclusions of the meeting.

  2. Interventions to Slow Aging in Humans: Are We Ready?

    Science.gov (United States)

    Longo, Valter D; Antebi, Adam; Bartke, Andrzej; Barzilai, Nir; Brown-Borg, Holly M; Caruso, Calogero; Curiel, Tyler J; de Cabo, Rafael; Franceschi, Claudio; Gems, David; Ingram, Donald K; Johnson, Thomas E; Kennedy, Brian K; Kenyon, Cynthia; Klein, Samuel; Kopchick, John J; Lepperdinger, Guenter; Madeo, Frank; Mirisola, Mario G; Mitchell, James R; Passarino, Giuseppe; Rudolph, Karl L; Sedivy, John M; Shadel, Gerald S; Sinclair, David A; Spindler, Stephen R; Suh, Yousin; Vijg, Jan; Vinciguerra, Manlio; Fontana, Luigi

    2015-01-01

    The workshop entitled ‘Interventions to Slow Aging in Humans: Are We Ready?’ was held in Erice, Italy, on October 8–13, 2013, to bring together leading experts in the biology and genetics of aging and obtain a consensus related to the discovery and development of safe interventions to slow aging and increase healthy lifespan in humans. There was consensus that there is sufficient evidence that aging interventions will delay and prevent disease onset for many chronic conditions of adult and old age. Essential pathways have been identified, and behavioral, dietary, and pharmacologic approaches have emerged. Although many gene targets and drugs were discussed and there was not complete consensus about all interventions, the participants selected a subset of the most promising strategies that could be tested in humans for their effects on healthspan. These were: (i) dietary interventions mimicking chronic dietary restriction (periodic fasting mimicking diets, protein restriction, etc.); (ii) drugs that inhibit the growth hormone/IGF-I axis; (iii) drugs that inhibit the mTOR–S6K pathway; or (iv) drugs that activate AMPK or specific sirtuins. These choices were based in part on consistent evidence for the pro-longevity effects and ability of these interventions to prevent or delay multiple age-related diseases and improve healthspan in simple model organisms and rodents and their potential to be safe and effective in extending human healthspan. The authors of this manuscript were speakers and discussants invited to the workshop. The following summary highlights the major points addressed and the conclusions of the meeting. PMID:25902704

  3. Development and evaluation of an emulsion containing lycopene for combating acceleration of skin aging

    Directory of Open Access Journals (Sweden)

    Letícia Caramori Cefali

    2015-09-01

    Full Text Available Lycopene, a carotenoid and potent antioxidant is found in large quantities in tomatoes. Lycopene combats diseases, such as cardiovascular disease and different types of cancer, including prostate cancer. However, its topical use in emulsion form for the combat of skin aging is under-explored. The aim of the present study was to develop an emulsion containing lycopene extracted from salad tomatoes and evaluate its cytotoxicity, stability, rheological behavior, antioxidant activity and phytocosmetic permeation. The developed cosmetic comprised an oil phase made up of shea derivatives and was evaluated in terms of its physiochemical stability, spreadability, thermal analysis, rheological behavior, microbiological quality, cytotoxicity, antioxidant activity, cutaneous permeation and retention. The results demonstrate that this phytocosmetic is stable, exhibits satisfactory rheological behavior for a topical formula and is a promising product for combating skin aging.

  4. Age effects in the human middle ear: Wideband acoustical measures

    Science.gov (United States)

    Feeney, M. Patrick; Sanford, Chris A.

    2004-12-01

    Studies that have examined age effects in the human middle ear using either admittance measures at 220 or 660 Hz or multifrequency tympanometry from 200 to 2000 Hz have had conflicting results. Several studies have suggested an increase in admittance with age, while several others have suggested a decrease in admittance with age. A third group of studies found no significant age effect. This study examined 226 Hz tympanometry and wideband energy reflectance and impedance at ambient pressure in a group of 40 young adults and a group of 30 adults with age >=60 years. The groups did not differ in admittance measures of the middle ear at 226 Hz. However, significant age effects were found in wideband energy reflectance and impedance. In particular, in older adults there was a comparative decrease in reflectance from 800 to 2000 Hz but an increase near 4000 Hz. The results suggest a decrease in middle-ear stiffness with age. The findings of this study hold relevance for understanding the aging process in the auditory system, for the establishment of normative data for wideband energy reflectance, for the possibility of a conductive component to presbycusis, and for the interpretation of otoacoustic emission measurements. .

  5. Natural ageing process accelerates the release of Ag from functional textile in various exposure scenarios

    Science.gov (United States)

    Ding, Dahu; Chen, Lulu; Dong, Shaowei; Cai, Hao; Chen, Jifei; Jiang, Canlan; Cai, Tianming

    2016-11-01

    Natural ageing process occurs throughout the life cycle of textile products, which may possess influences on the release behavior of additives such as silver nanoparticles (Ag NPs). In this study, we assessed the releasability of Ag NPs from a Ag NPs functionalized textile in five different exposure scenarios (i.e. tap water (TW), pond water (PW), rain water (RW), artificial sweat (AS), and detergent solution (DS) along with deionized water (DW) as reference), which were very likely to occur throughout the life cycle of the textile. For the pristine textile, although the most remarkable release was found in DW (6–15 μg Ag/g textile), the highest release rate was found in RW (around 7 μg Ag/(g textile·h)). After ageing treatment, the total released Ag could be increased by 75.7~386.0% in DW, AS and DS. Morphological analysis clearly showed that the Ag NPs were isolated from the surface of the textile fibre due to the ageing treatment. This study provides useful information for risk assessment of nano-enhanced textile products.

  6. Use of organic solderability preservatives on solderability retention of copper after accelerated aging

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez, C.L.; Sorensen, N.R.; Lucero, S.J.

    1997-02-01

    Organic solderability preservatives (OSP`s) have been used by the electronics industry for some time to maintain the solderability of circuit boards and components. Since solderability affects both manufacturing efficiency and product reliability, there is significant interest in maintaining good solder wettability. There is often a considerable time interval between the initial fabrication of a circuit board or component and its use at the assembly level. Parts are often stored under a variety of conditions, in many cases not well controlled. Solder wettability can deteriorate during storage, especially in harsh environments. This paper describes the ongoing efforts at Sandia National Laboratories to quantify solder watability on bare and aged copper surfaces. Benzotriazole and imidazole were applied to electronic grade copper to retard aging effects on solderability. The coupons were introduced into Sandia`s Facility for Atmospheric Corrosion Testing (FACT) to simulate aging in a typical indoor industrial environment. H{sub 2}S, NO{sub 2} and Cl{sub 2} mixed gas was introduced into the test cell and maintained at 35{degrees}C and 70% relative humidity for test periods of one day to two weeks. The OSP`s generally performed better than bare Cu, although solderability diminished with increasing exposure times.

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

    DEFF Research Database (Denmark)

    Scheibye-Knudsen, Morten; Scheibye-Alsing, Karsten; Canugovi, Chandrika

    2013-01-01

    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....

  8. Parkinson's disease accelerates age-related decline in haptic perception by altering somatosensory integration.

    Science.gov (United States)

    Konczak, Jürgen; Sciutti, Alessandra; Avanzino, Laura; Squeri, Valentina; Gori, Monica; Masia, Lorenzo; Abbruzzese, Giovanni; Sandini, Giulio

    2012-11-01

    This study investigated how Parkinson's disease alters haptic perception and the underlying mechanisms of somatosensory and sensorimotor integration. Changes in haptic sensitivity and acuity (the abilities to detect and to discriminate between haptic stimuli) due to Parkinson's disease were systematically quantified and contrasted to the performance of healthy older and young adults. Using a robotic force environment, virtual contours of various curvatures were presented. Participants explored these contours with their hands and indicated verbally whether they could detect or discriminate between two contours. To understand what aspects of sensory or sensorimotor integration are altered by ageing and disease, we manipulated the sensorimotor aspect of the task: the robot either guided the hand along the contour or the participant actively moved the hand. Active exploration relies on multimodal sensory and sensorimotor integration, while passive guidance only requires sensory integration of proprioceptive and tactile information. The main findings of the study are as follows: first, a decline in haptic precision can already be observed in adults before the age of 70 years. Parkinson's disease may lead to an additional decrease in haptic sensitivity well beyond the levels typically seen in middle-aged and older adults. Second, the haptic deficit in Parkinson's disease is general in nature. It becomes manifest as a decrease in sensitivity and acuity (i.e. a smaller perceivable range and a diminished ability to discriminate between two perceivable haptic stimuli). Third, thresholds during both active and passive exploration are elevated, but not significantly different from each other. That is, active exploration did not enhance the haptic deficit when compared to passive hand motion. This implies that Parkinson's disease affects early stages of somatosensory integration that ultimately have an impact on processes of sensorimotor integration. Our results suggest that

  9. Soluble carbohydrates in cereal (wheat, rye, triticale) seed after storage under accelerated ageing conditions

    OpenAIRE

    Agnieszka I. Piotrowicz-Cieślak; Maciej Niedzielski; Dariusz J. Michalczyk; Wiesław Łuczak; Barbara Adomas

    2011-01-01

    Germinability and the content of soluble carbohydrates were analysed in cereal seed (winter rye, cv. Warko; spring wheat, cv. Santa; hexaploid winter triticale, cv. Fidelio and cv. Woltario). Seed moisture content (mc) was equilibrated over silica gel to 0.08 g H2O/g dry mass and stored in a desiccator at 20oC for up to 205 weeks or were equilibrated to mc 0.06, 0.08 or 0.10 g H2O/g dm and subjected to artificial aging at 35oC in air-tight laminated aluminium foil packages for 205 weeks. It w...

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Vincent T van Hees

    Full Text Available 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

  12. Exploring the link between depression and accelerated cellular aging: telomeres hold the key

    Directory of Open Access Journals (Sweden)

    Yu R

    2015-12-01

    Full Text Available Ruby Yu, Jean Woo Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, SAR, China Abstract: Accumulating evidence suggests that telomeres may be a marker for biological aging and telomere length may be affected by multifactorial influences, including cumulative exposure to depression. Associations with telomere length have been reported for major depressive disorder, lifetime duration of depression, higher depression severity, and history of depression. The exact underling mechanisms for these associations have yet to be fully elucidated; however, oxidative stress, chronic inflammation, dysregulated hypothalamus-pituitary-adrenal axis, and altered cortisol levels may be important biochemical mediators. These mediators could also be influenced by psychological stress, unhealthy lifestyle behaviors, or other potential factors, such as childhood abuse, post-traumatic stress disorder, and anxiety that are commonly associated with depression. As such, stress reduction and lifestyle interventions that may affect the telomere maintenance system should be considered for individuals with depression.Keywords: depression, telomere length, biomarkers, cellular ageing

  13. Ultrastructural changes in the melanocytes of aging human choroid.

    Science.gov (United States)

    Nag, Tapas Chandra

    2015-12-01

    Retinal pigment epithelial cells as well as choroidal melanocytes (CM) possess melanin granules. The former show clear, age-related changes (formation of lipofuscin granules with a concomitant decrease in melanin content); however, data on changes in the CM with aging are fairly limited. We examined CM in human macular and mid-peripheral areas by light- and transmission electron microscopy in 50-94 year-old donor eyes (N=12). Unlike in the choroid of lower ages, the melanocytes from aging choroid (>75 years) showed partial fusion of about 8-15 melanosomes, forming rosettes-like structures. Besides, there was evidence of emptiness in cytoplasm caused by the loss of melanosomes in aged CM, as was confirmed by quantification in macular part of choroid. In advanced aged eyes (85-94-year-old), the CM possessed many lipid droplets as well as irregular lipofuscin granules, the latter had a tendency to fuse with melanosomes, as happens in aged retinal pigment epithelium. Macrophages in their cytoplasm contained abundant irregular as well as clumped melanosomes of variable size, suggesting that damaged granules/melanocytes are cleared by these phagocytes. These obvious changes in the CM are likely to make the choroid prone to damage by visible light.

  14. Thinking Differently About Aging: Changing Attitudes Through the Humanities.

    Science.gov (United States)

    Marshall, Leni

    2015-08-01

    Ageism has many cumulative negative health effects, so reducing ageism in college-age youths can have a significant, long-term impact on public health. Reduced ageism decreases the prevalence and severity of many negative health events, such as myocardial infarctions, and can add an average of 7.5 years to the life span. One of the few proven methods for reducing ageist ideation is through participation in a video screening and a pair of follow-up conversations. This intervention is similar to the regular activities of many faculty members in the humanities. Gerontologists' expertise with quantitative studies, qualitative studies, and data analysis is needed to determine what factors can improve the efficacy of the intervention and to demonstrate the long-term health impact of specific interventions. Humanities research also will benefit from expanded understandings of aging and old age. Organizations such as the Gerontological Society of America, the European Network in Aging Studies, and the North American Network in Aging Studies can facilitate interdisciplinary collaboration.

  15. Gene expression profiles of single human mature oocytes in relation to age

    DEFF Research Database (Denmark)

    Grøndahl, M L; Andersen, Claus Yding; Bogstad, J

    2010-01-01

    The development competence of human oocytes declines with increasing age. The objective of this study was to investigate the effect of age on gene expression profile in mature human oocytes.......The development competence of human oocytes declines with increasing age. The objective of this study was to investigate the effect of age on gene expression profile in mature human oocytes....

  16. Genomic and network patterns of schizophrenia genetic variation in human evolutionary accelerated regions.

    Science.gov (United States)

    Xu, Ke; Schadt, Eric E; Pollard, Katherine S; Roussos, Panos; Dudley, Joel T

    2015-05-01

    The population persistence of schizophrenia despite associated reductions in fitness and fecundity suggests that the genetic basis of schizophrenia has a complex evolutionary history. A recent meta-analysis of schizophrenia genome-wide association studies offers novel opportunities for assessment of the evolutionary trajectories of schizophrenia-associated loci. In this study, we hypothesize that components of the genetic architecture of schizophrenia are attributable to human lineage-specific evolution. Our results suggest that schizophrenia-associated loci enrich in genes near previously identified human accelerated regions (HARs). Specifically, we find that genes near HARs conserved in nonhuman primates (pHARs) are enriched for schizophrenia-associated loci, and that pHAR-associated schizophrenia genes are under stronger selective pressure than other schizophrenia genes and other pHAR-associated genes. We further evaluate pHAR-associated schizophrenia genes in regulatory network contexts to investigate associated molecular functions and mechanisms. We find that pHAR-associated schizophrenia genes significantly enrich in a GABA-related coexpression module that was previously found to be differentially regulated in schizophrenia affected individuals versus healthy controls. In another two independent networks constructed from gene expression profiles from prefrontal cortex samples, we find that pHAR-associated schizophrenia genes are located in more central positions and their average path lengths to the other nodes are significantly shorter than those of other schizophrenia genes. Together, our results suggest that HARs are associated with potentially important functional roles in the genetic architecture of schizophrenia.

  17. Periodic heat shock accelerated the chondrogenic differentiation of human mesenchymal stem cells in pellet culture.

    Directory of Open Access Journals (Sweden)

    Jing Chen

    Full Text Available Osteoarthritis (OA is one of diseases that seriously affect elderly people's quality of life. Human mesenchymal stem cells (hMSCs offer a potential promise for the joint repair in OA patients. However, chondrogenic differentiation from hMSCs in vitro takes a long time (∼ 6 weeks and differentiated cells are still not as functionally mature as primary isolated chondrocytes, though chemical stimulations and mechanical loading have been intensively studied to enhance the hMSC differentiation. On the other hand, thermal stimulations of hMSC chondrogenesis have not been well explored. In this study, the direct effects of mild heat shock (HS on the differentiation of hMSCs into chondrocytes in 3D pellet culture were investigated. Periodic HS at 41 °C for 1 hr significantly increased sulfated glycosaminoglycan in 3D pellet culture at Day 10 of chondrogenesis. Immunohistochemical and Western Blot analyses revealed an increased expression of collagen type II and aggrecan in heat-shocked pellets than non heat-shocked pellets on Day 17 of chondrogenesis. In addition, HS also upregulated the expression of collagen type I and X as well as heat shock protein 70 on Day 17 and 24 of differentiation. These results demonstrate that HS accelerated the chondrogenic differentiation of hMSCs and induced an early maturation of chondrocytes differentiated from hMSCs. The results of this study will guide the design of future protocols using thermal treatments to facilitate cartilage regeneration with human mesenchymal stem cells.

  18. Kinetics of Beta-14[14C] Carotene in a Human Subject Using Accelerator Mass Spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Dueker, S.R.; Lin, Y.; Follett, J.R.; Clifford, A.J.; Buchholz, B.A.

    2000-01-31

    {beta}-Carotene is a tetraterpenoid distributed widely throughout the plant kingdom. It is a member of a group of pigments referred to as carotenoids that have the distinction of serving as metabolic precursors to vitamin A in humans and many animals [1,2]. We used Accelerator Mass Spectrometry (AMS) [3] to determine the metabolic behavior of a physiologic oral dose of {beta}-[{sup 14}C]carotene (200 nanoCuries; 0.57 {micro}mol) in a healthy human subject. Serial blood specimens were collected for 210-d and complete urine and feces were collected for 17 and 10-d, respectively. Balance data indicated that the dose was 42% bioavailable. The absorbed {beta}-carotene was lost slowly via urine in accord with the slow body turnover of {beta}-carotene and vitamin A [4]. HPLC fractionation of plasma taken at early time points (0-24-h) showed the label was distributed between {beta}-carotene and retinyl esters (vitamin A) derived from intestinal metabolism.

  19. Determination of dideoxyosone precursors of AGEs in human lens proteins.

    Science.gov (United States)

    Linetsky, Mikhail; Kaid Johar, S R; Meltretter, Jasmin; Padmanabha, Smitha; Parmar, Trilok; Vasavada, Abhay R; Pischetsrieder, Monika; Nagaraj, Ram H

    2011-10-01

    Dideoxyosones (DDOs) are intermediates in the synthesis of advanced glycation endproducts (AGEs), such as pentosidine and glucosepane. Although the formation of pentosidine and glucosepane in the human lens has been firmly established, the formation of DDOs has not been demonstrated. The aim of this study was to develop a reliable method to detect DDOs in lens proteins. A specific DDO trapping agent, biotinyl-diaminobenzene (3,4-diamino-N-(3-[5-(2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanoyl]aminopropyl)benzamide) (BDAB) was added during in vitro protein glycation or during protein extraction from human lenses. In vitro glycated human lens protein showed strong reaction in monomeric and polymeric crosslinked proteins by Western blot and ELISA. Glycation of BSA in the presence of BDAB resulted in covalent binding of BDAB to the protein and inhibited pentosidine formation. Mass spectrometric analysis of lysozyme glycated in the presence of BDAB showed the presence of quinoxalines at lysine residues at positions K1, K33, K96, and K116. The ELISA results indicated that cataractous lens proteins contain significantly higher levels of DDO than non-cataractous lenses (101.9±67.8 vs. 31.7±19.5AU/mg protein, p<0.0001). This study provides first direct evidence of DDO presence in human tissue proteins and establishes that AGE crosslink synthesis in the human lens occurs via DDO intermediates. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Age, Health and Attractiveness Perception of Virtual (Rendered) Human Hair.

    Science.gov (United States)

    Fink, Bernhard; Hufschmidt, Carla; Hirn, Thomas; Will, Susanne; McKelvey, Graham; Lankhof, John

    2016-01-01

    The social significance of physical appearance and beauty has been documented in many studies. It is known that even subtle manipulations of facial morphology and skin condition can alter people's perception of a person's age, health and attractiveness. While the variation in facial morphology and skin condition cues has been studied quite extensively, comparably little is known on the effect of hair on social perception. This has been partly caused by the technical difficulty of creating appropriate stimuli for investigations of people's response to systematic variation of certain hair characteristics, such as color and style, while keeping other features constant. Here, we present a modeling approach to the investigation of human hair perception using computer-generated, virtual (rendered) human hair. In three experiments, we manipulated hair diameter (Experiment 1), hair density (Experiment 2), and hair style (Experiment 3) of human (female) head hair and studied perceptions of age, health and attractiveness. Our results show that even subtle changes in these features have an impact on hair perception. We discuss our findings with reference to previous studies on condition-dependent quality cues in women that influence human social perception, thereby suggesting that hair is a salient feature of human physical appearance, which contributes to the perception of beauty.

  1. Lipidomics of human brain aging and Alzheimer's disease pathology.

    Science.gov (United States)

    Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

    2015-01-01

    Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context. © 2015 Elsevier Inc. All rights reserved.

