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Sample records for accelerated human ageing

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

    PubMed

    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. PMID:25667091

  2. Menopause accelerates biological aging.

    PubMed

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

    2016-08-16

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

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

    PubMed Central

    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

    2016-01-01

    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. PMID:27479945

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

    PubMed

    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. PMID:27479945

  5. Accelerated aging and human immunodeficiency virus infection: emerging challenges of growing older in the era of successful antiretroviral therapy.

    PubMed

    Bhatia, Ramona; Ryscavage, Patrick; Taiwo, Babafemi

    2012-08-01

    HIV-infected patients are living longer as a result of potent antiretroviral therapy. Immuno-inflammatory phenomena implicated in the normal aging process, including immune senescence, depreciation of the adaptive immune system, and heightened systemic inflammation are also pathophysiologic sequelae of HIV infection, suggesting HIV infection can potentiate the biological mechanisms of aging. Aging HIV-infected patients manifest many comorbidities at earlier ages, and sometimes with more aggressive phenotypes compared to seronegative counterparts. In this review, we describe relevant biologic changes shared by normal aging and HIV infection and explore the growing spectrum of clinical manifestations associated with the accelerated aging phenotype in HIV-infected individuals. PMID:22205585

  6. Cable aging phenomena under accelerated aging conditions

    SciTech Connect

    Behera, A.K.; Beck, C.E.; Alsammarae, A.

    1996-06-01

    A test program was conducted to determine the impact of accelerated (temperature and radiation) aging on the insulation of power cables. The intent was to develop a more realistic model for cable degradation mechanisms, and a more realistic technique for determining a cable`s qualified life. Samples of new cables and samples of cables obtained from an operating plant were subjected to a series of tests. The test showed that the order of imposing the harsh conditions, the presence of oxygen, and the use of a compressive measurement technique each had a significant impact on the results. This paper discusses the test methodology and test samples, the order of imposing artificial aging, and the results. Also presented are issues planned to be addressed in future testing.

  7. Alterations in mitosis and cell cycle progression caused by a mutant lamin A known to accelerate human aging.

    PubMed

    Dechat, Thomas; Shimi, Takeshi; Adam, Stephen A; Rusinol, Antonio E; Andres, Douglas A; Spielmann, H Peter; Sinensky, Michael S; Goldman, Robert D

    2007-03-20

    Mutations in the gene encoding nuclear lamin A (LA) cause the premature aging disease Hutchinson-Gilford Progeria Syndrome. The most common of these mutations results in the expression of a mutant LA, with a 50-aa deletion within its C terminus. In this study, we demonstrate that this deletion leads to a stable farnesylation and carboxymethylation of the mutant LA (LADelta50/progerin). These modifications cause an abnormal association of LADelta50/progerin with membranes during mitosis, which delays the onset and progression of cytokinesis. Furthermore, we demonstrate that the targeting of nuclear envelope/lamina components into daughter cell nuclei in early G(1) is impaired in cells expressing LADelta50/progerin. The mutant LA also appears to be responsible for defects in the retinoblastoma protein-mediated transition into S-phase, most likely by inhibiting the hyperphosphorylation of retinoblastoma protein by cyclin D1/cdk4. These results provide insights into the mechanisms responsible for premature aging and also shed light on the role of lamins in the normal process of human aging. PMID:17360326

  8. Premature and accelerated aging: HIV or HAART?

    PubMed

    Smith, Reuben L; de Boer, Richard; Brul, Stanley; Budovskaya, Yelena; van Spek, Hans

    2012-01-01

    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 this difference invokes heavily on viral stimulus despite HAART efficiency in viral suppression. We propose here that the premature and accelerated aging 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-γ. 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 favor of the use of Caenorhabditis elegans as a novel model system for studying these effects. PMID:23372574

  9. Premature and accelerated aging: HIV or HAART?

    PubMed Central

    Smith, Reuben L.; de Boer, Richard; Brul, Stanley; Budovskaya, Yelena; van Spek, Hans

    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 this difference invokes heavily on viral stimulus despite HAART efficiency in viral suppression. We propose here that the premature and accelerated aging 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-γ. 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 favor of the use of Caenorhabditis elegans as a novel model system for studying these effects. PMID:23372574

  10. Testing of biomaterials, accelerated ageing.

    PubMed

    Prodinger, A; Krausler, S; Schima, H; Thoma, H; Wolner, E; Schneider, W

    1985-01-01

    The residual elongation is a critical property of materials used for manufacturing diaphragms of artificial hearts. It is therefore important to check goods received or to control manufactured diaphragms, whether their creep properties are within the required limits. Ordinary creep tests take at least several months, while the release of goods received or diaphragms manufactured should be possible within a few days. Acceleration of the creep test by increasing the test temperature permits an estimation whether the creep properties of a material are within the required limits within a week. PMID:3870605

  11. PETN Coarsening - Predictions from Accelerated Aging Data

    SciTech Connect

    Maiti, Amitesh; Gee, Richard H.

    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.

  12. Is schizophrenia a syndrome of accelerated aging?

    PubMed

    Kirkpatrick, Brian; Messias, Erick; Harvey, Philip D; Fernandez-Egea, Emilio; Bowie, Christopher R

    2008-11-01

    Schizophrenia is associated with a number of anatomical and physiological abnormalities outside of the brain, as well as with a decrease in average life span estimated at 20% in the United States. Some studies suggest that this increased mortality is not entirely due to associated causes such as suicide and the use of psychotropic medications. In this article, in order to focus greater attention on the increased mortality associated with schizophrenia, we present a special case of the hypothesis that physiological abnormalities associated with schizophrenia make a contribution to the increased mortality of schizophrenia: specifically, the hypothesis that schizophrenia is a syndrome of accelerated aging. Evidence consistent with this hypothesis comes from several areas. The biological plausibility of the hypothesis is supported by the existence of established syndromes of accelerated aging and by the sharing of risk factors between schizophrenia and other age-related conditions. We propose methods for testing the hypothesis. PMID:18156637

  13. Accelerated aging of wood-composite members

    SciTech Connect

    Sonti, S.S.; GangaRao, H.V.S.; Talakanti, D.R.

    1996-12-31

    This paper discusses the longterm performance of various adhesives under accelerated aging conditions, where the intended application of the adhesives is bonding wood member to composite fabric wraps. Northern Red Oak was used as the core and two types of composite fabrics were used (glass and carbon) as external reinforcements. The adhesives used for bonding include: Epoxy, Polyurethane, Isopolyester, Resorcinol Formaldehyde, and Phenolic based Resorcinol Formaldehyde. Results from the shear strength evaluations show that a primer/resin combination provided a better bond compared to the bond developed by resin system only. Also, it was observed that phenolic-based resins had higher retention of shear strength after being subjected to aging conditions.

  14. Insights into accelerated aging of SSL luminaires

    DOE PAGESBeta

    Davis, J. Lynn; Lamvik, Michael; Bittle, James; Shepherd, Sarah; Yaga, Robert; Baldasaro, Nick; Solano, Eric; Bobashev, Georgiy

    2013-09-30

    Although solid-state lighting (SSL) products are often intended to have product lifetimes of 15 years or more, the rapid change in technology has created a need for accelerated life tests (ALTs) that can be performed in the span of several months. A critical element of interpreting results from any systems-level ALT is understanding of the impact of the test environment on each component. Because of its ubiquity in electronics, the use of temperature-humidity environments as potential ALTs for SSL luminaires was investigated. Results from testing of populations of three commercial 6” downlights in environments of 85oC and 85% relative humiditymore » (RH) and 75oC and 75% RH are reported. These test environments were found to accelerate lumen depreciation of the entire luminaire optical system, including LEDs, lenses, and reflectors. The effects of aging were found to depend strongly on both the optical materials that were used and the design of the luminaire; this shows that the lumen maintenance behavior of SSL luminaires must be addressed at the optical systems level. Temperature-Humidity ALTs can be a useful test in understand lumainaire depreciation provided that proper consideration is given to the different aging rates of various materials. Since the impact of the temperature-humidity environment varies among components of the optical system, uniform aging of all system components in a single test is difficult to achieve.« less

  15. Insights into accelerated aging of SSL luminaires

    SciTech Connect

    Davis, J. Lynn; Lamvik, Michael; Bittle, James; Shepherd, Sarah; Yaga, Robert; Baldasaro, Nick; Solano, Eric; Bobashev, Georgiy

    2013-09-30

    Although solid-state lighting (SSL) products are often intended to have product lifetimes of 15 years or more, the rapid change in technology has created a need for accelerated life tests (ALTs) that can be performed in the span of several months. A critical element of interpreting results from any systems-level ALT is understanding of the impact of the test environment on each component. Because of its ubiquity in electronics, the use of temperature-humidity environments as potential ALTs for SSL luminaires was investigated. Results from testing of populations of three commercial 6” downlights in environments of 85oC and 85% relative humidity (RH) and 75oC and 75% RH are reported. These test environments were found to accelerate lumen depreciation of the entire luminaire optical system, including LEDs, lenses, and reflectors. The effects of aging were found to depend strongly on both the optical materials that were used and the design of the luminaire; this shows that the lumen maintenance behavior of SSL luminaires must be addressed at the optical systems level. Temperature-Humidity ALTs can be a useful test in understand lumainaire depreciation provided that proper consideration is given to the different aging rates of various materials. Since the impact of the temperature-humidity environment varies among components of the optical system, uniform aging of all system components in a single test is difficult to achieve.

  16. Insights into accelerated aging of SSL luminaires

    NASA Astrophysics Data System (ADS)

    Davis, J. Lynn; Lamvik, Michael; Bittle, James; Shepherd, Sarah; Yaga, Robert; Baldasaro, Nick; Solano, Eric; Bobashev, Georgiy

    2013-09-01

    Although solid-state lighting (SSL) products are often intended to have product lifetimes of 15 years or more, the rapid change in technology has created a need for accelerated life tests (ALTs) that can be performed in the span of several months. A critical element of interpreting results from any systems-level ALT is understanding of the impact of the test environment on each component. Because of its ubiquity in electronics, the use of temperature-humidity environments as potential ALTs for SSL luminaires was investigated. Results from testing of populations of three commercial 6" downlights in environments of 85°C and 85% relative humidity (RH) and 75°C and 75% RH are reported. These test environments were found to accelerate lumen depreciation of the entire luminaire optical system, including LEDs, lenses, and reflectors. The effects of aging were found to depend strongly on both the optical materials that were used and the design of the luminaire; this shows that the lumen maintenance behavior of SSL luminaires must be addressed at the optical systems level. Temperature-Humidity ALTs can be a useful test in understand lumainaire depreciation provided that proper consideration is given to the different aging rates of various materials. Since the impact of the temperature-humidity environment varies among components of the optical system, uniform aging of all system components in a single test is difficult to achieve.

  17. Accelerated Aging in Electrolytic Capacitors for Prognostics

    NASA Technical Reports Server (NTRS)

    Celaya, Jose R.; Kulkarni, Chetan; Saha, Sankalita; Biswas, Gautam; Goebel, Kai Frank

    2012-01-01

    The focus of this work is the analysis of different degradation phenomena based on thermal overstress and electrical overstress accelerated aging systems and the use of accelerated aging techniques for prognostics algorithm development. Results on thermal overstress and electrical overstress experiments are presented. In addition, preliminary results toward the development of physics-based degradation models are presented focusing on the electrolyte evaporation failure mechanism. An empirical degradation model based on percentage capacitance loss under electrical overstress is presented and used in: (i) a Bayesian-based implementation of model-based prognostics using a discrete Kalman filter for health state estimation, and (ii) a dynamic system representation of the degradation model for forecasting and remaining useful life (RUL) estimation. A leave-one-out validation methodology is used to assess the validity of the methodology under the small sample size constrain. The results observed on the RUL estimation are consistent through the validation tests comparing relative accuracy and prediction error. It has been observed that the inaccuracy of the model to represent the change in degradation behavior observed at the end of the test data is consistent throughout the validation tests, indicating the need of a more detailed degradation model or the use of an algorithm that could estimate model parameters on-line. Based on the observed degradation process under different stress intensity with rest periods, the need for more sophisticated degradation models is further supported. The current degradation model does not represent the capacitance recovery over rest periods following an accelerated aging stress period.

  18. Accelerated Aging of Lead-Free Propellant

    NASA Technical Reports Server (NTRS)

    Furrow, Keith W.; Jervey, David D.

    2000-01-01

    Following higher than expected 2-NDPA depletion rates in a lead-free doublebase formulation (RPD-422), an accelerated aging study was conducted to verify the depletion rates. A test plan was prepared to compare the aging characteristics of lead-free propellant and NOSIH-AA2. The study was also designed to determine which lead-free ballistic modifiers accelerated 2-NDPA depletion. The increased depletion rate occurred in propellants containing monobasic copper salicylate. Four lead-free propellants were then formulated to improved aging characteristics over previous lead-free propellant formulations. The new formulations reduced or replaced the monobasic copper salicylate. The new formulations had improved aging characteristics. Their burn rates, however, were unacceptable for use in a 2.75 inch rocket. To compare aging characteristics, stabilizer depletion rates of RPD-422, AA2, M28, and RLC 470/6A were measured or taken from the literature. The data were fit to a kinetic model. The model contained first and zero order terms which allowed the stabilizer concentration to go to zero. In the model, only the concentration of the primary stabilizer was considered. Derivatives beyond the first nitrated or nitroso derivative of 2-NPDA were not considered. The rate constants were fit to the Arrhenius equation and extrapolated to lower temperatures. The time to complete stabilizer depletion was estimated using the kinetic model. The four propellants were compared and the RPD-422 depleted faster at 45 C than both A22 and M28. These types of predictions depend on the validity of the model and on confidence in the Arrhenius relationship holding at lower temperatures. At 45 C, the zero order portion of the model dominates the depletion rate.

  19. Mechanisms of aging in senescence-accelerated mice

    PubMed Central

    Carter, Todd A; Greenhall, Jennifer A; Yoshida, Shigeo; Fuchs, Sebastian; Helton, Robert; Swaroop, Anand; Lockhart, David J; Barlow, Carrolee

    2005-01-01

    Background Progressive neurological dysfunction is a key aspect of human aging. Because of underlying differences in the aging of mice and humans, useful mouse models have been difficult to obtain and study. We have used gene-expression analysis and polymorphism screening to study molecular senescence of the retina and hippocampus in two rare inbred mouse models of accelerated neurological senescence (SAMP8 and SAMP10) that closely mimic human neurological aging, and in a related normal strain (SAMR1) and an unrelated normal strain (C57BL/6J). Results The majority of age-related gene expression changes were strain-specific, with only a few common pathways found for normal and accelerated neurological aging. Polymorphism screening led to the identification of mutations that could have a direct impact on important disease processes, including a mutation in a fibroblast growth factor gene, Fgf1, and a mutation in and ectopic expression of the gene for the chemokine CCL19, which is involved in the inflammatory response. Conclusion We show that combining the study of inbred mouse strains with interesting traits and gene-expression profiling can lead to the discovery of genes important for complex phenotypes. Furthermore, full-genome polymorphism detection, sequencing and gene-expression profiling of inbred mouse strains with interesting phenotypic differences may provide unique insights into the molecular genetics of late-manifesting complex diseases. PMID:15960800

  20. Degradation mechanisms and accelerated aging test design

    SciTech Connect

    Clough, R L; Gillen, K T

    1985-01-01

    The fundamental mechanisms underlying the chemical degradation of polymers can change as a function of environmental stress level. When this occurs, it greatly complicates any attempt to use accelerated tests for predicting long-term material degradation behaviors. Understanding how degradation mechanisms can change at different stress levels facilitates both the design and the interpretation of aging tests. Oxidative degradation is a predominant mechanism for many polymers exposed to a variety of different environments in the presence of air, and there are two mechanistic considerations which are widely applicable to material oxidation. One involves a physical process, oxygen diffusion, as a rate-limiting step. This mechanism can predominate at high stress levels. The second is a chemical process, the time-dependent decomposition of peroxide species. This leads to chain branching and can become a rate-controlling factor at lower stress levels involving time-scales applicable to use environments. The authors describe methods for identifying the operation of these mechanisms and illustrate the dramatic influence they can have on the degradation behaviors of a number of polymer types. Several commonly used approaches to accelerated aging tests are discussed in light of the behaviors which result from changes in degradation mechanisms. 9 references, 4 figures.

  1. Aging accelerates memory extinction and impairs memory restoration in Drosophila.

    PubMed

    Chen, Nannan; Guo, Aike; Li, Yan

    2015-05-15

    Age-related memory impairment (AMI) is a phenomenon observed from invertebrates to human. Memory extinction is proposed to be an active inhibitory modification of memory, however, whether extinction is affected in aging animals remains to be elucidated. Employing a modified paradigm for studying memory extinction in fruit flies, we found that only the stable, but not the labile memory component was suppressed by extinction, thus effectively resulting in higher memory loss in aging flies. Strikingly, young flies were able to fully restore the stable memory component 3 h post extinction, while aging flies failed to do so. In conclusion, our findings reveal that both accelerated extinction and impaired restoration contribute to memory impairment in aging animals. PMID:25842205

  2. US Particle Accelerators at Age 50.

    ERIC Educational Resources Information Center

    Wilson, R. R.

    1981-01-01

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

  3. Progranulin Knockout Accelerates Intervertebral Disc Degeneration in Aging Mice

    PubMed Central

    Zhao, Yun-peng; Tian, Qing-yun; Liu, Ben; Cuellar, Jason; Richbourgh, Brendon; Jia, Tang-hong; Liu, Chuan-ju

    2015-01-01

    Intervertebral disc (IVD) degeneration is a common degenerative disease, yet much is unknown about the mechanisms during its pathogenesis. Herein we investigated whether progranulin (PGRN), a chondroprotective growth factor, is associated with IVD degeneration. PGRN was detectable in both human and murine IVD. The levels of PGRN were upregulated in murine IVD tissue during aging process. Loss of PGRN resulted in an early onset of degenerative changes in the IVD tissue and altered expressions of the degeneration-associated molecules in the mouse IVD tissue. Moreover, PGRN knockout mice exhibited accelerated IVD matrix degeneration, abnormal bone formation and exaggerated bone resorption in vertebra with aging. The acceleration of IVD degeneration observed in PGRN null mice was probably due to the enhanced activation of NF-κB signaling and β-catenin signaling. Taken together, PGRN may play a critical role in homeostasis of IVD, and may serve as a potential molecular target for prevention and treatment of disc degenerative diseases. PMID:25777988

  4. Accelerated Aging of Polymer Composite Bridge Materials

    SciTech Connect

    J. G. Rodriguez; L. G. Blackwood; L. L. Torres; N. M. Carlson; T. S. Yoder

    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.

  5. Infection susceptibility and immune senescence with advancing age replicated in accelerated aging Lmna(Dhe) mice.

    PubMed

    Xin, Lijun; Jiang, Tony T; Kinder, Jeremy M; Ertelt, James M; Way, Sing Sing

    2015-12-01

    Aging confers increased susceptibility to common pathogens including influenza A virus. Despite shared vulnerability to infection with advancing age in humans and rodents, the relatively long time required for immune senescence to take hold practically restricts the use of naturally aged mice to investigate aging-induced immunological shifts. Here, we show accelerated aging Lmna(Dhe) mice with spontaneous mutation in the nuclear scaffolding protein, lamin A, replicate infection susceptibility, and substantial immune cell shifts that occur with advancing age. Naturally aged (≥ 20 month) and 2- to 3-month-old Lmna(Dhe) mice share near identically increased influenza A susceptibility compared with age-matched Lmna(WT) control mice. Increased mortality and higher viral burden after influenza infection in Lmna(Dhe) mice parallel reduced accumulation of lung alveolar macrophage cells, systemic expansion of immune suppressive Foxp3⁺ regulatory T cells, and skewed immune dominance among viral-specific CD8⁺T cells similar to the immunological phenotype of naturally aged mice. Thus, aging-induced infection susceptibility and immune senescence are replicated in accelerated aging Lmna(Dhe) mice. PMID:26248606

  6. Pathology of Mouse Models of Accelerated Aging.

    PubMed

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

    2016-03-01

    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," which aims at elucidating the molecular mechanisms involved in aging. Progeroid mouse models are frequently used in geroscience as they provide insight into the molecular mechanisms that are involved in the highly complex process of natural aging. This review provides an overview of the most commonly reported nonneoplastic macroscopic and microscopic pathologic findings in progeroid mouse models (eg, osteoporosis, osteoarthritis, degenerative joint disease, intervertebral disc degeneration, kyphosis, sarcopenia, cutaneous atrophy, wound healing, hair loss, alopecia, lymphoid atrophy, cataract, corneal endothelial dystrophy, retinal degenerative diseases, and vascular remodeling). Furthermore, several shortcomings in pathologic analysis and descriptions of these models are discussed. Progeroid mouse models are valuable models for aging, but thorough knowledge of both the mouse strain background and the progeria-related phenotype is required to guide interpretation and translation of the pathology data. PMID:26864891

  7. Age-Dependent Decrease and Alternative Splicing of Methionine Synthase mRNA in Human Cerebral Cortex and an Accelerated Decrease in Autism

    PubMed Central

    Muratore, Christina R.; Hodgson, Nathaniel W.; Trivedi, Malav S.; Abdolmaleky, Hamid M.; Persico, Antonio M.; Lintas, Carla; De La Monte, Suzanne; Deth, Richard C.

    2013-01-01

    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. PMID:23437274

  8. Metabolic Acceleration in Human Evolution.

    PubMed

    Isler, Karin

    2016-07-12

    Humans stand out among other primates by an unusual combination of a very large brain and high fertility. Pontzer et al. (2016a) present new data on daily energy expenditure in great apes and show that the metabolic rate increased during human evolution. PMID:27411003

  9. Acceleration of the aging process by oxygen

    NASA Technical Reports Server (NTRS)

    Miquel, J.; Lunderen, P. R.; Bensch, K. G.

    1975-01-01

    Tissue changes induced by hyperoxia have been compared with those of normal aging. Results of investigations using male flies prompt conclusion that normal aging, radiation syndrome, and hyperoxic injury share at least one common feature--lipid peroxidation damage to all mambranes resulting in accumulation of age pigment.

  10. Accelerated Aging of the M119 Simulator

    NASA Technical Reports Server (NTRS)

    Bixon, Eric R.

    2000-01-01

    This paper addresses the storage requirement, shelf life, and the reliability of M119 Whistling Simulator. Experimental conditions have been determined and the data analysis has been completed for the accelerated testing of the system. A general methodology to evaluate the shelf life of the system as a function of the storage time, temperature, and relative humidity is discussed.

  11. 'Accelerated aging': a primrose path to insight?

    PubMed

    Miller, Richard A

    2004-04-01

    Organism envy afflicts most researchers who work on aging in mice; how frustrating it is to see the worm and fly biologists nail down milestone after milestone, citation after citation! Surely genetic trickery can produce mice that age in a comparable jiffy? Alas, our near-total ignorance of what times the aging process makes it hard to guess what genes to tweak, if indeed aging can be mimicked a presto. Building a case that a given short-lived mutant ages quickly is a steep and thorny path, requiring more than just plucking a symptom here and there from a list of things that sometimes go wrong in old people or old mice. The hallmark of aging is that a lot goes wrong more or less at the same time, in 2-year-old mice, 10-year-old dogs and 70-year-old people. Finding ways to damage one or two systems in a 6-week or 6-month-old mouse is not too hard to do, but the implications of such studies for improved understanding of aging per se are at best indirect and at worst imaginary and distracting. PMID:15038817

  12. Accelerated food source location in aging Drosophila.

    PubMed

    Egenriether, Sada M; Chow, Eileen S; Krauth, Nathalie; Giebultowicz, Jadwiga M

    2015-10-01

    Adequate energy stores are essential for survival, and sophisticated neuroendocrine mechanisms evolved to stimulate foraging in response to nutrient deprivation. Food search behavior is usually investigated in young animals, and it is not known how aging alters this behavior. To address this question in Drosophila melanogaster, we compared the ability to locate food by olfaction in young and old flies using a food-filled trap. As aging is associated with a decline in motor functions, learning, and memory, we expected that aged flies would take longer to enter the food trap than their young counterparts. Surprisingly, old flies located food with significantly shorter latency than young ones. Robust food search behavior was associated with significantly lower fat reserves and lower starvation resistance in old flies. Food-finding latency (FFL) was shortened in young wild-type flies that were starved until their fat was depleted but also in heterozygous chico mutants with reduced insulin receptor activity and higher fat deposits. Conversely, food trap entry was delayed in old flies with increased insulin signaling. Our results suggest that the difference in FFL between young and old flies is linked to age-dependent differences in metabolic status and may be mediated by reduced insulin signaling. PMID:26102220

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

    NASA Technical Reports Server (NTRS)

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

    2011-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  15. Effects of horizontal acceleration on human visual acuity and stereopsis.

    PubMed

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

    2015-01-01

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

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

    SciTech Connect

    Mares, G.; Notingher, P.

    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.

  17. The origins of human ageing.

    PubMed Central

    Kirkwood, T B

    1997-01-01

    The origins of human ageing are to be found in the origins and evolution of senescence as a general feature in the life histories of higher animals. Ageing is an intriguing problem in evolutionary biology because a trait that limits the duration of life, including the fertile period, has a negative impact on Darwinian fitness. Current theory suggests that senescence occurs because the force of natural selection declines with age and because longevity is only acquired at some metabolic cost. In effect, organisms may trade late survival for enhanced reproductive investments in earlier life. The comparative study of ageing supports the general evolutionary theory and reveals that human senescence, while broadly similar to senescence in other mammalian species, has distinct features, such as menopause, that may derive from the interplay of biological and social evolution. PMID:9460059

  18. Sandia LSI accelerated aging and data acquisition techniques

    SciTech Connect

    Walker, J.E.

    1980-04-01

    The purpose of the Microelectronic Evaluation Laboratory at Sandia is to develop a program for evaluating CMOS LSI (complementary metal oxide silicon - large scale integrated) technology devices which are being used for the first time in a weapon system. These evaluations are based on accelerated aging studies and electrical tests to determine the reliability and life of the devices. In accelerated aging, specific, controlled stresses are applied to the device to accelerate time-to-failure. Data are used tin mathematical models to estimate life in acutal use. The stresses used for this technology are temperature and voltage. The devices are stored at temperatures with or without voltage applied (steady-state or cyclical) and periodically tested until at least 50% failures are encountered. Since most current technologies use epoxy-die-attachment, aging temperatures must be under 200/sup 0/C. This delays device failure, and a 16% failure level is used when this extrapolation is considered valid. Statistical analysis is performed on the resultant data to predict reliability with time. The equipment and procedures used for accelerated aging tests are described in detail. The data acquisition system and its use are discussed. All devices, after functional failure has occurred, are given to the failure analysis group for failure evaluations. In order to improve reliability predictions, failure analysis is most concerned with the separation of freak and main life mechanisms. Through these evaluations, higher reliability and longer device life have become a milestone of the future. (LCL)

  19. Many human accelerated regions are developmental enhancers

    PubMed Central

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

    2013-01-01

    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. PMID:24218637

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

    PubMed Central

    Perna, Giampaolo; Iannone, Giuseppe; Alciati, Alessandra; Caldirola, Daniela

    2016-01-01

    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. PMID:26881136

  1. Accelerated aging of GaAs concentrator solar cells

    SciTech Connect

    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.

  2. Toward GPGPU accelerated human electromechanical cardiac simulations

    PubMed Central

    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 Heart—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. PMID:24115492

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

    PubMed

    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. PMID:26900650

  4. Accelerated aging test results for aerospace wire insulation constructions

    NASA Technical Reports Server (NTRS)

    Dunbar, William G.

    1995-01-01

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

  5. Accelerated ageing and renal dysfunction links lower socioeconomic status and dietary phosphate intake

    PubMed Central

    McClelland, Ruth; Christensen, Kelly; Mohammed, Suhaib; McGuinness, Dagmara; Cooney, Josephine; Bakshi, Andisheh; Demou, Evangelia; MacDonald, Ewan; Caslake, Muriel; Stenvinkel, Peter; Shiels, Paul G.

    2016-01-01

    Background We have sought to explore the impact of dietary Pi intake on human age related health in the pSoBid cohort (n=666) to explain the disparity between health and deprivation status in this cohort. As hyperphosphataemia is a driver of accelerated ageing in rodent models of progeria we tested whether variation in Pi levels in man associate with measures of biological ageing and health. Results We observed significant relationships between serum Pi levels and markers of biological age (telomere length (p=0.040) and DNA methylation content (p=0.028), gender and chronological age (p=0.032). When analyses were adjusted for socio-economic status and nutritional factors, associations were observed between accelerated biological ageing (telomere length, genomic methylation content) and dietary derived Pi levels among the most deprived males, directly related to the frequency of red meat consumption. Conclusions Accelerated ageing is associated with high serum Pi levels and frequency of red meat consumption. Our data provide evidence for a mechanistic link between high intake of Pi and age-related morbidities tied to socio-economic status. PMID:27132985

  6. Magnesium deficiency accelerates cellular senescence in cultured human fibroblasts.

    PubMed

    Killilea, David W; Ames, Bruce N

    2008-04-15

    Magnesium inadequacy affects more than half of the U.S. population and is associated with increased risk for many age-related diseases, yet the underlying mechanisms are unknown. Altered cellular physiology has been demonstrated after acute exposure to severe magnesium deficiency, but few reports have addressed the consequences of long-term exposure to moderate magnesium deficiency in human cells. Therefore, IMR-90 human fibroblasts were continuously cultured in magnesium-deficient conditions to determine the long-term effects on the cells. These fibroblasts did not demonstrate differences in cellular viability or plating efficiency but did exhibit a decreased replicative lifespan in populations cultured in magnesium-deficient compared with standard media conditions, both at ambient (20% O(2)) and physiological (5% O(2)) oxygen tension. The growth rates for immortalized IMR-90 fibroblasts were not affected under the same conditions. IMR-90 fibroblast populations cultured in magnesium-deficient conditions had increased senescence-associated beta-galactosidase activity and increased p16(INK4a) and p21(WAF1) protein expression compared with cultures from standard media conditions. Telomere attrition was also accelerated in cell populations from magnesium-deficient cultures. Thus, the long-term consequence of inadequate magnesium availability in human fibroblast cultures was accelerated cellular senescence, which may be a mechanism through which chronic magnesium inadequacy could promote or exacerbate age-related disease. PMID:18391207

  7. Tracking accelerated aging of composites with ultrasonic attenuation measurements

    SciTech Connect

    Chinn, D.J.; Durbin, P.F.; Thomas, G.H.; Groves, S.E.

    1996-10-01

    Composite materials are steadily replacing traditional materials in many industries. For many carbon composite materials, particularly in aerospace applications, durability is a critical design parameter which must be accurately characterized. Lawrence Livermore National Laboratory (LLNL) and Boeing Commercial Airplane Group have established a cooperative research and development agreement (CRADA) to assist in the high speed research program at Boeing. LLNL`s expertise in fiber composites, computer modeling, mechanical testing, chemical analysis and nondestructive evaluation (ND) will contribute to the study of advanced composite materials in commercial aerospace applications. Through thermo-mechanical experiments with periodic chemical analysis and nondestructive evaluation, the aging mechanisms in several continuous fiber polymer composites will be studied. Several measurement techniques are being studied for their correlation with aging. This paper describes through-transmission ultrasonic attenuation measurements of isothermally aged composite materials and their use as a tracking parameter for accelerated aging.

  8. Coenzyme Q10 prevents accelerated cardiac aging in a rat model of poor maternal nutrition and accelerated postnatal growth.

    PubMed

    Tarry-Adkins, Jane L; Blackmore, Heather L; Martin-Gronert, Malgorzata S; Fernandez-Twinn, Denise S; McConnell, Josie M; Hargreaves, Iain P; Giussani, Dino A; Ozanne, Susan E

    2013-01-01

    Studies in human and animals have demonstrated that nutritionally induced low birth-weight followed by rapid postnatal growth increases the risk of metabolic syndrome and cardiovascular disease. Although the mechanisms underlying such nutritional programming are not clearly defined, increased oxidative-stress leading to accelerated cellular aging has been proposed to play an important role. Using an established rodent model of low birth-weight and catch-up growth, we show here that post-weaning dietary supplementation with coenzyme Q10, a key component of the electron transport chain and a potent antioxidant rescued many of the detrimental effects of nutritional programming on cardiac aging. This included a reduction in nitrosative and oxidative-stress, telomere shortening, DNA damage, cellular senescence and apoptosis. These findings demonstrate the potential for postnatal antioxidant intervention to reverse deleterious phenotypes of developmental programming and therefore provide insight into a potential translatable therapy to prevent cardiovascular disease in at risk humans. PMID:24327963

  9. Accelerated aging of outdoor insulation under acid rain conditions

    NASA Astrophysics Data System (ADS)

    Frost, Nancy Ellen

    2000-11-01

    Outdoor insulation has evolved from glass to ceramics to epoxy in the past decades, and more recently into the area of polymer composites. Accelerated aging must be performed to examine the effectiveness of materials prior to use under actual service conditions. Traditionally this aging has been performed with sodium chloride as the conductive component in the high humidity and wet tests. This approach does not necessarily represent actual service conditions, as globally the precipitation is acidic in nature and contains many constituents in addition to sodium and chloride. The main focus of this work was to examine the effect of acid precipitation on materials used in outdoor insulation applications. This was achieved through the use of a rotating tracking wheel and a controlled high humidity chamber with the application of a synthetic acid rain solution. The analysis techniques utilized to examine the results of the accelerated aging were leakage current monitoring, evaluation of changes in dielectric properties as well as electron microscopy. In addition, changes in hydrophobicity were quantified. Based on experimental observations, a first order life prediction model was developed to investigate the usefulness of the acid rain aging technique. This model was founded on the results of a series of tests conducted with varying solution conductivity, while maintaining constant acid content. This model permits the prediction of the life of a material at normal precipitation conductivity levels.

  10. Electrochemical migration technique to accelerate ageing of cementitious materials

    NASA Astrophysics Data System (ADS)

    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.

  11. In vitro accelerated aging of composites and a sealant.

    PubMed

    Powers, J M; Fan, P L; Marcotte, M

    1981-09-01

    The in vitro accelerated aging of conventional and microfilled composite restorative materials and a sealant was studied. Volume loss/surface area ranged from 2.0 x 10(-3) mm3/mm2 for I to 7.3 x 10(-3) mm3/mm2 for SF after 900 h of aging. Surface morphology of the conventional composites was characterized by crazing and exposure of filler particles. The surfaces of the microfilled composites also showed crazing. The surface morphology of the sealant appeared unchanged. Comparisons of infrared ATR spectra between zero and 900 h of aging showed that slight chemical changes occurred at the surface of AR but not SF. PMID:6943161

  12. Comparison of mice with accelerated aging caused by distinct mechanisms.

    PubMed

    Gurkar, Aditi U; Niedernhofer, Laura J

    2015-08-01

    Aging is the primary risk factor for numerous chronic, debilitating diseases. These diseases impact quality of life of the elderly and consume a large portion of health care costs. The cost of age-related diseases will only increase as the world's population continues to live longer. Thus it would be advantageous to consider aging itself as a therapeutic target, potentially stemming multiple age-related diseases simultaneously. While logical, this is extremely challenging as the molecular mechanisms that drive aging are still unknown. Furthermore, clinical trials to treat aging are impractical. Even in preclinical models, testing interventions to extend healthspan in old age are lengthy and therefore costly. One approach to expedite aging studies is to take advantage of mouse strains that are engineered to age rapidly. These strains are genetically and phenotypically quite diverse. This review aims to offer a comparison of several of these strains to highlight their relative strengths and weaknesses as models of mammalian and more specifically human aging. Additionally, careful identification of commonalities among the strains may lead to the identification of fundamental pathways of aging. PMID:25617508

  13. Accelerated aging tests of liners for uranium mill tailings disposal

    SciTech Connect

    Barnes, S.M.; Buelt, J.L.; Hale, V.Q.

    1981-11-01

    This document describes the results of accelerated aging tests to determine the long-term effectiveness of selected impoundment liner materials in a uranium mill tailings environment. The study was sponsored by the US Department of Energy under the Uranium Mill Tailings Remedial Action Project. The study was designed to evaluate the need for, and the performance of, several candidate liners for isolating mill tailings leachate in conformance with proposed Environmental Protection Agency and Nuclear Regulatory Commission requirements. The liners were subjected to conditions known to accelerate the degradation mechanisms of the various liners. Also, a test environment was maintained that modeled the expected conditions at a mill tailings impoundment, including ground subsidence and the weight loading of tailings on the liners. A comparison of installation costs was also performed for the candidate liners. The laboratory testing and cost information prompted the selection of a catalytic airblown asphalt membrane and a sodium bentonite-amended soil for fiscal year 1981 field testing.

  14. Accelerated Aging Experiments for Capacitor Health Monitoring and Prognostics

    NASA Technical Reports Server (NTRS)

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

    2012-01-01

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

  15. Spiked Alloy Production for Accelerated Aging of Plutonium

    SciTech Connect

    Wilk, P A; McNeese, J A; Dodson, K E; Williams, W L; Krikorian, O H; Blau, M S; Schmitz, J E; Bajao, F G; Mew, D A; Matz, T E; Torres, R A; Holck, D M; Moody, K J; Kenneally, J M

    2009-07-10

    The accelerated aging effects on weapons grade plutonium alloys are being studied using {sup 238}Pu-enriched plutonium metal to increase the rate of formation of defect structures. Pyrochemical processing methods have been used to produce two {sup 238}Pu-spiked plutonium alloys with nominal compositions of 7.5 wt% {sup 238}Pu. Processes used in the preparation of the alloys include direct oxide reduction of PuO{sub 2} with calcium and electrorefining. Rolled disks were prepared from the spiked alloys for sampling. Test specimens were cut out of the disks for physical property measurements.

  16. Deactivation of Accelerated Engine-Aged and Field-Aged Fe-Zeolite SCR Catalysts

    SciTech Connect

    Toops, Todd J; Nguyen, Ke; Foster, Adam; Bunting, Bruce G; Hagaman, Edward {Ed} W; Jiao, Jian

    2010-01-01

    A single-cylinder diesel engine with an emissions control system - diesel oxidation catalyst (DOC), Fe-zeolite selective catalytic reduction (SCR) catalyst, and diesel particulate filter (DPF) - was used to perform accelerated thermal aging of the SCR catalyst. Cyclic aging is performed at SCR inlet temperatures of 650, 750 and 850 degrees C for up to 50 aging cycles. To assess the validity of the implemented accelerated thermal aging protocol, a field-aged SCR catalyst of similar formulation was also evaluated. The monoliths were cut into sections and evaluated for NO{sub x} performance in a bench-flow reactor. While the rear section of both the field-aged and the accelerated engine-aged SCR catalysts maintained high NO{sub x}conversion, 75-80% at 400 degrees C, the front section exhibited a drastic decrease to only 20-35% at 400 degrees C. This two-tiered deactivation was also observed for field-aged samples that were analyzed in this study. To understand the observed performance changes, thorough materials characterization was performed which revealed two primary degradation mechanisms. The first mechanism is a general Fe-zeolite deterioration which led to surface area losses, dealumination of the zeolite, and Fe{sub 2}O{sub 3} crystal growth. This degradation accelerated above 750 degrees C, and the effects were generally more severe in the front of the catalyst. The second deactivation mechanism is linked to trace levels of Pt that are suspected to be volatizing from the DOC and depositing on the front section of the SCR catalyst. Chemical evidence of this can be seen in the high levels of NH{sub 3} oxidation (80% conversion at 400 degrees C), which coincides with the decrease in performance.

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

    PubMed Central

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

    2015-01-01

    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. PMID:25798213

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

    PubMed

    Lecocq, Antoine; Jensen, Annette Bruun; Kryger, Per; Nieh, James C

    2016-01-01

    Honey bees (Apis mellifera) are important pollinators and their health is threatened worldwide by persistent exposure to a wide range of factors including pesticides, poor nutrition, and pathogens. Nosema ceranae is a ubiquitous microsporidian associated with high colony mortality. We used lab micro-colonies of honey bees and video analyses to track the effects of N. ceranae infection and exposure on a range of individual and social behaviours in young adult bees. We provide detailed data showing that N. ceranae infection significantly accelerated the age polyethism of young bees, causing them to exhibit behaviours typical of older bees. Bees with high N. ceranae spore counts had significantly increased walking rates and decreased attraction to queen mandibular pheromone. Infected bees also exhibited higher rates of trophallaxis (food exchange), potentially reflecting parasite manipulation to increase colony infection. However, reduction in queen contacts could help bees limit the spread of infection. Such accelerated age polyethism may provide a form of behavioural immunity, particularly if it is elicited by a wide variety of pathogens. PMID:26912310

  19. Parasite infection accelerates age polyethism in young honey bees

    PubMed Central

    Lecocq, Antoine; Jensen, Annette Bruun; Kryger, Per; Nieh, James C.

    2016-01-01

    Honey bees (Apis mellifera) are important pollinators and their health is threatened worldwide by persistent exposure to a wide range of factors including pesticides, poor nutrition, and pathogens. Nosema ceranae is a ubiquitous microsporidian associated with high colony mortality. We used lab micro-colonies of honey bees and video analyses to track the effects of N. ceranae infection and exposure on a range of individual and social behaviours in young adult bees. We provide detailed data showing that N. ceranae infection significantly accelerated the age polyethism of young bees, causing them to exhibit behaviours typical of older bees. Bees with high N. ceranae spore counts had significantly increased walking rates and decreased attraction to queen mandibular pheromone. Infected bees also exhibited higher rates of trophallaxis (food exchange), potentially reflecting parasite manipulation to increase colony infection. However, reduction in queen contacts could help bees limit the spread of infection. Such accelerated age polyethism may provide a form of behavioural immunity, particularly if it is elicited by a wide variety of pathogens. PMID:26912310

  20. DNA methylation age of human tissues and cell types

    PubMed Central

    2013-01-01

    Background It is not yet known whether DNA methylation levels can be used to accurately predict age across a broad spectrum of human tissues and cell types, nor whether the resulting age prediction is a biologically meaningful measure. Results I developed a multi-tissue predictor of age that allows one to estimate the DNA methylation age of most tissues and cell types. The predictor, which is freely available, was developed using 8,000 samples from 82 Illumina DNA methylation array datasets, encompassing 51 healthy tissues and cell types. I found that DNA methylation age has the following properties: first, it is close to zero for embryonic and induced pluripotent stem cells; second, it correlates with cell passage number; third, it gives rise to a highly heritable measure of age acceleration; and, fourth, it is applicable to chimpanzee tissues. Analysis of 6,000 cancer samples from 32 datasets showed that all of the considered 20 cancer types exhibit significant age acceleration, with an average of 36 years. Low age-acceleration of cancer tissue is associated with a high number of somatic mutations and TP53 mutations, while mutations in steroid receptors greatly accelerate DNA methylation age in breast cancer. Finally, I characterize the 353 CpG sites that together form an aging clock in terms of chromatin states and tissue variance. Conclusions I propose that DNA methylation age measures the cumulative effect of an epigenetic maintenance system. This novel epigenetic clock can be used to address a host of questions in developmental biology, cancer and aging research. PMID:24138928

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

    PubMed Central

    Jurk, Diana; Wilson, Caroline; Passos, João F.; Oakley, Fiona; Correia-Melo, Clara; Greaves, Laura; Saretzki, Gabriele; Fox, Chris; Lawless, Conor; Anderson, Rhys; Hewitt, Graeme; Pender, Sylvia LF; 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-κB induces premature ageing in mice. We also show that these mice have reduced regeneration in liver and gut. nfkb1−/− fibroblasts exhibit aggravated cell senescence because of an enhanced autocrine and paracrine feedback through NF-κB, COX-2 and ROS, which stabilizes DNA damage. Preferential accumulation of telomere-dysfunctional senescent cells in nfkb1−/− tissues is blocked by anti-inflammatory or antioxidant treatment of mice, and this rescues tissue regenerative potential. Frequencies of senescent cells in liver and intestinal crypts quantitatively predict mean and maximum lifespan in both short- and long-lived mice cohorts. These data indicate that systemic chronic inflammation can accelerate ageing via ROS-mediated exacerbation of telomere dysfunction and cell senescence in the absence of any other genetic or environmental factor. PMID:24960204

  2. [Anti-aging studies on the senescence accelerated mouse (SAM) strains].

    PubMed

    Takahashi, Ryoya

    2010-01-01

    Senescence accelerated mouse (SAM), a murine model of accelerated senescence, was established by Toshio Takeda and colleagues. SAM consists of series of SAMP (prone) and SAMR (resistant) lines. All SAMP lines (from SAMP1 to SAMP11) are characterized by accelerated accumulation of senile features, earlier onset and faster progress of age-associated pathological phenotypes, such as amyloidosis, impaired immune response, senile osteoporosis and deficits in learning and memory. These SAMP lines are useful for evaluation of putative anti-aging therapies. For example, SAMP1 line is used to study the anti-aging effect of the antioxidant containing foods and various anti-oxidants, such as coenzyme Q10, vitamin C, lycopene. SAMP8 line exhibiting an early onset of impaired learning and memory is often used for test strategies for therapeutic intervention of dementia of early onset. SAMP6 is used as an animal model for developing new strategies for the treatment of osteoporosis in humans. Various lines of SAM (P1, P6, P8, P10 and R1) are now commercially available for research. In this review, I will briefly introduce various usages of SAM in anti-aging research. PMID:20046059

  3. Accelerated Aging System for Prognostics of Power Semiconductor Devices

    NASA Technical Reports Server (NTRS)

    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.

  4. The senescence-accelerated mouse (SAM): a higher oxidative stress and age-dependent degenerative diseases model.

    PubMed

    Chiba, Yoichi; Shimada, Atsuyoshi; Kumagai, Naoko; Yoshikawa, Keisuke; Ishii, Sanae; Furukawa, Ayako; Takei, Shiro; Sakura, Masaaki; Kawamura, Noriko; Hosokawa, Masanori

    2009-04-01

    The SAM strain of mice is actually a group of related inbred strains consisting of a series of SAMP (accelerated senescence-prone) and SAMR (accelerated senescence-resistant) strains. Compared with the SAMR strains, the SAMP strains show a more accelerated senescence process, a shorter lifespan, and an earlier onset and more rapid progress of age-associated pathological phenotypes similar to human geriatric disorders. The higher oxidative stress status observed in SAMP mice is partly caused by mitochondrial dysfunction, and may be a cause of this senescence acceleration and age-dependent alterations in cell structure and function. Based on our recent observations, we discuss a possible mechanism for mitochondrial dysfunction resulting in the excessive production of reactive oxygen species, and a role for the hyperoxidative stress status in neurodegeneration in SAMP mice. These SAM strains can serve as a useful tool to understand the cellular mechanisms of age-dependent degeneration, and to develop clinical interventions. PMID:18688709

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

    PubMed

    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. PMID:26796881

  6. [Experimental models of human skin aging].

    PubMed

    Nikolakis, G; Zoschke, C; Makrantonaki, E; Hausmann, C; Schäfer-Korting, M; Zouboulis, C C

    2016-02-01

    The skin is a representative model for the study of human aging. Despite the high regenerative capacity of the skin, skin physiology changes over the course of life. Medical and cosmetic research is trying to prevent aging, to slow, to stop, or to reverse it. Effects of age-related DNA damage and of changing skin structure on pharmacological parameters are largely unknown. This review article summarizes the state of scientific knowledge in the field of experimental models of human skin aging and shows approaches to improve organotypic skin models, to develop predictive models of aging, and improve aging research. PMID:26743051

  7. Effects of Accelerated Aging on Fiber Damage Thresholds

    SciTech Connect

    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.