  2. Age, Health and Attractiveness Perception of Virtual (Rendered) Human Hair

    Science.gov (United States)

    Fink, Bernhard; Hufschmidt, Carla; Hirn, Thomas; Will, Susanne; McKelvey, Graham; Lankhof, John

    2016-01-01

    The social significance of physical appearance and beauty has been documented in many studies. It is known that even subtle manipulations of facial morphology and skin condition can alter people’s perception of a person’s age, health and attractiveness. While the variation in facial morphology and skin condition cues has been studied quite extensively, comparably little is known on the effect of hair on social perception. This has been partly caused by the technical difficulty of creating appropriate stimuli for investigations of people’s response to systematic variation of certain hair characteristics, such as color and style, while keeping other features constant. Here, we present a modeling approach to the investigation of human hair perception using computer-generated, virtual (rendered) human hair. In three experiments, we manipulated hair diameter (Experiment 1), hair density (Experiment 2), and hair style (Experiment 3) of human (female) head hair and studied perceptions of age, health and attractiveness. Our results show that even subtle changes in these features have an impact on hair perception. We discuss our findings with reference to previous studies on condition-dependent quality cues in women that influence human social perception, thereby suggesting that hair is a salient feature of human physical appearance, which contributes to the perception of beauty. PMID:28066276

  3. Radiolysis as a solution for accelerated ageing studies of electrolytes in Lithium-ion batteries

    Science.gov (United States)

    Ortiz, Daniel; Steinmetz, Vincent; Durand, Delphine; Legand, Solène; Dauvois, Vincent; Maître, Philippe; Le Caër, Sophie

    2015-04-01

    Diethyl carbonate and dimethyl carbonate are prototype examples of eco-friendly solvents used in lithium-ion batteries. Nevertheless, their degradation products affect both the battery performance and its safety. Therefore, it is of paramount importance to understand the reaction mechanisms involved in the ageing processes. Among those, redox processes are likely to play a critical role. Here we show that radiolysis is an ideal tool to generate the electrolytes degradation products. The major gases detected after irradiation (H2, CH4, C2H6, CO and CO2) are identified and quantified. Moreover, the chemical compounds formed in the liquid phase are characterized by different mass spectrometry techniques. Reaction mechanisms are then proposed. The detected products are consistent with those of the cycling of Li-based cells. This demonstrates that radiolysis is a versatile and very helpful tool to better understand the phenomena occurring in lithium-ion batteries.

  4. TNF-alpha, leptin, and lymphocyte function in human aging

    DEFF Research Database (Denmark)

    Bruunsgaard, H.; Pedersen, Agnes Nadelmann; Schroll, M.

    2000-01-01

    associated with leptin, circulating interleukin-2 receptors (sIL-2R), and phytohaemagglutinin (PHA) induced IL-2 production in whole blood in elderly humans. Circulating levels of TNF-alpha and sIL-2R were higher in elderly humans (N=42) compared to a young control group (N=37) whereas...... regression analysis adjusting for the effect of gender and body mass index. Furthermore, TNF-alpha, but not leptin, was positively correlated to sIL-2R and negatively correlated to IL-2 production. In conclusion, increased plasma levels of TNF-alpha in aging is associated with poor IL-2 production ex vivo...

  5. Does recombinant human erythropoietin accelerate correction of post-ulcer-bleeding anaemia? A pilot study

    Institute of Scientific and Technical Information of China (English)

    Spiros D. Ladas; Dimitrios Polymeros; Thomas Pagonis; Konstantinos Triantafyllou; Gregorios Paspatis; Maria Hatziargiriou; Sotirios A.Raptis

    2004-01-01

    AIM: Anaemia caused by acute upper gastrointestinal bleeding is treated with blood transfusion or iron, but patients usually face a two-month recovery period from posthaemorrhage anaemia. This prospective, randomised, open,pilot study was designed to investigate whether recombinant human erythropoietin (Epoetin) therapy accelerate haematocrit increase in the post-bleeding recovery period.METHODS: We studied hospitalised patients admitted because of acute ulcer bleeding or haemorrhagic gastritis,who had a haematocrit of 27-33% and did not receive blood transfusions. One day after the endoscopic confirmation of cessation of bleeding, they were randomised either to erythropoietin (20 000 IU Epoetin alfa subcutaneously, on days 0, 4 and 6) plus iron (100 mg im, on days 1- 6, (G1) or iron only (G2). Haematocrit was measured on days 0, 6, 14,30, 45, and 60, respectively.RESULTS: One patient from G1 and two from G2 were lost to follow-up. Therefore, 14 and 13 patients from G1 and G2respectively were analysed. Demographic characteristics, serum iron, ferritin, total iron binding capacity, reticulocytes, and haematocrit were not significantly different at entry to the study.Median reticulocyte counts were significantly different between groups on day six (G1: 4.0, 3.0-6.4 vsG2: 3.5, 2.1-4.4%,P=0.03) and median haematocrit on day fourteen [G1: 35.9,30.7-41.0 vsG2: 32.5, 29.5-37.0% (median, range), P=0.04].CONCLUSION: Erythropoietin administration significantly accelerates correction of anemia after acute ulcer bleeding.The haematocrit gain is equivalent to one unit of transfused blood two weeks after the bleeding episode.

  6. Mitochondrial superoxide dismutase deficiency accelerates chronological aging in the fission yeast Schizosaccharomyces pombe.

    Science.gov (United States)

    Ogata, Toshiya; Senoo, Takanori; Kawano, Shinji; Ikeda, Shogo

    2016-01-01

    A mitochondrial superoxide dismutase (SOD2) is the first line of antioxidant defense against mitochondrial superoxide. Even though the involvement of SOD2 in lifespan has been studied extensively in several organisms, characterization of the aging process has not been performed for the sod2 mutant (sod2Δ) of a prominent model Schizosaccharomyces pombe. In this study, we measured the chronological lifespan of sod2Δ cells by their ability to survive in long-term culture. SOD2 deficiency drastically decreased cell viability in the stationary phase. The mutation frequency of nuclear DNA in sod2Δ was elevated in the stationary phase, and cellular proteins and nuclear DNA were extensively degraded, concurrent with cell death. The sod2 gene in wild-type cells could be induced by an increase in endogenous oxidative stresses, after which, SOD2 activity was substantially elevated during the stationary phase. Culture in a lower glucose concentration (calorie restriction) prominently extended the sod2Δ lifespan. Therefore, S. pombe SOD2 plays a critical role in longevity through its upregulation in the non-dividing phase.

  7. Linseed oil presents different patterns of oxidation in real-time and accelerated aging assays.

    Science.gov (United States)

    Douny, Caroline; Razanakolona, Rina; Ribonnet, Laurence; Milet, Jérôme; Baeten, Vincent; Rogez, Hervé; Scippo, Marie-Louise; Larondelle, Yvan

    2016-10-01

    This study aimed at verifying if the hypothesis that one day at 60°C is equivalent to one month at 20°C could be confirmed during linseed oil aging for 6months at 20°C and 6days at 60°C using the "Schaal oven stability test". Tests were conducted with linseed oil supplemented or not with myricetin or butyl-hydroxytoluene as antioxidants. Oxidation was evaluated with the peroxide and p-anisidine values, as well as the content in conjugated dienes and aldehydes. All four indicators of oxidation showed very different kinetic behaviors at 20 and 60°C. The hypothesis is thus not verified for linseed oil, supplemented or not with antioxidant. In the control oil, the conjugated dienes and the peroxide value observed were respectively of 41.8±0.8 Absorbance Unit (AU)/g oil and 254.3±5.8meq.O2/kg oil after 6months at 20°C. These values were of 18.2±1.3AU/g oil and 65.2±20.3meq.O2/kg after 6days at 60°C. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. First accelerated ageing cycling test on super capacitors for transportation applications: methodology, first results

    Energy Technology Data Exchange (ETDEWEB)

    Coquery, G.; Lallemand, R.; Kauv, J. [Institut National de Recherche sur les Transports et leur Securite (INRETS), Lab. des Technologies Nouvelles, 94 - Arcueil (France); Monts, A. de; Soucaze-Guillous, B. [Societe Nationale des Chemins de fer Francais (SNCF), Dir. de la Recherche, 75 - Paris (France); Chabas, J.; Darnault, A. [VALEO Electrical Energy Management, 94 - Creteil (France)

    2004-07-01

    Automotive and railway electrical traction systems are submitted to high power cycles due to the urban mission profiles. In order to increase the energy efficiency and to reduce global pollutant emission, the buffer energy storage by means super-capacitor offer major advantages to optimise the traction energy management with the highest level of regenerative braking energy. Super-capacitors are promising for the energy management between traction chain and electrical supplying systems. Because the effects of the charge-discharge cycles are a strong limitation of the batteries lifetime, it was decided to evaluate the capabilities of this technology concerning the ageing effects due to these strong cycling power stresses link to the urban traffic. Today, there are no publications to discuss about this phenomena, however it appears as a fundamental acknowledge to design the super-capacitors assembly. The first step was to establish a typical mission profile representative of the transportation working conditions, to propose a preliminary test plan, and to define a measurement methodology. The presented investigations are linked to research projects on automotive and railway applications. (authors)

  9. Human Ageing Genomic Resources: integrated databases and tools for the biology and genetics of ageing.

    Science.gov (United States)

    Tacutu, Robi; Craig, Thomas; Budovsky, Arie; Wuttke, Daniel; Lehmann, Gilad; Taranukha, Dmitri; Costa, Joana; Fraifeld, Vadim E; de Magalhães, João Pedro

    2013-01-01

    The Human Ageing Genomic Resources (HAGR, http://genomics.senescence.info) is a freely available online collection of research databases and tools for the biology and genetics of ageing. HAGR features now several databases with high-quality manually curated data: (i) GenAge, a database of genes associated with ageing in humans and model organisms; (ii) AnAge, an extensive collection of longevity records and complementary traits for >4000 vertebrate species; and (iii) GenDR, a newly incorporated database, containing both gene mutations that interfere with dietary restriction-mediated lifespan extension and consistent gene expression changes induced by dietary restriction. Since its creation about 10 years ago, major efforts have been undertaken to maintain the quality of data in HAGR, while further continuing to develop, improve and extend it. This article briefly describes the content of HAGR and details the major updates since its previous publications, in terms of both structure and content. The completely redesigned interface, more intuitive and more integrative of HAGR resources, is also presented. Altogether, we hope that through its improvements, the current version of HAGR will continue to provide users with the most comprehensive and accessible resources available today in the field of biogerontology.

  10. Human Ageing Genomic Resources: Integrated databases and tools for the biology and genetics of ageing

    Science.gov (United States)

    Tacutu, Robi; Craig, Thomas; Budovsky, Arie; Wuttke, Daniel; Lehmann, Gilad; Taranukha, Dmitri; Costa, Joana; Fraifeld, Vadim E.; de Magalhães, João Pedro

    2013-01-01

    The Human Ageing Genomic Resources (HAGR, http://genomics.senescence.info) is a freely available online collection of research databases and tools for the biology and genetics of ageing. HAGR features now several databases with high-quality manually curated data: (i) GenAge, a database of genes associated with ageing in humans and model organisms; (ii) AnAge, an extensive collection of longevity records and complementary traits for >4000 vertebrate species; and (iii) GenDR, a newly incorporated database, containing both gene mutations that interfere with dietary restriction-mediated lifespan extension and consistent gene expression changes induced by dietary restriction. Since its creation about 10 years ago, major efforts have been undertaken to maintain the quality of data in HAGR, while further continuing to develop, improve and extend it. This article briefly describes the content of HAGR and details the major updates since its previous publications, in terms of both structure and content. The completely redesigned interface, more intuitive and more integrative of HAGR resources, is also presented. Altogether, we hope that through its improvements, the current version of HAGR will continue to provide users with the most comprehensive and accessible resources available today in the field of biogerontology. PMID:23193293

  11. Mouse models of telomere dysfunction phenocopy skeletal changes found in human age-related osteoporosis

    Directory of Open Access Journals (Sweden)

    Tracy A. Brennan

    2014-05-01

    Full Text Available A major medical challenge in the elderly is osteoporosis and the high risk of fracture. Telomere dysfunction is a cause of cellular senescence and telomere shortening, which occurs with age in cells from most human tissues, including bone. Telomere defects contribute to the pathogenesis of two progeroid disorders characterized by premature osteoporosis, Werner syndrome and dyskeratosis congenital. It is hypothesized that telomere shortening contributes to bone aging. We evaluated the skeletal phenotypes of mice with disrupted telomere maintenance mechanisms as models for human bone aging, including mutants in Werner helicase (Wrn−/−, telomerase (Terc−/− and Wrn−/−Terc−/− double mutants. Compared with young wild-type (WT mice, micro-computerized tomography analysis revealed that young Terc−/− and Wrn−/−Terc−/− mice have decreased trabecular bone volume, trabecular number and trabecular thickness, as well as increased trabecular spacing. In cortical bone, young Terc−/− and Wrn−/−Terc−/− mice have increased cortical thinning, and increased porosity relative to age-matched WT mice. These trabecular and cortical changes were accelerated with age in Terc−/− and Wrn−/−Terc−/− mice compared with older WT mice. Histological quantification of osteoblasts in aged mice showed a similar number of osteoblasts in all genotypes; however, significant decreases in osteoid, mineralization surface, mineral apposition rate and bone formation rate in older Terc−/− and Wrn−/−Terc−/− bone suggest that osteoblast dysfunction is a prominent feature of precocious aging in these mice. Except in the Wrn−/− single mutant, osteoclast number did not increase in any genotype. Significant alterations in mechanical parameters (structure model index, degree of anistrophy and moment of inertia of the Terc−/− and Wrn−/−Terc−/− femurs compared with WT mice were also observed. Young Wrn

  12. Calcium isolation from large-volume human urine samples for 41Ca analysis by accelerator mass spectrometry.

    Science.gov (United States)

    Miller, James J; Hui, Susanta K; Jackson, George S; Clark, Sara P; Einstein, Jane; Weaver, Connie M; Bhattacharyya, Maryka H

    2013-08-01

    Calcium oxalate precipitation is the first step in preparation of biological samples for (41)Ca analysis by accelerator mass spectrometry. A simplified protocol for large-volume human urine samples was characterized, with statistically significant increases in ion current and decreases in interference. This large-volume assay minimizes cost and effort and maximizes time after (41)Ca administration during which human samples, collected over a lifetime, provide (41)Ca:Ca ratios that are significantly above background.

  13. Calcium Isolation from Large-Volume Human Urine Samples for 41Ca Analysis by Accelerator Mass Spectrometry

    Science.gov (United States)

    Miller, James J; Hui, Susanta K; Jackson, George S; Clark, Sara P; Einstein, Jane; Weaver, Connie M; Bhattacharyya, Maryka H

    2013-01-01

    Calcium oxalate precipitation is the first step in preparation of biological samples for 41Ca analysis by accelerator mass spectrometry. A simplified protocol for large-volume human urine samples was characterized, with statistically significant increases in ion current and decreases in interference. This large-volume assay minimizes cost and effort and maximizes time after 41Ca administration during which human samples, collected over a lifetime, provide 41Ca:Ca ratios that are significantly above background. PMID:23672965

  14. Molecular networks of human muscle adaptation to exercise and age.

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    Bethan E Phillips

    2013-03-01

    Full Text Available Physical activity and molecular ageing presumably interact to precipitate musculoskeletal decline in humans with age. Herein, we have delineated molecular networks for these two major components of sarcopenic risk using multiple independent clinical cohorts. We generated genome-wide transcript profiles from individuals (n = 44 who then undertook 20 weeks of supervised resistance-exercise training (RET. Expectedly, our subjects exhibited a marked range of hypertrophic responses (3% to +28%, and when applying Ingenuity Pathway Analysis (IPA up-stream analysis to ~580 genes that co-varied with gain in lean mass, we identified rapamycin (mTOR signaling associating with growth (P = 1.4 × 10(-30. Paradoxically, those displaying most hypertrophy exhibited an inhibited mTOR activation signature, including the striking down-regulation of 70 rRNAs. Differential analysis found networks mimicking developmental processes (activated all-trans-retinoic acid (ATRA, Z-score = 4.5; P = 6 × 10(-13 and inhibited aryl-hydrocarbon receptor signaling (AhR, Z-score = -2.3; P = 3 × 10(-7 with RET. Intriguingly, as ATRA and AhR gene-sets were also a feature of endurance exercise training (EET, they appear to represent "generic" physical activity responsive gene-networks. For age, we found that differential gene-expression methods do not produce consistent molecular differences between young versus old individuals. Instead, utilizing two independent cohorts (n = 45 and n = 52, with a continuum of subject ages (18-78 y, the first reproducible set of age-related transcripts in human muscle was identified. This analysis identified ~500 genes highly enriched in post-transcriptional processes (P = 1 × 10(-6 and with negligible links to the aforementioned generic exercise regulated gene-sets and some overlap with ribosomal genes. The RNA signatures from multiple compounds all targeting serotonin, DNA topoisomerase antagonism, and RXR activation were significantly related to

  15. Cigarette smoking accelerated brain aging and induced pre-Alzheimer-like neuropathology in rats.

    Science.gov (United States)

    Ho, Yuen-Shan; Yang, Xifei; Yeung, Sze-Chun; Chiu, Kin; Lau, Chi-Fai; Tsang, Andrea Wing-Ting; Mak, Judith Choi-Wo; Chang, Raymond Chuen-Chung

    2012-01-01

    Cigarette smoking has been proposed as a major risk factor for aging-related pathological changes and Alzheimer's disease (AD). To date, little is known for how smoking can predispose our brains to dementia or cognitive impairment. This study aimed to investigate the cigarette smoke-induced pathological changes in brains. Male Sprague-Dawley (SD) rats were exposed to either sham air or 4% cigarette smoke 1 hour per day for 8 weeks in a ventilated smoking chamber to mimic the situation of chronic passive smoking. We found that the levels of oxidative stress were significantly increased in the hippocampus of the smoking group. Smoking also affected the synapse through reducing the expression of pre-synaptic proteins including synaptophysin and synapsin-1, while there were no changes in the expression of postsynaptic protein PSD95. Decreased levels of acetylated-tubulin and increased levels of phosphorylated-tau at 231, 205 and 404 epitopes were also observed in the hippocampus of the smoking rats. These results suggested that axonal transport machinery might be impaired, and the stability of cytoskeleton might be affected by smoking. Moreover, smoking affected amyloid precursor protein (APP) processing by increasing the production of sAPPβ and accumulation of β-amyloid peptide in the CA3 and dentate gyrus region. In summary, our data suggested that chronic cigarette smoking could induce synaptic changes and other neuropathological alterations. These changes might serve as evidence of early phases of neurodegeneration and may explain why smoking can predispose brains to AD and dementia.

  16. Cigarette smoking accelerated brain aging and induced pre-Alzheimer-like neuropathology in rats.

    Directory of Open Access Journals (Sweden)

    Yuen-Shan Ho

    Full Text Available Cigarette smoking has been proposed as a major risk factor for aging-related pathological changes and Alzheimer's disease (AD. To date, little is known for how smoking can predispose our brains to dementia or cognitive impairment. This study aimed to investigate the cigarette smoke-induced pathological changes in brains. Male Sprague-Dawley (SD rats were exposed to either sham air or 4% cigarette smoke 1 hour per day for 8 weeks in a ventilated smoking chamber to mimic the situation of chronic passive smoking. We found that the levels of oxidative stress were significantly increased in the hippocampus of the smoking group. Smoking also affected the synapse through reducing the expression of pre-synaptic proteins including synaptophysin and synapsin-1, while there were no changes in the expression of postsynaptic protein PSD95. Decreased levels of acetylated-tubulin and increased levels of phosphorylated-tau at 231, 205 and 404 epitopes were also observed in the hippocampus of the smoking rats. These results suggested that axonal transport machinery might be impaired, and the stability of cytoskeleton might be affected by smoking. Moreover, smoking affected amyloid precursor protein (APP processing by increasing the production of sAPPβ and accumulation of β-amyloid peptide in the CA3 and dentate gyrus region. In summary, our data suggested that chronic cigarette smoking could induce synaptic changes and other neuropathological alterations. These changes might serve as evidence of early phases of neurodegeneration and may explain why smoking can predispose brains to AD and dementia.

  17. Cardiac and Carotid Markers Link With Accelerated Brain Atrophy: The AGES-Reykjavik Study (Age, Gene/Environment Susceptibility-Reykjavik).

    Science.gov (United States)

    Sabayan, Behnam; van Buchem, Mark A; Sigurdsson, Sigurdur; Zhang, Qian; Meirelles, Osorio; Harris, Tamara B; Gudnason, Vilmundur; Arai, Andrew E; Launer, Lenore J

    2016-11-01

    Pathologies in the heart-brain axis might, independently or in combination, accelerate the process of brain parenchymal loss. We aimed to investigate the association of serum N-terminal brain natriuretic peptide (NT-proBNP), as a marker of cardiac dysfunction, and carotid intima media thickness (CIMT), as a marker of carotid atherosclerosis burden, with structural brain changes. In the longitudinal population-based AGES-Reykjavik study (Age, Gene/Environment Susceptibility-Reykjavik), we included 2430 subjects (mean age, 74.6 years; 41.4% men) with baseline data on NT-proBNP and CITM (assessed by ultrasound imaging). Participants underwent a high-resolution brain magnetic resonance imaging at baseline and 5 years later to assess total brain (TBV), gray matter, and white matter volumes. Each unit higher log-transformed NT-proBNP was associated with 3.6 mL (95% confidence interval [CI], -6.0 to -1.1) decline in TBV and 3.5 mL (95% CI, -5.7 to -1.3) decline in gray matter volume. Likewise, each millimeter higher CIMT was associated with 10.8 mL (95% CI, -17.3 to -4.2) decline in TBV and 8.6 mL (95% CI, -14.4 to -2.8) decline in gray matter volume. There was no association between NT-proBNP and CIMT and changes in white matter volume. Compared with participants with low NT-proBNP and CIMT, participants with both high NT-proBNP and CIMT had 3.8 mL (95% CI, -6.0 to -1.6) greater decline in their TBV and 4 mL (95% CI, -6.0 to -2.0) greater decline in GMW. These associations were independent of sociodemographic and cardiovascular factors. Older subjects with both cardiac dysfunction and carotid atherosclerosis are at an increased risk for brain parenchymal loss. Accumulated pathologies in the heart-brain axis might accelerate brain atrophy. © 2016 American Heart Association, Inc.