  8. Lamin Mutations Accelerate Aging via Defective Export of Mitochondrial mRNAs through Nuclear Envelope Budding.

    PubMed

    Li, Yihang; Hassinger, Linda; Thomson, Travis; Ding, Baojin; Ashley, James; Hassinger, William; Budnik, Vivian

    2016-08-01

    Defective RNA metabolism and transport are implicated in aging and degeneration [1, 2], but the underlying mechanisms remain poorly understood. A prevalent feature of aging is mitochondrial deterioration [3]. Here, we link a novel mechanism for RNA export through nuclear envelope (NE) budding [4, 5] that requires A-type lamin, an inner nuclear membrane-associated protein, to accelerated aging observed in Drosophila LaminC (LamC) mutations. These LamC mutations were modeled after A-lamin (LMNA) mutations causing progeroid syndromes (PSs) in humans. We identified mitochondrial assembly regulatory factor (Marf), a mitochondrial fusion factor (mitofusin), as well as other transcripts required for mitochondrial integrity and function, in a screen for RNAs that exit the nucleus through NE budding. PS-modeled LamC mutations induced premature aging in adult flight muscles, including decreased levels of specific mitochondrial protein transcripts (RNA) and progressive mitochondrial degradation. PS-modeled LamC mutations also induced the accelerated appearance of other phenotypes associated with aging, including a progressive accumulation of polyubiquitin aggregates [6, 7] and myofibril disorganization [8, 9]. Consistent with these observations, the mutants had progressive jumping and flight defects. Downregulating marf alone induced the above aging defects. Nevertheless, restoring marf was insufficient for rescuing the aging phenotypes in PS-modeled LamC mutations, as other mitochondrial RNAs are affected by inhibition of NE budding. Analysis of NE budding in dominant and recessive PS-modeled LamC mutations suggests a mechanism by which abnormal lamina organization prevents the egress of these RNAs via NE budding. These studies connect defects in RNA export through NE budding to progressive loss of mitochondrial integrity and premature aging. PMID:27451905

  9. Accelerated aging studies and environmental stability of prototype tamper tapes

    SciTech Connect

    Wright, B.W.; Wright, C.W.; Bunk, A.R.

    1995-05-01

    This report describes the results of accelerated aging experiments (weathering) conducted on prototype tamper tapes bonded to a variety of surface materials. The prototype tamper tapes were based on the patented Confirm{reg_sign} tamper-indicating technology developed and produced by 3M Company. Tamper tapes bonded to surfaces using pressure sensitive adhesive (PSA) and four rapid-set adhesives were evaluated. The configurations of the PSA-bonded tamper tapes were 1.27-cm-wide Confirm{reg_sign} 1700 windows with vinyl underlay and 2.54-cm-wide Confirm{reg_sign} 1700 windows with vinyl and polyester underlays. The configurations of the rapid-set adhesive-bonded tamper tapes were 2.54-cm-wide Confirm{reg_sign} (1700, 1500 with and without primer, and 1300) windows with vinyl underlay. Surfaces used for bonding included aluminum, steel, stainless steel, Kevlar{reg_sign}, brass, copper, fiberglass/resin with and without gel coat, polyurethane-painted steel, acrylonitrile:butadiene:styrene plastic, polyester fiberglass board, Lexan polycarbonate, and cedar wood. Weathering conditions included a QUV cabinet (ultraviolet light at 60{degrees}C, condensing humidity at 40{degrees}C), a thermal cycling cabinet (-18{degrees}C to 46{degrees}C), a Weather-O-Meter (Xenon lamp), and exposure outdoors in Daytona Beach, Florida. Environmental aging exposures lasted from 7 weeks to 5 months. After exposure, the tamper tapes were visually examined and tested for transfer resistance. Tamper tapes were also exposed to a variety of chemical liquids (including organic solvents, acids, bases, and oxidizing liquids) to determine chemical resistance and to sand to determine abrasion resistance.

  10. Statistical analysis of accelerated temperature aging of semiconductor devices

    NASA Astrophysics Data System (ADS)

    Johnson, W. A.; Milles, M. F.

    1981-05-01

    A number of semiconductor devices taken from a distribution were operated at several elevated temperatures to induce failure in all devices within a reasonable time. Assuming general characteristics of the device failure probability density function (pdf) and its temperature dependence, the expected cumulative failure function (cff) for devices in normal operation were estimated based on statistical inference, taking the average probability of a random device (from the same distribution but operated at a normal temperature) failing as a function of time. A review of the mathematical formalism employed in semiconductor reliability discussions is included. Three failure pdf's at particular usefulness to this analysis--exponential, normal, and lognormal - are discussed. The cff, at times orders of magnitude loss then, at times comparable to the desired system useful, life (*10 to the 4th power to 10 to the 5th power hr) is considered. A review of accelerated temperature aging is presented, and the assumption concerning the general characteristics of the failure pdf, which are fundamental to this analysis, are emphasized.

  11. Genotype × age interaction in human transcriptional ageing

    PubMed Central

    Kent, Jack W.; Göring, Harald H. H.; Charlesworth, Jac C.; Drigalenko, Eugene; Diego, Vincent P.; Curran, Joanne E.; Johnson, Matthew P.; Dyer, Thomas D.; Cole, Shelley A.; Jowett, Jeremy B. M.; Mahaney, Michael C.; Comuzzie, Anthony G.; Almasy, Laura; Moses, Eric K.; Blangero, John; Williams-Blangero, Sarah

    2012-01-01

    Individual differences in biological ageing (i.e., the rate of physiological response to the passage of time) may be due in part to genotype-specific variation in gene action. However, the sources of heritable variation in human age-related gene expression profiles are largely unknown. We have profiled genome-wide expression in peripheral blood mononuclear cells from 1,240 individuals in large families and found 4,472 human autosomal transcripts, representing ~4,349 genes, significantly correlated with age. We identified 623 transcripts that show genotype by age interaction in addition to a main effect of age, defining a large set of novel candidates for characterization of the mechanisms of differential biological ageing. We applied a novel SNP genotype×age interaction test to one of these candidates, the ubiquilin-like gene UBQLNL, and found evidence of joint cis-association and genotype by age interaction as well as trans-genotype by age interaction for UBQLNL expression. Both UBQLNL expression levels at recruitment and cis genotype are associated with longitudinal cancer risk in our study cohort. PMID:22871458

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

    PubMed

    Shalev, Idan; Belsky, Jay

    2016-05-01

    Two seemingly independent bodies of research suggest a two-hit model of accelerated aging, one highlighting early-life stress and the other reproduction. The first, informed by developmental models of early-life stress, highlights reduced longevity effects of early adversity on telomere erosion, whereas the second, informed by evolutionary theories of aging, highlights such effects with regard to reproductive cost (in females). The fact that both early-life adversity and reproductive effort are associated with shorter telomeres and increased oxidative stress raises the prospect, consistent with life-history theory, that these two theoretical frameworks currently informing much research are tapping into the same evolutionary-developmental process of increased senescence and reduced longevity. Here we propose a mechanistic view of a two-hit model of accelerated aging in human females through (a) early-life adversity and (b) early reproduction, via a process of telomere erosion, while highlighting mediating biological embedding mechanisms that might link these two developmental aging processes. PMID:27063083

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

    PubMed Central

    Boesten, Daniëlle M. P. H. J.; de Vos-Houben, Joyce M. J.; Timmermans, Leen; den Hartog, Gertjan J. M.; Bast, Aalt; Hageman, Geja J.

    2013-01-01

    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. PMID:24319532

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

    PubMed

    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) demonstrated no statistically significant differences among the groups (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 < 0.05). After 300 hours, Group 4 specimens (13.84 ± 0.71) presented the lowest color alteration in comparison with the other groups, with a statistically significant difference (p < 0.05). It was concluded that the repair performed in Group 4 provided greater esthetic recovery, made possible by the regression in the ΔE values of the restorations after repair, and less color alteration of the restorations over the course of time. PMID:23032241

  15. Advance techniques for monitoring human tolerance to +Gz accelerations.

    NASA Technical Reports Server (NTRS)

    Pelligra, R.; Sandler, H.; Rositano, S.; Skrettingland, K.; Mancini, R.

    1972-01-01

    Standard techniques for monitoring the acceleration-stressed human subject have been augmented by measuring (1) temporal, brachial and/or radial arterial blood flow, and (2) indirect systolic and diastolic blood pressure at 60-sec intervals. Results show that the response of blood pressure to positive accelerations is complex and dependent on an interplay of hydrostatic forces, diminishing venous return, redistribution of blood, and other poorly defined compensatory reflexes.

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

    USGS Publications Warehouse

    Stafford, Thomas W., Jr.; Jull, A.J.T.; Zabel, T.H.; Donahue, D.J.; Duhamel, R.C.; Brendel, K.; Haynes, C.V., Jr.; 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.

  17. Humans use internal models to estimate gravity and linear acceleration.

    PubMed

    Merfeld, D M; Zupan, L; Peterka, R J

    1999-04-15

    Because sensory systems often provide ambiguous information, neural processes must exist to resolve these ambiguities. It is likely that similar neural processes are used by different sensory systems. For example, many tasks require neural processing to distinguish linear acceleration from gravity, but Einstein's equivalence principle states that all linear accelerometers must measure both linear acceleration and gravity. Here we investigate whether the brain uses internal models, defined as neural systems that mimic physical principles, to help estimate linear acceleration and gravity. Internal models may be used in motor contro, sensorimotor integration and sensory processing, but direct experimental evidence for such models is limited. To determine how humans process ambiguous gravity and linear acceleration cues, subjects were tilted after being rotated at a constant velocity about an Earth-vertical axis. We show that the eye movements evoked by this post-rotational tilt include a response component that compensates for the estimated linear acceleration even when no actual linear acceleration occurs. These measured responses are consistent with our internal model predictions that the nervous system can develop a non-zero estimate of linear acceleration even when no true linear acceleration is present. PMID:10217143

  18. Resonance of human brain under head acceleration.

    PubMed

    Laksari, Kaveh; Wu, Lyndia C; Kurt, Mehmet; Kuo, Calvin; Camarillo, David C

    2015-07-01

    Although safety standards have reduced fatal head trauma due to single severe head impacts, mild trauma from repeated head exposures may carry risks of long-term chronic changes in the brain's function and structure. To study the physical sensitivities of the brain to mild head impacts, we developed the first dynamic model of the skull-brain based on in vivo MRI data. We showed that the motion of the brain can be described by a rigid-body with constrained kinematics. We further demonstrated that skull-brain dynamics can be approximated by an under-damped system with a low-frequency resonance at around 15 Hz. Furthermore, from our previous field measurements, we found that head motions in a variety of activities, including contact sports, show a primary frequency of less than 20 Hz. This implies that typical head exposures may drive the brain dangerously close to its mechanical resonance and lead to amplified brain-skull relative motions. Our results suggest a possible cause for mild brain trauma, which could occur due to repetitive low-acceleration head oscillations in a variety of recreational and occupational activities. PMID:26063824

  19. Resonance of human brain under head acceleration

    PubMed Central

    Laksari, Kaveh; Wu, Lyndia C.; Kurt, Mehmet; Kuo, Calvin; Camarillo, David C.

    2015-01-01

    Although safety standards have reduced fatal head trauma due to single severe head impacts, mild trauma from repeated head exposures may carry risks of long-term chronic changes in the brain's function and structure. To study the physical sensitivities of the brain to mild head impacts, we developed the first dynamic model of the skull–brain based on in vivo MRI data. We showed that the motion of the brain can be described by a rigid-body with constrained kinematics. We further demonstrated that skull–brain dynamics can be approximated by an under-damped system with a low-frequency resonance at around 15 Hz. Furthermore, from our previous field measurements, we found that head motions in a variety of activities, including contact sports, show a primary frequency of less than 20 Hz. This implies that typical head exposures may drive the brain dangerously close to its mechanical resonance and lead to amplified brain–skull relative motions. Our results suggest a possible cause for mild brain trauma, which could occur due to repetitive low-acceleration head oscillations in a variety of recreational and occupational activities. PMID:26063824

  20. Invited review: aging and human temperature regulation.

    PubMed

    Kenney, W Larry; Munce, Thayne A

    2003-12-01

    This mini-review focuses on the effects of aging on human temperature regulation. Although comprehensive reviews have been published on this topic (Kenney WL. Exercise and Sport Sciences Reviews, Baltimore: Williams & Wilkins, 1997, p. 41-76; Pandolf KB. Exp Aging Res 17: 189-204, 1991; Van Someren EJ, Raymann RJ, Scherder EJ, Daanen HA, and Swaab DF. Ageing Res Rev 1: 721-778, 2002; and Young AJ. Exp Aging Res 17: 205-213, 1991), this mini-review concisely summarizes the present state of knowledge about human temperature regulation and aging in thermoneutral conditions, as well as during hypo- and hyperthermic challenges. First, we discuss age-related effects on baseline body core temperature and phasing rhythms of the circadian temperature cycle. We then examine the altered physiological responses to cold stress that result from aging, including attenuated peripheral vasoconstriction and reduced cold-induced metabolic heat production. Finally, we present the age-related changes in sweating and cardiovascular function associated with heat stress. Although epidemiological evidence of increased mortality among older adults from hypo- and hyperthermia exists, this outcome does not reflect an inability to thermoregulate with advanced age. In fact, studies that have attempted to separate the effects of chronological age from concurrent factors, such as fitness level, body composition, and the effects of chronic disease, have shown that thermal tolerance appears to be minimally compromised by age. PMID:14600165

  1. Models to explore genetics of human aging.

    PubMed

    Karasik, David; Newman, Anne

    2015-01-01

    Genetic studies have bestowed insight into the biological mechanisms underlying inter-individual differences in susceptibility to (or resistance to) organisms’ aging. Recent advances in molecular and genetic epidemiology provide tools to explore the genetic sources of the variability in biological aging in humans. To be successful, the genetic study of a complex condition such as aging requires the clear definition of essential traits that can characterize the aging process phenotypically. Phenotypes of human aging have long relied on mortality rate or exceptional longevity. Genome-wide association studies (GWAS) have been shown to present an unbiased approach to the identification of new candidate genes for human diseases. The GWAS approach can also be used for positive health phenotypes such as longevity or a delay in age-related chronic disease, as well as for other age related changes such as loss of telomere length or lens transparency. Sequencing, either in targeted regions or across the whole genome can further identify rare variation that may contribute to the biological aging mechanisms. To date, the results of the GWAS for longevity are rather disappointing, possibly in part due to the small number of individuals with GWAS data who have reached advanced old age.Human aging phenotypes are needed that can be assessed prior to death, and should be both heritable and validated as predictors of longevity. Potentially, phenotypes that focus on “successful” or “healthy” aging will be more powerful as they can be measured in large numbers of people and also are clinically relevant.We postulate that construction of an integrated phenotype of aging can be achieved capitalizing on multiple traits that may have weak correlations, but a shared underlying genetic architecture. This is based on a hypothesis that convergent results from multiple individual aging-related traits will point out the pleiotropic signals responsible for the overall rate of aging of

  2. A higher oxidative status accelerates senescence and aggravates age-dependent disorders in SAMP strains of mice.

    PubMed

    Hosokawa, Masanori

    2002-11-01

    The SAM strain of mice is actually a group of related inbred strains consisting of series of SAMP (accelerated senescence-prone, short-lived) and SAMR (accelerated senescence-resistant, longer-lived) strains. Comparing with the SAMR strains, the SAMP strains of mice show a more accelerated senescence process, shorter lifespan, and an earlier onset and more rapid progress of age-associated pathological phenotypes similar to several geriatric disorders observed in humans, including senile osteoporosis, degenerative joint disease, age-related deficits in learning and memory, olfactory bulb and forebrain atrophy, presbycusis and retinal atrophy, senile amyloidosis, immunosenescence, senile lungs, and diffuse medial thickening of the aorta. The higher oxidative stress observed in the SAMP strains of mice are partly caused by mitochondrial dysfunction, and may be one cause of the senescence acceleration and age-dependent alterations in cell structure and function, including neuronal cell degeneration. This senescence acceleration is also observed during senescence/crisis in cultures of isolated fibroblast-like cells from SAMP strains of mice, and was associated with a hyperoxidative status. These observations suggest that the SAM strains are useful tools in the attempt to understand the mechanisms of age-dependent degeneration of cells and tissues, and their aggravation, and to develop clinical interventions. PMID:12470893

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

    PubMed

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

    2014-06-01

    Currently, the oxidative stress (or free radical) theory of aging is the most popular explanation of how aging occurs at the molecular level. Accordingly, a stress-induced senescence-like phenotype of human dermal fibroblasts can be induced in vitro by the exposure of human diploid fibroblasts to subcytotoxic concentrations of hydrogen peroxide. However, several biomarkers of replicative senescence e.g. cell cycle arrest and enlarged morphology are abrogated 14 days after treatment, indicating that reactive oxygen species (ROS) rather acts as a trigger for short-term senescence (1-3 days) than being responsible for the maintenance of the senescence-like phenotype. Further, DNA-damaging factors are discussed resulting in a permanent senescent cell type. To induce long-term premature senescence and to understand the molecular alterations occurring during the aging process, we analyzed mitomycin C (MMC) as an alkylating DNA-damaging agent and ROS producer. Human dermal fibroblasts (HDF), used as model for skin aging, were exposed to non-cytotoxic concentrations of MMC and analyzed for potential markers of cellular aging, for example enlarged morphology, activity of senescence-associated-ß-galactosidase, cell cycle arrest, increased ROS production and MMP1-activity, which are well-documented for HDF in replicative senescence. Our data show that mitomycin C treatment results in a drug-induced accelerated senescence (DIAS) with long-term expression of senescence markers, demonstrating that a combination of different susceptibility factors, here ROS and DNA alkylation, are necessary to induce a permanent senescent cell type. PMID:24833306

  4. The challenges of human population ageing

    PubMed Central

    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

  5. Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing.

    PubMed

    Scaffidi, Paola; Misteli, Tom

    2008-04-01

    The premature-ageing disease Hutchinson-Gilford Progeria Syndrome (HGPS) is caused by constitutive production of progerin, a mutant form of the nuclear architectural protein lamin A. Progerin is also expressed sporadically in wild-type cells and has been linked to physiological ageing. Cells from HGPS patients exhibit extensive nuclear defects, including abnormal chromatin structure and increased DNA damage. At the organismal level, HGPS affects several tissues, particularly those of mesenchymal origin. How the cellular defects of HGPS cells lead to the organismal defects has been unclear. Here, we provide evidence that progerin interferes with the function of human mesenchymal stem cells (hMSCs). We find that expression of progerin activates major downstream effectors of the Notch signalling pathway. Induction of progerin in hMSCs changes their molecular identity and differentiation potential. Our results support a model in which accelerated ageing in HGPS patients, and possibly also physiological ageing, is the result of adult stem cell dysfunction and progressive deterioration of tissue functions. PMID:18311132

  6. Reproductive aging patterns in primates reveal that humans are distinct

    PubMed Central

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

    2013-01-01

    Women rarely give birth after ∼45 y of age, and they experience the cessation of reproductive cycles, menopause, at ∼50 y of age after a fertility decline lasting almost two decades. Such reproductive senescence in mid-lifespan is an evolutionary puzzle of enduring interest because it should be inherently disadvantageous. Furthermore, comparative data on reproductive senescence from other primates, or indeed other mammals, remains relatively rare. Here we carried out a unique detailed comparative study of reproductive senescence in seven species of nonhuman primates in natural populations, using long-term, individual-based data, and compared them to a population of humans experiencing natural fertility and mortality. In four of seven primate species we found that reproductive senescence occurred before death only in a small minority of individuals. In three primate species we found evidence of reproductive senescence that accelerated throughout adulthood; however, its initial rate was much lower than mortality, so that relatively few individuals experienced reproductive senescence before death. In contrast, the human population showed the predicted and well-known pattern in which reproductive senescence occurred before death for many women and its rate accelerated throughout adulthood. These results provide strong support for the hypothesis that reproductive senescence in midlife, although apparent in natural-fertility, natural-mortality populations of humans, is generally absent in other primates living in such populations. PMID:23898189

  7. GPU-Accelerated Molecular Modeling Coming Of Age

    PubMed Central

    Stone, John E.; Hardy, David J.; Ufimtsev, Ivan S.

    2010-01-01

    Graphics processing units (GPUs) have traditionally been used in molecular modeling solely for visualization of molecular structures and animation of trajectories resulting from molecular dynamics simulations. Modern GPUs have evolved into fully programmable, massively parallel co-processors that can now be exploited to accelerate many scientific computations, typically providing about one order of magnitude speedup over CPU code and in special cases providing speedups of two orders of magnitude. This paper surveys the development of molecular modeling algorithms that leverage GPU computing, the advances already made and remaining issues to be resolved, and the continuing evolution of GPU technology that promises to become even more useful to molecular modeling. Hardware acceleration with commodity GPUs is expected to benefit the overall computational biology community by bringing teraflops performance to desktop workstations and in some cases potentially changing what were formerly batch-mode computational jobs into interactive tasks. PMID:20675161

  8. Endocrine and metabolic changes in human aging.

    PubMed

    Banks, W A; Morley, J E

    2000-04-01

    Numerous alterations in hormonal secretion occur with aging. In general, these tend towards a disintegration of the normal cyclic secretory patterns resulting in lower total circulating levels. In addition, declines in receptors and postreceptor function further decreases the ability of the hormonal orchestra to maintain coordinated function throughout the organism. Clues to some of these age-related changes in humans may come from the study of simpler organisms where regulatory systems are known to modulate the aging process. In particular, the interactions among the environment, hormones, and insulin receptor genes have led to new insights into the genetic control of longevity and the development of syndrome X. PMID:23604844

  9. Aging and sleep in Williams syndrome: accelerated sleep deterioration and decelerated slow wave sleep decrement.

    PubMed

    Bódizs, Róbert; Gombos, Ferenc; Gerván, Patrícia; Szőcs, Katalin; Réthelyi, János M; Kovács, Ilona

    2014-12-01

    Specific developmental and aging trajectories characterize sleep electroencephalogram (EEG) of typically developing (TD) subjects. Williams syndrome (WS) is marked by sleep alterations and accelerated aging of several anatomo-functional and cognitive measures. Here we test the hypothesis of a premature aging of sleep in WS. Age-related changes of home recorded sleep EEG of 42 subjects (21 WS, 21 age- and gender matched TD subjects, age: 6-29 years) were tested by Pearson correlations and homogeneity-of-slopes analysis. Typical developmental/aging effects of sleep EEGs were observed in TD subjects. Accelerated aging in WS was confirmed by overall sleep/wake measures. Specifically, premature aging was evident in accelerated age-dependent declines in WS subjects' sleep efficiency, as well as in steeper age-related rises in wakefulness and wake after sleep onset (WASO) of the WS group. In contrast, NREM sleep-related measures indicated atypical decelerations of the developmental trends of WS subjects, characterized by the slowing down of the age-related slow wave sleep (SWS) declines mirrored by the lack of age-dependent increase in Stage 2 (S2) sleep. Age-effects in sleep EEG power spectra were not different among the groups. Objectively measured sleep disruption of subjects with WS is age-dependent and increasing with age. Moreover, these data suggest atypical pre- and postpubertal neural development in WS, with sleep/wake balance and REM sleep time indicating accelerated aging while NREM sleep composition revealing signs of an as yet unidentified, perhaps compensatory developmental delay. PMID:25178705

  10. Stiffening of Human Skin Fibroblasts with Age

    PubMed Central

    Schulze, Christian; Wetzel, Franziska; Kueper, Thomas; Malsen, Anke; Muhr, Gesa; Jaspers, Soeren; Blatt, Thomas; Wittern, Klaus-Peter; Wenck, Horst; Käs, Josef A.

    2010-01-01

    Changes in mechanical properties are an essential characteristic of the aging process of human skin. Previous studies attribute these changes predominantly to the altered collagen and elastin organization and density of the extracellular matrix. Here, we show that individual dermal fibroblasts also exhibit a significant increase in stiffness during aging in vivo. With the laser-based optical cell stretcher we examined the viscoelastic biomechanics of dermal fibroblasts isolated from 14 human donors aged 27 to 80. Increasing age was clearly accompanied by a stiffening of the investigated cells. We found that fibroblasts from old donors exhibited an increase in rigidity of ∼60% with respect to cells of the youngest donors. A FACS analysis of the content of the cytoskeletal polymers shows a shift from monomeric G-actin to polymerized, filamentous F-actin, but no significant changes in the vimentin and microtubule content. The rheological analysis of fibroblast-populated collagen gels demonstrates that cell stiffening directly results in altered viscoelastic properties of the collagen matrix. These results identify a new mechanism that may contribute to the age-related impairment of elastic properties in human skin. The altered mechanical behavior might influence cell functions involving the cytoskeleton, such as contractility, motility, and proliferation, which are essential for reorganization of the extracellular matrix. PMID:20959083

  11. DNA methylation and healthy human aging.

    PubMed

    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. PMID:25913071

  12. Nylon 6.6 accelerated aging studies : thermal-oxidative degradation and its interaction with hydrolysis.

    SciTech Connect

    Bernstein, Robert; Derzon, Dora Kay; Gillen, Kenneth T.

    2004-06-01

    Accelerated aging of Nylon 6.6 fibers used in parachutes has been conducted by following the tensile strength loss under both thermal-oxidative and 100% relative humidity conditions. Thermal-oxidative studies (air circulating ovens) were performed for time periods of weeks to years at temperatures ranging from 37 C to 138 C. Accelerated aging humidity experiments (100% RH) were performed under both an argon atmosphere to examine the 'pure' hydrolysis pathway, and under an oxygen atmosphere (oxygen partial pressure close to that occurring in air) to mimic true aging conditions. As expected the results indicated that degradation caused by humidity is much more important than thermal-oxidative degradation. Surprisingly when both oxygen and humidity were present the rate of degradation was dramatically enhanced relative to humidity aging in the absence of oxygen. This significant and previously unknown phenomena underscores the importance of careful accelerated aging that truly mimics real world storage conditions.

  13. Aged Garlic Extract Modifies Human Immunity.

    PubMed

    Percival, Susan S

    2016-02-01

    Garlic contains numerous compounds that have the potential to influence immunity. Immune cells, especially innate immune cells, are responsible for the inflammation necessary to kill pathogens. Two innate lymphocytes, γδ-T and natural killer (NK) cells, appear to be susceptible to diet modification. The purpose of this review was to summarize the influence of aged garlic extract (AGE) on the immune system. The author's laboratory is interested in AGE's effects on cell proliferation and activation and inflammation and to learn whether those changes might affect the occurrence and severity of colds and flu. Healthy human participants (n = 120), between 21 and 50 y of age, were recruited for a randomized, double-blind, placebo-controlled parallel-intervention study to consume 2.56 g AGE/d or placebo supplements for 90 d during the cold and flu season. Peripheral blood mononuclear cells were isolated before and after consumption, and γδ-T and NK cell function was assessed by flow cytometry. The effect on cold and flu symptoms was determined by using daily diary records of self-reported illnesses. After 45 d of AGE consumption, γδ-T and NK cells proliferated better and were more activated than cells from the placebo group. After 90 d, although the number of illnesses was not significantly different, the AGE group showed reduced cold and flu severity, with a reduction in the number of symptoms, the number of days participants functioned suboptimally, and the number of work/school days missed. These results suggest that AGE supplementation may enhance immune cell function and may be partly responsible for the reduced severity of colds and flu reported. The results also suggest that the immune system functions well with AGE supplementation, perhaps with less accompanying inflammation. This trial was registered at clinicaltrials.gov as NCT01390116. PMID:26764332

  14. Anti-muscarinic adjunct therapy accelerates functional human oligodendrocyte repair.

    PubMed

    Abiraman, Kavitha; Pol, Suyog U; O'Bara, Melanie A; Chen, Guang-Di; Khaku, Zainab M; Wang, Jing; Thorn, David; Vedia, Bansi H; Ekwegbalu, Ezinne C; Li, Jun-Xu; Salvi, Richard J; Sim, Fraser J

    2015-02-25

    Therapeutic repair of myelin disorders may be limited by the relatively slow rate of human oligodendrocyte differentiation. To identify appropriate pharmacological targets with which to accelerate differentiation of human oligodendrocyte progenitors (hOPCs) directly, we used CD140a/O4-based FACS of human forebrain and microarray to hOPC-specific receptors. Among these, we identified CHRM3, a M3R muscarinic acetylcholine receptor, as being restricted to oligodendrocyte-biased CD140a(+)O4(+) cells. Muscarinic agonist treatment of hOPCs resulted in a specific and dose-dependent blockade of oligodendrocyte commitment. Conversely, when hOPCs were cocultured with human neurons, M3R antagonist treatment stimulated oligodendrocytic differentiation. Systemic treatment with solifenacin, an FDA-approved muscarinic receptor antagonist, increased oligodendrocyte differentiation of transplanted hOPCs in hypomyelinated shiverer/rag2 brain. Importantly, solifenacin treatment of engrafted animals reduced auditory brainstem response interpeak latency, indicative of increased conduction velocity and thereby enhanced functional repair. Therefore, solifenacin and other selective muscarinic antagonists represent new adjunct approaches to accelerate repair by engrafted human progenitors. PMID:25716865

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

    SciTech Connect

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

    1997-10-01

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

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

    NASA Astrophysics Data System (ADS)

    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.

  17. Traumatic stress, oxidative stress and posttraumatic stress disorder: neurodegeneration and the accelerated-aging hypothesis

    PubMed Central

    Miller, Mark W.; Sadeh, Naomi

    2014-01-01

    Posttraumatic stress disorder (PTSD) is associated with elevated risk for a variety of age-related diseases and neurodegeneration. In this paper, we review evidence relevant to the hypothesis that chronic PTSD constitutes a form of persistent life stress that potentiates oxidative stress (OXS) and accelerates cellular aging. We provide an overview of empirical studies that have examined the effects of psychological stress on OXS, discuss the stress-perpetuating characteristics of PTSD, and then identify mechanisms by which PTSD might promote OXS and accelerated aging. We review studies on OXS-related genes and the role that they may play in moderating the effects of PTSD on neural integrity and conclude with a discussion of directions for future research on antioxidant treatments and biomarkers of accelerated aging in PTSD. PMID:25245500

  18. Human serum metabolic profiles are age dependent.

    PubMed

    Yu, Zhonghao; Zhai, Guangju; Singmann, Paula; He, Ying; Xu, Tao; Prehn, Cornelia; Römisch-Margl, Werner; Lattka, Eva; Gieger, Christian; Soranzo, Nicole; Heinrich, Joachim; Standl, Marie; Thiering, Elisabeth; Mittelstraß, Kirstin; Wichmann, Heinz-Erich; Peters, Annette; Suhre, Karsten; Li, Yixue; Adamski, Jerzy; Spector, Tim D; Illig, Thomas; Wang-Sattler, Rui

    2012-12-01

    Understanding the complexity of aging is of utmost importance. This can now be addressed by the novel and powerful approach of metabolomics. However, to date, only a few metabolic studies based on large samples are available. Here, we provide novel and specific information on age-related metabolite concentration changes in human homeostasis. We report results from two population-based studies: the KORA F4 study from Germany as a discovery cohort, with 1038 female and 1124 male participants (32-81 years), and the TwinsUK study as replication, with 724 female participants. Targeted metabolomics of fasting serum samples quantified 131 metabolites by FIA-MS/MS. Among these, 71/34 metabolites were significantly associated with age in women/men (BMI adjusted). We further identified a set of 13 independent metabolites in women (with P values ranging from 4.6 × 10(-04) to 7.8 × 10(-42) , α(corr) = 0.004). Eleven of these 13 metabolites were replicated in the TwinsUK study, including seven metabolite concentrations that increased with age (C0, C10:1, C12:1, C18:1, SM C16:1, SM C18:1, and PC aa C28:1), while histidine decreased. These results indicate that metabolic profiles are age dependent and might reflect different aging processes, such as incomplete mitochondrial fatty acid oxidation. The use of metabolomics will increase our understanding of aging networks and may lead to discoveries that help enhance healthy aging. PMID:22834969

  19. Accelerated thermal aging of petroleum-based ferrofluids

    NASA Astrophysics Data System (ADS)

    Segal, V.; Nattrass, D.; Raj, K.; Leonard, D.

    1999-07-01

    The effect of elevated temperature on the physical and insulating properties of ferrofluid specifically developed for use as a liquid dielectric (D-fluid) for power transformers has been investigated. The D-fluid was produced as a colloidal mix of a specifically synthesized ferrofluid with a conventional mineral oil, and it was subjected to thermal aging conditions modeled after a typical power transformer where the insulation fluid is expected to retain its dielectric performance for about 40 years of continuous service in a sealed tank. The well-known Arrhenius relationship was employed to model "life in service" for up to 40 years at 105°C which corresponded to holding the samples in sealed jars for 10 weeks at 185°C. Another set of small ampules (5 ml) was prepared to test the main physical properties after even longer aging. D-fluid tested after a period of 34 and 50 weeks at 185°C showed no degradation of thermal or colloid stability. The dielectric colloid was also subjected to a 21 day-long test at 110°C in a sealed jar in the presence of typical transformer materials: copper, cellulose, and silicon steel (so-called "bomb" test). Finally, the ferrofluid went through an oxidation stability test (ASTM D2440). Test results show that the newly developed dielectric colloid satisfies the long-term service requirements the transformer users typically apply to conventional mineral oils.

  20. Fine-pore aeration diffusers: accelerated membrane ageing studies.

    PubMed

    Kaliman, An; Rosso, Diego; Leu, Shao-Yuan; Stenstrom, Michael K

    2008-01-01

    Polymeric membranes are widely used in aeration systems for biological treatment. These membranes may degrade over time and are sensitive to fouling and scaling. Membrane degradation is reflected in a decline in operating performance and higher headloss, resulting in increased energy costs. Mechanical property parameters, such as membrane hardness, Young's modulus, and orifice creep, were used to characterize the performance of membranes over time in operation and to predict their failure. Used diffusers from municipal wastewater treatment plants were collected and tested for efficiency and headloss, and then dissected to facilitate measurements of Young's modulus, hardness, and orifice creep. Higher degree of membrane fouling corresponded consistently with larger orifice creep. A lab-scale membrane ageing simulation was performed with polyurethane and four different ethylene-propylene-diene (EPDM) membrane diffusers by subjecting them to chemical ageing cycles and periodic testing. The results confirmed full-scale plant results and showed the superiority of orifice creep over Young's modulus and hardness in predicting diffuser deterioration. PMID:17706264

  1. The Age of Human Cerebral Cortex Neurons

    SciTech Connect

    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.

  2. Accelerated aging and flashover tests on 138 kV nonceramic line post insulators

    SciTech Connect

    Schneider, H.M.; Guidi, W.W. ); Burnham, J.T. ); Gorur, R.S. ); Hall, J.F. )

    1993-01-01

    The behavior of 138 kV nonceramic line post insulators is investigated by means of clean fog tests conducted before and after aging in a specially designed accelerated aging chamber. The laboratory aging cycles are justified on the basis of actual weather in the coastal regions of Florida. Analytical measurements quantifying the degree of artificial aging are discussed and comparisons of artificial aging with service experience are presented. Observations of audible noise and radio influence voltage during the clean fog tests are reported.

  3. Comprehensive identification and analysis of human accelerated regulatory DNA

    PubMed Central

    Gittelman, Rachel M.; Hun, Enna; Ay, Ferhat; Madeoy, Jennifer; Pennacchio, Len; Noble, William S.; Hawkins, R. David; Akey, Joshua M.

    2015-01-01

    It has long been hypothesized that changes in gene regulation have played an important role in human evolution, but regulatory DNA has been much more difficult to study compared with protein-coding regions. Recent large-scale studies have created genome-scale catalogs of DNase I hypersensitive sites (DHSs), which demark potentially functional regulatory DNA. To better define regulatory DNA that has been subject to human-specific adaptive evolution, we performed comprehensive evolutionary and population genetics analyses on over 18 million DHSs discovered in 130 cell types. We identified 524 DHSs that are conserved in nonhuman primates but accelerated in the human lineage (haDHS), and estimate that 70% of substitutions in haDHSs are attributable to positive selection. Through extensive computational and experimental analyses, we demonstrate that haDHSs are often active in brain or neuronal cell types; play an important role in regulating the expression of developmentally important genes, including many transcription factors such as SOX6, POU3F2, and HOX genes; and identify striking examples of adaptive regulatory evolution that may have contributed to human-specific phenotypes. More generally, our results reveal new insights into conserved and adaptive regulatory DNA in humans and refine the set of genomic substrates that distinguish humans from their closest living primate relatives. PMID:26104583

  4. Comprehensive identification and analysis of human accelerated regulatory DNA.

    PubMed

    Gittelman, Rachel M; Hun, Enna; Ay, Ferhat; Madeoy, Jennifer; Pennacchio, Len; Noble, William S; Hawkins, R David; Akey, Joshua M

    2015-09-01

    It has long been hypothesized that changes in gene regulation have played an important role in human evolution, but regulatory DNA has been much more difficult to study compared with protein-coding regions. Recent large-scale studies have created genome-scale catalogs of DNase I hypersensitive sites (DHSs), which demark potentially functional regulatory DNA. To better define regulatory DNA that has been subject to human-specific adaptive evolution, we performed comprehensive evolutionary and population genetics analyses on over 18 million DHSs discovered in 130 cell types. We identified 524 DHSs that are conserved in nonhuman primates but accelerated in the human lineage (haDHS), and estimate that 70% of substitutions in haDHSs are attributable to positive selection. Through extensive computational and experimental analyses, we demonstrate that haDHSs are often active in brain or neuronal cell types; play an important role in regulating the expression of developmentally important genes, including many transcription factors such as SOX6, POU3F2, and HOX genes; and identify striking examples of adaptive regulatory evolution that may have contributed to human-specific phenotypes. More generally, our results reveal new insights into conserved and adaptive regulatory DNA in humans and refine the set of genomic substrates that distinguish humans from their closest living primate relatives. PMID:26104583

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

    PubMed Central

    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

  6. Analysis of human accelerated DNA regions using archaic hominin genomes.

    PubMed

    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

  7. Senescence-accelerated mouse (SAM): a biogerontological resource in aging research.

    PubMed

    Takeda, T

    1999-01-01

    The senescence-accelerated mouse (SAM), consisting of 14 senescence-prone inbred strains (SAMP) and 4 senescence-resistant inbred strains (SAMR) has been under development since 1970 through the selective inbreeding of AKR/J strain mice donated by the Jackson laboratory in 1968, based on the data of the grading score of senescence, life span, and pathologic phenotypes. The characteristic feature of aging common to all SAMP and SAMR mice is accelerated senescence and normal aging, respectively. Furthermore, SAMP and SAMR strains manifest various pathobiological phenotypes which include such neurobiological phenotypes as deficits in learning and memory, emotional disorders, abnormal circadian rhythms, brain atrophy, hearing impairment, etc., and are often characteristic enough to differentiate the strains. Various efforts are currently being made using the SAM model to clarify the underlying mechanisms in accelerated senescence as well as the etiopathogenic mechanisms in age-associated pathobiologies. Genetic background and significance of SAM development are discussed. PMID:10537019

  8. Bitter Taste Receptor Polymorphisms and Human Aging

    PubMed Central

    Carrai, Maura; Crocco, Paolina; Montesanto, Alberto; Canzian, Federico; Rose, Giuseppina; Rizzato, Cosmeri

    2012-01-01

    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. PMID:23133589

  9. Accelerated Human Mutant Tau Aggregation by Knocking Out Murine Tau in a Transgenic Mouse Model

    PubMed Central

    Ando, Kunie; Leroy, Karelle; Héraud, Céline; Yilmaz, Zehra; Authelet, Michèle; Suain, Valèrie; De Decker, Robert; Brion, Jean-Pierre

    2011-01-01

    Many models of human tauopathies have been generated in mice by expression of a human mutant tau with maintained expression of mouse endogenous tau. Because murine tau might interfere with the toxic effects of human mutant tau, we generated a model in which a pathogenic human tau protein is expressed in the absence of wild-type tau protein, with the aim of facilitating the study of the pathogenic role of the mutant tau and to reproduce more faithfully a human tauopathy. The Tg30 line is a tau transgenic mouse model overexpressing human 1N4R double-mutant tau (P301S and G272V) that develops Alzheimer's disease-like neurofibrillary tangles in an age-dependent manner. By crossing Tg30 mice with mice invalidated for their endogenous tau gene, we obtained Tg30xtau−/− mice that express only exogenous human double-mutant 1N4R tau. Although Tg30xtau−/− mice express less tau protein compared with Tg30, they exhibit signs of decreased survival, increased proportion of sarkosyl-insoluble tau in the brain and in the spinal cord, increased number of Gallyas-positive neurofibrillary tangles in the hippocampus, increased number of inclusions in the spinal cord, and a more severe motor phenotype. Deletion of murine tau accelerated tau aggregation during aging of this mutant tau transgenic model, suggesting that murine tau could interfere with the development of tau pathology in transgenic models of human tauopathies. PMID:21281813

  10. Chronological ageing of human hair keratin fibres.

    PubMed

    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. PMID:20384898

  11. Genome Integrity in Aging: Human Syndromes, Mouse Models, and Therapeutic Options.

    PubMed

    Vermeij, Wilbert P; Hoeijmakers, Jan H J; Pothof, Joris

    2016-01-01

    Human syndromes and mouse mutants that exhibit accelerated but bona fide aging in multiple organs and tissues have been invaluable for the identification of nine denominators of aging: telomere attrition, genome instability, epigenetic alterations, mitochondrial dysfunction, deregulated nutrient sensing, altered intercellular communication, loss of proteostasis, cellular senescence and adult stem cell exhaustion. However, whether and how these instigators of aging interrelate or whether they have one root cause is currently largely unknown. Rare human progeroid syndromes and corresponding mouse mutants with resolved genetic defects highlight the dominant importance of genome maintenance for aging. A second class of aging-related disorders reveals a cross connection with metabolism. As genome maintenance and metabolism are closely interconnected, they may constitute the main underlying biology of aging. This review focuses on the role of genome stability in aging, its crosstalk with metabolism, and options for nutritional and/or pharmaceutical interventions that delay age-related pathology. PMID:26514200

  12. p63 deficiency activates a program of cellular senescence and leads to accelerated aging

    PubMed Central

    Keyes, William M.; Wu, Ying; Vogel, Hannes; Guo, Xuecui; Lowe, Scott W.; Mills, Alea A.

    2005-01-01

    The p53 tumor suppressor plays a key role in organismal aging. A cellular mechanism postulated to drive the aging process is cellular senescence, mediated in part by p53. Although senescent cells accumulate in elderly individuals, most studies have relied on correlating in vitro senescence assays with in vivo phenotypes of aging. Here, using two different mouse models in which the p53-related protein p63 is compromised, we demonstrate that cellular senescence and organismal aging are intimately linked and that these processes are mediated by p63 loss. We found that p63+/- mice have a shortened life span and display features of accelerated aging. Both germline and somatically induced p63 deficiency activates widespread cellular senescence with enhanced expression of senescent markers SA-β-gal, PML, and p16INK4a. Using an inducible tissue-specific p63 conditional model, we further show that p63 deficiency induces cellular senescence and causes accelerated aging phenotypes in the adult. Our results thus suggest a causative link between cellular senescence and aging in vivo, and demonstrate that p63 deficiency accelerates this process. PMID:16107615

  13. Seismic-fragility tests of new and accelerated-aged Class 1E battery cells

    SciTech Connect

    Bonzon, L.L.; Janis, W.J.; Black, D.A.; Paulsen, G.A.

    1987-01-01

    The seismic-fragility response of naturally-aged nuclear station safety-related batteries is of interest for two reasons: (1) to determine actual failure modes and thresholds and (2) to determine the validity of using the electrical capacity of individual cells as an indicator of the potential survivability of a battery given a seismic event. Prior reports in this series discussed the seismic-fragility tests and results for three specific naturally-aged cell types: 12-year old NCX-2250, 10-year old LCU-13, and 10-year old FHC-19. This report focuses on the complementary approach, namely, the seismic-fragility response of accelerated-aged batteries. Of particular interest is the degree to which such approaches accurately reproduce the actual failure modes and thresholds. In these tests the significant aging effects observed, in terms of seismic survivability, were: embrittlement of cell cases, positive bus material and positive plate grids; and excessive sulphation of positive plate active material causing hardening and expansion of positive plates. The IEEE Standard 535 accelerated aging method successfully reproduced seismically significant aging effects in new cells but accelerated grid embrittlement an estimated five years beyond the conditional age of other components.

  14. GENETICS OF HUMAN AGE RELATED DISORDERS.

    PubMed

    Srivastava, I; Thukral, N; Hasija, Y

    2015-01-01

    Aging is an inevitable biological phenomenon. The incidence of age related disorders (ARDs) such as cardiovascular diseases, cancer, arthritis, dementia, osteoporosis, diabetes, neurodegenerative diseases increase rapidly with aging. ARDs are becoming a key social and economic trouble for the world's elderly population (above 60 years), which is expected to reach 2 billion by 2050. Advancement in understanding of genetic associations, particularly through genome wide association studies (GWAS), has revealed a substantial contribution of genes to human aging and ARDs. In this review, we have focused on the recent understanding of the extent to which genetic predisposition may influence the aging process. Further analysis of the genetic association studies through pathway analysis several genes associated with multiple ARDs have been highlighted such as apolipoprotein E (APOE), brain-derived neurotrophic factor (BDNF), cadherin 13 (CDH13), CDK5 regulatory subunit associated protein 1 (CDKAL-1), methylenetetrahydrofolate reductase (MTHFR), disrupted in schizophrenia 1 (DISC1), nitric oxide synthase 3 (NOS3), paraoxonase 1 (PON1), indicating that these genes could play a pivotal role in ARD causation. These genes were found to be significantly enriched in Jak-STAT signalling pathway, asthma and allograft rejection. Further, interleukin-6 (IL-6), insulin (INS), vascular endothelial growth factor A (VEGFA), estrogen receptor1 (ESR1), transforming growth factor, beta 1(TGFB1) and calmodulin 1 (CALM1) were found to be highly interconnected in network analysis. We believe that extensive research on the presence of common genetic variants among various ARDs may facilitate scientists to understand the biology behind ARDs causation. PMID:26856084

  15. Aging attenuates the vestibulosympathetic reflex in humans

    NASA Technical Reports Server (NTRS)

    Ray, Chester A.; Monahan, Kevin D.

    2002-01-01

    BACKGROUND: The vestibular system contributes to sympathetic activation by engagement of the otolith organs. However, there is a significant loss of vestibular function with aging. Therefore, the purpose of the present study was to determine if young and older individuals differ in their cardiovascular and sympathetic responses to otolithic stimulation (ie, head-down rotation, HDR). We hypothesized that responses to otolithic stimulation would be attenuated in older adults because of morphological and physiological alterations that occur in the vestibular system with aging. METHODS AND RESULTS: Arterial blood pressure, heart rate, muscle sympathetic nerve activity (MSNA), and head rotation were measured during HDR in 11 young (26 +/- 1 years) and 11 older (64 +/- 1 years) subjects in the prone posture. Five older subjects performed head rotation (chin to chest) in the lateral decubitus position, which simulates HDR but does not alter afferent inputs from the vestibular system. MSNA responses to HDR were significantly attenuated in older as compared with young subjects (P<0.01). MSNA increased in the older subjects by only 12 +/- 5% as compared with 85 +/- 16% in the young. Furthermore, HDR elicited significant reductions in mean arterial blood pressure in older (Delta-6 +/- 1 mm Hg; P<0.01) but not young subjects (Delta1 +/- 1 mm Hg). In contrast to HDR, head rotation performed in the lateral decubitus position did not elicit hypotension. MSNA responses to baroreceptor unloading and the cold pressor test were not different between the age groups. CONCLUSIONS: These data indicate that aging attenuates the vestibulosympathetic reflex in humans and may contribute to the increased prevalence of orthostatic hypotension with age.