  18. Characteristic pattern of human prostatic growth with age

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Aim:To study the characteristic pattern of the age-related growth of the human prostate gland.Methods:The volume (weight) of the prostate in 1,601 males,aged from newborn to 92 years,was determined by Bultrasonography.Results:Prostatic volume determination by B-ultrasonography in 1601 males (1301 normal subjects and 300 BPH patients) pointed out that the age-stratified growth of human prostate could be categorized into 4 life stages:(1) the first slow growing phase(from newborn to 9 years):the prostate grows slowly at a rate of 0.14g per year;(2)the first rapid growing phase (from 10 to 30 years):the prostate grows at a rate of 0.84g per year;(3)the second slow growing phase (from 30 to 50 years),the prostate grows at a rate of 0.21g per year;(4)the second rapid growing phase (from 50 to 90 years):the prostate grows at one of the following rates:in one group the growth rate is of 0.50g per year and in the other 1.20g per year,leading to benign prostatic hyperplasia(BPH).Conclusion:The volumes of the prostate are different in different age groups and it grows with age at different rates in four life phases.The prostate growth in phases can be expressed by the following equation:Y=19.36+1.36X'-0.58X'2+0.33X'3,where Y=prostate volume,X=age(up to 70 years),X'=(X-35.5)/10.

  19. Microscopic study of human spleen in different age groups

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    Lizamma Alex

    2015-07-01

    Full Text Available Background: The microscopic structure of spleen is variable depending on the developmental stage of the organ, and the age and immune status of the individual. The aim of the investigation was to study the microscopic structure of human spleen in different age groups, starting from a six month old foetus up to the eighth decade of life. Methods: Seventy formalin fixed human spleens obtained postmortem, were included in the study. They were classified into different age groups, in both sexes, for a detailed study of the microscopic details. Results: The white pulp of spleen showed peri-arteriolar lymphatic sheath (PALS and lymphatic follicles. The corona or mantle zone and the germinal centre were discernible in many of the Malpighian bodies. The marginal zone separating the red pulp from the white pulp also could be clearly demarcated. The marginal sinus and peri-follicular zone could be seen in some sections only. The capsule thickness, trabecular network, cellularity of white pulp and red pulp, the connective tissue framework seen in the red pulp etc., showed variations in the different age groups. Conclusion: The microscopic structure of spleen varies in different age groups, with the PALS and the white pulp showing scanty cellularity in the six month foetus, and almost uniform cellularity in all areas of spleen at full term. Thereafter the follicles showed increase in its cellularity up to the third decade, and then seemed becoming progressively atrophic. Further studies are required on age related changes in the cellular architecture of this organ correlating with its functions. [Int J Res Med Sci 2015; 3(7.000: 1701-1706

  20. The developmental brain gene NPAS3 contains the largest number of accelerated regulatory sequences in the human genome.

    Science.gov (United States)

    Kamm, Gretel B; Pisciottano, Francisco; Kliger, Rafi; Franchini, Lucía F

    2013-05-01

    To identify the evolutionary genetic novelties that contributed to shape human-specific traits such as the use of a complex language, long-term planning and exceptional learning abilities is one of the ultimate frontiers of modern biology. Evolutionary signatures of functional shifts could be detected by comparing noncoding regions that are highly conserved across mammals or primates and rapidly accumulated nucleotide substitutions only in the lineage leading to humans. As gene loci densely populated with human-accelerated elements (HAEs) are more likely to have contributed to human-specific novelties, we sought to identify the transcriptional units and genomic 1 Mb intervals of the entire human genome carrying the highest number of HAEs. To this end, we took advantage of four available data sets of human genomic accelerated regions obtained through different comparisons and algorithms and performed a meta-analysis of the combined data. We found that the brain developmental transcription factor neuronal PAS domain-containing protein 3 (NPAS3) contains the largest cluster of noncoding-accelerated regions in the human genome with up to 14 elements that are highly conserved in mammals, including primates, but carry human-specific nucleotide substitutions. We then tested the ability of the 14 HAEs identified at the NPAS3 locus to act as transcriptional regulatory sequences in a reporter expression assay performed in transgenic zebrafish. We found that 11 out of the 14 HAEs present in NPAS3 act as transcriptional enhancers during development, particularly within the nervous system. As NPAS3 is known to play a crucial role during mammalian brain development, our results indicate that the high density of HAEs present in the human NPAS3 locus could have modified the spatiotemporal expression pattern of NPAS3 in the developing human brain and, therefore, contributed to human brain evolution.

  1. Quick Preparation of Moisture-Saturated Carbon Fiber-Reinforced Plastics and Their Accelerated Ageing Tests Using Heat and Moisture

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    Masao Kunioka

    2016-06-01

    Full Text Available A quick method involving the control of heat and water vapor pressure for preparing moisture-saturated carbon fiber-reinforced plastics (CFRP, 8 unidirectional prepreg layers, 1.5 mm thickness, epoxy resin has been developed. The moisture-saturated CFRP sample was obtained at 120 °C and 0.2 MPa water vapor in 72 h by this method using a sterilizer (autoclave. The bending strength and viscoelastic properties measured by a dynamic mechanical analysis (DMA remained unchanged during repetitive saturation and drying steps. No degradation and molecular structural change occurred. Furthermore an accelerated ageing test with two ageing factors, i.e., heat and moisture was developed and performed at 140–160 °C and 0.36–0.62 MPa water vapor pressure by using a sealed pressure-proof stainless steel vessel (autoclave. The bending strength of the sample decreased from 1107 to 319 MPa at 160 °C and 0.63 MPa water vapor pressure in 9 days. Degraded samples were analyzed by DMA. The degree of degradation for samples was analyzed by DMA. CFRP and degraded CFRP samples were analyzed by using a surface and interfacial cutting analysis system (SAICAS and an electron probe micro-analyzer (EPMA equipped in a scanning electron microscope.

  2. Human fibrocyte-derived exosomes accelerate wound healing in genetically diabetic mice.

    Science.gov (United States)

    Geiger, Adolf; Walker, Audrey; Nissen, Erwin

    2015-11-13

    Diabetic ulcers represent a substantial societal and healthcare burden worldwide and scarcely respond to current treatment strategies. This study was addressed to evaluate the therapeutic potential of exosomes secreted by human circulating fibrocytes, a population of mesenchymal progenitors involved in normal wound healing via paracrine signaling. The exosomes released from cells sequentially stimulated with platelet-derived growth factor-BB and transforming growth factor-β1, in the presence of fibroblast growth factor 2, did not show potential immunogenicity. These exosomes exhibited in-vitro proangiogenic properties, activated diabetic dermal fibroblasts, induced the migration and proliferation of diabetic keratinocytes, and accelerated wound closure in diabetic mice in vivo. Important components of the exosomal cargo were heat shock protein-90α, total and activated signal transducer and activator of transcription 3, proangiogenic (miR-126, miR-130a, miR-132) and anti-inflammatory (miR124a, miR-125b) microRNAs, and a microRNA regulating collagen deposition (miR-21). This proof-of-concept study demonstrates the feasibility of the use of fibrocytes-derived exosomes for the treatment of diabetic ulcers.

  3. Magnetic shielding accelerates the proliferation of human neuroblastoma cell by promoting G1-phase progression.

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    Wei-chuan Mo

    Full Text Available Organisms have been exposed to the geomagnetic field (GMF throughout evolutionary history. Exposure to the hypomagnetic field (HMF by deep magnetic shielding has recently been suggested to have a negative effect on the structure and function of the central nervous system, particularly during early development. Although changes in cell growth and differentiation have been observed in the HMF, the effects of the HMF on cell cycle progression still remain unclear. Here we show that continuous HMF exposure significantly increases the proliferation of human neuroblastoma (SH-SY5Y cells. The acceleration of proliferation results from a forward shift of the cell cycle in G1-phase. The G2/M-phase progression is not affected in the HMF. Our data is the first to demonstrate that the HMF can stimulate the proliferation of SH-SY5Y cells by promoting cell cycle progression in the G1-phase. This provides a novel way to study the mechanism of cells in response to changes of environmental magnetic field including the GMF.

  4. Magnetic shielding accelerates the proliferation of human neuroblastoma cell by promoting G1-phase progression.

    Science.gov (United States)

    Mo, Wei-chuan; Zhang, Zi-jian; Liu, Ying; Bartlett, Perry F; He, Rong-qiao

    2013-01-01

    Organisms have been exposed to the geomagnetic field (GMF) throughout evolutionary history. Exposure to the hypomagnetic field (HMF) by deep magnetic shielding has recently been suggested to have a negative effect on the structure and function of the central nervous system, particularly during early development. Although changes in cell growth and differentiation have been observed in the HMF, the effects of the HMF on cell cycle progression still remain unclear. Here we show that continuous HMF exposure significantly increases the proliferation of human neuroblastoma (SH-SY5Y) cells. The acceleration of proliferation results from a forward shift of the cell cycle in G1-phase. The G2/M-phase progression is not affected in the HMF. Our data is the first to demonstrate that the HMF can stimulate the proliferation of SH-SY5Y cells by promoting cell cycle progression in the G1-phase. This provides a novel way to study the mechanism of cells in response to changes of environmental magnetic field including the GMF.

  5. Human activity accelerating the rapid desertification of the Mu Us Sandy Lands, North China

    Science.gov (United States)

    Miao, Yunfa; Jin, Heling; Cui, Jianxin

    2016-03-01

    Over the past several thousand years, arid and semiarid China has experienced a series of asynchronous desertification events in its semiarid sandy and desert regions, but the precise identification of the driving forces of such events has remained elusive. In this paper we identify two rapid desertification events (RDEs) at ~4.6 ± 0.2 ka BP and ~3.3 ± 0.2 ka BP from the JJ Profile, located in the eastern Mu Us Sandy Lands. These RDEs appear to have occurred immediately following periods marked by persistently frequent and intense fires. We argue that such fire patterns, directly linked to an uncontrolled human use of vegetation as fuel, played a key role in accelerating RDEs by ensuring that the land surface was degraded beyond the threshold required for rapid desertification. This would suggest that the future use of a massive and sustained ecological program of vegetation rehabilitation should reduce the risk of destructive fire.

  6. Human ankle plantar flexor muscle–tendon mechanics and energetics during maximum acceleration sprinting

    Science.gov (United States)

    Schache, Anthony G.; Brown, Nicholas A. T.; Pandy, Marcus G.

    2016-01-01

    Tendon elastic strain energy is the dominant contributor to muscle–tendon work during steady-state running. Does this behaviour also occur for sprint accelerations? We used experimental data and computational modelling to quantify muscle fascicle work and tendon elastic strain energy for the human ankle plantar flexors (specifically soleus and medial gastrocnemius) for multiple foot contacts of a maximal sprint as well as for running at a steady-state speed. Positive work done by the soleus and medial gastrocnemius muscle fascicles decreased incrementally throughout the maximal sprint and both muscles performed more work for the first foot contact of the maximal sprint (FC1) compared with steady-state running at 5 m s−1 (SS5). However, the differences in tendon strain energy for both muscles were negligible throughout the maximal sprint and when comparing FC1 to SS5. Consequently, the contribution of muscle fascicle work to stored tendon elastic strain energy was greater for FC1 compared with subsequent foot contacts of the maximal sprint and compared with SS5. We conclude that tendon elastic strain energy in the ankle plantar flexors is just as vital at the start of a maximal sprint as it is at the end, and as it is for running at a constant speed. PMID:27581481

  7. Differential changes in retina function with normal aging in humans.

    Science.gov (United States)

    Freund, Paul R; Watson, Juliane; Gilmour, Gregory S; Gaillard, Frédéric; Sauvé, Yves

    2011-06-01

    We evaluated the full field electroretinogram (ERG) to assess age-related changes in retina function in humans. ERG recordings were performed on healthy subjects with normal fundus appearance, lack of cataract and 20/20 acuity, aged 20-39 years (n = 27; mean age 25 ± 5, standard deviation), 40-59 years (n = 20; mean 53 ± 5), and 60-82 years (n = 18; mean 69 ± 5). Multiple ERG tests were applied, including light and dark-adapted stimulus-response function, dark adaptation and dynamic of recovery from a single bright flash under dark-adapted conditions. Changes in ERG properties were found in the oldest age group when compared with the two younger age groups. (1) The photopic hill effect was less pronounced. (2) Both photopic a-wave and b-wave amplitudes and implicit times were increased at high stimulus strengths. (3) Dark adaptation time was delayed for pure rod and L/M cone-driven responses, respectively. (4) Dark-adapted a-wave but not b-wave amplitudes were reduced, yielding higher B/A ratios. (5) Dark-adapted a- and b-waves implicit times were prolonged: there was a direct proportional correlation between minimal a-wave implicit times and age. (6) The dynamic of dark current recovery from a bright flash, under dark-adapted conditions, was transiently faster at intervals between 0.9 and 2 s. These results denote that aging of the healthy retina is accompanied by specific functional changes, which must be taken into account to optimally diagnose potential pathologies.

  8. Cross-pollination of research findings, although uncommon, may accelerate discovery of human disease genes

    Directory of Open Access Journals (Sweden)

    Duda Marlena

    2012-11-01

    Full Text Available Abstract Background Technological leaps in genome sequencing have resulted in a surge in discovery of human disease genes. These discoveries have led to increased clarity on the molecular pathology of disease and have also demonstrated considerable overlap in the genetic roots of human diseases. In light of this large genetic overlap, we tested whether cross-disease research approaches lead to faster, more impactful discoveries. Methods We leveraged several gene-disease association databases to calculate a Mutual Citation Score (MCS for 10,853 pairs of genetically related diseases to measure the frequency of cross-citation between research fields. To assess the importance of cooperative research, we computed an Individual Disease Cooperation Score (ICS and the average publication rate for each disease. Results For all disease pairs with one gene in common, we found that the degree of genetic overlap was a poor predictor of cooperation (r2=0.3198 and that the vast majority of disease pairs (89.56% never cited previous discoveries of the same gene in a different disease, irrespective of the level of genetic similarity between the diseases. A fraction (0.25% of the pairs demonstrated cross-citation in greater than 5% of their published genetic discoveries and 0.037% cross-referenced discoveries more than 10% of the time. We found strong positive correlations between ICS and publication rate (r2=0.7931, and an even stronger correlation between the publication rate and the number of cross-referenced diseases (r2=0.8585. These results suggested that cross-disease research may have the potential to yield novel discoveries at a faster pace than singular disease research. Conclusions Our findings suggest that the frequency of cross-disease study is low despite the high level of genetic similarity among many human diseases, and that collaborative methods may accelerate and increase the impact of new genetic discoveries. Until we have a better

  9. Adding value through accelerator mass spectrometry-enabled first in human studies.

    Science.gov (United States)

    Seymour, Mark A

    2016-12-01

    Accelerator mass spectrometry (AMS) is an ultra-sensitive technique for the analysis of radiocarbon. It is applicable to bioanalysis of any (14) C-labelled analyte and any sample type. The increasing body of data generated using LC+AMS indicates that the methodology is robust and reliable, and capable of meeting the same validation criteria as conventional bioanalytical techniques. Because it is a tracer technique, AMS is capable of discriminating between an administered radiolabelled dose and endogenous compound or non-radiolabelled compound administered separately. This paper discusses how it can be used to enhance the design of first in human (FIH) clinical studies and generate significant additional data, including: fundamental pharmacokinetics (CL and V), absolute bioavailability, mass balance, routes and rates of excretion, metabolic fate (including first-pass metabolism, identification of biliary metabolites and quantitative data to address metabolite safety testing issues), and tissue disposition of parent compound and metabolites. Because the (14) C-labelled microtracer dose is administered at the same time as a pharmacologically relevant non-radiolabelled dose, there is no concern about dose-linearity. However the mass of the microtracer dose itself is negligible and therefore does not affect the outcome of the FIH study. The addition of microtracer doses to a FIH study typically requires little additional expense, apart from the AMS analytics, making the approach cost-effective. It can also save significant time, compared to conventional approaches, and, by providing reliable human in vivo data as early as possible, prevent unnecessary expenditure later in drug development.

  10. THE CAPILLARY PATTERN IN HUMAN MASSETER MUSCLE DURING AGEING

    Directory of Open Access Journals (Sweden)

    Erika Cvetko

    2013-10-01

    Full Text Available The effect of ageing on the capillary network in skeletal muscles has produced conflicting results in both, human and animals studies. Some of the inconsistencies are due to non-comparable and biased methods that were applied on thin transversal sections, especially in muscles with complicated morphological structures, such as in human masseter muscle. We present a new immunohistochemical method for staining capillaries and muscle fibres in 100 µm thick sections as well as novel approach to 3D visualization of capillaries and muscle fibres. Applying confocal microscopy and virtual 3D stereological grids, or tracing capillaries in virtual reality, length of capillaries within a muscle volume or length of capillaries adjacent to muscle fibre per fibre length, fibre surface or fibre volume were evaluated in masseter muscle of young and old subjects by an unbiased approach. Our findings show that anatomic capillarity is well maintained in masseter muscle in old subjects; however, vascular remodelling occurs with age, which could be a response to changed muscle function and age-related muscle fibre type transformations.

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

    Science.gov (United States)

    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

    2015-08-18

    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.

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

    Science.gov (United States)

    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

  13. Supplementation with Lactobacillus plantarum WCFS1 prevents Decline of Mucus Barrier in Colon of Accelerated Aging Ercc1-/Δ7 Mice

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    Adriaan A Van Beek

    2016-10-01

    Full Text Available Although it is clear that probiotics improve intestinal barrier function, little is known about the effects of probiotics on the aging intestine. We investigated effects of 10-wk bacterial supplementation of Lactobacillus plantarum WCFS1, Lactobacillus casei BL23, or Bifidobacterium breve DSM20213 on gut barrier and immunity in 16-week-old accelerated aging Ercc1-/Δ7 mice, which have a median lifespan of ~20wk, and their wild-type littermates. The colonic barrier in Ercc1-/Δ7 mice was characterized by a thin (<10µm mucus layer. L. plantarum prevented this decline in mucus integrity in Ercc1-/Δ7 mice, whereas B. breve exacerbated it. Bacterial supplementations affected the expression of immune-related genes, including Toll-like receptor 4. Regulatory T cell frequencies were increased in the mesenteric lymph nodes of L. plantarum- and L. casei-treated Ercc1-/Δ7 mice. L. plantarum- and L. casei-treated Ercc1-/Δ7 mice showed increased specific antibody production in a T cell-dependent immune response in vivo. By contrast, the effects of bacterial supplementation on wild-type control mice were negligible. Thus, supplementation with L. plantarum – but not with L. casei and B. breve – prevented the decline in the mucus barrier in Ercc1-/Δ7 mice. Our data indicate that age is an important factor influencing beneficial or detrimental effects of candidate probiotics. These findings also highlight the need for caution in translating beneficial effects of probiotics observed in young animals or humans to the elderly.

  14. Supplementation with Lactobacillus plantarum WCFS1 Prevents Decline of Mucus Barrier in Colon of Accelerated Aging Ercc1−/Δ7 Mice

    Science.gov (United States)

    van Beek, Adriaan A.; Sovran, Bruno; Hugenholtz, Floor; Meijer, Ben; Hoogerland, Joanne A.; Mihailova, Violeta; van der Ploeg, Corine; Belzer, Clara; Boekschoten, Mark V.; Hoeijmakers, Jan H. J.; Vermeij, Wilbert P.; de Vos, Paul; Wells, Jerry M.; Leenen, Pieter J. M.; Nicoletti, Claudio; Hendriks, Rudi W.; Savelkoul, Huub F. J.

    2016-01-01

    Although it is clear that probiotics improve intestinal barrier function, little is known about the effects of probiotics on the aging intestine. We investigated effects of 10-week bacterial supplementation of Lactobacillus plantarum WCFS1, Lactobacillus casei BL23, or Bifidobacterium breve DSM20213 on gut barrier and immunity in 16-week-old accelerated aging Ercc1−/Δ7 mice, which have a median lifespan of ~20 weeks, and their wild-type littermates. The colonic barrier in Ercc1−/Δ7 mice was characterized by a thin (< 10 μm) mucus layer. L. plantarum prevented this decline in mucus integrity in Ercc1−/Δ7 mice, whereas B. breve exacerbated it. Bacterial supplementations affected the expression of immune-related genes, including Toll-like receptor 4. Regulatory T cell frequencies were increased in the mesenteric lymph nodes of L. plantarum- and L. casei-treated Ercc1−/Δ7 mice. L. plantarum- and L. casei-treated Ercc1−/Δ7 mice showed increased specific antibody production in a T cell-dependent immune response in vivo. By contrast, the effects of bacterial supplementation on wild-type control mice were negligible. Thus, supplementation with L. plantarum – but not with L. casei and B. breve – prevented the decline in the mucus barrier in Ercc1−/Δ7 mice. Our data indicate that age is an important factor influencing beneficial or detrimental effects of candidate probiotics. These findings also highlight the need for caution in translating beneficial effects of probiotics observed in young animals or humans to the elderly. PMID:27774093

  15. Body acceleration distribution and O2 uptake in humans during running and jumping

    Science.gov (United States)

    Bhattacharya, A.; Mccutcheon, E. P.; Shvartz, E.; Greenleaf, J. E.