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

    NASA Technical Reports Server (NTRS)

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

    2009-01-01

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

  17. Survivability of integrated PVDF film sensors to accelerated ageing conditions in aeronautical/aerospace structures

    NASA Astrophysics Data System (ADS)

    Guzman, E.; Cugnoni, J.; Gmür, T.; Bonhôte, P.; Schorderet, A.

    2013-06-01

    This work validates the use of integrated polyvinylidene fluoride (PVDF) film sensors for dynamic testing, even after being subjected to UV-thermo-hygro-mechanical accelerated ageing conditions. The verification of PVDF sensors’ survivability in these environmental conditions, typically confronted by civil and military aircraft, is the main concern of the study. The evaluation of survivability is made by a comparison of dynamic testing results provided by the PVDF patch sensors subjected to an accelerated ageing protocol, and those provided by neutral non-aged sensors (accelerometers). The available measurements are the time-domain response signals issued from a modal analysis procedure, and the corresponding frequency response functions (FRF). These are in turn used to identify the constitutive properties of the samples by extraction of the modal parameters, in particular the natural frequencies. The composite specimens in this study undergo different accelerated ageing processes. After several weeks of experimentation, the samples exhibit a loss of stiffness, represented by a decrease in the elastic moduli down to 10%. Despite the ageing, the integrated PVDF sensors, subjected to the same ageing conditions, are still capable of providing reliable data to carry out a close followup of these changes. This survivability is a determinant asset in order to use integrated PVDF sensors to perform structural health monitoring (SHM) in the future of full-scale composite aeronautical structures.

  18. Effects of accelerated aging and p-coumaric on crimson clover (Trifolium incarnatium L.) seed germination.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several phenolic acids, including p-coumaric acid, have been described as allelochemicals that may inhibit seed germination or seedling growth. Whether these effects are exacerbated in forage species by environmental stressors is unknown. Accelerated seed aging (high temperature (41 C) and high hum...

  19. Interaction of accelerated aging and p-coumaric acid on crimson clover seed germination

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several phenolic acids, including p-coumaric acid, have been described as allelochemicals that may inhibit seed germination or seedling growth. Accelerated seed aging (high temperature (41 C) and high humidity (100%)) reduces germination and seedling vigor, and provides some indication as to seed g...

  20. Accelerated Vascular Aging as a Paradigm for Hypertensive Vascular Disease: Prevention and Therapy.

    PubMed

    Barton, Matthias; Husmann, Marc; Meyer, Matthias R

    2016-05-01

    Aging is considered the most important nonmodifiable risk factor for cardiovascular disease and death after age 28 years. Because of demographic changes the world population is expected to increase to 9 billion by the year 2050 and up to 12 billion by 2100, with several-fold increases among those 65 years of age and older. Healthy aging and prevention of aging-related diseases and associated health costs have become part of political agendas of governments around the world. Atherosclerotic vascular burden increases with age; accordingly, patients with progeria (premature aging) syndromes die from myocardial infarctions or stroke as teenagers or young adults. The incidence and prevalence of arterial hypertension also increases with age. Arterial hypertension-like diabetes and chronic renal failure-shares numerous pathologies and underlying mechanisms with the vascular aging process. In this article, we review how arterial hypertension resembles premature vascular aging, including the mechanisms by which arterial hypertension (as well as other risk factors such as diabetes mellitus, dyslipidemia, or chronic renal failure) accelerates the vascular aging process. We will also address the importance of cardiovascular risk factor control-including antihypertensive therapy-as a powerful intervention to interfere with premature vascular aging to reduce the age-associated prevalence of diseases such as myocardial infarction, heart failure, hypertensive nephropathy, and vascular dementia due to cerebrovascular disease. Finally, we will discuss the implementation of endothelial therapy, which aims at active patient participation to improve primary and secondary prevention of cardiovascular disease. PMID:27118295

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

    PubMed

    Iriondo-DeHond, Amaia; Martorell, Patricia; Genovés, Salvador; Ramón, Daniel; Stamatakis, Konstantinos; Fresno, Manuel; Molina, Antonio; Del Castillo, Maria Dolores

    2016-01-01

    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. PMID:27258247

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

    PubMed

    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. PMID:22019846

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

    NASA Astrophysics Data System (ADS)

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

    PubMed

    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. 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. PMID:27573984

  5. DNA damage drives accelerated bone aging via an NF-κB-dependent mechanism

    PubMed Central

    Chen, Qian; Liu, Kai; Robinson, Andria R.; Clauson, Cheryl L.; Blair, Harry C.; Robbins, Paul D.; Niedernhofer, Laura J.; Ouyang, Hongjiao

    2013-01-01

    Advanced age is one of the most important risk factors for osteoporosis. Accumulation of oxidative DNA damage has been proposed to contribute to age-related deregulation of osteoblastic and osteoclastic cells. ERCC1 (Excision Repair Cross Complementary group 1)-XPF (Xeroderma Pigmentosum Group F) is an evolutionarily conserved structure-specific endonuclease that is required for multiple DNA repair pathways. Inherited mutations affecting expression of ERCC1-XPF cause a severe progeroid syndrome in humans, including early onset of osteopenia and osteoporosis, or anomalies in skeletal development. Herein, we used progeroid ERCC1-XPF deficient mice, including Ercc1-null (Ercc1−/−) and hypomorphic (Ercc1−/Δ) mice, to investigate the mechanism by which DNA damage leads to accelerated bone aging. Compared to their wild-type littermates, both Ercc1−/− and Ercc1−/Δ mice display severe, progressive osteoporosis caused by reduced bone formation and enhanced osteoclastogenesis. ERCC1 deficiency leads to atrophy of osteoblastic progenitors in the bone marrow stromal cell (BMSC) population. There is increased cellular senescence of BMSCs and osteoblastic cells, as characterized by reduced proliferation, accumulation of DNA damage and a senescence-associated secretory phenotype (SASP). This leads to enhanced secretion of inflammatory cytokines known to drive osteoclastogenesis, such as IL-6, TNFα, and RANKL and thereby induces an inflammatory bone microenvironment favoring osteoclastogenesis. Furthermore, we found that the transcription factor NF-κB is activated in osteoblastic and osteoclastic cells of the Ercc1 mutant mice. Importantly, we demonstrated that haploinsufficiency of the p65 NF-κB subunit partially rescued the osteoporosis phenotype of Ercc1−/Δ mice. Finally, pharmacological inhibition of the NF-κB signaling via an IKK inhibitor reversed cellular senescence and SASP in Ercc1−/Δ BMSCs. These results demonstrate that DNA damage drives

  6. Acceleration factors for oxidative aging of polymeric materials by oxygen detection.

    SciTech Connect

    Assink, Roger Alan; Celina, Mathias Christopher; Skutnik, Julie Michelle

    2005-01-01

    Three methods that were used to measure the chemical changes associated with oxidative degradation of polymeric materials are presented. The first method is based on the nuclear activation of {sup 18}O in an elastomer that was thermally aged in an {sup 18}O{sub 2} atmosphere. Second, the alcohol groups in a thermally aged elastomer were derivatized with trifluoroacetic anhydride and their concentration measured via {sup 19}F NMR spectroscopy. Finally, a respirometer was used to directly measure the oxidative rates of a polyurethane foam as a function of aging temperature. The measurement of the oxidation rates enabled acceleration factors for oxidative degradation of these materials to be calculated.

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

    PubMed

    Ford, Judith H

    2013-01-01

    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

  8. The Role of Calcium in Human Aging

    PubMed Central

    2015-01-01

    Calcium is an essential nutrient that is necessary for many functions in human health. Calcium is the most abundant mineral in the body with 99% found in teeth and bone. Only 1% is found in serum. The serum calcium level is tightly monitored to remain within normal range by a complex metabolic process. Calcium metabolism involves other nutrients including protein, vitamin D, and phosphorus. Bone formation and maintenance is a lifelong process. Early attention to strong bones in childhood and adulthood will provide more stable bone mass during the aging years. Research has shown that adequate calcium intake can reduce the risk of fractures, osteoporosis, and diabetes in some populations. The dietary requirements of calcium and other collaborative nutrients vary slightly around the world. Lactose intolerance due to lactase deficiency is a common cause of low calcium intake. Strategies will be discussed for addressing this potential barrier to adequate intake. The purpose of this narrative review is a) to examine the role of calcium in human health, b) to compare nutrient requirements for calcium across lifecycle groups and global populations, c) to review relationships between calcium intake, chronic disease risk, and fractures, and d) to discuss strategies to address diet deficiencies and lactose intolerance. PMID:25713787

  9. The role of calcium in human aging.

    PubMed

    Beto, Judith A

    2015-01-01

    Calcium is an essential nutrient that is necessary for many functions in human health. Calcium is the most abundant mineral in the body with 99% found in teeth and bone. Only 1% is found in serum. The serum calcium level is tightly monitored to remain within normal range by a complex metabolic process. Calcium metabolism involves other nutrients including protein, vitamin D, and phosphorus. Bone formation and maintenance is a lifelong process. Early attention to strong bones in childhood and adulthood will provide more stable bone mass during the aging years. Research has shown that adequate calcium intake can reduce the risk of fractures, osteoporosis, and diabetes in some populations. The dietary requirements of calcium and other collaborative nutrients vary slightly around the world. Lactose intolerance due to lactase deficiency is a common cause of low calcium intake. Strategies will be discussed for addressing this potential barrier to adequate intake. The purpose of this narrative review is a) to examine the role of calcium in human health, b) to compare nutrient requirements for calcium across lifecycle groups and global populations, c) to review relationships between calcium intake, chronic disease risk, and fractures, and d) to discuss strategies to address diet deficiencies and lactose intolerance. PMID:25713787

  10. Modulating Human Aging and Age-Associated Diseases

    PubMed Central

    Fontana, Luigi

    2009-01-01

    Population aging is progressing rapidly in many industrialized countries. The United States population aged 65 and over is expected to double in size within the next 25 years. In sedentary people eating Western diets aging is associated with the development of serious chronic diseases, including type 2 diabetes mellitus, cancer and cardiovascular diseases. About 80 percent of adults over 65 years of age have at least one chronic disease, and 50 percent have at least two chronic diseases. These chronic diseases are the most important cause of illness and mortality burden, and they have become the leading driver of healthcare costs, constituting an important burden for our society. Data from epidemiological studies and clinical trials indicate that many age-associated chronic diseases can be prevented, and even reversed, with the implementation of healthy lifestyle interventions. Several recent studies suggest that more drastic interventions (i.e. calorie restriction without malnutrition and moderate protein restriction with adequate nutrition) may have additional beneficial effects on several metabolic and hormonal factors that are implicated in the biology of aging itself. Additional studies are needed to understand the complex interactions of factors that regulate aging and age-associated chronic disease. PMID:19364477

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

    PubMed Central

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

    Background 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. Methods 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. Results 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). Conclusions 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. PMID:26512982

  14. Accelerated brain aging in schizophrenia and beyond: a neuroanatomical marker of psychiatric disorders.

    PubMed

    Koutsouleris, Nikolaos; Davatzikos, Christos; Borgwardt, Stefan; Gaser, Christian; Bottlender, Ronald; Frodl, Thomas; Falkai, Peter; Riecher-Rössler, Anita; Möller, Hans-Jürgen; Reiser, Maximilian; Pantelis, Christos; Meisenzahl, Eva

    2014-09-01

    Structural brain abnormalities are central to schizophrenia (SZ), but it remains unknown whether they are linked to dysmaturational processes crossing diagnostic boundaries, aggravating across disease stages, and driving the neurodiagnostic signature of the illness. Therefore, we investigated whether patients with SZ (N = 141), major depression (MD; N = 104), borderline personality disorder (BPD; N = 57), and individuals in at-risk mental states for psychosis (ARMS; N = 89) deviated from the trajectory of normal brain maturation. This deviation was measured as difference between chronological and the neuroanatomical age (brain age gap estimation [BrainAGE]). Neuroanatomical age was determined by a machine learning system trained to individually estimate age from the structural magnetic resonance imagings of 800 healthy controls. Group-level analyses showed that BrainAGE was highest in SZ (+5.5 y) group, followed by MD (+4.0), BPD (+3.1), and the ARMS (+1.7) groups. Earlier disease onset in MD and BPD groups correlated with more pronounced BrainAGE, reaching effect sizes of the SZ group. Second, BrainAGE increased across at-risk, recent onset, and recurrent states of SZ. Finally, BrainAGE predicted both patient status as well as negative and disorganized symptoms. These findings suggest that an individually quantifiable "accelerated aging" effect may particularly impact on the neuroanatomical signature of SZ but may extend also to other mental disorders. PMID:24126515

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

    PubMed

    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. PMID:26243899

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

    PubMed Central

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

    PubMed

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

    2013-12-01

    This study evaluated the colour stability of temporary prosthetic restorations with different thicknesses submitted to artificial accelerated aging. The occlusal surfaces of 40 molars were grinded to obtain flat enamel surfaces. Twenty acrylic resin specimens [Polymethyl methacrylate (Duralay) and Bis-methyl acrylate (Luxatemp)] were made with two different thicknesses, 0.5 mm and 1.0 mm. Temporary restorations were fixed on enamel and CIE L*a*b* colour parameters of each specimen were assessed before and after artificial accelerated aging. All groups showed colour alterations above the clinically acceptable limit. Luxatemp showed the lowest colour alteration regardless its thickness and Duralay showed the greatest alteration with 0.5 mm. PMID:24479216

  18. Correlating outdoor exposure with accelerated aging tests for aluminum solar reflectors

    NASA Astrophysics Data System (ADS)

    Wette, Johannes; Sutter, Florian; Fernández-García, Aránzazu

    2016-05-01

    Guaranteeing the durability of concentrated solar power (CSP) components is crucial for the success of the technology. The reflectors of the solar field are a key component of CSP plants, requiring reliable methods for service lifetime prediction. So far, no proven correlations exist to relate accelerated aging test results in climate chambers with relevant CSP exposure sites. In this work, correlations have been derived for selected testing conditions that excite the same degradation mechanisms as for outdoor exposure. Those testing conditions have been identified by performing an extensive microscopic comparison of the appearing degradation mechanisms on reference samples that have been weathered outdoors with samples that underwent a high variety of accelerated aging experiments. The herein developed methodology is derived for aluminum reflectors and future work will study its applicability to silvered-glass mirrors.

  19. Accelerated Brain Aging in Schizophrenia and Beyond: A Neuroanatomical Marker of Psychiatric Disorders

    PubMed Central

    Koutsouleris, Nikolaos; Davatzikos, Christos; Borgwardt, Stefan; Gaser, Christian; Bottlender, Ronald; Frodl, Thomas; Falkai, Peter; Riecher-Rössler, Anita; Möller, Hans-Jürgen; Reiser, Maximilian; Pantelis, Christos; Meisenzahl, Eva

    2014-01-01

    Structural brain abnormalities are central to schizophrenia (SZ), but it remains unknown whether they are linked to dysmaturational processes crossing diagnostic boundaries, aggravating across disease stages, and driving the neurodiagnostic signature of the illness. Therefore, we investigated whether patients with SZ (N = 141), major depression (MD; N = 104), borderline personality disorder (BPD; N = 57), and individuals in at-risk mental states for psychosis (ARMS; N = 89) deviated from the trajectory of normal brain maturation. This deviation was measured as difference between chronological and the neuroanatomical age (brain age gap estimation [BrainAGE]). Neuroanatomical age was determined by a machine learning system trained to individually estimate age from the structural magnetic resonance imagings of 800 healthy controls. Group-level analyses showed that BrainAGE was highest in SZ (+5.5 y) group, followed by MD (+4.0), BPD (+3.1), and the ARMS (+1.7) groups. Earlier disease onset in MD and BPD groups correlated with more pronounced BrainAGE, reaching effect sizes of the SZ group. Second, BrainAGE increased across at-risk, recent onset, and recurrent states of SZ. Finally, BrainAGE predicted both patient status as well as negative and disorganized symptoms. These findings suggest that an individually quantifiable “accelerated aging” effect may particularly impact on the neuroanatomical signature of SZ but may extend also to other mental disorders. PMID:24126515

  20. Influence of the humidity on leakage current under accelerated aging of polymer insulating materials

    SciTech Connect

    Otsubo, M.; Shimono, Y.; Hikami, T.; Honda, C.

    1996-12-31

    This paper describes the experimental results of accelerated aging tests conducted on three different types of polymer materials. Salt fog chamber tests were used to study the surface degradation modes for all materials. The work presented here was performed using a newly constructed fog chamber system that was able to control both chamber humidity and UV radiation. The changes in the surface morphology, material structure and leakage current were examined to study the influence of environmental humidity.

  1. On the Use of Accelerated Aging Methods for Screening High Temperature Polymeric Composite Materials

    NASA Technical Reports Server (NTRS)

    Gates, Thomas S.; Grayson, Michael A.

    1999-01-01

    A rational approach to the problem of accelerated testing of high temperature polymeric composites is discussed. The methods provided are considered tools useful in the screening of new materials systems for long-term application to extreme environments that include elevated temperature, moisture, oxygen, and mechanical load. The need for reproducible mechanisms, indicator properties, and real-time data are outlined as well as the methodologies for specific aging mechanisms.

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

    PubMed

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

    2016-06-01

    First-generation (irradiated and remelted or annealed) and second-generation (irradiated and vitamin E blended or doped) highly crosslinked polyethylenes were introduced in the last decade to solve the problems of wear and osteolysis. In this study, the influence of the Vitamin-E addition on crosslinked polyethylene (XLPE_VE) was evaluated by comparing the in vitro wear behavior of crosslinked polyethylene (XLPE) versus Vitamin-E blended polyethylene XLPE and conventional ultra-high molecular weight polyethylene (STD_PE) acetabular cups, after accelerated ageing according to ASTM F2003-02 (70.0±0.1°C, pure oxygen at 5bar for 14 days). The test was performed using a hip joint simulator run for two millions cycles, under bovine calf serum as lubricant. Mass loss was found to decrease along the series XLPE_VE>STD_PE>XLPE, although no statistically significant differences were found between the mass losses of the three sets of cups. Micro-Raman spectroscopy was used to investigate at a molecular level the morphology changes induced by wear. The spectroscopic analyses showed that the accelerated ageing determined different wear mechanisms and molecular rearrangements during testing with regards to the changes in both the chain orientation and the distribution of the all-trans sequences within the orthorhombic, amorphous and third phases. The results of the present study showed that the addition of vitamin E was not effective to improve the gravimetric wear of PE after accelerated ageing. However, from a molecular point of view, the XLPE_VE acetabular cups tested after accelerated ageing appeared definitely less damaged than the STD_PE ones and comparable to XLPE samples. PMID:26970299

  3. Intrauterine growth restriction programs an accelerated age-related increase in cardiovascular risk in male offspring.

    PubMed

    Dasinger, John Henry; Intapad, Suttira; Backstrom, Miles A; Carter, Anthony J; Alexander, Barbara T

    2016-08-01

    Placental insufficiency programs an increase in blood pressure associated with a twofold increase in serum testosterone in male growth-restricted offspring at 4 mo of age. Population studies indicate that the inverse relationship between birth weight and blood pressure is amplified with age. Thus, we tested the hypothesis that intrauterine growth restriction programs an age-related increase in blood pressure in male offspring. Growth-restricted offspring retained a significantly higher blood pressure at 12 but not at 18 mo of age compared with age-matched controls. Blood pressure was significantly increased in control offspring at 18 mo of age relative to control counterparts at 12 mo; however, blood pressure was not increased in growth-restricted at 18 mo relative to growth-restricted counterparts at 12 mo. Serum testosterone levels were not elevated in growth-restricted offspring relative to control at 12 mo of age. Thus, male growth-restricted offspring no longer exhibited a positive association between blood pressure and testosterone at 12 mo of age. Unlike hypertension in male growth-restricted offspring at 4 mo of age, inhibition of the renin-angiotensin system with enalapril (250 mg/l for 2 wk) did not abolish the difference in blood pressure in growth-restricted offspring relative to control counterparts at 12 mo of age. Therefore, these data suggest that intrauterine growth restriction programs an accelerated age-related increase in blood pressure in growth-restricted offspring. Furthermore, this study suggests that the etiology of increased blood pressure in male growth-restricted offspring at 12 mo of age differs from that at 4 mo of age. PMID:27147668

  4. Colour stability of denture teeth submitted to different cleaning protocols and accelerated artificial aging.

    PubMed

    Freire, T S; Aguilar, F G; Garcia, L da Fonseca Roberti; Pires-de-Souza, F de Carvalho Panzeri

    2014-03-01

    Acrylic resin is widely used for artificial teeth manufacturing due to several important characteristics; however, this material do not present acceptable colour stability over the course of time. This study evaluated the effect of different cleaning protocols and accelerated artificial aging on colour stability of denture teeth made of acrylic resin. Sixty denture teeth in dark and light shades were used, and separated according to the treatment to which they were submitted. Results demonstrated that colour stability of artificial teeth is influenced by the cleaning solution and artificial aging, being dark teeth more susceptible to colour alteration than lighter ones. PMID:24922996

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

    PubMed Central

    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. PMID:25474200

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

    PubMed

    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. PMID:25474200

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

    PubMed Central

    GOIATO, Marcelo Coelho; dos SANTOS, Daniela Micheline; SOUZA, Josiene Firmino; MORENO, Amália; PESQUEIRA, Aldiéris Alves

    2010-01-01

    Esthetics and durability of materials used to fabricate artificial eyes has been an important eissue since artificial eyes are essential to restore esthetics and function, protect the remaining tissues and help with patients' psychological therapy. However, these materials are submitted to degrading effects of environmental agents on the physical properties of the acrylic resin. Objective This study assessed the color stability of acrylic resins used to fabricate sclera in three basic shades (N1, N2 and N3) when subjected to accelerated aging, mechanical and chemical polishing. Material and methods Specimens of each resin were fabricated and submitted to mechanical and chemical polishing. Chromatic analysis was performed before and after accelerated aging through ultraviolet reflection spectrophotometry. Results All specimens revealed color alteration following polishing and accelerated aging. The resins presented statistically significant chromatic alteration (p<0.01) between the periods of 252 and 1008 h. Conclusions Both polishing methods presented no significant difference between the values of color derivatives of resins. PMID:21308298

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

    NASA Astrophysics Data System (ADS)

    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.

  9. Surface degradation of polymer insulators under accelerated climatic aging in weather-ometer

    SciTech Connect

    Xu, G.; McGrath, P.B.; Burns, C.W.

    1996-12-31

    Climatic aging experiments were conducted on two types of outdoor polymer insulators by using a programmable weather-ometer. The housing materials for the insulators were silicone rubber (SR) and ethylene propylene diene monomer (EPDM). The accelerated aging stresses were comprised of ultraviolet radiation, elevated temperature, temperature cycling, thermal shock and high humidity. Their effects on the insulator surface conditions and electrical performance wee examined through visual inspection and SEM studies, contact angle measurements, thermogravimetric analysis (TGA), energy dispersive spectroscopy (EDS) analysis, and 50% impulse flashover voltage tests. The results showed a significant damage on the insulator surface caused by some of the imposed aging stresses. The EDS analysis suggested a photooxidation process that happened on the insulator surface during the aging period.

  10. Do US Black Women Experience Stress-Related Accelerated Biological Aging?

    PubMed Central

    Hicken, Margaret T.; Pearson, Jay A.; Seashols, Sarah J.; Brown, Kelly L.; Cruz, Tracey Dawson

    2010-01-01

    We hypothesize that black women experience accelerated biological aging in response to repeated or prolonged adaptation to subjective and objective stressors. Drawing on stress physiology and ethnographic, social science, and public health literature, we lay out the rationale for this hypothesis. We also perform a first population-based test of its plausibility, focusing on telomere length, a biomeasure of aging that may be shortened by stressors. Analyzing data from the Study of Women's Health Across the Nation (SWAN), we estimate that at ages 49–55, black women are 7.5 years biologically “older” than white women. Indicators of perceived stress and poverty account for 27% of this difference. Data limitations preclude assessing objective stressors and also result in imprecise estimates, limiting our ability to draw firm inferences. Further investigation of black-white differences in telomere length using large-population-based samples of broad age range and with detailed measures of environmental stressors is merited. PMID:20436780

  11. Monitoring migration and transformation of nanomaterials in polymeric composites during accelerated aging

    NASA Astrophysics Data System (ADS)

    Vilar, G.; Fernández-Rosas, E.; Puntes, V.; Jamier, V.; Aubouy, L.; Vázquez-Campos, S.

    2013-04-01

    The incorporation of small amounts of nanoadditives in polymeric compounds can introduce new mechanical, physical, electrical, magnetic, thermal and/or optical properties. The properties of these advanced materials have enabled new applications in several industrial sectors (electronics, automotive, textile...). In particular, for the nanomaterials (NM) described in this work, multi-walled carbon nanotubes (MWCNT) and silicon dioxide nanoparticles (SiO2 NP), the following properties have been described: MWCNT act as nucleating agents in thermoplastics, and change viscosity, affecting dispersion, orientation, and therefore mechanical, thermal, and electrical properties; and SiO2 NP act as flame retardant and display improved electrical and mechanical properties. The work described here is focused on the evaluation of the migration and transformation of NM included in polymer nanocomposites (NC) during accelerated climatic ageing. To this aim, we generated polyamide 6 (PA6) NC with different degree of compatibility between the NM and the polymeric matrix. These NC were submitted to accelerated aging conditions to simulate outdoor conditions (simulation of the use phase of the polymeric NC). The NC contain as nanofillers MWCNT and SiO2 NP with different surface properties to influence the compatibility with the polymeric matrix. The generated NC were evaluated by scanning electron microscopy (SEM), transmission electron microscopy (TEM) with Energy-dispersive X-ray spectroscopy (EDX), thermogravimetry (TGA) and differential scanning calorimetry (DSC) before and after the aging process, to monitor the compatibility of the NM with the matrix: dispersion within the matrix, migration during aging, and modification of the polymer properties. The dispersion of SiO2 NP in the NC depended on their compatibility with the matrix. However, independently of their compatibility with the matrix, SiO2 NP were aggregated at the end of the accelerated aging process. In addition

  12. The influence of the accelerated ageing on the black screen element of the Electroink prints

    NASA Astrophysics Data System (ADS)

    Majnaric, I.; Bolanca, Z.; Bolanca Mirkovic, I.

    2010-06-01

    Printing material and prints undergo changes during ageing which can be recognized in deterioration in the physical, chemical and optical properties. The aim of this work is to determine the optical changes of the prints caused by ageing of the printing material and of the prints obtained by the application of the indirect electrophotography. The change of the screen elements in lighter halftone areas, which was obtained by the usage of the microscopic image analysis, has been discussed in the article. For the preparation of samples the following papers were used: fine art paper, recycled paper and offset paper as well as black Electroink. Three sample series were observed: prints on nonaged paper and ElectroInk, prints on aged paper and ElectroInk and prints on aged paper and nonaged ElectroInk. The investigation results show that by ageing of the uncoated printing substrates the decrease of the dots on prints can be expected, while the printing on the aged paper results in the increased reproduction of the halftone dots. The obtained results are the contribution to the explanation of the influence of the accelerated ageing process of papers which are used for printing and the aged prints on the halftone dot changes. Except the mentioned determined scientific contribution the results are applicable in the area of the printing product quality as well as in the forensic science.

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

    SciTech Connect

    Clifford, A. J.; Arjomand, A.; Duecker, S. R.; Johnson, H.; Schneider, P. D.; Zulim, R. A.; Bucholz, B. A.; Vogel, J. S.

    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.

  14. Mutagenesis in human cells with accelerated H and Fe ions

    NASA Technical Reports Server (NTRS)

    Kronenberg, Amy

    1994-01-01

    The overall goals of this research were to determine the risks of mutation induction and the spectra of mutations induced by energetic protons and iron ions at two loci in human lymphoid cells. During the three year grant period the research has focused in three major areas: (1) the acquisition of sufficient statistics for human TK6 cell mutation experiments using Fe ions (400 MeV/amu), Fe ions (600 MeV/amu) and protons (250 MeV/amu); (2) collection of thymidine kinase- deficient (tk) mutants or hypoxanthine phosphoribosyltransferase deficient (hprt) mutants induced by either Fe 400 MeV/amu, Fe 600 MeV/amu, or H 250 MeV/amu for subsequent molecular analysis; and (3) molecular characterization of mutants isolated after exposure to Fe ions (600 MeV/amu). As a result of the shutdown of the BEVALAC heavy ion accelerator in December 1992, efforts were rearranged somewhat in time to complete our dose-response studies and to complete mutant collections in particular for the Fe ion beams prior to the shutdown. These goals have been achieved. A major effort was placed on collection, re-screening, and archiving of 3 different series of mutants for the various particle beam exposures: tk-ng mutants, tk-sg mutants, and hprt-deficient mutants. Where possible, groups of mutants were isolated for several particle fluences. Comparative analysis of mutation spectra has occured with characterization of the mutation spectrum for hprt-deficient mutants obtained after exposure of TK6 cells to Fe ions (600 MeV/amu) and a series of spontaneous mutants.

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

    PubMed

    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. PMID:14517400

  16. Increased Oxidative and Nitrative Stress Accelerates Aging of the Retinal Vasculature in the Diabetic Retina

    PubMed Central

    Lamoke, Folami; Shaw, Sean; Yuan, Jianghe; Ananth, Sudha; Duncan, Michael; Martin, Pamela; Bartoli, Manuela

    2015-01-01

    Hyperglycemia-induced retinal oxidative and nitrative stress can accelerate vascular cell aging, which may lead to vascular dysfunction as seen in diabetes. There is no information on whether this may contribute to the progression of diabetic retinopathy (DR). In this study, we have assessed the occurrence of senescence-associated markers in retinas of streptozotocin-induced diabetic rats at 8 and 12 weeks of hyperglycemia as compared to normoglycemic aging (12 and 14 months) and adult (4.5 months) rat retinas. We have found that in the diabetic retinas there was an up-regulation of senescence-associated markers SA-β-Gal, p16INK4a and miR34a, which correlated with decreased expression of SIRT1, a target of miR34a. Expression of senescence-associated factors primarily found in retinal microvasculature of diabetic rats exceeded levels measured in adult and aging rat retinas. In aging rats, retinal expression of senescence associated-factors was mainly localized at the level of the retinal pigmented epithelium and only minimally in the retinal microvasculature. The expression of oxidative/nitrative stress markers such as 4-hydroxynonenal and nitrotyrosine was more pronounced in the retinal vasculature of diabetic rats as compared to normoglycemic aging and adult rat retinas. Treatments of STZ-rats with the anti-nitrating drug FeTPPS (10mg/Kg/day) significantly reduced the appearance of senescence markers in the retinal microvasculature. Our results demonstrate that hyperglycemia accelerates retinal microvascular cell aging whereas physiological aging affects primarily cells of the retinal pigmented epithelium. In conclusion, hyperglycemia-induced retinal vessel dysfunction and DR progression involve vascular cell senescence due to increased oxidative/nitrative stress. PMID:26466127

  17. Age-accelerated atherosclerosis correlates with failure to upregulate antioxidant genes.

    PubMed

    Collins, Alan R; Lyon, Christopher J; Xia, Xuefeng; Liu, Joey Z; Tangirala, Rajendra K; Yin, Fen; Boyadjian, Rima; Bikineyeva, Alfiya; Praticò, Domenico; Harrison, David G; Hsueh, Willa A

    2009-03-27

    Excess food intake leads to obesity and diabetes, both of which are well-known independent risk factors for atherosclerosis, and both of which are growing epidemics in an aging population. We hypothesized that aging enhances the metabolic and vascular effects of high fat diet (HFD) and therefore examined the effect of age on atherosclerosis and insulin resistance in lipoprotein receptor knockout (LDLR(-/-)) mice. We found that 12-month-old (middle-aged) LDLR(-/-) mice developed substantially worse metabolic syndrome, diabetes, and atherosclerosis than 3-month-old (young) LDLR(-/-) mice when both were fed HFD for 3 months, despite similar elevations in total cholesterol levels. Microarray analyses were performed to analyze the mechanism responsible for the marked acceleration of atherosclerosis in middle-aged mice. Chow-fed middle-aged mice had greater aortic expression of multiple antioxidant genes than chow-fed young mice, including glutathione peroxidase-1 and -4, catalase, superoxide dismutase-2, and uncoupling protein-2. Aortic expression of these enzymes markedly increased in young mice fed HFD but decreased or only modestly increased in middle-aged mice fed HFD, despite the fact that systemic oxidative stress and vascular reactive oxygen species generation, measured by plasma F2alpha isoprostane concentration (systemic) and dihydroethidium conversion and p47phox expression (vascular), were greater in middle-aged mice fed HFD. Thus, the mechanism for the accelerated vascular injury in older LDLR(-/-) mice was likely the profound inability to mount an antioxidant response. This effect was related to a decrease in vascular expression of 2 key transcriptional pathways regulating the antioxidant response, DJ-1 and forkhead box, subgroup O family (FOXOs). Treatment of middle-aged mice fed HFD with the antioxidant apocynin attenuated atherosclerosis, whereas treatment with the insulin sensitizer rosiglitazone attenuated both metabolic syndrome and atherosclerosis

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

    PubMed

    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. PMID:25555260

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

    PubMed

    Rickabaugh, Tammy M; Baxter, Ruth M; Sehl, Mary; Sinsheimer, Janet S; Hultin, Patricia M; Hultin, Lance E; Quach, Austin; Martínez-Maza, Otoniel; Horvath, Steve; Vilain, Eric; Jamieson, Beth D

    2015-01-01

    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 are

  20. Aging after noise exposure: acceleration of cochlear synaptopathy in "recovered" ears.

    PubMed

    Fernandez, Katharine A; Jeffers, Penelope W C; Lall, Kumud; Liberman, M Charles; Kujawa, Sharon G

    2015-05-13

    Cochlear synaptic loss, rather than hair cell death, is the earliest sign of damage in both noise- and age-related hearing impairment (Kujawa and Liberman, 2009; Sergeyenko et al., 2013). Here, we compare cochlear aging after two types of noise exposure: one producing permanent synaptic damage without hair cell loss and another producing neither synaptopathy nor hair cell loss. Adult mice were exposed (8-16 kHz, 100 or 91 dB SPL for 2 h) and then evaluated from 1 h to ∼ 20 months after exposure. Cochlear function was assessed via distortion product otoacoustic emissions and auditory brainstem responses (ABRs). Cochlear whole mounts and plastic sections were studied to quantify hair cells, cochlear neurons, and the synapses connecting them. The synaptopathic noise (100 dB) caused 35-50 dB threshold shifts at 24 h. By 2 weeks, thresholds had recovered, but synaptic counts and ABR amplitudes at high frequencies were reduced by up to ∼ 45%. As exposed animals aged, synaptopathy was exacerbated compared with controls and spread to lower frequencies. Proportional ganglion cell losses followed. Threshold shifts first appeared >1 year after exposure and, by ∼ 20 months, were up to 18 dB greater in the synaptopathic noise group. Outer hair cell losses were exacerbated in the same time frame (∼ 10% at 32 kHz). In contrast, the 91 dB exposure, producing transient threshold shift without acute synaptopathy, showed no acceleration of synaptic loss or cochlear dysfunction as animals aged, at least to ∼ 1 year after exposure. Therefore, interactions between noise and aging may require an acute synaptopathy, but a single synaptopathic exposure can accelerate cochlear aging. PMID:25972177

  1. Aging after Noise Exposure: Acceleration of Cochlear Synaptopathy in “Recovered” Ears

    PubMed Central

    Fernandez, Katharine A.; Jeffers, Penelope W.C.; Lall, Kumud; Liberman, M. Charles

    2015-01-01

    Cochlear synaptic loss, rather than hair cell death, is the earliest sign of damage in both noise- and age-related hearing impairment (Kujawa and Liberman, 2009; Sergeyenko et al., 2013). Here, we compare cochlear aging after two types of noise exposure: one producing permanent synaptic damage without hair cell loss and another producing neither synaptopathy nor hair cell loss. Adult mice were exposed (8–16 kHz, 100 or 91 dB SPL for 2 h) and then evaluated from 1 h to ∼20 months after exposure. Cochlear function was assessed via distortion product otoacoustic emissions and auditory brainstem responses (ABRs). Cochlear whole mounts and plastic sections were studied to quantify hair cells, cochlear neurons, and the synapses connecting them. The synaptopathic noise (100 dB) caused 35–50 dB threshold shifts at 24 h. By 2 weeks, thresholds had recovered, but synaptic counts and ABR amplitudes at high frequencies were reduced by up to ∼45%. As exposed animals aged, synaptopathy was exacerbated compared with controls and spread to lower frequencies. Proportional ganglion cell losses followed. Threshold shifts first appeared >1 year after exposure and, by ∼20 months, were up to 18 dB greater in the synaptopathic noise group. Outer hair cell losses were exacerbated in the same time frame (∼10% at 32 kHz). In contrast, the 91 dB exposure, producing transient threshold shift without acute synaptopathy, showed no acceleration of synaptic loss or cochlear dysfunction as animals aged, at least to ∼1 year after exposure. Therefore, interactions between noise and aging may require an acute synaptopathy, but a single synaptopathic exposure can accelerate cochlear aging. PMID:25972177

  2. Olfactory phenotypic expression unveils human aging

    PubMed Central

    Mazzatenta, Andrea; Cellerino, Alessandro; Origlia, Nicola; Barloscio, Davide; Sartucci, Ferdinando; Giulio, Camillo Di; Domenici, Luciano

    2016-01-01

    The mechanism of the natural aging of olfaction and its declinein the absence of any overt disease conditions remains unclear. Here, we investigated this mechanism through measurement of one of the parameters of olfactory function, the absolute threshold, in a healthy population from childhood to old age. The absolute olfactory threshold data were collected from an Italian observational study with 622 participants aged 5-105 years. A subjective testing procedure of constant stimuli was used, which was also compared to the ‘staircase’ method, with the calculation of the reliability. The n-butanol stimulus was used as an ascending series of nine molar concentrations that were monitored using an electronic nose. The data were analyzed using nonparametric statistics because of the multimodal distribution. We show that the age-related variations in the absolute olfactory threshold are not continuous; instead, there are multiple olfactory phenotypes. Three distinct age-related phenotypes were defined, termed as ‘juvenile’, ‘mature’ and ‘elder’. The frequency of these three phenotypes depends on age. Our data suggest that the sense of smell does not decrease linearly with aging. Our findings provide the basis for further understanding of olfactory loss as an anticipatory sign of aging and neurodegenerative processes. PMID:27027240

  3. Human information processing in different age.

    PubMed

    Korobeynikov, G

    2002-01-01

    The aim of investigation was to study the aging pecularities of information processing organization. 60 men and 90 women in four age groups: 30-39, 40-49, 50-59 and 60-65 were examined. The information processing was modeled by special computer test with working algorithm changes. The time and accuracy of each assignment were registered for each person. The psychophysiological mechanisms of informational processing were studied by informative mathematical methods. The results are showed that within the aging reduction of perception, processing and speed of reaction in older. As a result of the negative influence of aging shows the decline of mental activity efficiency. Aging decrease on mental capability provokes the compensation of psychophysiological mechanisms of adaptation. The main mechanism increases the psychophysiological organization stochastic and changes the type organization in informational processing to a self-finishing quest response. (Tab. 5, Ref. 22.) PMID:12518996

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

    PubMed

    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. PMID:25528930

  5. Advance techniques for monitoring human tolerance to positive Gz accelerations

    NASA Technical Reports Server (NTRS)

    Pelligra, R.; Sandler, H.; Rositano, S.; Skrettingland, K.; Mancini, R.

    1973-01-01

    Tolerance to positive g accelerations was measured in ten normal male subjects using both standard and advanced techniques. In addition to routine electrocardiogram, heart rate, respiratory rate, and infrared television, monitoring techniques during acceleration exposure included measurement of peripheral vision loss, noninvasive temporal, brachial, and/or radial arterial blood flow, and automatic measurement of indirect systolic and diastolic blood pressure at 60-sec intervals. Although brachial and radial arterial flow measurements reflected significant cardiovascular changes during and after acceleration, they were inconsistent indices of the onset of grayout or blackout. Temporal arterial blood flow, however, showed a high correlation with subjective peripheral light loss.

  6. Three-dimensional human facial morphologies as robust aging markers

    PubMed Central

    Chen, Weiyang; Qian, Wei; Wu, Gang; Chen, Weizhong; Xian, Bo; Chen, Xingwei; Cao, Yaqiang; Green, Christopher D; Zhao, Fanghong; Tang, Kun; Han, Jing-Dong J

    2015-01-01

    Aging is associated with many complex diseases. Reliable prediction of the aging process is important for assessing the risks of aging-associated diseases. However, despite intense research, so far there is no reliable aging marker. Here we addressed this problem by examining whether human 3D facial imaging features could be used as reliable aging markers. We collected > 300 3D human facial images and blood profiles well-distributed across ages of 17 to 77 years. By analyzing the morphological profiles, we generated the first comprehensive map of the aging human facial phenome. We identified quantitative facial features, such as eye slopes, highly associated with age. We constructed a robust age predictor and found that on average people of the same chronological age differ by ± 6 years in facial age, with the deviations increasing after age 40. Using this predictor, we identified slow and fast agers that are significantly supported by levels of health indicators. Despite a close relationship between facial morphological features and health indicators in the blood, facial features are more reliable aging biomarkers than blood profiles and can better reflect the general health status than chronological age. PMID:25828530

  7. Three-dimensional human facial morphologies as robust aging markers.

    PubMed

    Chen, Weiyang; Qian, Wei; Wu, Gang; Chen, Weizhong; Xian, Bo; Chen, Xingwei; Cao, Yaqiang; Green, Christopher D; Zhao, Fanghong; Tang, Kun; Han, Jing-Dong J

    2015-05-01

    Aging is associated with many complex diseases. Reliable prediction of the aging process is important for assessing the risks of aging-associated diseases. However, despite intense research, so far there is no reliable aging marker. Here we addressed this problem by examining whether human 3D facial imaging features could be used as reliable aging markers. We collected > 300 3D human facial images and blood profiles well-distributed across ages of 17 to 77 years. By analyzing the morphological profiles, we generated the first comprehensive map of the aging human facial phenome. We identified quantitative facial features, such as eye slopes, highly associated with age. We constructed a robust age predictor and found that on average people of the same chronological age differ by ± 6 years in facial age, with the deviations increasing after age 40. Using this predictor, we identified slow and fast agers that are significantly supported by levels of health indicators. Despite a close relationship between facial morphological features and health indicators in the blood, facial features are more reliable aging biomarkers than blood profiles and can better reflect the general health status than chronological age. PMID:25828530

  8. Accelerated fibrosis and apoptosis with ageing and in atrial fibrillation: Adaptive responses with maladaptive consequences.

    PubMed

    Xu, Guo-Jun; Gan, Tian-Yi; Tang, Bao-Peng; Chen, Zu-Heng; Mahemuti, Ailiman; Jiang, Tao; Song, Jian-Guo; Guo, Xia; Li, Yao-Dong; Miao, Hai-Jun; Zhou, Xian-Hui; Zhang, Yu; Li, Jin-Xin

    2013-03-01

    The aim of this study was to investigate whether abnormal expression of matrix metalloproteinase (MMP)-9/tissue inhibitors of MMPs (TIMP)-1 and B cell lymphoma 2 (BCL-2)/BCL-2-associated X protein (BAX) are correlated with the characteristic accelerated fibrosis and apoptosis during ageing and in atrial fibrillation (AF). Four groups of dogs were studied: adult dogs in sinus rhythm (SR), aged dogs in SR, adult dogs with AF induced by rapid atrial pacing and aged dogs with AF induced by rapid atrial pacing. The mRNA and protein expression levels of the target gene in the left atrium were measured by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis. Pathohistological and ultrastructural changes were assessed by light and electron microscopy. The apoptotic indices of myocytes were detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL). The mRNA and protein expression levels of MMP-9 and BAX and those of TIMP-1 and BCL-2 were significantly upregulated and down-regulated, respectively, in the aged groups compared with the adult groups. Compared with the control groups, the adult and aged groups with AF exhibited significantly increased mRNA and protein expression levels of MMP-9 and BAX and decreased expression levels of TIMP-1 and BCL-2. Samples of atrial tissue demonstrated abnormal pathohistological and ultrastructural changes, accelerated fibrosis and apoptosis. MMP-9/TIMP-1 and BCL-2/BAX hold potential for use as substrates conducive to AF and their abnormal expression plays a major role in structural remodeling of the atrium. PMID:23403858

  9. Age, human performance, and physical employment standards.

    PubMed

    Kenny, Glen P; Groeller, Herbert; McGinn, Ryan; Flouris, Andreas D

    2016-06-01

    The proportion of older workers has increased substantially in recent years, with over 25% of the Canadian labour force aged ≥55 years. Along with chronological age comes age-related declines in functional capacity associated with impairments to the cardiorespiratory and muscular systems. As a result, older workers are reported to exhibit reductions in work output and in the ability to perform and/or sustain the required effort when performing work tasks. However, research has presented some conflicting views on the consequences of aging in the workforce, as physically demanding occupations can be associated with improved or maintained physical function. Furthermore, the current methods for evaluating physical function in older workers often lack specificity and relevance to the actual work tasks, leading to an underestimation of physical capacity in the older worker. Nevertheless, industry often lacks the appropriate information and/or tools to accommodate the aging workforce, particularly in the context of physical employment standards. Ultimately, if appropriate workplace strategies and work performance standards are adopted to optimize the strengths and protect against the vulnerability of the aging workers, they can perform as effectively as their younger counterparts. Our aim in this review is to evaluate the impact of different individual (including physiological decline, chronic disease, lifestyle, and physical activity) and occupational (including shift work, sleep deprivation, and cold/heat exposure) factors on the physical decline of older workers, and therefore the risk of work-related injuries or illness. PMID:27277571

  10. Myths of Human Sexuality in the Aging.

    ERIC Educational Resources Information Center

    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…

  11. Aging and vascular endothelial function in humans

    PubMed Central

    SEALS, Douglas R.; JABLONSKI, Kristen L.; DONATO, Anthony J.