    1980-01-01

    The distribution of body acceleration and associated oxygen uptake and heart rate responses are investigated in treadmill running and trampoline jumping. Accelerations in the +Gz direction were measured at the lateral ankle, lumbosacral region and forehead of eight young men during level treadmill walking and running at four speeds and trampoline jumping at four heights, together with corresponding oxygen uptake and heart rate. With increasing treadmill speed, peak acceleration at the ankle is found always to exceed that at the back and forehead, and acceleration profiles with higher frequency components than those observed during jumping are observed. Acceleration levels are found to be more uniformly distributed with increasing height in jumping, although comparable oxygen uptake and heat rates are obtained. Results indicate that the magnitude of the biomechanical stimuli is greater in trampoline jumping than in running, which finding could be of use in the design of procedures to avert deconditioning in persons exposed to weightlessness.

  16. Elastic hysteresis in human eyes is age dependent value.

    Science.gov (United States)

    Ishii, Kotaro; Saito, Kei; Kameda, Toshihiro; Oshika, Tetsuro

    2012-06-19

    Background:  The elastic hysteresis phenomenon is observed when cyclic loading is applied to a viscoelastic system. The purpose of this study was to quantitatively evaluate elastic hysteresis in living human eyes against an external force. Design:  Prospective case series. Participants:  Twenty-four eyes of 24 normal human subjects (mean age: 41.5 ± 10.6 years) were recruited. Methods:  A non-contact tonometry process was recorded with a high-speed camera. Central corneal thickness (CCT), corneal thickness at 4 mm from the center, corneal curvature, and anterior chamber depth (ACD) were measured. Intraocular pressure (IOP) was also measured using Goldmann applanation tonometry (GAT) and dynamic contour tonometer (DCT). Main Outcome Measures:  Energy loss due to elastic hysteresis was calculated and graphed. Results:  The mean CCT was 552.5 ± 36.1 µm, corneal curvature was 7.84 ± 0.26 mm, and ACD was 2.83 ± 0.29 mm. The mean GAT-IOP was 14.2 ± 2.7 mmHg and DCT-IOP was 16.3 ± 3.5 mmHg. The mean energy loss due to elastic hysteresis was 3.90 × 10(-6) ± 2.49 × 10(-6) Nm. Energy loss due to elastic hysteresis correlated significantly with age (Pearson correlation coefficient = 0.596, p = 0.0016). There were no significant correlations between energy loss due to elastic hysteresis and other measurements. Conclusion:  Energy loss due to elastic hysteresis in the eyes of subjects was found to positively correlate with age, independent of anterior eye structure or IOP. Therefore, it is believed that the viscosity of the eye increases with age. © 2010 The Authors. Clinical and Experimental Ophthalmology © 2010 Royal Australian and New Zealand College of Ophthalmologists.

  17. Effect of accelerated electron beam on mechanical properties of human cortical bone: influence of different processing methods.

    Science.gov (United States)

    Kaminski, Artur; Grazka, Ewelina; Jastrzebska, Anna; Marowska, Joanna; Gut, Grzegorz; Wojciechowski, Artur; Uhrynowska-Tyszkiewicz, Izabela

    2012-08-01

    Accelerated electron beam (EB) irradiation has been a sufficient method used for sterilisation of human tissue grafts for many years in a number of tissue banks. Accelerated EB, in contrast to more often used gamma photons, is a form of ionizing radiation that is characterized by lower penetration, however it is more effective in producing ionisation and to reach the same level of sterility, the exposition time of irradiated product is shorter. There are several factors, including dose and temperature of irradiation, processing conditions, as well as source of irradiation that may influence mechanical properties of a bone graft. The purpose of this study was to evaluate the effect e-beam irradiation with doses of 25 or 35 kGy, performed on dry ice or at ambient temperature, on mechanical properties of non-defatted or defatted compact bone grafts. Left and right femurs from six male cadaveric donors, aged from 46 to 54 years, were transversely cut into slices of 10 mm height, parallel to the longitudinal axis of the bone. Compact bone rings were assigned to the eight experimental groups according to the different processing method (defatted or non-defatted), as well as e-beam irradiation dose (25 or 35 kGy) and temperature conditions of irradiation (ambient temperature or dry ice). Axial compression testing was performed with a material testing machine. Results obtained for elastic and plastic regions of stress-strain curves examined by univariate analysis are described. Based on multivariate analysis, including all groups, it was found that temperature of e-beam irradiation and defatting had no consistent significant effect on evaluated mechanical parameters of compact bone rings. In contrast, irradiation with both doses significantly decreased the ultimate strain and its derivative toughness, while not affecting the ultimate stress (bone strength). As no deterioration of mechanical properties was observed in the elastic region, the reduction of the energy

  18. Raman spectroscopy of human skin: looking for a quantitative algorithm to reliably estimate human age

    Science.gov (United States)

    Pezzotti, Giuseppe; Boffelli, Marco; Miyamori, Daisuke; Uemura, Takeshi; Marunaka, Yoshinori; Zhu, Wenliang; Ikegaya, Hiroshi

    2015-06-01

    The possibility of examining soft tissues by Raman spectroscopy is challenged in an attempt to probe human age for the changes in biochemical composition of skin that accompany aging. We present a proof-of-concept report for explicating the biophysical links between vibrational characteristics and the specific compositional and chemical changes associated with aging. The actual existence of such links is then phenomenologically proved. In an attempt to foster the basics for a quantitative use of Raman spectroscopy in assessing aging from human skin samples, a precise spectral deconvolution is performed as a function of donors' ages on five cadaveric samples, which emphasizes the physical significance and the morphological modifications of the Raman bands. The outputs suggest the presence of spectral markers for age identification from skin samples. Some of them appeared as authentic "biological clocks" for the apparent exactness with which they are related to age. Our spectroscopic approach yields clear compositional information of protein folding and crystallization of lipid structures, which can lead to a precise identification of age from infants to adults. Once statistically validated, these parameters might be used to link vibrational aspects at the molecular scale for practical forensic purposes.

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

    Science.gov (United States)

    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.

  20. Effect of Accelerated Xenon Lamp Aging on the Mechanical Properties and Structure of Thermoplastic Polyurethane for Stratospheric Airship Envelope

    Institute of Scientific and Technical Information of China (English)

    LIU Yuyan; LIU Yuxi; LIU Shaozhu; TAN Huifeng

    2014-01-01

    This study aimed to investigate the effect of artificial weathering test on the photoaging behavior of TPU films. Changes in mechanical properties, morphology and chemical structures are studied by tensile test, scanning electron microscopy, atomic force microscopy, Fourier-transformed infrared, and X-ray photoelectron spectroscopy. The results show that the photoaging negatively affects the initial modulus and stress at break values of TPU films. The surface of the specimen that is exposed to irradiation becomes rough, and some visible micro-defects such as blisters and voids can be detected. The morphology of the fracture surfaces illustrates that irradiation reduces the plasticity but increases the brittleness of the TPU films. The chemical structure analyses of the accelerated aged films prove that chemical structural changes in TPU films occur. The irradiation may break the long molecular chains on the surface of the specimens and form the low-molecular weight oxygen-containing groups. The number of chain scissions increases with the increase in exposure time.

  1. Folate Acts in E. coli to Accelerate C. elegans Aging Independently of Bacterial Biosynthesis.

    Science.gov (United States)

    Virk, Bhupinder; Jia, Jie; Maynard, Claire A; Raimundo, Adelaide; Lefebvre, Jolien; Richards, Shane A; Chetina, Natalia; Liang, Yen; Helliwell, Noel; Cipinska, Marta; Weinkove, David

    2016-02-23

    Folates are cofactors for biosynthetic enzymes in all eukaryotic and prokaryotic cells. Animals cannot synthesize folate and must acquire it from their diet or microbiota. Previously, we showed that inhibiting E. coli folate synthesis increases C. elegans lifespan. Here, we show that restriction or supplementation of C. elegans folate does not influence lifespan. Thus, folate is required in E. coli to shorten worm lifespan. Bacterial proliferation in the intestine has been proposed as a mechanism for the life-shortening influence of E. coli. However, we found no correlation between C. elegans survival and bacterial growth in a screen of 1,000+ E. coli deletion mutants. Nine mutants increased worm lifespan robustly, suggesting specific gene regulation is required for the life-shortening activity of E. coli. Disrupting the biosynthetic folate cycle did not increase lifespan. Thus, folate acts through a growth-independent route in E. coli to accelerate animal aging.

  2. The Influence of Irradiation and Accelerated Aging on the Mechanical and Tribological Properties of the Graphene Oxide/Ultra-High-Molecular-Weight Polyethylene Nanocomposites

    Directory of Open Access Journals (Sweden)

    Guodong Huang

    2016-01-01

    Full Text Available Graphene oxide/ultra-high-molecular-weight polyethylene (GO/UHMWPE nanocomposite is a potential and promising candidate for artificial joint applications. However, after irradiation and accelerated aging, the mechanical and tribological behaviors of the nanocomposites are still unclear and require further investigation. GO/UHMWPE nanocomposites were successfully fabricated using ultrasonication dispersion, ball-milling, and hot-pressing process. Then, the nanocomposites were irradiated by gamma ray at doses of 100 kGy. Finally, GO/UHMWPE nanocomposites underwent accelerated aging at 80°C for 21 days in air. The mechanical and tribological properties of GO/UHMWPE nanocomposites have been evaluated after irradiation and accelerated aging. The results indicated that the incorporation of GO could enhance the mechanical, wear, and antiscratch properties of UHMWPE. After irradiation, these properties could be further enhanced, compared to unirradiated ones. After accelerated aging, however, these properties have been significantly reduced when compared to unirradiated ones. Moreover, GO and irradiation can synergistically enhance these properties.

  3. HUMAN MASS BALANCE STUDY OF TAS-102 USING 14C ANALYZED BY ACCELERATOR MASS SPECTROMETRY

    Science.gov (United States)

    Lee, James J.; Seraj, Jabed; Yoshida, Kenichiro; Mizuguchi, Hirokazu; Strychor, Sandra; Fiejdasz, Jillian; Faulkner, Tyeler; Parise, Robert A.; Fawcett, Patrick; Pollice, Laura; Mason, Scott; Hague, Jeremy; Croft, Marie; Nugteren, James; Tedder, Charles; Sun, Weijing; Chu, Edward; Beumer, Jan Hendrik

    2016-01-01

    Background TAS-102 is an oral fluoropyrimidine prodrug composed of trifluridine (FTD) and tipiracil hydrochloride (TPI) in a 1:0.5 ratio. FTD is a thymidine analog, and it is degraded by thymidine phosphorylase (TP) to the inactive trifluoromethyluracil (FTY) metabolite. TPI inhibits degradation of FTD by TP, increasing systemic exposure to FTD. Methods Patients with advanced solid tumors (6 M/2 F; median age 58 years; PS 0–1) were enrolled on this study. Patients in group A (N = 4) received 60 mg TAS-102 with 200 nCi [14C]-FTD, while patients in group B (N = 4) received 60 mg TAS-102 with 1000 nCi [14C]-TPI orally. Plasma, blood, urine, feces, and expired air (group A only) were collected up to 168 h, and were analyzed for 14C by accelerator mass spectrometry and analytes by LC-MS/MS. Results FTD: 59.8% of the 14C dose was recovered; 54.8% in urine mostly as FTY and FTD glucuronide isomers. The extractable radioactivity in the pooled plasma consisted of 52.7% FTD and 33.2% FTY. TPI: 76.8% of the 14C dose was recovered; 27.0% in urine mostly as TPI, and 49.7% in feces. The extractable radioactivity in the pooled plasma consisted of 53.1% TPI and 30.9% 6-HMU, the major metabolite of TPI. Conclusion Absorbed 14C-FTD was metabolized and mostly excreted in urine. The majority of 14C-TPI was recovered in feces, and the majority of absorbed TPI was excreted in urine. The current data with the ongoing hepatic and renal dysfunction studies will provide an enhanced understanding of the TAS-102 elimination profile. PMID:26787503

  4. Human mass balance study of TAS-102 using (14)C analyzed by accelerator mass spectrometry.

    Science.gov (United States)

    Lee, James J; Seraj, Jabed; Yoshida, Kenichiro; Mizuguchi, Hirokazu; Strychor, Sandra; Fiejdasz, Jillian; Faulkner, Tyeler; Parise, Robert A; Fawcett, Patrick; Pollice, Laura; Mason, Scott; Hague, Jeremy; Croft, Marie; Nugteren, James; Tedder, Charles; Sun, Weijing; Chu, Edward; Beumer, Jan Hendrik

    2016-03-01

    TAS-102 is an oral fluoropyrimidine prodrug composed of trifluridine (FTD) and tipiracil hydrochloride (TPI) in a 1:0.5 ratio. FTD is a thymidine analog, and it is degraded by thymidine phosphorylase (TP) to the inactive trifluoromethyluracil (FTY) metabolite. TPI inhibits degradation of FTD by TP, increasing systemic exposure to FTD. Patients with advanced solid tumors (6 M/2 F; median age 58 years; PS 0-1) were enrolled on this study. Patients in group A (N = 4) received 60 mg TAS-102 with 200 nCi [(14)C]-FTD, while patients in group B (N = 4) received 60 mg TAS-102 with 1000 nCi [(14)C]-TPI orally. Plasma, blood, urine, feces, and expired air (group A only) were collected up to 168 h and were analyzed for (14)C by accelerator mass spectrometry and analytes by LC-MS/MS. FTD: 59.8% of the (14)C dose was recovered: 54.8% in urine mostly as FTY and FTD glucuronide isomers. The extractable radioactivity in the pooled plasma consisted of 52.7% FTD and 33.2% FTY. TPI: 76.8% of the (14)C dose was recovered: 27.0% in urine mostly as TPI and 49.7% in feces. The extractable radioactivity in the pooled plasma consisted of 53.1% TPI and 30.9% 6-HMU, the major metabolite of TPI. Absorbed (14)C-FTD was metabolized and mostly excreted in urine. The majority of (14)C-TPI was recovered in feces, and the majority of absorbed TPI was excreted in urine. The current data with the ongoing hepatic and renal dysfunction studies will provide an enhanced understanding of the TAS-102 elimination profile.

  5. Ages for the Middle Stone Age of southern Africa: implications for human behavior and dispersal.

    Science.gov (United States)

    Jacobs, Zenobia; Roberts, Richard G; Galbraith, Rex F; Deacon, Hilary J; Grün, Rainer; Mackay, Alex; Mitchell, Peter; Vogelsang, Ralf; Wadley, Lyn

    2008-10-31

    The expansion of modern human populations in Africa 80,000 to 60,000 years ago and their initial exodus out of Africa have been tentatively linked to two phases of technological and behavioral innovation within the Middle Stone Age of southern Africa-the Still Bay and Howieson's Poort industries-that are associated with early evidence for symbols and personal ornaments. Establishing the correct sequence of events, however, has been hampered by inadequate chronologies. We report ages for nine sites from varied climatic and ecological zones across southern Africa that show that both industries were short-lived (5000 years or less), separated by about 7000 years, and coeval with genetic estimates of population expansion and exit times. Comparison with climatic records shows that these bursts of innovative behavior cannot be explained by environmental factors alone.

  6. Gut Bifidobacteria Populations in Human Health and Aging

    Science.gov (United States)

    Arboleya, Silvia; Watkins, Claire; Stanton, Catherine; Ross, R. Paul

    2016-01-01

    The intestinal microbiota has increasingly been shown to have a vital role in various aspects of human health. Indeed, several studies have linked alterations in the gut microbiota with the development of different diseases. Among the vast gut bacterial community, Bifidobacterium is a genus which dominates the intestine of healthy breast-fed infants whereas in adulthood the levels are lower but relatively stable. The presence of different species of bifidobacteria changes with age, from childhood to old age. Bifidobacterium longum, B. breve, and B. bifidum are generally dominant in infants, whereas B. catenulatum, B. adolescentis and, as well as B. longum are more prevalent in adults. Increasingly, evidence is accumulating which shows beneficial effects of supplementation with bifidobacteria for the improvement of human health conditions ranging from protection against infection to different extra- and intra-intestinal positive effects. Moreover, bifidobacteria have been associated with the production of a number of potentially health promoting metabolites including short chain fatty acids, conjugated linoleic acid and bacteriocins. The aim of this mini-review is to describe the bifidobacteria compositional changes associated with different stages in life, highlighting their beneficial role, as well as their presence or absence in many disease states. PMID:27594848

  7. Blood-Brain Barrier Breakdown in the Aging Human Hippocampus

    Science.gov (United States)

    Montagne, Axel; Barnes, Samuel R.; Sweeney, Melanie D.; Halliday, Matthew R.; Sagare, Abhay P.; Zhao, Zhen; Toga, Arthur W.; Jacobs, Russell E.; Liu, Collin Y.; Amezcua, Lilyana; Harrington, Michael G.; Chui, Helena C.; Law, Meng; Zlokovic, Berislav V.

    2014-01-01

    Summary The blood-brain barrier (BBB) limits entry of blood-derived products, pathogens and cells into the brain that is essential for normal neuronal functioning and information processing. Post-mortem tissue analysis indicates BBB damage in Alzheimer’s disease (AD). The timing of BBB breakdown remains, however, elusive. Using an advanced dynamic contrast-enhanced magnetic resonance imaging protocol with high spatial and temporal resolutions to quantify regional BBB permeability in the living human brain, we show an age-dependent BBB breakdown in the hippocampus, a region critical for learning and memory that is affected early in AD. The BBB breakdown in the hippocampus and its CA1 and dentate gyrus subdivisions worsened with mild cognitive impairment that correlated with injury to BBB-associated pericytes, as shown by the cerebrospinal fluid analysis. Our data suggest that BBB breakdown is an early event in the aging human brain that begins in the hippocampus and may contribute to cognitive impairment. PMID:25611508

  8. Gut bifidobacteria populations in human health and aging

    Directory of Open Access Journals (Sweden)

    Silvia Arboleya

    2016-08-01

    Full Text Available The intestinal microbiota has increasingly been shown to have a vital role in various aspects of human health. Indeed, several studies have linked alterations in the gut microbiota with the development of different diseases. Among the vast gut bacterial community, Bifidobacterium is a genus which dominates the intestine of healthy breast-fed infants whereas in adulthood the levels are lower but relatively stable. The presence of different species of bifidobacteria changes with age, from the childhood to old age. Bifidobacterium longum, Bifidobacterium breve and Bifidobacterium bifidum are generally dominant in infants whereas Bifidobacterium catenulatum, Bifidobacterium adolescentis and, as well as B. longum are more dominant in adults. Increasingly, evidence is accumulating which shows beneficial effect of supplementation with bifidobacteria for the improvement of human health conditions ranging from protection against infection to different extra- and intra-intestinal positive effects. Moreover, bifidobacteria can be associated with the production of a number of potentially health promoting metabolites including short chain fatty acids, conjugated linoleic acid and bacteriocins. The aim of this mini-review is to describe the bifidobacteria composition changes associated with different stages in life, highlighting their beneficial role, as well as their presence in commonly known disease states.

  9. Calcification of human vascular smooth muscle cells: associations with osteoprotegerin expression and acceleration by high-dose insulin

    DEFF Research Database (Denmark)

    Olesen, Ping; Knudsen, Kirsten Quyen Nguyen; Wogensen, Lise

    2007-01-01

    Arterial medial calcifications occur often in diabetic individuals as part of the diabetic macroangiopathy. The pathogenesis is unknown, but the presence of calcifications predicts risk of cardiovascular events. We examined the effects of insulin on calcifying smooth muscle cells in vitro...... and measured the expression of the bone-related molecule osteoprotegerin (OPG). Human vascular smooth muscle cells (VSMCs) were grown from aorta from kidney donors. Induction of calcification was performed with beta-glycerophosphate. The influence of insulin (200 microU/ml or 1,000 microU/ml) on calcification...... calcification in human smooth muscle cells from a series of donors after variable time in culture. Decreased OPG amounts were observed from the cells during the accelerated calcification phase. High dose of insulin (1,000 microU/ml) accelerated the calcification, whereas lower concentrations (200 microU/ml) did...

  10. ACCELERATED AGING OF OLERACEOUS SPECIES SEEDS ENVELHECIMENTO ACELERADO DE SEMENTES DE ESPÉCIES OLERÁCEAS

    Directory of Open Access Journals (Sweden)

    Denis Santiago da Costa

    2011-07-01

    Full Text Available

    The quality of seeds used in the agricultural production process is one of the main factors considered for the development of a crop. This study investigated the effect of vigor level in the performance of six oleraceous species seeds. Commercial seeds of lettuce, eggplant, broccoli, cauliflower, rocket, and tomato were subjected to accelerated aging, for 48 and 72 hours, to obtain lots with three vigor levels, resulting in one regular lot and two lots aged for different periods. After that, the seeds were submitted to germination tests, electrical conductivity, seedling emergence in trays, seedling length and dry weight. The effect of accelerated aging becomes stronger when the exposure time of seeds to high air relative humidity and temperature increases. This exposure reduces more emphatically the seed quality for some species, such as lettuce, cauliflower, and rocket, than for others, such as broccoli, tomato and eggplant. Less vigorous seeds, in addition to lower germination and emergence, show delays in

  11. Convergence of the innate and adaptive immunity during human aging

    Directory of Open Access Journals (Sweden)

    Branca Isabel Pereira

    2016-11-01

    Full Text Available Aging is associated with profound changes in the human immune system, a phenomenon referred to as immunosenescence. This complex immune remodeling affects the adaptive immune system and the CD8+ T cell compartment in particular, leading to the accumulation of terminally differentiated T cells, which can rapidly exert their effector functions at the expenses of a limited proliferative potential. In this review we will discuss evidence suggesting that senescent αβCD8+ T cells acquire the hallmarks of innate-like T cells and use recently acquired NK cell receptors as an alternative mechanism to mediate rapid effector functions. These cells concomitantly lose expression of co-stimulatory receptors and exhibit decreased TCR signaling suggesting a functional shift away from antigen specific activation. The convergence of innate and adaptive features in senescent T cells challenges the classic division between innate and adaptive immune systems. Innate-like T cells are particularly important for stress and tumor surveillance and we propose a new role for these cells in aging, where the acquisition of innate-like functions may represent a beneficial adaptation to an increased burden of malignancy with age, although it may also pose a higher risk of autoimmune disorders.