    2012-01-01

    Advancing age is the major risk factor for the development of CVD (cardiovascular diseases). This is attributable, in part, to the development of vascular endothelial dysfunction, as indicated by reduced peripheral artery EDD (endothelium-dependent dilation) in response to chemical [typically ACh (acetylcholine)] or mechanical (intravascular shear) stimuli. Reduced bioavailability of the endothelium-synthesized dilating molecule NO (nitric oxide) as a result of oxidative stress is the key mechanism mediating reduced EDD with aging. Vascular oxidative stress increases with age as a consequence of greater production of reactive oxygen species (e.g. superoxide) without a compensatory increase in antioxidant defences. Sources of increased superoxide production include up-regulation of the oxidant enzyme NADPH oxidase, uncoupling of the normally NO-producing enzyme, eNOS (endothelial NO synthase) (due to reduced availability of the cofactor tetrahydrobiopterin) and increased mitochondrial synthesis during oxidative phosphorylation. Increased bioactivity of the potent endothelial-derived constricting factor ET-1 (endothelin-1), reduced endothelial production of/responsiveness to dilatory prostaglandins, the development of vascular inflammation, formation of AGEs (advanced glycation end-products), an increased rate of endothelial apoptosis and reduced expression of oestrogen receptor α (in postmenopausal females) also probably contribute to impaired EDD with aging. Several lifestyle and biological factors modulate vascular endothelial function with aging, including regular aerobic exercise, dietary factors (e.g. processed compared with non-processed foods), body weight/fatness, vitamin D status, menopause/oestrogen deficiency and a number of conventional and non-conventional risk factors for CVD. Given the number of older adults now and in the future, more information is needed on effective strategies for the prevention and treatment of vascular endothelial aging. PMID

  12. Improving Bone Microarchitecture in Aging with Diosgenin Treatment: A Study in Senescence-Accelerated OXYS Rats.

    PubMed

    Tikhonova, Maria A; Ting, Che-Hao; Kolosova, Nataliya G; Hsu, Chao-Yu; Chen, Jian-Horng; Huang, Chi-Wen; Tseng, Ging-Ting; Hung, Ching-Sui; Kao, Pan-Fu; Amstislavskaya, Tamara G; Ho, Ying-Jui

    2015-10-31

    Osteoporosis is a major disease associated with aging. We have previously demonstrated that diosgenin prevents osteoporosis in both menopause and D-galactose-induced aging rats. OXYS rats reveal an accelerated senescence and are used as a suitable model of osteoporosis. The aim of the present study was to analyze microarchitecture and morphological changes in femur of OXYS rats using morphological tests and microcomputed tomography scanning, and to evaluate the effects of oral administration of diosgenin at 10 and 50 mg/kg/day on femur in OXYS rats. The result showed that, compared with age-matched Wistar rats, the femur of OXYS rats revealed lower bone length, bone weight, bone volume, frame volume, frame density, void volume, porosity, external and internal diameters, cortical bone area, BV/TV, Tb.N, and Tb.Th, but higher Tb.Sp. Eight weeks of diosgenin treatment decreased porosity and Tb.Sp, but increased BV/TV, cortical bone area, Tb.N and bone mineral density, compared with OXYS rats treated with vehicle. These data reveal that microarchitecture and morphological changes in femur of OXYS rats showed osteoporotic aging features and suggest that diosgenin may have beneficial effects on aging-induced osteoporosis. PMID:26387656

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

    PubMed Central

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

    2016-01-01

    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. PMID:26869336

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

    PubMed

    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. PMID:26869336

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

    NASA Astrophysics Data System (ADS)

    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. Oxidative Stress in Aging Human Skin

    PubMed Central

    Rinnerthaler, Mark; Bischof, Johannes; Streubel, Maria Karolin; Trost, Andrea; Richter, Klaus

    2015-01-01

    Oxidative stress in skin plays a major role in the aging process. This is true for intrinsic aging and even more for extrinsic aging. Although the results are quite different in dermis and epidermis, extrinsic aging is driven to a large extent by oxidative stress caused by UV irradiation. In this review the overall effects of oxidative stress are discussed as well as the sources of ROS including the mitochondrial ETC, peroxisomal and ER localized proteins, the Fenton reaction, and such enzymes as cyclooxygenases, lipoxygenases, xanthine oxidases, and NADPH oxidases. Furthermore, the defense mechanisms against oxidative stress ranging from enzymes like superoxide dismutases, catalases, peroxiredoxins, and GSH peroxidases to organic compounds such as L-ascorbate, α-tocopherol, beta-carotene, uric acid, CoQ10, and glutathione are described in more detail. In addition the oxidative stress induced modifications caused to proteins, lipids and DNA are discussed. Finally age-related changes of the skin are also a topic of this review. They include a disruption of the epidermal calcium gradient in old skin with an accompanying change in the composition of the cornified envelope. This modified cornified envelope also leads to an altered anti-oxidative capacity and a reduced barrier function of the epidermis. PMID:25906193

  17. Analysis of cancer genomes reveals basic features of human aging and its role in cancer development

    PubMed Central

    Podolskiy, Dmitriy I.; Lobanov, Alexei V.; Kryukov, Gregory V.; Gladyshev, Vadim N.

    2016-01-01

    Somatic mutations have long been implicated in aging and disease, but their impact on fitness and function is difficult to assess. Here by analysing human cancer genomes we identify mutational patterns associated with aging. Our analyses suggest that age-associated mutation load and burden double approximately every 8 years, similar to the all-cause mortality doubling time. This analysis further reveals variance in the rate of aging among different human tissues, for example, slightly accelerated aging of the reproductive system. Age-adjusted mutation load and burden correlate with the corresponding cancer incidence and precede it on average by 15 years, pointing to pre-clinical cancer development times. Behaviour of mutation load also exhibits gender differences and late-life reversals, explaining some gender-specific and late-life patterns in cancer incidence rates. Overall, this study characterizes some features of human aging and offers a mechanism for age being a risk factor for the onset of cancer. PMID:27515585

  18. Analysis of cancer genomes reveals basic features of human aging and its role in cancer development.

    PubMed

    Podolskiy, Dmitriy I; Lobanov, Alexei V; Kryukov, Gregory V; Gladyshev, Vadim N

    2016-01-01

    Somatic mutations have long been implicated in aging and disease, but their impact on fitness and function is difficult to assess. Here by analysing human cancer genomes we identify mutational patterns associated with aging. Our analyses suggest that age-associated mutation load and burden double approximately every 8 years, similar to the all-cause mortality doubling time. This analysis further reveals variance in the rate of aging among different human tissues, for example, slightly accelerated aging of the reproductive system. Age-adjusted mutation load and burden correlate with the corresponding cancer incidence and precede it on average by 15 years, pointing to pre-clinical cancer development times. Behaviour of mutation load also exhibits gender differences and late-life reversals, explaining some gender-specific and late-life patterns in cancer incidence rates. Overall, this study characterizes some features of human aging and offers a mechanism for age being a risk factor for the onset of cancer. PMID:27515585

  19. The electrical performance of polymeric insulating materials under accelerated aging in a fog chamber

    SciTech Connect

    Gorur, R.S.; Cherney, E.A.; Hackam, R. ); Orbeck, T. )

    1988-07-01

    A comparative study of the ac (60 Hz) surface aging in a fog chamber is reported on cylindrical rod samples of high temperature vulcanized (HTV) silicone rubber and ethylene propylene diene monomer (EPDM) rubber containing various amounts of alumina trihydrate (ATH) and/or silica fillers. In low conductivity (250 ..mu..S/cm) fog, silicone rubber performed better than EPDM samples whereas in high conductivity (1000 ..mu..S/cm) fog, the order of performance was reversed. The mechanisms by which fillers impart tracking and erosion resistance to materials is discussed as influenced by the experimental conditions of the accelerated aging tests. Surface studies by ESCA (Electron Spectroscopy for Chemical Analysis) demonstrate that the hydrophobicity of silicone rubber, despite the accumulation of surface contamination, can be attributed to migration of low molecular weight polymer chains and/or mobile fluids, such as silicone oil.

  20. Impact absorption of four processed soft denture liners as influenced by accelerated aging.

    PubMed

    Kawano, F; Koran, A; Nuryanti, A; Inoue, S

    1997-01-01

    The cushioning effect of soft denture liners was evaluated by using a free drop test with an accelerometer. Materials tested included SuperSoft (Coe Laboratories, Chicago, IL), Kurepeet-Dough (Kreha Chemical, Tokyo), Molteno Soft (Molten, Hiroshima, Japan), and Molloplast-B (Molloplast Regneri, Karlsruhe, Germany). All materials were found to reduce the impact force when compared to acrylic denture base resin. A 2.4-mm layer of soft denture material demonstrated good impact absorption, and Molloplast-B and Molteno had excellent impact absorption. When the soft denture liner was kept in an accelerated aging chamber for 900 hours, the damping effect recorded increased for all materials tested. Aging of all materials also affected the cushioning effect. PMID:9484071

  1. High sensitivity to autoxidation in neonatal calf erythrocytes: possible mechanism of accelerated cell aging.

    PubMed

    Imre, S; Csornai, M; Balazs, M

    2001-01-01

    The suspension viscosity, formation of methaemoglobin and production of malondialdehyde (MDA) associated with the non-enzymatic oxidation of polyunsaturated fatty acids during auto-oxidation conditions in vitro have been compared in erythrocytes from young calves (2, 4 and 6 weeks of age) and mature cattle. The autoxidation conditions were designed to simulate the oxidative stress to which neonatal erythrocytes are exposed in vivo. Characterisation of lipid peroxidation was also undertaken by a combination of lipid fluorescent measurements and quantification of the superoxide dismutase (SOD) activities of the erythrocytes. The results demonstrated that high SOD activities in the erythrocytes of the neonatal calf was insufficient to afford protection against the increased autoxidation of haemoglobin and subsequent accumulation of lipid peroxidation products. High levels of methaemoglobin formation and lipid peroxidation were able to provide an explanation for an observed reduction in rheological adaptability (increased suspension viscosity) and an accelerated aging of the neonatal cells under in vivo conditions. PMID:11163624

  2. Glyoxalase I activity and immunoreactivity in the aging human lens

    PubMed Central

    Mailankot, Maneesh; Padmanabha, Smitha; Pasupuleti, NagaRekha; Major, Denice; Howell, Scott

    2013-01-01

    Glyoxalase I (GLOI) is the first enzyme of the glyoxalase system that catalyzes the metabolism of reactive dicarbonyls, such as methylglyoxal (MGO). During aging and cataract development, human lens proteins are chemically modified by MGO, which is likely due to inadequate metabolism of MGO by the glyoxalase system. In this study, we have determined the effect of aging on GLOI activity and the immunoreactivity and morphological distribution of GLOI in the human lens. A monoclonal antibody was developed against human GLOI. GLOI immunoreactivity was strongest in the anterior epithelial cells and weaker in rest of the lens. Cultured human lens epithelial cells showed immunostaining throughout the cytoplasm. In the human lens, GLOI activity and immunoreactivity both decreased with age. We believe that this would lead to promotion of MGO-modification in aging lens proteins. PMID:19238574

  3. THE ANOREXIA OF AGING IN HUMANS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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), psycholog...

  4. A Model-based Prognostics Methodology for Electrolytic Capacitors Based on Electrical Overstress Accelerated Aging

    NASA Technical Reports Server (NTRS)

    Celaya, Jose; Kulkarni, Chetan; Biswas, Gautam; Saha, Sankalita; Goebel, Kai

    2011-01-01

    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.

  5. Physical property comparison of 11 soft denture lining materials as a function of accelerated aging.

    PubMed

    Dootz, E R; Koran, A; Craig, R G

    1993-01-01

    Soft denture-lining materials are an important treatment option for patients who have chronic soreness associated with dental prostheses. Three distinctly different types of materials are generally used. These are plasticized polymers or copolymers, silicones, or polyphosphazene fluoroelastomer. The acceptance of these materials by patients and dentists is variable. The objective of this study is to compare the tensile strength, percent elongation, hardness, tear strength, and tear energy of eight plasticized polymers or copolymers, two silicones, and one polyphosphazene fluoroelastomer. Tests were run at 24 hours after specimen preparation and repeated after 900 hours of accelerated aging in a Weather-Ometer device. The data indicated a wide range of physical properties for soft denture-lining materials and showed that accelerated aging dramatically affected the physical and mechanical properties of many of the elastomers. No soft denture liner proved to be superior to all others. The data obtained should provide clinicians with useful information for selecting soft denture lining materials for patients. PMID:8455156

  6. Aging of the Human Vestibular System.

    PubMed

    Zalewski, Christopher K

    2015-08-01

    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

  7. Aging of the Human Vestibular System

    PubMed Central

    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

  8. Fat-specific Dicer deficiency accelerates aging and mitigates several effects of dietary restriction in mice.

    PubMed

    Reis, Felipe C G; Branquinho, Jéssica L O; Brandão, Bruna B; Guerra, Beatriz A; Silva, Ismael D; Frontini, Andrea; Thomou, Thomas; Sartini, Loris; Cinti, Saverio; Kahn, C Ronald; Festuccia, William T; Kowaltowski, Alicia J; Mori, Marcelo A

    2016-06-01

    Aging increases the risk of type 2 diabetes, and this can be prevented by dietary restriction (DR). We have previously shown that DR inhibits the downregulation of miRNAs and their processing enzymes - mainly Dicer - that occurs with aging in mouse white adipose tissue (WAT). Here we used fat-specific Dicer knockout mice (AdicerKO) to understand the contributions of adipose tissue Dicer to the metabolic effects of aging and DR. Metabolomic data uncovered a clear distinction between the serum metabolite profiles of Lox control and AdicerKO mice, with a notable elevation of branched-chain amino acids (BCAA) in AdicerKO. These profiles were associated with reduced oxidative metabolism and increased lactate in WAT of AdicerKO mice and were accompanied by structural and functional changes in mitochondria, particularly under DR. AdicerKO mice displayed increased mTORC1 activation in WAT and skeletal muscle, where Dicer expression is not affected. This was accompanied by accelerated age-associated insulin resistance and premature mortality. Moreover, DR-induced insulin sensitivity was abrogated in AdicerKO mice. This was reverted by rapamycin injection, demonstrating that insulin resistance in AdicerKO mice is caused by mTORC1 hyperactivation. Our study evidences a DR-modulated role for WAT Dicer in controlling metabolism and insulin resistance. PMID:27241713

  9. Fat-specific Dicer deficiency accelerates aging and mitigates several effects of dietary restriction in mice

    PubMed Central

    Reis, Felipe C. G.; Branquinho, Jéssica L. O.; Brandão, Bruna B.; Guerra, Beatriz A.; Silva, Ismael D.; Frontini, Andrea; Thomou, Thomas; Sartini, Loris; Cinti, Saverio; Kahn, C. Ronald; Festuccia, William T.; Kowaltowski, Alicia J.; Mori, Marcelo A.

    2016-01-01

    Aging increases the risk of type 2 diabetes, and this can be prevented by dietary restriction (DR). We have previously shown that DR inhibits the downregulation of miRNAs and their processing enzymes - mainly Dicer - that occurs with aging in mouse white adipose tissue (WAT). Here we used fat-specific Dicer knockout mice (AdicerKO) to understand the contributions of adipose tissue Dicer to the metabolic effects of aging and DR. Metabolomic data uncovered a clear distinction between the serum metabolite profiles of Lox control and AdicerKO mice, with a notable elevation of branched-chain amino acids (BCAA) in AdicerKO. These profiles were associated with reduced oxidative metabolism and increased lactate in WAT of AdicerKO mice and were accompanied by structural and functional changes in mitochondria, particularly under DR. AdicerKO mice displayed increased mTORC1 activation in WAT and skeletal muscle, where Dicer expression is not affected. This was accompanied by accelerated age-associated insulin resistance and premature mortality. Moreover, DR-induced insulin sensitivity was abrogated in AdicerKO mice. This was reverted by rapamycin injection, demonstrating that insulin resistance in AdicerKO mice is caused by mTORC1 hyperactivation. Our study evidences a DR-modulated role for WAT Dicer in controlling metabolism and insulin resistance. PMID:27241713

  10. T CELL REPLICATIVE SENESCENCE IN HUMAN AGING

    PubMed Central

    Chou, Jennifer P.; Effros, Rita B.

    2013-01-01

    The decline of the immune system appears to be an intractable consequence of aging, leading to increased susceptibility to infections, reduced effectiveness of vaccination and higher incidences of many diseases including osteoporosis and cancer in the elderly. These outcomes can be attributed, at least in part, to a phenomenon known as T cell replicative senescence, a terminal state characterized by dysregulated immune function, loss of the CD28 costimulatory molecule, shortened telomeres and elevated production of pro-inflammatory cytokines. Senescent CD8 T cells, which accumulate in the elderly, have been shown to frequently bear antigen specificity against cytomegalovirus (CMV), suggesting that this common and persistent infection may drive immune senescence and result in functional and phenotypic changes to the T cell repertoire. Senescent T cells have also been identified in patients with certain cancers, autoimmune diseases and chronic infections, such as HIV. This review discusses the in vivo and in vitro evidence for the contribution of CD8 T cell replicative senescence to a plethora of age-related pathologies and a few possible therapeutic avenues to delay or prevent this differentiative end-state in T cells. The age-associated remodeling of the immune system, through accumulation of senescent T cells has far-reaching consequences on the individual and society alike, for the current healthcare system needs to meet the urgent demands of the increasing proportions of the elderly in the US and abroad. PMID:23061726

  11. Human Values in a Technological Age.

    ERIC Educational Resources Information Center

    Gorman, Michael

    2001-01-01

    Discusses technology and its effects on society and humans, particularly library and information technology. Highlights include the evolving history of technology; and values related to technology in libraries, including democracy, stewardship, service, intellectual freedom, privacy, literacy and learning, rationalism, and equity of access. (LRW)

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

    PubMed

    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. PMID:19662799

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

    NASA Astrophysics Data System (ADS)

    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

  14. Age effects on B cells and humoral immunity in humans

    PubMed Central

    Frasca, Daniela; Diaz, Alain; Romero, Maria; Landin, Ana Marie; Blomberg, Bonnie B

    2010-01-01

    Both humoral and cellular immune responses are impaired in aged individuals, leading to decreased vaccine responses. Although T cell defects occur, defects in B cells play a significant role in age-related humoral immune changes. The ability to undergo class switch recombination (CSR), the enzyme for CSR, AID (activation-induced cytidine deaminase) and the transcription factor E47 are all decreased in aged stimulated B cells. We here present an overview of age-related changes in human B cell markers and functions, and also discuss some controversies in the field of B cell aging. PMID:20728581

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

    SciTech Connect

    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 detectable WRN or LMNA mutations, however, no cases of altered LMNA copy number were detected. Nevertheless, our findings raise a hypothesis that changes in lamina organization may cause accelerated telomere attrition, with different kinetics for overexpession of wild-type and mutant lamin A, which leads to rapid replicative senescence and progroid phenotypes.

  16. Heat waves, aging, and human cardiovascular health.

    PubMed

    Kenney, W Larry; Craighead, Daniel H; Alexander, Lacy M

    2014-10-01

    This brief review is based on a President's Lecture presented at the Annual Meeting of the American College of Sports Medicine in 2013. The purpose of this review was to assess the effects of climate change and consequent increases in environmental heat stress on the aging cardiovascular system. The earth's average global temperature is slowly but consistently increasing, and along with mean temperature changes come increases in heat wave frequency and severity. Extreme passive thermal stress resulting from prolonged elevations in ambient temperature and prolonged physical activity in hot environments creates a high demand on the left ventricle to pump blood to the skin to dissipate heat. Even healthy aging is accompanied by altered cardiovascular function, which limits the extent to which older individuals can maintain stroke volume, increase cardiac output, and increase skin blood flow when exposed to environmental extremes. In the elderly, the increased cardiovascular demand during heat waves is often fatal because of increased strain on an already compromised left ventricle. Not surprisingly, excess deaths during heat waves 1) occur predominantly in older individuals and 2) are overwhelmingly cardiovascular in origin. Increasing frequency and severity of heat waves coupled with a rapidly growing at-risk population dramatically increase the extent of future untoward health outcomes. PMID:24598696

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

    SciTech Connect

    Vaziri, H.; Uchida, I.; Lan Wei; Harley, C.B. ); Schaechter, F.; Cohen, D. ); Xiaoming Zhu; Effros, R. )

    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.

  18. Chronologic versus Biologic Aging of the Human Choroid

    PubMed Central

    May, Christian Albrecht

    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, chronologic aging should not be used as a factor for physiological changes in the human choroid. Longitudinal study designs are necessary to further establish the impact of age. Meanwhile, a more biologic oriented model of aging processes in the choroid should be established, including specified conditions (e.g., light exposure and refractory state). This would help to define more individual strategies for prevention and early stages of a certain defined disease. PMID:24453840

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

    PubMed Central

    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

  20. From randomly accelerated particles to Lévy walks: non-ergodic behavior and aging

    NASA Astrophysics Data System (ADS)

    Radons, Guenter; Albers, Tony; Institute of Physics, Complex Systems; Nonlinear Dynamics Team

    For randomly accelerated particles we detected, and were able to analyze in detail (PRL 113, 184101 (2014)), the phenomenon of weak-ergodicity breaking (WEB), i.e. the inequivalence of ensemble- and time-averaged mean-squared displacements (MSD). These results, including their aging time dependence, are relevant for anomalous chaotic diffusion in Hamiltonian systems, for passive tracer transport in turbulent flows, and many other systems showing momentum diffusion. There are, however, several related models, such as the integrated random excursion model, or, space-time correlated Lévy walks and flights, with similar statistical behavior. We compare the WEB related properties of these models and find surprising differences although, for equivalent parameters, all of them are supposed to lead to the same ensemble-averaged MSD. Our findings are relevant for distinguishing possible models for the anomalous diffusion occurring in experimental situations.

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

    SciTech Connect

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

    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.

  2. Effect of disinfection and accelerated ageing on dimensional stability and detail reproduction of a facial silicone with nanoparticles.

    PubMed

    Pesqueira, A A; Goiato, M C; Dos Santos, D M; Haddad, M F; Moreno, A

    2012-05-01

    The aim of the present study was to evaluate the effect of disinfection and accelerated ageing on the dimensional stability and detail reproduction of a facial silicone with different types of nanoparticle. A total of 60 specimens were fabricated with Silastic MDX 4-4210 silicone and they were divided into three groups: colourless and pigmented with nanoparticles (make-up powder and ceramic powder). Half of the specimens of each group were disinfected with Efferdent tablets and half with neutral soap for 60 days. Afterwards, all specimens were subjected to accelerated ageing. Both dimensional stability and detail reproduction tests were performed after specimen fabrication (initial period), after chemical disinfection, and after accelerated ageing periods (252, 504 and 1008 hours). The dimensional stability test was conducted using AutoCAD software, while detail reproduction was analysed using a stereoscope magnifying glass. Dimensional stability values were statistically evaluated by analysis of variance (ANOVA) followed by Tukey's test (p < 0.01). Detail reproduction results were compared using a score. Chemical disinfection and also accelerated ageing affected the dimensional stability of the facial silicone with statistically significant results. The silicone's detail reproduction was not affected by these two factors regardless of nanoparticle type, disinfection and accelerated ageing. PMID:22428808

  3. Effect of Age on Regulation of Human Osteoclast Differentiation

    PubMed Central

    Chung, Ping-Lin; Zhou, Shuanhu; Eslami, Behnam; Shen, Longxiang; LeBoff, Meryl S.; Glowacki, Julie

    2014-01-01

    Human skeletal aging is characterized as a gradual loss of bone mass due to an excess of bone resorption not balanced by new bone formation. Using human marrow cells, we tested the hypothesis that there is an age-dependent increase in osteoclastogenesis due to intrinsic changes in regulatory factors [macrophage-colony stimulating factor (M-CSF), receptor activator of NF-κB ligand (RANKL), and osteoprotegerin (OPG)] and their receptors [c-fms and RANK]. In bone marrow cells (BMCs), c-fms (r=0.61, p=0.006) and RANK expression (r=0.59, p=0.008) were increased with age (27-82 years, n=19). In vitro generation of osteoclasts was increased with age (r=0.89, p=0.007). In enriched marrow stromal cells (MSCs), constitutive expression of RANKL was increased with age (r=0.41, p=0.049) and expression of OPG was inversely correlated with age (r=-0.43, p=0.039). Accordingly, there was an age-related increase in RANKL/OPG (r=0.56, p=0.005). These data indicate an age-related increase in human osteoclastogenesis that is associated with an intrinsic increase in expression of c-fms and RANK in osteoclast progenitors, and, in the supporting MSCs, an increase in pro-osteoclastogenic RANKL expression and a decrease in anti-osteoclastogenic OPG. These findings support the hypothesis that human marrow cells and their products can contribute to skeletal aging by increasing the generation of bone-resorbing osteoclasts. These findings help to explain underlying molecular mechanisms of progressive bone loss with advancing age in humans. PMID:24700654

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

    PubMed

    Ames, Bruce N

    2006-11-21

    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

  5. Uniquely Human Self-Control Begins at School Age

    ERIC Educational Resources Information Center

    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…

  6. [Senescence-accelerated mouse (SAM): with special reference to age-associated pathologies and their modulation].