  12. Aging and Fracture of Human Cortical Bone and Tooth Dentin

    Energy Technology Data Exchange (ETDEWEB)

    Ager, Joel; Koester, Kurt J.; Ager III, Joel W.; Ritchie, Robert O.

    2008-05-07

    Mineralized tissues, such as bone and tooth dentin, serve as structural materials in the human body and, as such, have evolved to resist fracture. In assessing their quantitative fracture resistance or toughness, it is important to distinguish between intrinsic toughening mechanisms which function ahead of the crack tip, such as plasticity in metals, and extrinsic mechanisms which function primarily behind the tip, such as crack bridging in ceramics. Bone and dentin derive their resistance to fracture principally from extrinsic toughening mechanisms which have their origins in the hierarchical microstructure of these mineralized tissues. Experimentally, quantification of these toughening mechanisms requires a crack-growth resistance approach, which can be achieved by measuring the crack-driving force, e.g., the stress intensity, as a function of crack extension ("R-curve approach"). Here this methodology is used to study of the effect of aging on the fracture properties of human cortical bone and human dentin in order to discern the microstructural origins of toughness in these materials.

  13. Metabolomics of human brain aging and age-related neurodegenerative diseases.

    Science.gov (United States)

    Jové, Mariona; Portero-Otín, Manuel; Naudí, Alba; Ferrer, Isidre; Pamplona, Reinald

    2014-07-01

    Neurons in the mature human central nervous system (CNS) perform a wide range of motor, sensory, regulatory, behavioral, and cognitive functions. Such diverse functional output requires a great diversity of CNS neuronal and non-neuronal populations. Metabolomics encompasses the study of the complete set of metabolites/low-molecular-weight intermediates (metabolome), which are context-dependent and vary according to the physiology, developmental state, or pathologic state of the cell, tissue, organ, or organism. Therefore, the use of metabolomics can help to unravel the diversity-and to disclose the specificity-of metabolic traits and their alterations in the brain and in fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of aging and neurodegenerative diseases. Here, we review the current applications of metabolomics in studies of CNS aging and certain age-related neurodegenerative diseases such as Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Neurometabolomics will increase knowledge of the physiologic and pathologic functions of neural cells and will place the concept of selective neuronal vulnerability in a metabolic context.

  14. Influence of finishing/polishing on color stability and surface roughness of composites submitted to accelerated artificial aging

    Directory of Open Access Journals (Sweden)

    Gustavo Da Col dos Santos Pinto

    2013-01-01

    Full Text Available Aim: To assess the influence of finishing/polishing procedure on color stability (ΔE and surface roughness (Ra of composites (Heliomolar and Tetric - color A2 submitted to accelerated artificial aging (AAA. Materials and Methods : Sixty test specimens were made of each composite (12 mm × 2 mm and separated into six groups (n = 10, according to the type of finishing/polishing to which they were submitted: C, control; F, tip 3195 F; FF, tip 3195 FF; FP, tip 3195 F + diamond paste; FFP, tip 3195 FF + diamond paste; SF, Sof-Lex discs. After polishing, controlled by an electromechanical system, initial color (spectrophotometer PCB 6807 BYK GARDNER and Ra (roughness meter Surfcorder SE 1700, cut-off 0.25 mm readings were taken. Next, the test specimens were submitted to the AAA procedure (C-UV Comexim for 384 hours, and at the end of this period, new color readings and R a were taken. Results: Statistical analysis [2-way analysis of variance (ANOVA, Bonferroni, P < 0.05] showed that all composites demonstrated ΔE alteration above the clinically acceptable limits, with the exception of Heliomolar composite in FP. The greatest ΔE alteration occurred for Tetric composite in SF (13.38 ± 2.10 statistically different from F and FF (P < 0.05. For Ra , Group F showed rougher samples than FF with statistically significant difference (P < 0.05. Conclusion: In spite of the surface differences, the different finishing/polishing procedures were not capable of providing color stability within the clinically acceptable limits.

  15. Metodologia para o teste de envelhecimento acelerado em sementes de ervilha Accelerated aging test on pea seeds

    Directory of Open Access Journals (Sweden)

    Warley Marcos Nascimento

    2007-06-01

    ível identificar os lotes de melhor qualidade.Pea production in Brazil uses seeds produced in the country. The objective of this study was to examine the efficiency of the accelerated aging test for vigor evaluation of pea seeds. Five seed lots of cultivar Axé (wrinkled seeds and five seed lots of cultivar Mikado (smooth seeds were used. The initial quality of each seed lot was evaluated by germination test, first counting, and seedling emergence in the field. Seed moisture content was also assessed. The accelerated aging test was set at 41ºC for periods of 24; 48; and 72 hours, with and without saturated NaCl solution. The experiment was carried out in a completely randomized design. The accelerated aging test was efficient for vigor evaluation of pea seeds, and the period of 48 hours at 41ºC, using saturated NaCl solution was the most adequate procedure to indicate vigor levels of pea seeds. However, the seed germination after this period was very low when compared to 24 hour-period (80% for both cultivars, even in higher vigor seed lots (35% for Axé and 38% for Mikado. In the saturated NaCl solution, the period of 48 hours at 41ºC was the most adequate for separate seeds through vigor levels. In these conditions, seed lots of highest vigor showed germination of 68% and 79% for Axé and Mikado, respectively. Results of the germination test, first counting, and seedling emergence were not effective in discriminating physiological seed quality when used individually. Nevertheless, when results from these tests were used all together, it was possible to identify the best seed lots.

  16. Accelerated increase and decrease in subjective age as a function of changes in loneliness and objective social indicators over a four-year period: results from the health and retirement study.

    Science.gov (United States)

    Ayalon, Liat; Palgi, Yuval; Avidor, Sharon; Bodner, Ehud

    2016-07-01

    The study examined the role of changes in loneliness and objective social indicators in the formation of changes in subjective age over a four-year period. The Health and Retirement Study is a US nationally representative study of older adults over 50 and their spouse of any age. We restricted the sample to individuals, 65 years of age and older (n = 2591). An accelerated increase in subjective age was defined as an increase in subjective age over the two waves greater than five years. An accelerated decrease in subjective age was defined as a difference that was lower than three years. These were examined against a change in subjective age in the range of three to five years (i.e., change consistent with the passage of time). For 23.4% of the sample, changes in subjective age were consistent with the passage of time. A total of 38.3% had an accelerated decrease in subjective age, whereas 38.3% had an accelerated increase. A decrease in loneliness over the two waves resulted in an accelerated decrease in subjective age, whereas an increase in depressive symptoms resulted in an accelerated increase in subjective age. Changes in objective social indicators, physical difficulties or medical comorbidity did not predict changes in subjective age. This is one of very few studies that examined changes in subjective age over time. Changes in subjective age represent an important construct that corresponding to other changes in subjective experiences.

  17. Human face processing is tuned to sexual age preferences

    DEFF Research Database (Denmark)

    Ponseti, J; Granert, O; van Eimeren, T

    2014-01-01

    . In paedophilia, sexual attraction is directed to sexually immature children. Therefore, we hypothesized that brain networks that normally are tuned to mature faces of the preferred gender show an abnormal tuning to sexual immature faces in paedophilia. Here, we use functional magnetic resonance imaging (f......Human faces can motivate nurturing behaviour or sexual behaviour when adults see a child or an adult face, respectively. This suggests that face processing is tuned to detecting age cues of sexual maturity to stimulate the appropriate reproductive behaviour: either caretaking or mating......MRI) to test directly for the existence of a network which is tuned to face cues of sexual maturity. During fMRI, participants sexually attracted to either adults or children were exposed to various face images. In individuals attracted to adults, adult faces activated several brain regions significantly more...

  18. Twins for epigenetic studies of human aging and development

    DEFF Research Database (Denmark)

    Tan, Qihua; Christiansen, Lene; Thomassen, Mads

    2013-01-01

    , our understanding of genetic and environmental influences on the epigenetic processes remains limited. Twins are of special interest for genetic studies due to their genetic similarity and rearing-environment sharing. The classical twin design has made a great contribution in dissecting the genetic...... and environmental contributions to human diseases and complex traits. In the era of functional genomics, the valuable sample of twins is helping to bridge the gap between gene activity and the environments through epigenetic mechanisms unlimited by DNA sequence variations. We propose to extend the classical twin...... design to study the aging-related molecular epigenetic phenotypes and link them with environmental exposures especially early life events. Different study designs and application issues will be highlighted and novel approaches introduced with aim at making uses of twins in assessing the environmental...

  19. Twins for epigenetic studies of human aging and development

    DEFF Research Database (Denmark)

    Tan, Qihua; Christiansen, Lene; Thomassen, Mads

    2013-01-01

    Most of the complex traits including aging phenotypes are caused by the interaction between genome and environmental conditions and the interface of epigenetics may be a central mechanism. Although modern technologies allow us high-throughput profiling of epigenetic patterns already at genome level......, our understanding of genetic and environmental influences on the epigenetic processes remains limited. Twins are of special interest for genetic studies due to their genetic similarity and rearing-environment sharing. The classical twin design has made a great contribution in dissecting the genetic...... and environmental contributions to human diseases and complex traits. In the era of functional genomics, the valuable sample of twins is helping to bridge the gap between gene activity and the environments through epigenetic mechanisms unlimited by DNA sequence variations. We propose to extend the classical twin...

  20. Valuable human capital: the aging health care worker.

    Science.gov (United States)

    Collins, Sandra K; Collins, Kevin S

    2006-01-01

    With the workforce growing older and the supply of younger workers diminishing, it is critical for health care managers to understand the factors necessary to capitalize on their vintage employees. Retaining this segment of the workforce has a multitude of benefits including the preservation of valuable intellectual capital, which is necessary to ensure that health care organizations maintain their competitive advantage in the consumer-driven market. Retaining the aging employee is possible if health care managers learn the motivators and training differences associated with this category of the workforce. These employees should be considered a valuable resource of human capital because without their extensive expertise, intense loyalty and work ethic, and superior customer service skills, health care organizations could suffer severe economic repercussions in the near future.

  1. Inhibition of a solid phase reaction among excipients that accelerates drug release from a solid dispersion with aging.

    Science.gov (United States)

    Mizuno, Masayasu; Hirakura, Yutaka; Yamane, Ikuro; Miyanishi, Hideo; Yokota, Shoji; Hattori, Munetaka; Kajiyama, Atsushi

    2005-11-23

    Hydrophobic drug substances can be formulated as a solid dispersion or solution using macromolecular matrices with high glass transition temperatures to attain satisfactory dissolution. However, very few marketed products have previously relied on solid dispersion technology due to physical and chemical instability problems, and processing difficulties. In the present study, a modified release product of a therapeutic drug for hypertension, Barnidipine hydrochloride, was developed. The drug product consisted of solid dispersion based on a matrix of carboxymethylethylcellulose (CMEC), which was produced using the spray-coating method. An enteric coat layer was sprayed on the surface of the solid dispersion to control drug release. Interestingly, the release rate accelerated as the drug product aged, while there were no indications of deceleration of the release rate which was due to crystallization of the drug substance. To prevent changes in the dissolution kinetics during storage periods, a variety of processing conditions were tried. It was found that not only use of non-aqueous solvents but also a reduction in coating temperatures consistently resulted in stable solid dispersions. The molecular bases of dissolution of the drug substance from those matrices were investigated. The molecular weight of CMEC was found to be a dominant factor that determined dissolution kinetics, which followed zero-order release, suggesting an involvement of an osmotic pumping mechanism. While dissolution was faster using a higher molecular weight CMEC, the molecular weight of CMEC in the drug product slowly increased with aging (solid phase reaction) depending on the processing conditions, causing the time-induced elevation of dissolution. While no crystalline components were found in the solid dispersion, the amorphous structure maintained a degree of non-equilibrium by nature. Plasticization by water in the coating solution relaxed the amorphous system and facilitated phase

  2. Beta-catenin accelerates human papilloma virus type-16 mediated cervical carcinogenesis in transgenic mice.

    Directory of Open Access Journals (Sweden)

    Gülay Bulut

    Full Text Available Human papilloma virus (HPV is the principal etiological agent of cervical cancer in women, and its DNA is present in virtually all of these tumors. However, exposure to the high-risk HPV types alone is insufficient for tumor development. Identifying specific collaborating factors that will lead to cervical cancer remains an unanswered question, especially because millions of women are exposed to HPV. Our earlier work using an in vitro model indicated that activation of the canonical Wnt pathway in HPV-positive epithelial cells was sufficient to induce anchorage independent growth. We therefore hypothesized that constitutive activation of this pathway might function as the "second hit." To address this possibility, we developed two double-transgenic (DT mouse models, K14-E7/ΔN87βcat and K14-HPV16/ΔN87βcat that express either the proteins encoded by the E7 oncogene or the HPV16 early region along with constitutively active β-catenin, which was expressed by linking it to the keratin-14 (K14 promoter. We initiated tumor formation by treating all groups with estrogen for six months. Invasive cervical cancer was observed in 11% of the K14-ΔN87βcat mice, expressing activated β-catenin and in 50% of the animals expressing the HPV16 E7 oncogene. In double-transgenic mice, coexpression of β-catenin and HPV16 E7 induced invasive cervical cancer at about 7 months in 94% of the cases. We did not observe cervical cancer in any group unless the mice were treated with estrogen. In the second model, K14-HPV16 mice suffered cervical dysplasias, but this phenotype was not augmented in HPV16/ΔN87βcat mice. In summary, the phenotypes of the K14-E7/ΔN87βcat mice support the hypothesis that activation of the Wnt/β-catenin pathway in HPV-associated premalignant lesions plays a functional role in accelerating cervical carcinogenesis.

  3. A hybrid CPU-GPU accelerated framework for fast mapping of high-resolution human brain connectome.

    Science.gov (United States)

    Wang, Yu; Du, Haixiao; Xia, Mingrui; 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.

  4. A hybrid CPU-GPU accelerated framework for fast mapping of high-resolution human brain connectome.

    Directory of Open Access Journals (Sweden)

    Yu Wang

    Full Text Available 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.

  5. Degradation of impact fracture during accelerated aging of weld metal on microalloyed steel; Degradacion de la tenacidad al impacto durante el envejecimiento acelerado de soldadura en acero microaleado

    Energy Technology Data Exchange (ETDEWEB)

    Vargas-Arista, B.; Hallen, J. M.; Albiter, A.; Angeles-Chavez, C.

    2008-07-01

    The effect of accelerated aging on the toughness and fracture of the longitudinal weld metal on an API5L-X52 line pipe steel was evaluated by Charpy V-notch impact test, fracture analysis and transmission electron microscopy. Aging was performed at 250 degree centigrade for 100 to 1000 h. The impact results indicated a significant reduction in the fracture energy and impact toughness as a function of aging time, which were achieved by the scanning electron microscope fractography that showed a decrease in the vol fraction of microvoids by Charpy ductile failure with the aging time, which favored the brittle fracture by transgranular cleavage. The minimum vol fraction of microvoids was reached at 500 h due to the peak aged. The microstructural analysis indicated the precipitation of transgranular iron nano carbides in the aged specimens, which was related to the deterioration of toughness and change in the ductile to brittle behavior. (Author) 15 refs.

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

    Science.gov (United States)

    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

  7. Effects of aging on nitrergic system in human basal nuclei

    Directory of Open Access Journals (Sweden)

    Bruno Lopes dos Santos

    2014-10-01

    Full Text Available Nitric oxide (NO is a gaseous molecule that plays a role in a number of physiologic processes. The available evidence suggests that NO is a major neurotransmitter involved in motor control and emotion/behavior modulation. To investigate the distribution and morphology of the nitrergic system in human basal nuclei, we studied samples from the striatum, globus pallidus, subthalamic nucleus, substantia nigra and pedunculopontine nucleus of 20 human brains from subjects without neurologic/psychiatric diseases. The samples were stained for NADPH-diaphorase using histochemistry and for neuronal NO synthase using immunohistochemistry. We then analyzed the nitrergic neuronal density and its morphometric parameters. Our data demonstrated that: (I the most posterior regions of the striatum exhibit a higher neuronal density; (II the limbic cortex-associated areas of the striatum exhibit higher neuronal density than other functional subdivisions; (III approximately 90% of the neurons in the subthalamic nucleus express NO; (IV the pedunculopontine nucleus exhibits a massive nitrergic neuronal density; (V in the globus pallidus, there is a marked presence of NO neurons in the medial medullary lamina; and (VI nitrergic neurons were not detected in the substantia nigra. Aging did not change the neuronal density or the morphometric parameters of nitrergic neurons in the analyzed nuclei.

  8. Accelerator mass spectrometry in the study of vitamin and mineral metabolism in humans

    Science.gov (United States)

    Accelerator mass spectrometry is an isotopic ratio method that can estimate the concentrations of long-lived radioisotopes such as carbon-14 and calcium-41, making it useful in biochemical and physiological research. It is capable of measuring radio-labeled nutrients and their metabolites in attomol...

  9. Assessment of spatio-temporal gait parameters from trunk accelerations during human walking

    NARCIS (Netherlands)

    Zijlstra, W; Hof, AL

    2003-01-01

    This paper studies the feasibility of an analysis of spatio-temporal gait parameters based upon accelerometry. To this purpose, acceleration patterns of the trunk and their relationships with spatio-temporal gait parameters were analysed in healthy subjects. Based on model predictions of the body's

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

    Science.gov (United States)

    2009-10-01

    experienced pain , the acceleration level was either repeated for reliability or was increased by 1 to 2 Gs. Thus the volunteers stationed at NBDL...Neck Ht Axilla Ht Suprasternale Ht Substernale Ht 10th Rib Ht Waist Ht (Omph) Iliocristale Ht ASIS Ht Trochanterion Ht Gluteal Furrow Ht Tibiale

  11. Assessment of spatio-temporal gait parameters from trunk accelerations during human walking

    NARCIS (Netherlands)

    Zijlstra, W; Hof, AL

    2003-01-01

    This paper studies the feasibility of an analysis of spatio-temporal gait parameters based upon accelerometry. To this purpose, acceleration patterns of the trunk and their relationships with spatio-temporal gait parameters were analysed in healthy subjects. Based on model predictions of the body's

  12. Enhanced and accelerated age hardening response of Al-5.2Mg-0.45Cu (wt%) alloy with Zn addition

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Cheng [State Key Laboratory of Advanced Metals and Materials, University of Science and Technology Beijing, Beijing 100083 (China); Zhang, Di, E-mail: zhangdi@skl.ustb.edu.cn [State Key Laboratory of Advanced Metals and Materials, University of Science and Technology Beijing, Beijing 100083 (China); He, Zhanbing [State Key Laboratory of Advanced Metals and Materials, University of Science and Technology Beijing, Beijing 100083 (China); Zhuang, Linzhong [State Key Laboratory of Advanced Metals and Materials, University of Science and Technology Beijing, Beijing 100083 (China); Tata Steel, 1970 CA IJmuiden (Netherlands); Zhang, Jishan [State Key Laboratory of Advanced Metals and Materials, University of Science and Technology Beijing, Beijing 100083 (China)

    2016-06-01

    The age hardening responses of the Al-5.2Mg-0.45Cu alloy with Zn addition have been investigated in this study. It is found that the age hardening process of the Zn-containing Al-5.2Mg-0.45Cu alloys can be divided into four stages, namely the initial jump(Ⅰ), the linear increase (Ⅱ), the accelerated increase to the peak (Ⅲ) and the overage (Ⅳ). The addition of Zn to the Al-5.2Mg-0.45Cu alloy leads to an enhanced and accelerated age-hardening response in two aspects: firstly introducing the T-[Mg{sub 32}(Al, Zn){sub 49}] phase resulting from the high Mg/Zn ratio and relatively high aging temperature; secondly stimulating the precipitation of the Guinier-Preston-Bagaryatsky (GPB) zones by increasing the supersaturation upon quenching, and accelerating the precipitation of S-Al{sub 2}MgCu phase by increasing Cu/Mg ratio in the matrix due to the formation of the T phase. The peak hardness is from the synergetic effects of the S and T phases. The clustering and partitioning behaviors of solutes after 1 h aging treatment have been investigated in detail using atom probe tomography (APT) and high resolution transmission electron microscopy (HRTEM). It is shown that the formation of Mg-Cu clusters (precursor of the S phase) precedes that of Mg-Zn clusters (precursor of T phase), and the Mg-Cu clusters are responsible for the age hardening during the first two age hardening stages in the Cu-bearing alloys.

  13. Tamanho da semente e o teste de envelhecimento acelerado para soja Seed size and the accelerated aging vigor test for soybean

    Directory of Open Access Journals (Sweden)

    Júlio Marcos Filho

    2000-09-01

    Full Text Available A pesquisa teve como objetivo avaliar a possível relação entre efeitos da utilização de sementes de soja com diferentes tamanhos nos resultados do teste de envelhecimento acelerado. Foram analisados lotes dos cultivares BR-37 e Embrapa 48 (sementes não classificadas e de três tamanhos, classificadas em peneiras de crivos oblongos. Para cada lote e peneira, foram distribuídas três subamostras de 42,5 g de sementes, em camadas simples ou pré-pesadas (42,5 g na superfície da tela metálica de cada compartimento individual (caixa plástica, utilizado como câmara interna para a condução do teste. Cada caixa plástica recebeu 40 mL de água (constituindo ambiente com 100% U.R. do ar ou 40 mL de solução saturada de cloreto de sódio (ambiente com 76% U.R.. Estudaram-se os períodos de 48 e 72 horas de envelhecimento das sementes, em BOD, a 41°C. O teste de germinação subseqüente foi avaliado no quarto dia após a semeadura. A distribuição de amostras com massa uniforme não elimina os efeitos do tamanho das sementes. Desta maneira, o teste de envelhecimento acelerado, em sementes de soja, fornece informações mais consistentes quando as amostras comparadas são constituídas por sementes de tamanho semelhante. O uso de solução salina torna o teste menos severo, mas não reduz sua eficiência.The accelerated aging test is one of the most useful soybean seed vigor tests. This test exposes seeds to a stress of high relative humidity (100% and high temperature (41°C for 48 or 72 h. The main purpose of this study was to determine whether seed size affects water uptake during the accelerated aging test and its influence on the results of this test. Soybean seed lots from cultivars BR-37 and Embrapa 48 were separated into small (11x3/4", medium (13x3/34", and large (14x3/4" size classes. These seeds were subjected to the germination and accelerated aging tests; this test was conducted as recommended by the Association of Official

  14. Evaluation of laser desorption mass spectrometry and UV accelerated aging of dyes on paper as tools for the evaluation of a questioned document.

    Science.gov (United States)

    Grim, Donzna M; Siegel, Jay; Allison, John

    2002-11-01

    Laser desorption mass spectrometry (LDMS) may be used for the detection and identification of dyes found in inks. Naturally-aged and artificially-aged blue and black ballpoint pen inks containing the cationic dye methyl violet were analyzed on paper. The average molecular weight of the dye sample was calculated from LD mass spectral data and plotted versus time. The resulting aging curves demonstrate that, as dye degradation increases, the average molecular weight of the dye decreases. Typical variables involved in ink aging, such as the type of paper and ink formulation, were investigated. Results show that these variables influence the rate of dye degradation. Furthermore, UV accelerated aging has been developed and tested as an alternative to thermal approaches.

  15. Benchmark Accelerated Aging of Harvested Hypalon/Epr and Cspe/Xlpe Power and I&C Cable in Nuclear Power Plants

    Energy Technology Data Exchange (ETDEWEB)

    Duckworth, Robert C.; Frame, Emily; Fifield, Leonard S.; Glass, Samuel W.

    2016-08-30

    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 that 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

  16. BENCHMARK ACCELERATED AGING OF HARVESTED HYPALON/EPR AND CSPE/XLPE POWER AND I&C CABLE IN NUCLEAR POWER PLANTS

    Energy Technology Data Exchange (ETDEWEB)

    Duckworth, Robert C [ORNL; Fifield, Dr Leonard S [Pacific Northwest National Laboratory (PNNL)

    2016-01-01

    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 that 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

  17. STUDIES ON HUMAN FALLOPIAN TUBAL EPITHELIUM IN DIFFERENT AGE GROUPS

    Directory of Open Access Journals (Sweden)

    Jayasri

    2016-02-01

    Full Text Available BACKGROUND AND AIMS The “fallopian tubes” (oviducts or uterine tubes are long paired flexuous reproductive organ which transports ova, spermatozoa, zygotes, the pre-implantation morulae and blastocyst. It has major role during reproductive period, but it remains as if vestigial organ before puberty and after menopause. Due to increasing rate of tubal block and infertility, oviducts and their structures gaining importance and have become a subject of research in present days particularly epithelium. The aim of the study is to ascertain any histological difference of tubal epithelium in different age groups and the research work could be utilized for investigation and management of infertility. MATERIALS AND METHODS Seven samples of each group i.e., prereproductive, reproductive & postmenopausal were collected from fresh unembalmed human cadavers received in the department of Anatomy, FAA Medical College, Barpeta, Assam. The slides were prepared using the standard laboratory procedure. Under low and high power objectives the type of cells were observed and epithelial height was measured in the different segments. Stress was given for any significant difference of epithelial height between the different age groups. RESULTS Study revealed that among the groups within the same segment, epithelial height was recorded highest (33.57µm in reproductive group as against the lowest (22.91µm in post-menopausal group. Epithelial structures of the prereproductive and reproductive groups were significantly differed (p<0.01 from the postmenopausal group. CONCLUSIONS From the findings of the present study it can be concluded that: 1. In all the groups fallopian tubal epithelium is of simple columnar type and contains three types of cells. Cells are ciliated, secretory & peg (intercalary cells. 2. In all the groups same type of increasing trend of epithelial height from intramural segment to ampullary segment was recorded. 3. In intergroup comparison of

  18. Attenuated noradrenergic sensitivity during local cooling in aged human skin

    Science.gov (United States)

    Thompson, Caitlin S; Holowatz, Lacy A; Kenney, W. Larry

    2005-01-01

    Reflex-mediated cutaneous vasoconstriction (VC) is impaired in older humans; however, it is unclear whether this blunted VC also occurs during local cooling, which mediates VC through different mechanisms. We tested the hypothesis that the sensitization of cutaneous vessels to noradrenaline (NA) during direct skin cooling seen in young skin is blunted in aged skin. In 11 young (18–30 years) and 11 older (62–76 years) men and women, skin blood flow was monitored at two forearm sites with laser Doppler (LD) flowmetry while local skin temperature was cooled and clamped at 24°C. Cutaneous vascular conductance (CVC; LD flux/mean arterial pressure) was expressed as percentage change from baseline (%ΔCVCbase). At one site, five doses of NA (10−10–10−2m) were sequentially infused via intradermal microdialysis during cooling while the other 24°C site served as control (Ringer solution + cooling). At control sites, VC due to cooling alone was similar in young versus older (−54 ± 5 versus −56 ± 3%ΔCVCbase, P= 0.46). In young, NA infusions induced additional dose-dependent VC (10−8, 10−6, 10−4 and 10−2m: −70 ± 2, −72 ± 3, −78 ± 3 and −79 ± 4%ΔCVCbase; P older skin does not display enhanced VC capacity until treated with saturating doses of NA, possibly due to age-associated decrements in Ca2+ availability or α2C-adrenoceptor function. PMID:15705648

  19. Accelerating the Development of 21st-Century Toxicology: Outcome of a Human Toxicology Project Consortium Workshop

    Science.gov (United States)

    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

  20. A transcriptional profile of aging in the human kidney.

    Directory of Open Access Journals (Sweden)

    Graham E J Rodwell

    2004-12-01

    Full Text Available In this study, we found 985 genes that change expression in the cortex and the medulla of the kidney with age. Some of the genes whose transcripts increase in abundance with age are known to be specifically expressed in immune cells, suggesting that immune surveillance or inflammation increases with age. The age-regulated genes show a similar aging profile in the cortex and the medulla, suggesting a common underlying mechanism for aging. Expression profiles of these age-regulated genes mark not only age, but also the relative health and physiology of the kidney in older individuals. Finally, the set of aging-regulated kidney genes suggests specific mechanisms and pathways that may play a role in kidney degeneration with age.

  1. A transcriptional profile of aging in the human kidney.

    Science.gov (United States)

    Rodwell, Graham E J; Sonu, Rebecca; Zahn, Jacob M; Lund, James; Wilhelmy, Julie; Wang, Lingli; Xiao, Wenzhong; Mindrinos, Michael; Crane, Emily; Segal, Eran; Myers, Bryan D; Brooks, James D; Davis, Ronald W; Higgins, John; Owen, Art B; Kim, Stuart K

    2004-12-01

    In this study, we found 985 genes that change expression in the cortex and the medulla of the kidney with age. Some of the genes whose transcripts increase in abundance with age are known to be specifically expressed in immune cells, suggesting that immune surveillance or inflammation increases with age. The age-regulated genes show a similar aging profile in the cortex and the medulla, suggesting a common underlying mechanism for aging. Expression profiles of these age-regulated genes mark not only age, but also the relative health and physiology of the kidney in older individuals. Finally, the set of aging-regulated kidney genes suggests specific mechanisms and pathways that may play a role in kidney degeneration with age.

  2. Natural and Sun-Induced Aging of Human Skin

    OpenAIRE

    Rittié, Laure; Fisher, Gary J.

    2015-01-01

    With worldwide expansion of the aging population, research on age-related pathologies is receiving growing interest. In this review, we discuss current knowledge regarding the decline of skin structure and function induced by the passage of time (chronological aging) and chronic exposure to solar UV irradiation (photoaging). Nearly every aspect of skin biology is affected by aging. The self-renewing capability of the epidermis, which provides vital barrier function, is diminished with age. Vi...

  3. Human face processing is tuned to sexual age preferences.

    Science.gov (United States)

    Ponseti, J; Granert, O; van Eimeren, T; Jansen, O; Wolff, S; Beier, K; Deuschl, G; Bosinski, H; Siebner, H

    2014-05-01

    Human faces can motivate nurturing behaviour or sexual behaviour when adults see a child or an adult face, respectively. This suggests that face processing is tuned to detecting age cues of sexual maturity to stimulate the appropriate reproductive behaviour: either caretaking or mating. In paedophilia, sexual attraction is directed to sexually immature children. Therefore, we hypothesized that brain networks that normally are tuned to mature faces of the preferred gender show an abnormal tuning to sexual immature faces in paedophilia. Here, we use functional magnetic resonance imaging (fMRI) to test directly for the existence of a network which is tuned to face cues of sexual maturity. During fMRI, participants sexually attracted to either adults or children were exposed to various face images. In individuals attracted to adults, adult faces activated several brain regions significantly more than child faces. These brain regions comprised areas known to be implicated in face processing, and sexual processing, including occipital areas, the ventrolateral prefrontal cortex and, subcortically, the putamen and nucleus caudatus. The same regions were activated in paedophiles, but with a reversed preferential response pattern.

  4. Telomerase prevents accelerated senescence in glucose-6-phosphate dehydrogenase (G6PD-deficient human fibroblasts

    Directory of Open Access Journals (Sweden)

    Wu Yi-Hsuan

    2009-02-01

    Full Text Available Abstract Fibroblasts derived from glucose-6-phosphate dehydrogenase (G6PD-deficient patients display retarded growth and accelerated cellular senescence that is attributable to increased accumulation of oxidative DNA damage and increased sensitivity to oxidant-induced senescence, but not to accelerated telomere attrition. Here, we show that ectopic expression of hTERT stimulates telomerase activity and prevents accelerated senescence in G6PD-deficient cells. Stable clones derived from hTERT-expressing normal and G6PD-deficient fibroblasts have normal karyotypes, and display no sign of senescence beyond 145 and 105 passages, respectively. Activation of telomerase, however, does not prevent telomere attrition in earlier-passage cells, but does stabilize telomere lengths at later passages. In addition, we provide evidence that ectopic expression of hTERT attenuates the increased sensitivity of G6PD-deficient fibroblasts to oxidant-induced senescence. These results suggest that ectopic expression of hTERT, in addition to acting in telomere length maintenance by activating telomerase, also functions in regulating senescence induction.

  5. Analysis and Management of Accelerated Aging of Relay in NPPs%核电厂继电器加速老化分析及管理研究

    Institute of Scientific and Technical Information of China (English)

    张圣; 马沂荩; 江虹; 陈世均; 黄立军; 莫春铌

    2013-01-01

    This paper reveals the main factors of accelerated the aging of relay through statistical analysis of aging and failure data of intermediate relay and output relay for MV distribution board in Daya Bay nuclear power plant and Ling'ao nuclear power plant The factors of accelerating relay aging are operation context including humidity, temperature, vibration impact, and etc., and aging mechanism including oxidation corrosion, mechanical wear, electrical wear, organic gas corrosion, insulation aging, electromagnetic interference, and etc. The suggested measures are the classified management, relay replacement, periodic check, and periodic replacement or maintenance.%通过对大亚湾和岭澳核电站中压配电盘的中间和出口继电器老化与失效数据进行统计,分析核电厂继电器加速老化的主要因素.继电器加速老化的影响因素为运行环境,主要是湿度、温度和振动冲击;老化机理为氧化腐蚀、机械磨损、电磨损、有机气体腐蚀、绝缘老化和电磁干扰.建议对继电器分类管理、替代使用,进行周期检测、更换或维护.

  6. Natural and sun-induced aging of human skin.

    Science.gov (United States)

    Rittié, Laure; Fisher, Gary J

    2015-01-05

    With worldwide expansion of the aging population, research on age-related pathologies is receiving growing interest. In this review, we discuss current knowledge regarding the decline of skin structure and function induced by the passage of time (chronological aging) and chronic exposure to solar UV irradiation (photoaging). Nearly every aspect of skin biology is affected by aging. The self-renewing capability of the epidermis, which provides vital barrier function, is diminished with age. Vital thermoregulation function of eccrine sweat glands is also altered with age. The dermal collagenous extracellular matrix, which comprises the bulk of skin and confers strength and resiliency, undergoes gradual fragmentation, which deleteriously impacts skin mechanical properties and dermal cell functions. Aging also affects wound repair, pigmentation, innervation, immunity, vasculature, and subcutaneous fat homeostasis. Altogether, age-related alterations of skin lead to age-related skin fragility and diseases.

  7. Low-dose radiation accelerates aging of the T-cell receptor repertoire in CBA/Ca mice.

    Science.gov (United States)

    Candéias, Serge M; Mika, Justyna; Finnon, Paul; Verbiest, Tom; Finnon, Rosemary; Brown, Natalie; Bouffler, Simon; Polanska, Joanna; Badie, Christophe

    2017-06-30

    While the biological effects of high-dose-ionizing radiation on human health are well characterized, the consequences of low-dose radiation exposure remain poorly defined, even though they are of major importance for radiological protection. Lymphocytes are very radiosensitive, and radiation-induced health effects may result from immune cell loss and/or immune system impairment. To decipher the mechanisms of effects of low doses, we analyzed the modulation of the T-cell receptor gene repertoire in mice exposed to a single low (0.1 Gy) or high (1 Gy) dose of radiation. High-throughput T-cell receptor gene profiling was used to visualize T-lymphocyte dynamics over time in control and irradiated mice. Radiation exposure induces "aging-like" effects on the T-cell receptor gene repertoire, detectable as early as 1 month post-exposure and for at least 6 months. Surprisingly, these effects are more pronounced in animals exposed to 0.1 Gy than to 1 Gy, where partial correction occurs over time. Importantly, we found that low-dose radiation effects are partially due to the hematopoietic stem cell impairment. Collectively, our findings show that acute low-dose radiation exposure specifically results in long-term alterations of the T-lymphocyte repertoire.

  8. Analyzing age-specific genetic effects on human extreme age survival in cohort-based longitudinal studies

    DEFF Research Database (Denmark)

    Tan, Qihua; Jacobsen, Rune; Sørensen, Mette

    2013-01-01

    The analysis of age-specific genetic effects on human survival over extreme ages is confronted with a deceleration pattern in mortality that deviates from traditional survival models and sparse genetic data available. As human late life is a distinct phase of life history, exploring the genetic...... effects on extreme age survival can be of special interest to evolutionary biology and health science. We introduce a non-parametric survival analysis approach that combines population survival information with individual genotype data in assessing the genetic effects in cohort-based longitudinal studies...

  9. Faster increases in human life expectancy could lead to slower population aging.

    Directory of Open Access Journals (Sweden)

    Warren C Sanderson

    Full Text Available Counterintuitively, faster increases in human life expectancy could lead to slower population aging. The conventional view that faster increases in human life expectancy would lead to faster population aging is based on the assumption that people become old at a fixed chronological age. A preferable alternative is to base measures of aging on people's time left to death, because this is more closely related to the characteristics that are associated with old age. Using this alternative interpretation, we show that faster increases in life expectancy would lead to slower population aging. Among other things, this finding affects the assessment of the speed at which countries will age.

  10. Faster Increases in Human Life Expectancy Could Lead to Slower Population Aging

    Science.gov (United States)

    2015-01-01

    Counterintuitively, faster increases in human life expectancy could lead to slower population aging. The conventional view that faster increases in human life expectancy would lead to faster population aging is based on the assumption that people become old at a fixed chronological age. A preferable alternative is to base measures of aging on people’s time left to death, because this is more closely related to the characteristics that are associated with old age. Using this alternative interpretation, we show that faster increases in life expectancy would lead to slower population aging. Among other things, this finding affects the assessment of the speed at which countries will age. PMID:25876033

  11. Time to accelerate integration of human factors and ergonomics in patient safety.

    Science.gov (United States)

    Gurses, Ayse P; Ozok, A Ant; Pronovost, Peter J

    2012-04-01

    Progress toward improving patient safety has been slow despite engagement of the health care community in improvement efforts. A potential reason for this sluggish pace is the inadequate integration of human factors and ergonomics principles and methods in these efforts. Patient safety problems are complex and rarely caused by one factor or component of a work system. Thus, health care would benefit from human factors and ergonomics evaluations to systematically identify the problems, prioritize the right ones, and develop effective and practical solutions. This paper gives an overview of the discipline of human factors and ergonomics and describes its role in improving patient safety. We provide examples of how human factors and ergonomics principles and methods have improved both care processes and patient outcomes. We provide five major recommendations to better integrate human factors and ergonomics in patient safety improvement efforts: build capacity among health care workers to understand human factors and ergonomics, create market forces that demand the integration of human factors and ergonomics design principles into medical technologies, increase the number of human factors and ergonomic practitioners in health care organizations, expand investments in improvement efforts informed by human factors and ergonomics, and support interdisciplinary research to improve patient safety. In conclusion, human factors and ergonomics must play a more prominent role in health care if we want to increase the pace in improving patient safety.

  12. Combined small-molecule inhibition accelerates the derivation of functional cortical neurons from human pluripotent stem cells.

    Science.gov (United States)

    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

    2017-02-01

    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 to rapidly differentiate 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 six 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 d 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.

  13. Obesity-induced chronic inflammation in high fat diet challenged C57BL/6J mice is associated with acceleration of age-dependent renal amyloidosis.

    Science.gov (United States)

    van der Heijden, Roel A; Bijzet, Johan; Meijers, Wouter C; Yakala, Gopala K; Kleemann, Robert; Nguyen, Tri Q; de Boer, Rudolf A; Schalkwijk, Casper G; Hazenberg, Bouke P C; Tietge, Uwe J F; Heeringa, Peter

    2015-11-13

    Obesity-induced inflammation presumably accelerates the development of chronic kidney diseases. However, little is known about the sequence of these inflammatory events and their contribution to renal pathology. We investigated the effects of obesity on the evolution of age-dependent renal complications in mice in conjunction with the development of renal and systemic low-grade inflammation (LGI). C57BL/6J mice susceptible to develop age-dependent sclerotic pathologies with amyloid features in the kidney, were fed low (10% lard) or high-fat diets (45% lard) for 24, 40 and 52 weeks. HFD-feeding induced overt adiposity, altered lipid and insulin homeostasis, increased systemic LGI and adipokine release. HFD-feeding also caused renal upregulation of pro-inflammatory genes, infiltrating macrophages, collagen I protein, increased urinary albumin and NGAL levels. HFD-feeding severely aggravated age-dependent structural changes in the kidney. Remarkably, enhanced amyloid deposition rather than sclerosis was observed. The degree of amyloidosis correlated significantly with body weight. Amyloid deposits stained positive for serum amyloid A (SAA) whose plasma levels were chronically elevated in HFD mice. Our data indicate obesity-induced chronic inflammation as a risk factor for the acceleration of age-dependent renal amyloidosis and functional impairment in mice, and suggest that obesity-enhanced chronic secretion of SAA may be the driving factor behind this process.

  14. Effects of accelerated artificial daylight aging on bending strength and bonding of glass fibers in fiber-embedded maxillofacial silicone prostheses.

    Science.gov (United States)

    Hatamleh, Muhanad M; Watts, David C

    2010-07-01

    The purpose of this study was to test the effect of different periods of accelerated artificial daylight aging on bond strength of glass fiber bundles embedded into maxillofacial silicone elastomer and on bending strength of the glass fiber bundles. Forty specimens were fabricated by embedding resin-impregnated fiber bundles (1.5-mm diameter, 20-mm long) into maxillofacial silicone elastomer. Specimens were randomly allocated into four groups, and each group was subjected to different periods of accelerated daylight aging as follows (in hours); 0, 200, 400, and 600. The aging cycle included continuous exposure to quartz-filtered visible daylight (irradiance 760 W/m(2)) under an alternating weathering cycle (wet for 18 minutes, dry for 102 minutes). Pull-out tests were performed to evaluate bond strength between fiber bundles and silicone using a universal testing machine at 1 mm/min crosshead speed. Also a three-point bending test was performed to evaluate bending strength of the fiber bundles. One-way ANOVA and Bonferroni post hoc tests were carried out to detect statistical significance (p bending strengths of fiber bundles were in the range of 917.72 MPa to 1124.06 MPa. Bending strength significantly increased after 200 and 400 hours of aging only. After 200 hours of exposure to artificial daylight and moisture conditions, bond strength between glass fibers and heat-cured silicones is optimal, and the bending strength of the glass fiber bundles is enhanced.

  15. Salivary Alpha Amylase Activity in Human Beings of Different Age Groups Subjected to Psychological Stress

    National Research Council Canada - National Science Library

    Sahu, Gopal K; Upadhyay, Seema; Panna, Shradha M

    2014-01-01

    ... in different age groups is least studied. This article reports the activity of sAA in human subjects of different age groups subjected to psychological stress induced through stressful video clip...

  16. The transcriptional landscape of age in human peripheral blood

    Science.gov (United States)

    Peters, Marjolein J.; Joehanes, Roby; Pilling, Luke C.; Schurmann, Claudia; Conneely, Karen N.; Powell, Joseph; Reinmaa, Eva; Sutphin, George L.; Zhernakova, Alexandra; Schramm, Katharina; Wilson, Yana A.; Kobes, Sayuko; Tukiainen, Taru; Nalls, Michael A.; Hernandez, Dena G.; Cookson, Mark R.; Gibbs, Raphael J.; Hardy, John; Ramasamy, Adaikalavan; Zonderman, Alan B.; Dillman, Allissa; Traynor, Bryan; Smith, Colin; Longo, Dan L.; Trabzuni, Daniah; Troncoso, Juan; van der Brug, Marcel; Weale, Michael E.; O'Brien, Richard; Johnson, Robert; Walker, Robert; Zielke, Ronald H.; Arepalli, Sampath; Ryten, Mina; Singleton, Andrew B.; Ramos, Yolande F.; Göring, Harald H. H.; Fornage, Myriam; Liu, Yongmei; Gharib, Sina A.; Stranger, Barbara E.; De Jager, Philip L.; Aviv, Abraham; Levy, Daniel; Murabito, Joanne M.; Munson, Peter J.; Huan, Tianxiao; Hofman, Albert; Uitterlinden, André G.; Rivadeneira, Fernando; van Rooij, Jeroen; Stolk, Lisette; Broer, Linda; Verbiest, Michael M. P. J.; Jhamai, Mila; Arp, Pascal; Metspalu, Andres; Tserel, Liina; Milani, Lili; Samani, Nilesh J.; Peterson, Pärt; Kasela, Silva; Codd, Veryan; Peters, Annette; Ward-Caviness, Cavin K.; Herder, Christian; Waldenberger, Melanie; Roden, Michael; Singmann, Paula; Zeilinger, Sonja; Illig, Thomas; Homuth, Georg; Grabe, Hans-Jörgen; Völzke, Henry; Steil, Leif; Kocher, Thomas; Murray, Anna; Melzer, David; Yaghootkar, Hanieh; Bandinelli, Stefania; Moses, Eric K.; Kent, Jack W.; Curran, Joanne E.; Johnson, Matthew P.; Williams-Blangero, Sarah; Westra, Harm-Jan; McRae, Allan F.; Smith, Jennifer A.; Kardia, Sharon L. R.; Hovatta, Iiris; Perola, Markus; Ripatti, Samuli; Salomaa, Veikko; Henders, Anjali K.; Martin, Nicholas G.; Smith, Alicia K.; Mehta, Divya; Binder, Elisabeth B.; Nylocks, K Maria; Kennedy, Elizabeth M.; Klengel, Torsten; Ding, Jingzhong; Suchy-Dicey, Astrid M.; Enquobahrie, Daniel A.; Brody, Jennifer; Rotter, Jerome I.; Chen, Yii-Der I.; Houwing-Duistermaat, Jeanine; Kloppenburg, Margreet; Slagboom, P. Eline; Helmer, Quinta; den Hollander, Wouter; Bean, Shannon; Raj, Towfique; Bakhshi, Noman; Wang, Qiao Ping; Oyston, Lisa J.; Psaty, Bruce M.; Tracy, Russell P.; Montgomery, Grant W.; Turner, Stephen T.; Blangero, John; Meulenbelt, Ingrid; Ressler, Kerry J.; Yang, Jian; Franke, Lude; Kettunen, Johannes; Visscher, Peter M.; Neely, G. Gregory; Korstanje, Ron; Hanson, Robert L.; Prokisch, Holger; Ferrucci, Luigi; Esko, Tonu; Teumer, Alexander; van Meurs, Joyce B. J.; Johnson, Andrew D.

    2015-01-01

    Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the ‘transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts. PMID:26490707

  17. Soiling of building envelope surfaces and its effect on solar reflectance – Part II: Development of an accelerated aging method for roofing materials

    Energy Technology Data Exchange (ETDEWEB)

    Sleiman, Mohamad [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Kirchstetter, Thomas W. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States); Berdahl, Paul [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Gilbert, Haley E. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Quelen, Sarah [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Marlot, Lea [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Preble, Chelsea V. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States); Chen, Sharon [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Montalbano, Amandine [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Rosseler, Olivier [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Akbari, Hashem [Concordia Univ., Montreal (Canada); Levinson, Ronnen [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Destaillats, Hugo [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    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, 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.

  18. Androgen receptor accelerates premature senescence of human dermal papilla cells in association with DNA damage.

    Directory of Open Access Journals (Sweden)

    Yi-Chien Yang

    Full Text Available The dermal papilla, located in the hair follicle, expresses androgen receptor and plays an important role in hair growth. Androgen/Androgen receptor actions have been implicated in the pathogenesis of androgenetic alopecia, but the exact mechanism is not well known. Recent studies suggest that balding dermal papilla cells exhibit premature senescence, upregulation of p16(INK4a, and nuclear expression of DNA damage markers. To investigate whether androgen/AR signaling influences the premature senescence of dermal papilla cells, we first compared frontal scalp dermal papilla cells of androgenetic alopecia patients with matched normal controls and observed that premature senescence is more prominent in the dermal papilla cells of androgenetic alopecia patients. Exposure of androgen induced premature senescence in dermal papilla cells from non-balding frontal and transitional zone of balding scalp follicles but not in beard follicles. Overexpression of the AR promoted androgen-induced premature senescence in association with p16(INK4a upregulation, whereas knockdown of the androgen receptor diminished the effects of androgen. An analysis of γ-H2AX expression in response to androgen/androgen receptor signaling suggested that DNA damage contributes to androgen/androgen receptor-accelerated premature senescence. These results define androgen/androgen receptor signaling as an accelerator of premature senescence in dermal papilla cells and suggest that the androgen/androgen receptor-mediated DNA damage-p16(INK4a axis is a potential therapeutic target in the treatment of androgenetic alopecia.

  19. Human Age Estimation Method Robust to Camera Sensor and/or Face Movement

    OpenAIRE

    Dat Tien Nguyen; So Ra Cho; Tuyen Danh Pham; Kang Ryoung Park

    2015-01-01

    Human age can be employed in many useful real-life applications, such as customer service systems, automatic vending machines, entertainment, etc. In order to obtain age information, image-based age estimation systems have been developed using information from the human face. However, limitations exist for current age estimation systems because of the various factors of camera motion and optical blurring, facial expressions, gender, etc. Motion blurring can usually be presented on face images...

  20. PET Imaging of Tau Deposition in the Aging Human Brain.

    Science.gov (United States)

    Schöll, Michael; Lockhart, Samuel N; Schonhaut, Daniel R; O'Neil, James P; Janabi, Mustafa; Ossenkoppele, Rik; Baker, Suzanne L; Vogel, Jacob W; Faria, Jamie; Schwimmer, Henry D; Rabinovici, Gil D; Jagust, William J

    2016-03-02

    Tau pathology is a hallmark of Alzheimer's disease (AD) but also occurs in normal cognitive aging. Using the tau PET agent (18)F-AV-1451, we examined retention patterns in cognitively normal older people in relation to young controls and AD patients. Age and β-amyloid (measured using PiB PET) were differentially associated with tau tracer retention in healthy aging. Older age was related to increased tracer retention in regions of the medial temporal lobe, which predicted worse episodic memory performance. PET detection of tau in other isocortical regions required the presence of cortical β-amyloid and was associated with decline in global cognition. Furthermore, patterns of tracer retention corresponded well with Braak staging of neurofibrillary tau pathology. The present study defined patterns of tau tracer retention in normal aging in relation to age, cognition, and β-amyloid deposition.

  1. The effect of aging on human induced pluripotent stem cells

    OpenAIRE

    Sardo, Valentina Lo; Ferguson, William; Erikson, Galina A.; Topol, Eric J; Baldwin, Kristin K; Torkamani, Ali

    2016-01-01

    Induced pluripotent stem cells (iPSCs) are being developed as a source for autologous cell therapies, many of which aim to treat aged patients1?5. To explore the impact of age on iPSC quality, we produced iPSCs from blood cells of 16 donors aged 21?100. We find that while reprogramming resets most of the epigenome, iPSCs retain an epigenetic signature of age that diminishes with passaging. Reprogramming via clonal expansion also exposes somatic mutations present in individual donor cells, whi...

  2. Elevated IKKα accelerates the differentiation of human neuronal progenitor cells and induces MeCP2-dependent BDNF expression.

    Directory of Open Access Journals (Sweden)

    Ali Khoshnan

    Full Text Available The IκB kinase α (IKKα is implicated in the differentiation of epithelial and immune cells. We examined whether IKKα also plays a role in the differentiation and maturation of embryonic human neuronal progenitor cells (NPCs. We find that expression of an extra copy of IKKα (IKKα+ blocks self-renewal and accelerates the differentiation of NPCs. This coincides with reduced expression of the Repressor Element Silencing Transcription Factor/Neuron-Restrictive Silencing Factor (REST/NRSF, which is a prominent inhibitor of neurogenesis, and subsequent induction of the pro-differentiation non-coding RNA, miR-124a. However, the effects of IKKα on REST/NRSF and miR-124a expression are likely to be indirect. IKKα+ neurons display extensive neurite outgrowth and accumulate protein markers of neuronal maturation such as SCG10/stathmin-2, postsynaptic density 95 (PSD95, syntaxin, and methyl-CpG binding protein 2 (MeCP2. Interestingly, IKKα associates with MeCP2 in the nuclei of human neurons and can phosphorylate MeCP2 in vitro. Using chromatin immunoprecipitation assays, we find that IKKα is recruited to the exon-IV brain-derived neurotrophic factor (BDNF promoter, which is a well-characterized target of MeCP2 activity. Moreover, IKKα induces the transcription of BDNF and knockdown expression of MeCP2 interferes with this event. These studies highlight a role for IKKα in accelerating the differentiation of human NPCs and identify IKKα as a potential regulator of MeCP2 function and BDNF expression.

  3. The problem of aging human remains and living individuals

    DEFF Research Database (Denmark)

    Cunha, E; Baccino, E; Martrille, L

    2009-01-01

    Forensic anthropology is affected by the unavoidable limits concerning difficulties in standardization of methods and procedures; age estimation is one of the main tasks of forensic anthropology and odontology, both on the dead and the living: literature has shown several methods of age estimatio...

  4. The transcriptional landscape of age in human peripheral blood

    NARCIS (Netherlands)

    M.J. Peters (Marjolein); R. Joehanes (Roby); L.C. Pilling (Luke); C. Schurmann (Claudia); K.N. Conneely (Karen N.); J.E. Powell (Joseph); E. Reinmaa (Eva); G.L. Sutphin (George L.); A. Zhernakova (Alexandra); K. Schramm (Katharina); Y.A. Wilson (Yana A.); S. Kobes (Sayuko); T. Tukiainen (Taru); Y.F.M. Ramos (Yolande); H.H.H. Göring (Harald H.); M. Fornage (Myriam); Y. Liu (Yongmei); S.A. Gharib (Sina); B.E. Stranger (Barbara); P.L. de Jager (Philip); A. Aviv (Abraham); D. Levy (Daniel); J. Murabito (Joanne); P.J. Munson (Peter J.); T. Huan (Tianxiao); A. Hofman (Albert); A.G. Uitterlinden (Andre G.); F. Rivadeneira Ramirez (Fernando); J. van Rooij (Jeroen); L. Stolk (Lisette); L. Broer (Linda); M.M.P.J. Verbiest (Michael); M. Jhamai (Mila); P.P. Arp (Pascal); A. Metspalu (Andres); L. Tserel (Liina); L. Milani (Lili); N.J. Samani (Nilesh); P. Peterson (Pärt); S. Kasela (Silva); V. Codd (Veryan); A. Peters (Annette); C.K. Ward-Caviness (Cavin K.); C. Herder (Christian); M. Waldenberger (Melanie); M. Roden (Michael); P. Singmann (Paula); S. Zeilinger (Sonja); T. Illig (Thomas); G. Homuth (Georg); H.J. Grabe (Hans Jörgen); H. Völzke (Henry); L. Steil (Leif); T. Kocher (Thomas); A. Murray (Anna); D. Melzer (David); H. Yaghootkar (Hanieh); S. Bandinelli; E.K. Moses (Eric); J.W. Kent (Jack); J.E. Curran (Joanne); M.P. Johnson (Matthew); S. Williams-Blangero (Sarah); H.J. Westra (Harm-Jan); A.F. McRae (Allan F.); J.A. Smith (Jennifer A); S.L.R. Kardia (Sharon); I. Hovatta (Iiris); M. Perola (Markus); S. Ripatti (Samuli); V. Salomaa (Veikko); A.K. Henders (Anjali); N.G. Martin (Nicholas); A.K. Smith (Alicia K.); D. Mehta (Divya); E.B. Binder (Elisabeth B.); K.M. Nylocks (K. Maria); E.M. Kennedy (Elizabeth M.); T. Klengel (Torsten); J. Ding (Jingzhong); A. Suchy-Dicey (Astrid); D. Enquobahrie; J. Brody (Jennifer); J.I. Rotter (Jerome I.); Y.-D.I. Chen (Yii-Der I.); J.J. Houwing-Duistermaat (Jeanine); M. Kloppenburg (Margreet); P.E. Slagboom (Eline); Q. Helmer (Quinta); W. den Hollander (Wouter); S. Bean (Shannon); T. Raj (Towfique); N. Bakhshi (Noman); Q.P. Wang (Qiao Ping); L.J. Oyston (Lisa J.); B.M. Psaty (Bruce); R.P. Tracy (Russell); G.W. Montgomery (Grant); S.T. Turner (Stephen); J. Blangero (John); I. Meulenbelt (Ingrid); K.J. Ressler (Kerry); J. Yang (Jian); L. Franke (Lude); J. Kettunen (Johannes); P.M. Visscher (Peter); G.G. Neely (G. Gregory); R. Korstanje (Ron); R.L. Hanson (Robert L.); H. Prokisch (Holger); L. Ferrucci (Luigi); T. Esko (Tõnu); A. Teumer (Alexander); J.B.J. van Meurs (Joyce); A.D. Johnson (Andrew D.); M.A. Nalls (Michael); D.G. Hernandez (Dena); M.R. Cookson (Mark); R.J. Gibbs (Raphael J.); J. Hardy (John); A. Ramasamy (Adaikalavan); A.B. Zonderman (Alan B.); A. Dillman (Allissa); B. Traynor (Bryan); C. Smith (Colin); D.L. Longo (Dan L.); D. Trabzuni (Danyah); J.C. Troncoso (Juan); M.P. van der Brug (Marcel); M.E. Weale (Michael); R. O'Brien (Richard); R. Johnson (Robert); R. Walker (Robert); R.H. Zielke (Ronald H.); S. Arepalli (Sampath); M. Ryten (Mina); A. Singleton

    2015-01-01

    textabstractDisease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) a

  5. The transcriptional landscape of age in human peripheral blood

    NARCIS (Netherlands)

    Peters, Marjolein J; Joehanes, Roby; Pilling, Luke C; Schurmann, Claudia; Conneely, Karen N; Powell, Joseph; Reinmaa, Eva; Sutphin, George L; Zhernakova, Alexandra; Schramm, Katharina; Wilson, Yana A; Kobes, Sayuko; Tukiainen, Taru; Ramos, Yolande F; Göring, Harald H H; Fornage, Myriam; Liu, Yongmei; Gharib, Sina A; Stranger, Barbara E; De Jager, Philip L; Aviv, Abraham; Levy, Daniel; Murabito, Joanne M; Munson, Peter J; Huan, Tianxiao; Hofman, Albert; Uitterlinden, André G; Rivadeneira, Fernando; van Rooij, Jeroen; Stolk, Lisette; Broer, Linda; Verbiest, Michael M P J; Jhamai, Mila; Arp, Pascal; Metspalu, Andres; Tserel, Liina; Milani, Lili; Samani, Nilesh J; Peterson, Pärt; Kasela, Silva; Codd, Veryan; Peters, Annette; Ward-Caviness, Cavin K; Herder, Christian; Waldenberger, Melanie; Roden, Michael; Singmann, Paula; Zeilinger, Sonja; Illig, Thomas; Homuth, Georg; Grabe, Hans-Jörgen; Völzke, Henry; Steil, Leif; Kocher, Thomas; Murray, Anna; Melzer, David; Yaghootkar, Hanieh; Bandinelli, Stefania; Moses, Eric K; Kent, Jack W; Curran, Joanne E; Johnson, Matthew P; Williams-Blangero, Sarah; Westra, Harm-Jan; McRae, Allan F; Smith, Jennifer A; Kardia, Sharon L R; Hovatta, Iiris; Perola, Markus; Ripatti, Samuli; Salomaa, Veikko; Henders, Anjali K; Martin, Nicholas G; Smith, Alicia K; Mehta, Divya; Binder, Elisabeth B; Nylocks, K Maria; Kennedy, Elizabeth M; Klengel, Torsten; Ding, Jingzhong; Suchy-Dicey, Astrid M; Enquobahrie, Daniel A; Brody, Jennifer; Rotter, Jerome I; Chen, Yii-Der I; Houwing-Duistermaat, Jeanine; Kloppenburg, Margreet; Slagboom, P Eline; Helmer, Quinta; den Hollander, Wouter; Bean, Shannon; Raj, Towfique; Bakhshi, Noman; Wang, Qiao Ping; Oyston, Lisa J; Psaty, Bruce M; Tracy, Russell P; Montgomery, Grant W; Turner, Stephen T; Blangero, John; Meulenbelt, Ingrid; Ressler, Kerry J; Yang, Jian; Franke, Lude; Kettunen, Johannes; Visscher, Peter M; Neely, G Gregory; Korstanje, Ron; Hanson, Robert L; Prokisch, Holger; Ferrucci, Luigi; Esko, Tonu; Teumer, Alexander; van Meurs, Joyce B J; Johnson, Andrew D

    2015-01-01

    Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify

  6. Hsp60 and human aging: Les liaisons dangereuses.

    Science.gov (United States)

    Cappello, Francesco; Conway de Macario, Everly; Marino Gammazza, Antonella; Bonaventura, Giuseppe; Carini, Francesco; Czarnecka, Anna M; Farina, Felicia; Zummo, Giovanni; Macario, Alberto J L

    2013-01-01

    Stressors can cause abnormal intracellular accumulation of Hsp60 and its localization in extramitochondrial sites, secretion, and circulation, with immune system activation. Dysfunction of chaperones associated with their quantitative and qualitative decline with aging (chaperonopathies of aging) characterizes senescence and is a potential causal factor in the physiological deterioration that occurs with it. The role of Hsp60 in aging is not easy to elucidate, because aging is accompanied by pathologies (e.g., cardiovascular and neurodegenerative disorders, osteoporosis, diabetes, cancer, etc.) in which Hsp60 has been implicated but, although those disorders are more frequent in the elderly, they are not unique to them. Therefore, it is difficult to determine what is due to aging and what to an associated disease that can occur regardless of age. Does Hsp60 contribute to the pathogenesis? How and when does Hsp60 interact with the immune system and, thus, contributes to the initiation-progression of the generalized chronic inflammation characteristic of aging? These and related issues are discussed here in the light of reports showing the participation of Hsp60 in aging-associated disorders.

  7. The transcriptional landscape of age in human peripheral blood

    NARCIS (Netherlands)

    Peters, Marjolein J.; Joehanes, Roby; Pilling, Luke C.; Schurmann, Claudia; Conneely, Karen N.; Powell, Joseph; Reinmaa, Eva; Sutphin, George L.; Zhernakova, Alexandra; Schramm, Katharina; Wilson, Yana A.; Kobes, Sayuko; Tukiainen, Taru; Ramos, Yolande F.; Goering, Harald H. H.; Fornage, Myriam; Liu, Yongmei; Gharib, Sina A.; Stranger, Barbara E.; De Jager, Philip L.; Aviv, Abraham; Levy, Daniel; Murabito, Joanne M.; Munson, Peter J.; Huan, Tianxiao; Hofman, Albert; Uitterlinden, Andre G.; Rivadeneira, Fernando; van Rooij, Jeroen; Stolk, Lisette; Broer, Linda; Verbiest, Michael M. P. J.; Jhamai, Mila; Arp, Pascal; Metspalu, Andres; Tserel, Liina; Milani, Lili; Samani, Nilesh J.; Peterson, Paert; Kasela, Silva; Codd, Veryan; Peters, Annette; Ward-Caviness, Cavin K.; Herder, Christian; Waldenberger, Melanie; Roden, Michael; Singmann, Paula; Zeilinger, Sonja; Illig, Thomas; Homuth, Georg; Grabe, Hans-Joergen; Voelzke, Henry; Steil, Leif; Kocher, Thomas; Murray, Anna; Melzer, David; Yaghootkar, Hanieh; Bandinelli, Stefania; Moses, Eric K.; Kent, Jack W.; Curran, Joanne E.; Johnson, Matthew P.; Williams-Blangero, Sarah; Westra, Harm-Jan; Mcrae, Allan F.; Smith, Jennifer A.; Kardia, Sharon L. R.; Hovatta, Iiris; Perola, Markus; Ripatti, Samuli; Salomaa, Veikko; Henders, Anjali K.; Martin, Nicholas G.; Smith, Alicia K.; Mehta, Divya; Binder, Elisabeth B.; Nylocks, K. Maria; Kennedy, Elizabeth M.; Klengel, Torsten; Ding, Jingzhong; Suchy-Dicey, Astrid M.; Enquobahrie, Daniel A.; Brody, Jennifer; Rotter, Jerome I.; Chen, Yii-Der I.; Houwing-Duistermaat, Jeanine; Kloppenburg, Margreet; Slagboom, P. Eline; Helmer, Quinta; den Hollander, Wouter; Bean, Shannon; Raj, Towfique; Bakhshi, Noman; Wang, Qiao Ping; Oyston, Lisa J.; Psaty, Bruce M.; Tracy, Russell P.; Montgomery, Grant W.; Turner, Stephen T.; Blangero, John; Meulenbelt, Ingrid; Ressler, Kerry J.; Yang, Jian; Franke, Lude; Kettunen, Johannes; Visscher, Peter M.; Neely, G. Gregory; Korstanje, Ron; Hanson, Robert L.; Prokisch, Holger; Ferrucci, Luigi; Esko, Tonu; Teumer, Alexander; van Meurs, Joyce B. J.; Johnson, Andrew D.

    2015-01-01

    Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify

  8. The transcriptional landscape of age in human peripheral blood

    NARCIS (Netherlands)

    M.J. Peters (Marjolein); R. Joehanes (Roby); L.C. Pilling (Luke); C. Schurmann (Claudia); K.N. Conneely (Karen N.); J.E. Powell (Joseph); E. Reinmaa (Eva); G.L. Sutphin (George L.); A. Zhernakova (Alexandra); K. Schramm (Katharina); Y.A. Wilson (Yana A.); S. Kobes (Sayuko); T. Tukiainen (Taru); Y.F.M. Ramos (Yolande); H.H.H. Göring (Harald H.); M. Fornage (Myriam); Y. Liu (Yongmei); S.A. Gharib (Sina); B.E. Stranger (Barbara); P.L. de Jager (Philip); A. Aviv (Abraham); D. Levy (Daniel); J. Murabito (Joanne); P.J. Munson (Peter J.); T. Huan (Tianxiao); A. Hofman (Albert); A.G. Uitterlinden (André); F. Rivadeneira Ramirez (Fernando); J. van Rooij (Jeroen); L. Stolk (Lisette); L. Broer (Linda); M.M.P.J. Verbiest (Michael); M. Jhamai (Mila); P.P. Arp (Pascal); A. Metspalu (Andres); L. Tserel (Liina); L. Milani (Lili); N.J. Samani (Nilesh); P. Peterson (Pärt); S. Kasela (Silva); V. Codd (Veryan); A. Peters (Annette); C.K. Ward-Caviness (Cavin K.); C. Herder (Christian); M. Waldenberger (Melanie); M. Roden (Michael); P. Singmann (Paula); S. Zeilinger (Sonja); T. Illig (Thomas); G. Homuth (Georg); H.J. Grabe (Hans Jörgen); H. Völzke (Henry); L. Steil (Leif); T. Kocher (Thomas); A. Murray (Anna); D. Melzer (David); H. Yaghootkar (Hanieh); S. Bandinelli; E.K. Moses (Eric); J.W. Kent (Jack); J.E. Curran (Joanne); M.P. Johnson (Matthew); S. Williams-Blangero (Sarah); H.J. Westra (Harm-Jan); A.F. McRae (Allan F.); J.A. Smith (Jennifer A); S.L.R. Kardia (Sharon); I. Hovatta (Iiris); M. Perola (Markus); S. Ripatti (Samuli); V. Salomaa (Veikko); A.K. Henders (Anjali); N.G. Martin (Nicholas); A.K. Smith (Alicia K.); D. Mehta (Divya); E.B. Binder (Elisabeth B.); K.M. Nylocks (K. Maria); E.M. Kennedy (Elizabeth M.); T. Klengel (Torsten); J. Ding (Jingzhong); A. Suchy-Dicey (Astrid); D. Enquobahrie; J. Brody (Jennifer); J.I. Rotter (Jerome I.); Y.-D.I. Chen (Yii-Der I.); J.J. Houwing-Duistermaat (Jeanine); M. Kloppenburg (Margreet); P.E. Slagboom (Eline); Q. Helmer (Quinta); W. den Hollander (Wouter); S. Bean (Shannon); T. Raj (Towfique); N. Bakhshi (Noman); Q.P. Wang (Qiao Ping); L.J. Oyston (Lisa J.); B.M. Psaty (Bruce); R.P. Tracy (Russell); G.W. Montgomery (Grant); S.T. Turner (Stephen); J. Blangero (John); I. Meulenbelt (Ingrid); K.J. Ressler (Kerry); J. Yang (Jian); L. Franke (Lude); J. Kettunen (Johannes); P.M. Visscher (Peter); G.G. Neely (G. Gregory); R. Korstanje (Ron); R.L. Hanson (Robert L.); H. Prokisch (Holger); L. Ferrucci (Luigi); T. Esko (Tõnu); A. Teumer (Alexander); J.B.J. van Meurs (Joyce); A.D. Johnson (Andrew D.); M.A. Nalls (Michael); D.G. Hernandez (Dena); M.R. Cookson (Mark); R.J. Gibbs (Raphael J.); J. Hardy (John); A. Ramasamy (Adaikalavan); A.B. Zonderman (Alan B.); A. Dillman (Allissa); B. Traynor (Bryan); C. Smith (Colin); D.L. Longo (Dan L.); D. Trabzuni (Danyah); J.C. Troncoso (Juan); M.P. van der Brug (Marcel); M.E. Weale (Michael); R. O'Brien (Richard); R. Johnson (Robert); R. Walker (Robert); R.H. Zielke (Ronald H.); S. Arepalli (Sampath); M. Ryten (Mina); A. Singleton

    2015-01-01

    textabstractDisease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) a

  9. Lamin A-dependent nuclear defects in human aging.

    Science.gov (United States)

    Scaffidi, Paola; Misteli, Tom

    2006-05-19

    Mutations in the nuclear structural protein lamin A cause the premature aging syndrome Hutchinson-Gilford progeria (HGPS). Whether lamin A plays any role in normal aging is unknown. We show that the same molecular mechanism responsible for HGPS is active in healthy cells. Cell nuclei from old individuals acquire defects similar to those of HGPS patient cells, including changes in histone modifications and increased DNA damage. Age-related nuclear defects are caused by sporadic use, in healthy individuals, of the same cryptic splice site in lamin A whose constitutive activation causes HGPS. Inhibition of this splice site reverses the nuclear defects associated with aging. These observations implicate lamin A in physiological aging.

  10. The cost of transport of human running is not affected, as in walking, by wide acceleration/deceleration cycles.

    Science.gov (United States)

    Minetti, Alberto E; Gaudino, Paolo; Seminati, Elena; Cazzola, Dario

    2013-02-15

    Although most of the literature on locomotion energetics and biomechanics is about constant-speed experiments, humans and animals tend to move at variable speeds in their daily life. This study addresses the following questions: 1) how much extra metabolic energy is associated with traveling a unit distance by adopting acceleration/deceleration cycles in walking and running, with respect to constant speed, and 2) how can biomechanics explain those metabolic findings. Ten males and ten females walked and ran at fluctuating speeds (5 ± 0, ± 1, ± 1.5, ± 2, ± 2.5 km/h for treadmill walking, 11 ± 0, ± 1, ± 2, ± 3, ± 4 km/h for treadmill and field running) in cycles lasting 6 s. Field experiments, consisting of subjects following a laser spot projected from a computer-controlled astronomic telescope, were necessary to check the noninertial bias of the oscillating-speed treadmill. Metabolic cost of transport was found to be almost constant at all speed oscillations for running and up to ±2 km/h for walking, with no remarkable differences between laboratory and field results. The substantial constancy of the metabolic cost is not explained by the predicted cost of pure acceleration/deceleration. As for walking, results from speed-oscillation running suggest that the inherent within-stride, elastic energy-free accelerations/decelerations when moving at constant speed work as a mechanical buffer for among-stride speed fluctuations, with no extra metabolic cost. Also, a recent theory about the analogy between sprint (level) running and constant-speed running on gradients, together with the mechanical determinants of gradient locomotion, helps to interpret the present findings.

  11. Role of Age-Associated Alterations of the Dermal Extracellular Matrix Microenvironment in Human Skin Aging: A Mini-Review.

    Science.gov (United States)

    Quan, Taihao; Fisher, Gary J

    2015-01-01

    Human skin is largely composed of a collagen-rich connective tissue, which provides structural and functional support. The collagen-rich connective tissue is produced, organized, and maintained by dermal fibroblasts. During aging, dermal collagen fibrils undergo progressive loss and fragmentation, leading to thin and structurally weakened skin. Age-related alterations of collagen fibrils impairs skin structure and function and creates a tissue microenvironment that promotes age-related skin diseases, such as delayed wound healing and skin cancer development. This mini-review describes cellular mechanisms that give rise to self-perpetuating, collagen fibril fragmentation that creates an age-associated dermal microenvironment, which contributes to decline of human skin function.

  12. Normal aging in rats and pathological aging in human Alzheimer's disease decrease FAAH activity: modulation by cannabinoid agonists.

    Science.gov (United States)

    Pascual, A C; Martín-Moreno, A M; Giusto, N M; de Ceballos, M L; Pasquaré, S J

    2014-12-01

    Anandamide is an endocannabinoid involved in several physiological functions including neuroprotection. Anandamide is synthesized on demand and its endogenous level is regulated through its degradation, where fatty acid amide hydrolase plays a major role. The aim of this study was to characterize anandamide breakdown in physiological and pathological aging and its regulation by CB1 and CB2 receptor agonists. Fatty acid amide hydrolase activity was analyzed in an independent cohort of human cortical membrane samples from control and Alzheimer's disease patients, and in membrane and synaptosomes from adult and aged rat cerebral cortex. Our results demonstrate that fatty acid amide hydrolase activity decreases in the frontal cortex from human patients with Alzheimer's disease and this effect is mimicked by Aβ(1-40) peptide. This activity increases and decreases in aged rat cerebrocortical membranes and synaptosomes, respectively. Also, while the presence of JWH-133, a CB2 selective agonist, slightly increases anandamide hydrolysis in human controls, it decreases this activity in adults and aged rat cerebrocortical membranes and synaptosomes. In the presence of WIN55,212-2, a mixed CB1/CB2 agonist, anandamide hydrolysis increases in Alzheimer's disease patients but decreases in human controls as well as in adult and aged rat cerebrocortical membranes and synaptosomes. Although a similar profile is observed in fatty acid amide hydrolase activity between aged rat synaptic endings and human Alzheimer's disease brains, it is differently modulated by CB1/CB2 agonists. This modulation leads to a reduced availability of anandamide in Alzheimer's disease and to an increased availability of this endocannabinoid in aging.

  13. Human gut microbiome viewed across age and geography

    Science.gov (United States)

    Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ among human populations, we characterized bacterial species in fecal samples from 531 individuals, plus the gene content of 110 of them. The cohort encompassed healthy child...

  14. Human Age Estimation Based on Locality and Ordinal Information.

    Science.gov (United States)

    Li, Changsheng; Liu, Qingshan; Dong, Weishan; Zhu, Xiaobin; Liu, Jing; Lu, Hanqing

    2015-11-01

    In this paper, we propose a novel feature selection-based method for facial age estimation. The face aging is a typical temporal process, and facial images should have certain ordinal patterns in the aging feature space. From the geometrical perspective, a facial image can be usually seen as sampled from a low-dimensional manifold embedded in the original high-dimensional feature space. Thus, we first measure the energy of each feature in preserving the underlying local structure information and the ordinal information of the facial images, respectively, and then we intend to learn a low-dimensional aging representation that can maximally preserve both kinds of information. To further improve the performance, we try to eliminate the redundant local information and ordinal information as much as possible by minimizing nonlinear correlation and rank correlation among features. Finally, we formulate all these issues into a unified optimization problem, which is similar to linear discriminant analysis in format. Since it is expensive to collect the labeled facial aging images in practice, we extend the proposed supervised method to a semi-supervised learning mode including the semi-supervised feature selection method and the semi-supervised age prediction algorithm. Extensive experiments are conducted on the FACES dataset, the Images of Groups dataset, and the FG-NET aging dataset to show the power of the proposed algorithms, compared to the state-of-the-arts.

  15. Biodemography of old-age mortality in humans and rodents.

    Science.gov (United States)

    Gavrilova, Natalia S; Gavrilov, Leonid A

    2015-01-01

    The growing number of persons living beyond age 80 underscores the need for accurate measurement of mortality at advanced ages and understanding the old-age mortality trajectories. It is believed that exponential growth of mortality with age (Gompertz law) is followed by a period of deceleration, with slower rates of mortality increase at older ages. This pattern of mortality deceleration is traditionally described by the logistic (Kannisto) model, which is considered as an alternative to the Gompertz model. Mortality deceleration was observed for many invertebrate species, but the evidence for mammals is controversial. We compared the performance (goodness-of-fit) of two competing models-the Gompertz model and the logistic (Kannisto) model using data for three mammalian species: 22 birth cohorts of U.S. men and women, eight cohorts of laboratory mice, and 10 cohorts of laboratory rats. For all three mammalian species, the Gompertz model fits mortality data significantly better than the "mortality deceleration" Kannisto model (according to the Akaike's information criterion as the goodness-of-fit measure). These results suggest that mortality deceleration at advanced ages is not a universal phenomenon, and survival of mammalian species follows the Gompertz law up to very old ages.

  16. Normal Human Aging and Early-Stage Schizophrenia Share Common Molecular Profiles

    OpenAIRE

    Tang, Bin; Chang, Wei-Li; Lanigan, Caroline M.; Dean, Brian; Sutcliffe, J. Gregor; Thomas, Elizabeth A.

    2009-01-01

    We examined genome-wide expression datasets from human frontal cortex of normal and schizophrenic individuals ranging from 19 to 81 years of age. We found that changes in gene expression that are correlated with aging in normal subjects differ dramatically from those observed with aging in schizophrenic subjects. Only 2.5% of genes were correlated with age in both groups. Surprisingly, we also found a significant overlap (29−34%) between those genes whose expression was correlated with aging ...

  17. Accelerated Recruitment of New Brain Development Genes into the Human Genome

    Science.gov (United States)

    Zhang, Yong E.; Landback, Patrick; Vibranovski, Maria D.; Long, Manyuan

    2011-01-01

    How the human brain evolved has attracted tremendous interests for decades. Motivated by case studies of primate-specific genes implicated in brain function, we examined whether or not the young genes, those emerging genome-wide in the lineages specific to the primates or rodents, showed distinct spatial and temporal patterns of transcription compared to old genes, which had existed before primate and rodent split. We found consistent patterns across different sources of expression data: there is a significantly larger proportion of young genes expressed in the fetal or infant brain of humans than in mouse, and more young genes in humans have expression biased toward early developing brains than old genes. Most of these young genes are expressed in the evolutionarily newest part of human brain, the neocortex. Remarkably, we also identified a number of human-specific genes which are expressed in the prefrontal cortex, which is implicated in complex cognitive behaviors. The young genes upregulated in the early developing human brain play diverse functional roles, with a significant enrichment of transcription factors. Genes originating from different mechanisms show a similar expression bias in the developing brain. Moreover, we found that the young genes upregulated in early brain development showed rapid protein evolution compared to old genes also expressed in the fetal brain. Strikingly, genes expressed in the neocortex arose soon after its morphological origin. These four lines of evidence suggest that positive selection for brain function may have contributed to the origination of young genes expressed in the developing brain. These data demonstrate a striking recruitment of new genes into the early development of the human brain. PMID:22028629

  18. The anti-aging effects of LW-AFC via correcting immune dysfunctions in senescence accelerated mouse resistant 1 (SAMR1) strain.

    Science.gov (United States)

    Wang, Jianhui; Cheng, Xiaorui; Zhang, Xiaorui; Cheng, Junping; Xu, Yiran; Zeng, Ju; Zhou, Wenxia; Zhang, Yongxiang

    2016-05-10

    Although there were considerable advances in the anti-aging medical field, it is short of therapeutic drug for anti-aging. Mounting evidence indicates that the immunosenescence is the key physiopathological mechanism of aging. This study showed the treatment of LW-AFC, an herbal medicine, decreased the grading score of senescence, increased weight, prolonged average life span and ameliorated spatial memory impairment in 12- and 24-month-old senescence accelerated mouse resistant 1 (SAMR1) strain. And these anti-aging effects of LW-AFC were more excellent than melatonin. The administration of LW-AFC enhanced ConA- and LPS-induced splenocyte proliferation in aged SAMR1 mice. The treatment of LW-AFC not only reversed the decreased the proportions of helper T cells, suppressor T cells and B cells, the increased regulatory T cells in the peripheral blood of old SAMR1 mice, but also could modulate the abnormal secretion of IL-1β, IL-2, IL-6, IL-17, IL-23, GM-CSF, IFN-γ, TNF-α, TNF-β, RANTES, eotaxin, MCP-1, IL-4, IL-5, IL-10 and G-CSF. These data indicated that LW-AFC reversed the immunosenescence status by restoring immunodeficiency and decreasing chronic inflammation and suggested LW-AFC may be an effective anti-aging agent.

  19. Accelerated Evolution of Conserved Noncoding Sequences in theHuman Genome

    Energy Technology Data Exchange (ETDEWEB)

    Prambhakar, Shyam; Noonan, James P.; Paabo, Svante; Rubin, EdwardM.

    2006-07-06

    Genomic comparisons between human and distant, non-primatemammals are commonly used to identify cis-regulatory elements based onconstrained sequence evolution. However, these methods fail to detect"cryptic" functional elements, which are too weakly conserved amongmammals to distinguish from nonfunctional DNA. To address this problem,we explored the potential of deep intra-primate sequence comparisons. Wesequenced the orthologs of 558 kb of human genomic sequence, coveringmultiple loci involved in cholesterol homeostasis, in 6 nonhumanprimates. Our analysis identified 6 noncoding DNA elements displayingsignificant conservation among primates, but undetectable in more distantcomparisons. In vitro and in vivo tests revealed that at least three ofthese 6 elements have regulatory function. Notably, the mouse orthologsof these three functional human sequences had regulatory activity despitetheir lack of significant sequence conservation, indicating that they arecryptic ancestral cis-regulatory elements. These regulatory elementscould still be detected in a smaller set of three primate speciesincluding human, rhesus and marmoset. Since the human and rhesus genomesequences are already available, and the marmoset genome is activelybeing sequenced, the primate-specific conservation analysis describedhere can be applied in the near future on a whole-genome scale, tocomplement the annotation provided by more distant speciescomparisons.

  20. Characterization of Skin Aging-Associated Secreted Proteins (SAASP) Produced by Dermal Fibroblasts Isolated from Intrinsically Aged Human Skin.

    Science.gov (United States)

    Waldera Lupa, Daniel M; Kalfalah, Faiza; Safferling, Kai; Boukamp, Petra; Poschmann, Gereon; Volpi, Elena; Götz-Rösch, Christine; Bernerd, Francoise; Haag, Laura; Huebenthal, Ulrike; Fritsche, Ellen; Boege, Fritz; Grabe, Niels; Tigges, Julia; Stühler, Kai; Krutmann, Jean

    2015-08-01

    Most molecular hallmarks of cellular senescence have been identified in studies of cells aged in vitro by driving them into replicative or stress-induced senescence. Comparatively, less is known about the characteristic features of cells that have aged in vivo. Here we provide a systematic molecular analysis of normal human dermal fibroblasts (NHDFs) that were isolated from intrinsically aged human skin of young versus middle aged versus old donors. Intrinsically aged NHDFs in culture exhibited more frequently nuclear foci positive for p53 binding protein 1 and promyelocytic leukemia protein reminiscent of 'DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS)'. Formation of such foci was neither accompanied by increased DNA double strand breaks, nor decreased cell viability, nor telomere shortening. However, it was associated with the development of a secretory phenotype, indicating incipient cell senescence. By quantitative analysis of the entire secretome present in conditioned cell culture supernatant, combined with a multiplex cytokine determination, we identified 998 proteins secreted by intrinsically aged NHDFs in culture. Seventy of these proteins exhibited an age-dependent secretion pattern and were accordingly denoted 'skin aging-associated secreted proteins (SAASP)'. Systematic comparison of SAASP with the classical senescence-associated secretory phenotype (SASP) revealed that matrix degradation as well as proinflammatory processes are common aspects of both conditions. However, secretion of 27 proteins involved in the biological processes of 'metabolism' and 'adherens junction interactions' was unique for NHDFs isolated from intrinsically aged skin. In conclusion, fibroblasts isolated from intrinsically aged skin exhibit some, but not all, molecular hallmarks of cellular senescence. Most importantly, they secrete a unique pattern of proteins that is distinct from the canonical SASP and might reflect specific processes of skin aging.

  1. Stereology of human myometrium in pregnancy: influence of maternal body mass index and age.

    LENUS (Irish Health Repository)

    Sweeney, Eva M

    2013-04-01

    Knowledge of the stereology of human myometrium in pregnancy is limited. Uterine contractile performance may be altered in association with maternal obesity and advanced maternal age. The aim of this study was to investigate the stereology of human myometrium in pregnancy, and to evaluate a potential influence of maternal body mass index (BMI) and age.

  2. TNF-alpha, leptin, and lymphocyte function in human aging

    D