    PubMed

    Takeda, T

    1996-07-01

    The senescence-accelerated mouse (SAM) has been under development by our research team at Kyoto University since 1970 through selective inbreeding of the AKR/J strain of mice donated by the Jackson Laboratory in 1968, based on the data of the grading score of senescence, life span, and pathologic phenotypes. At present, there are 12 lines of SAM; the 9 senescence-prone inbred strains (SAMP) include SAMP1, SAMP2, SAMP3, SAMP6, SAMP7, SAMP8, SAMP9, SAMP10 and SAMP11, and the 3 senescence-resistant inbred strains (SAMR) SAMR1, SANR4 and SAMR5. Data from survival curves, the Gompertzian function and the grading score of senescence, together with growth patterns of body weight of these SAMP and SAMR mice revealed that the characteristic feature of aging common to all SAMP mice is "accelerated senescence": early onset and irreversible advance of senescence manifested by several signs and gross lesions such as the loss of normal behavior, various skin lesions, increased lordokyphosis, etc., after a period of normal development. Routine postmortem examinations and the pathobiological features revealed by systematically designed studies have shown several pathologic phenotypes, which are often characteristic enough to differentiate among the various SAM strains: senile amyloidosis in SAMP1, -P2, -P7, -P9, -P10 and -P11, secondary amyloidosis in SAMP2 and -P6, contracted kidney in SAMP1, -P2, -P10, -P11, immunoblastic lymphoma in SAMR1 and -R4, histiocytic sarcoma in SAMR1 and -R4, ovarian cysts in SAMR1, impaired immune response in SAMP1, -P2 and -P8, hyperinflation of the lungs in SAMP1, hearing impairment in SAMP1, degenerative temporomandibular joint disease in SAMP3, senile osteoporosis in SAMP6, deficits in learning and memory in SAMP8 and -P10, emotional disorders in SAMP8 and -P10, cataracts in SAMP9, and brain atrophy in SAMP10. These are all age-associated pathologies, the incidence and severity of which increase with advancing age. The SAM model in which these

  7. Epigenetic Mechanisms of the Aging Human Retina

    PubMed Central

    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

  8. Glycosaminoglycans in the Human Cornea: Age-Related Changes

    PubMed Central

    Pacella, Elena; Pacella, Fernanda; De Paolis, Giulio; Parisella, Francesca Romana; Turchetti, Paolo; Anello, Giulia; Cavallotti, Carlo

    2015-01-01

    AIM To investigate possible age-related changes in glycosaminoglycans (GAGs) in the human cornea. The substances today called GAGs were previously referred to as mucopolysaccharides. METHODS Samples of human cornea were taken from 12 younger (age 21 ± 1.2) and 12 older (age 72 ± 1.6) male subjects. Samples were weighed, homogenized, and used for biochemical and molecular analyses. All the quantitative results were statistically analyzed. RESULTS The human cornea appears to undergo age-related changes, as evidenced by our biochemical and molecular results. The total GAG and hyaluronic acid counts were significantly higher in the younger subjects than in the older subjects. The sulfated heavy GAGs, such as chondroitin, dermatan, keratan, and heparan sulfate, were lower in the younger subjects than in the older subjects. DISCUSSION GAGs of the human cornea undergo numerous age-related changes. Their quantity is significantly altered in the elderly in comparison with younger subjects. GAGs play an important role in age-related diseases of the human cornea. PMID:25674020

  9. 27-Hydroxycholesterol accelerates cellular senescence in human lung resident cells.

    PubMed

    Hashimoto, Yuichiro; Sugiura, Hisatoshi; Togo, Shinsaku; Koarai, Akira; Abe, Kyoko; Yamada, Mitsuhiro; Ichikawa, Tomohiro; Kikuchi, Takashi; Numakura, Tadahisa; Onodera, Katsuhiro; Tanaka, Rie; Sato, Kei; Yanagisawa, Satoru; Okazaki, Tatsuma; Tamada, Tsutomu; Kikuchi, Toshiaki; Hoshikawa, Yasushi; Okada, Yoshinori; Ichinose, Masakazu

    2016-06-01

    Cellular senescence is reportedly involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). We previously showed that 27-hydroxycholesterol (27-OHC) is elevated in the airways of COPD patients compared with those in healthy subjects. The aim of this study was to investigate whether lung fibroblasts of COPD patients are senescent and to determine the effects of 27-OHC on senescence of lung resident cells, including fibroblasts and airway epithelial cells. Localization of senescence-associated proteins and sterol 27-hydroxylase was investigated in the lungs of COPD patients by immunohistochemical staining. To evaluate whether 27-OHC accelerates cellular senescence, lung resident cells were exposed to 27-OHC. Senescence markers and fibroblast-mediated tissue repair were investigated in the 27-OHC-treated cells. Expression of senescence-associated proteins was significantly enhanced in lung fibroblasts of COPD patients. Similarly, expression of sterol 27-hydroxylase was significantly upregulated in lung fibroblasts and alveolar macrophages in these patients. Treatment with the concentration of 27-OHC detected in COPD airways significantly augmented expression of senescence-associated proteins and senescence-associated β-galactosidase activity, and delayed cell growth through the prostaglandin E2-reactive nitrogen species pathway. The 27-OHC-treated fibroblasts impaired tissue repair function. Fibroblasts from lungs of COPD patients showed accelerated senescence and were more susceptible to 27-OHC-induced cellular senescence compared with those of healthy subjects. In conclusion, 27-OHC accelerates cellular senescence in lung resident cells and may play a pivotal role in cellular senescence in COPD. PMID:27036870

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

    PubMed

    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. PMID:24855737

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

    PubMed Central

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

    2016-01-01

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

  12. Characteristics of age-related behavioral changes in senescence-accelerated mouse SAMP8 and SAMP10.

    PubMed

    Miyamoto, M

    1997-01-01

    Senescence-Accelerated Mouse (SAM), a murine model of accelerated senescence, has been established by Takeda et al. (1981). SAM consists of senescence-accelerated-prone mouse (SAMP) and senescence-accelerated-resistant mouse (SAMR), the latter of which shows normal aging characteristics. In 1991 there were eight different substrains in the P-series, which commonly exhibited accelerated aging with a shortened life span (Takeda et al., 1991). Among the P-series, we have found that SAMP8 mice show significant impairments in a variety of learning tasks when compared with SAMR1 mice (Miyamoto et al., 1986). Further studies suggest that SAMP8 exhibits an age-related emotional disorder characterized by reduced anxiety-like behavior (Miyamoto et al., 1992). On the other hand, it has been shown that SAMP10 exhibits brain atrophy and learning impairments in an avoidance task (Shimada et al., 1992, 1993). Here, characteristics of age-related deficits in learning and memory, changes in emotional behavior, and abnormality of circadian rhythms in SAMP8 and SAMP10 mice are described. In the experiments, SAMP8/Ta (SAMP8), SAMP10/(/)Ta (SAMP10) and SAMR1TA (SAMR1) reared under specific pathogen-free conditions at Takeda Chemical Industries were used. PMID:9088911

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

    SciTech Connect

    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.

  14. Accelerating neuronal aging in in vitro model brain disorders: a focus on reactive oxygen species

    PubMed Central

    Campos, Priscila Britto; Paulsen, Bruna S.; Rehen, Stevens K.

    2014-01-01

    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 reactive oxygen species (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. PMID:25386139

  15. Complexity of human gait pattern at different ages assessed using multiscale entropy: From development to decline.

    PubMed

    Bisi, M C; Stagni, R

    2016-06-01

    Multiscale entropy (MSE) has been applied in biomechanics to evaluate gait stability during human gait and was found to be a promising method for evaluating fall risk in elderly and/or pathologic subjects. The hypothesis of this work is that gait complexity is a relevant parameter of gait development during life, decreasing from immature to mature gait and then increasing again during old age. In order to verify this hypothesis, MSE was applied on trunk acceleration data collected during gait of subjects of different ages: toddlers at the onset of walking, pre-scholar and scholar children, adolescents, young adults, adults and elderlies. MSE was estimated by calculating sample entropy (SEN) on raw unfiltered data of L5 acceleration along the three axes, using values of τ ranging from 1 to 6. In addition, other performance parameters (cadence, stride time variability and harmonic ratio) were evaluated. The results followed the hypothesized trend when MSE was applied on the vertical and/or anteroposterior axis of trunk acceleration: an age effect was found and adult SEN values were significantly different from children ones. From young adults to elderlies a slight increase in SEN values was shown although not statistically significant. While performance gait parameters showed adolescent gait similar to the one of adults, SEN highlighted that their gait maturation is not complete yet. In conclusion, present results suggest that the complexity of gait, evaluated on the sagittal plane, can be used as a characterizing parameter of the maturation of gait control. PMID:27264400

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

    PubMed Central

    Knibbe-Hollinger, Jaclyn S.; Fields, Natasha R.; Chaudoin, Tammy R; Epstein, Adrian A.; Makarov, Edward; Akhter, Sidra P.; Gorantla, Santhi; Bonasera, Stephen J.; Gendelman, Howard E.; Poluektova, Larisa Y.

    2015-01-01

    ABSTRACT 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. PMID:26353862

  17. Age-Dependent Pancreatic Gene Regulation Reveals Mechanisms Governing Human β Cell Function.

    PubMed

    Arda, H Efsun; Li, Lingyu; Tsai, Jennifer; Torre, Eduardo A; Rosli, Yenny; Peiris, Heshan; Spitale, Robert C; Dai, Chunhua; Gu, Xueying; Qu, Kun; Wang, Pei; Wang, Jing; Grompe, Markus; Scharfmann, Raphael; Snyder, Michael S; Bottino, Rita; Powers, Alvin C; Chang, Howard Y; Kim, Seung K

    2016-05-10

    Intensive efforts are focused on identifying regulators of human pancreatic islet cell growth and maturation to accelerate development of therapies for diabetes. After birth, islet cell growth and function are dynamically regulated; however, establishing these age-dependent changes in humans has been challenging. Here, we describe a multimodal strategy for isolating pancreatic endocrine and exocrine cells from children and adults to identify age-dependent gene expression and chromatin changes on a genomic scale. These profiles revealed distinct proliferative and functional states of islet α cells or β cells and histone modifications underlying age-dependent gene expression changes. Expression of SIX2 and SIX3, transcription factors without prior known functions in the pancreas and linked to fasting hyperglycemia risk, increased with age specifically in human islet β cells. SIX2 and SIX3 were sufficient to enhance insulin content or secretion in immature β cells. Our work provides a unique resource to study human-specific regulators of islet cell maturation and function. PMID:27133132

  18. Characterizing cognitive aging in humans with links to animal models

    PubMed Central

    Alexander, Gene E.; Ryan, Lee; Bowers, Dawn; Foster, Thomas C.; Bizon, Jennifer L.; Geldmacher, David S.; Glisky, Elizabeth L.

    2012-01-01

    With the population of older adults expected to grow rapidly over the next two decades, it has become increasingly important to advance research efforts to elucidate the mechanisms associated with cognitive aging, with the ultimate goal of developing effective interventions and prevention therapies. Although there has been a vast research literature on the use of cognitive tests to evaluate the effects of aging and age-related neurodegenerative disease, the need for a set of standardized measures to characterize the cognitive profiles specific to healthy aging has been widely recognized. Here we present a review of selected methods and approaches that have been applied in human research studies to evaluate the effects of aging on cognition, including executive function, memory, processing speed, language, and visuospatial function. The effects of healthy aging on each of these cognitive domains are discussed with examples from cognitive/experimental and clinical/neuropsychological approaches. Further, we consider those measures that have clear conceptual and methodological links to tasks currently in use for non-human animal studies of aging, as well as those that have the potential for translation to animal aging research. Having a complementary set of measures to assess the cognitive profiles of healthy aging across species provides a unique opportunity to enhance research efforts for cross-sectional, longitudinal, and intervention studies of cognitive aging. Taking a cross-species, translational approach will help to advance cognitive aging research, leading to a greater understanding of associated neurobiological mechanisms with the potential for developing effective interventions and prevention therapies for age-related cognitive decline. PMID:22988439

  19. Chronologic and actinically induced aging in human facial skin

    SciTech Connect

    Gilchrest, B.A.; Szabo, G.; Flynn, E.; Goldwyn, R.M.

    1983-06-01

    Clinical and histologic stigmata of aging are much more prominent in habitually sun-exposed skin than in sun-protected skin, but other possible manifestations of actinically induced aging are almost unexplored. We have examined the interrelation of chronologic and actinic aging using paired preauricular (sun-exposed) and postauricular (sun-protected) skin specimens. Keratinocyte cultures derived from sun-exposed skin consistently had a shorter in vitro lifespan but increased plating efficiency compared with cultures derived from adjacent sun-protected skin of the same individual, confirming a previous study of different paired body sites. Electron microscopic histologic sections revealed focal abnormalities of keratinocyte proliferation and alignment in vitro especially in those cultures derived from sun-exposed skin and decreased intercellular contact in stratified colonies at late passage, regardless of donor site. One-micron histologic sections of the original biopsy specimens revealed no striking site-related keratinocyte alterations, but sun-exposed specimens had fewer epidermal Langerhans cells (p less than 0.001), averaging approximately 50 percent the number in sun-protected skin, a possible exaggeration of the previously reported age-associated decrease in this cell population. These data suggest that sun exposure indeed accelerates aging by several criteria and that, regardless of mechanism, environmental factors may adversely affect the appearance and function of aging skin in ways amenable to experimental quantitation.

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

    PubMed

    Shagina, N B; Tolstykh, E I; Degteva, M O; Anspaugh, L R; Napier, B 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 limitations 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 (90)Sr 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 a similar structure to the ICRP model for the alkaline earth elements. The following parameters were mainly re-evaluated: gastrointestinal 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 populations exposed to ingested strontium radioisotopes. PMID:25574605

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

    SciTech Connect

    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.

  2. Dysregulation of Human Toll-like Receptor Function in Aging

    PubMed Central

    Shaw, Albert C.; Panda, Alexander; Joshi, Samit R.; Qian, Feng; Allore, Heather G.; Montgomery, Ruth R.

    2010-01-01

    Studies addressing immunosenescence in the immune system have expanded to focus on the innate as well as the adaptive responses. In particular, aging results in alterations in the function of Toll-like receptors (TLRs), the first described pattern recognition receptor family of the innate immune system. Recent studies have begun to elucidate the consequences of aging on TLR function in human cohorts and add to existing findings performed in animal models. In general, these studies show that human TLR function is impaired in the context of aging, and in addition there is evidence for inappropriate persistence of TLR activation in specific systems. These findings are consistent with an overarching theme of age-associated dysregulation of TLR signaling that likely contributes to the increased morbidity and mortality from infectious diseases found in geriatric patients. PMID:21074638

  3. Deterioration of muscle function in the human esophagus with age.

    PubMed

    Gregersen, Hans; Pedersen, Jan; Drewes, Asbjørn Mohr

    2008-12-01

    Most studies on the effect of aging on esophageal motor function have shown that peristaltic function deteriorates with age. Esophageal motor function is traditionally studied by means of manometry and radiography. Distension of the esophagus with evaluation of active and passive mechanical parameters have become available during recent years. In this study, we did a manometric swallow analysis and used the distension method to study esophageal properties and function during aging. An impedance planimetric probe with a bag for distension was placed in the distal esophagus of 25 healthy volunteers with a median age of 35 (range 23-86) years. Distensions were done at an infusion rate of 25 ml min(-1) with and without relaxation of neuromuscular activity with butylscopolamine. The infusion was reversed when moderate pain was experienced by the subjects. Swallow-induced contraction amplitudes decreased as function of age for persons older than 40 years (P < 0.05). The total and passive tension showed an exponential increase as function of the change in radius, whereas the active tension increased until it reached a local maximum point. The maximum active tension deteriorated as a function of age after the age of 40 years (P < 0.05). Furthermore, esophagus became stiffer with age. In conclusion, age-related changes of increased stiffness and reduced primary and secondary peristalsis were found in the human esophagus with a deterioration of esophageal function after the age of 40 years. Such changes may contribute to the high prevalence of reflux disease in elderly. PMID:18461452

  4. Do glutathione levels decline in aging human brain?

    PubMed

    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. PMID:26845616

  5. Accelerated ageing of an EAF black slag by carbonation and percolation for long-term behaviour assessment.

    PubMed

    Gurtubay, L; Gallastegui, G; Elias, A; Rojo, N; Barona, A

    2014-07-01

    The efficient reuse of industrial by-products, such as the electric arc furnace (EAF) black slag, is still hindered by concern over their long-term behaviour in outdoor environments. The aim of this study was to develop an accelerated ageing method to simulate the long-term natural carbonation of EAF slag exposed to the elements. The degree of carbonation achieved in a freshly produced slag after accelerated ageing and in a slag used on a fifteen-year-old unpaved road was very similar. The influence of particle size on accelerated carbonation was assessed, with it being concluded that the slag sample with a particle size bigger than 5-6 mm underwent slight carbonation over time when it was exposed to CO2. The accelerated ageing procedure based on percolating a previously carbonated water solution through the slag column allowed gradual leaching with simulated acid rain, as well as providing information about the gradual and total chemical release from the slag. Three classification groups were established according to the release rate of the determined elements. The joint use of the accelerated carbonation method and the percolation test is proposed as a useful tool for environmental risk assessment concerning the long-term air exposure of EAF black slag. PMID:24726964

  6. Relationship between Human Aging Muscle and Oxidative System Pathway

    PubMed Central

    Doria, Enrico; Buonocore, Daniela; Focarelli, Angela; Marzatico, Fulvio

    2012-01-01

    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). PMID:22685621

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

    PubMed

    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. PMID:1719051

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

    PubMed

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

    2016-01-01

    The aim of this study was to evaluate the influence of accelerated aging (AAA) on the color stability of resin cements for bonding ceramic laminate veneers of different thicknesses. The occlusal surfaces of 80 healthy human molars were flattened. Ceramic laminate veneers (IPS e-max Ceram) of two thicknesses (0.5 and 1.0 mm) were bonded with three types of luting agents: light-cured, conventional dual and self-adhesive dual cement. Teeth without restorations and cement samples (0.5 mm) were used as control. After initial color evaluations, the samples were subjected to AAA for 580 h. After this, new color readouts were made, and the color stability (ΔE) and luminosity (ΔL) data were analyzed. The greatest color changes (p<0.05) occurred when 0.5 mm veneers were fixed with light-cured cement and the lowest when 1.0 mm veneers were fixed with conventional dual cement. There was no influence of the restoration thickness when the self-adhesive dual cement was used. When veneers were compared with the control groups, it was verified that the cement samples presented the greatest alterations (p<0.05) in comparison with both substrates and restored teeth. Therefore, it was concluded that the thickness of the restoration influences color and luminosity changes for conventional dual and light-cured cements. The changes in self-adhesive cement do not depend on restoration thickness. PMID:27007354

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

    PubMed

    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. PMID:22529643

  10. Degradation mechanism of LiCoO2/mesocarbon microbeads battery based on accelerated aging tests

    NASA Astrophysics Data System (ADS)

    Guan, Ting; Zuo, Pengjian; Sun, Shun; Du, Chunyu; Zhang, Lingling; Cui, Yingzhi; Yang, Lijie; Gao, Yunzhi; Yin, Geping; Wang, Fuping

    2014-12-01

    A series of LiCoO2/mesocarbon microbeads (MCMB) commercial cells cycled at different rates (0.6C, 1.2C, 1.5C, 1.8C, 2.4C and 3.0C) are disassembled and the capacity fade mechanism is proposed by analyzing the structure, morphology and electrochemical performance evolution at the capacity retention of 95%, 90%, 85%, 80%. The capacity deterioration of the commercial cell is mainly caused by the decay of the reversible capacity of LiCoO2 cathode, the irreversible loss of active lithium and the lithium remaining in anode. The proportions of effects by the above three factors are calculated accurately. The consumption of the active lithium leads to a cell imbalance between the anode and the cathode. The electrochemical test results indicate that the capacity fade of the active materials at the low rate is more obvious than that at the high rate. The influence of the active lithium is gradually increscent with the increasing rate. The rate of 1.5C is the optimal value to accelerate the aging of the full cell by comparing the testing results at different capacity retentions in the specific condition of low charge/discharge rate and shallow depth of discharge.

  11. Accelerated Aging Experiments for Prognostics of Damage Growth in Composite Materials

    NASA Technical Reports Server (NTRS)

    Saxena, Abhinav; Goebel, Kai Frank; Larrosa, Cecilia C.; Janapati, Vishnuvardhan; Roy, Surajit; Chang, Fu-Kuo

    2011-01-01

    Composite structures are gaining importance for use in the aerospace industry. Compared to metallic structures their behavior is less well understood. This lack of understanding may pose constraints on their use. One possible way to deal with some of the risks associated with potential failure is to perform in-situ monitoring to detect precursors of failures. Prognostic algorithms can be used to predict impending failures. They require large amounts of training data to build and tune damage model for making useful predictions. One of the key aspects is to get confirmatory feedback from data as damage progresses. These kinds of data are rarely available from actual systems. The next possible resource to collect such data is an accelerated aging platform. To that end this paper describes a fatigue cycling experiment with the goal to stress carbon-carbon composite coupons with various layups. Piezoelectric disc sensors were used to periodically interrogate the system. Analysis showed distinct differences in the signatures of growing failures between data collected at conditions. Periodic X-radiographs were taken to assess the damage ground truth. Results after signal processing showed clear trends of damage growth that were correlated to damage assessed from the X-ray images.

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

    PubMed Central

    Foronda, Miguel; Martínez, Paula; Schoeftner, Stefan; Gómez-López, Gonzalo; Schneider, Ralph; Flores, Juana M.; Pisano, David G.; Blasco, Maria A.

    2016-01-01

    Summary 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. PMID:25043184

  13. Mechanisms of maladaptive repair after AKI leading to accelerated kidney ageing and CKD

    PubMed Central

    Ferenbach, David A.; Bonventre, Joseph V.

    2015-01-01

    Acute kidney injury is an increasingly common complication of hospital admission and is associated with high levels of morbidity and mortality. A hypotensive, septic, or toxic insult can initiate a cascade of events, resulting in impaired microcirculation, activation of inflammatory pathways and tubular cell injury or death. These processes ultimately result in acutely impaired kidney function and initiation of a repair response. This Review explores the various mechanisms responsible for the initiation and propagation of acute kidney injury, the prototypic mechanisms by which a substantially damaged kidney can regenerate its normal architecture, and how the adaptive processes of repair can become maladaptive. These mechanisms, which include G2/M cell-cycle arrest, cell senescence, profibrogenic cytokine production, and activation of pericytes and interstitial myofibroblasts, contribute to the development of progressive fibrotic kidney disease. The end result is a state that mimics accelerated kidney ageing. These mechanisms present important opportunities for the design of targeted therapeutic strategies to promote adaptive renal recovery and minimize progressive fibrosis and chronic kidney disease after acute insults. PMID:25643664

  14. Evaluation of stone durability using a combination of ultrasound, mechanical and accelerated aging tests

    NASA Astrophysics Data System (ADS)

    Molina, E.; Cultrone, G.; Sebastián, E.; Alonso, F. J.

    2013-06-01

    The durability of a rock when exposed to decay agents is an important criterion when assessing its quality as a building material. Our study focuses on six varieties of natural stone (two limestones, one dolostone, one travertine and two sandstones) that are widely used in both new and historical buildings. In order to assess their quality, we measured and characterized their dynamic elastic properties using ultrasounds, we measured their compressive strength using the uniaxial compression test and we evaluated their durability by means of accelerated aging tests (freeze-thaw and salt crystallization). In order to get a full picture of the decay suffered by the different stones, we determined the composition and amount of the clay fraction of the six stones. We also observed small fragments subjected to the salt crystallization test under an environmental scanning electron microscope to study any textural change and measured the changes of colour on the surface with a spectrophotometer. Finally, we analysed the pore system of the stones before and after their deterioration using mercury injection porosimetry. We then compared the results for the different stones and found that dolostone obtained the best results, while the two limestones proved to be the least durable and had the lowest compressive strength.

  15. The many faces of human ageing: toward a psychological culture of old age.

    PubMed

    Baltes, P B

    1991-11-01

    In an effort to distil major findings about the nature of human ageing, seven propositions are presented as a guiding frame of reference. This propositional framework is then used to specify some conditions for a positive culture of old age and to advance one possible model of good psychological ageing. This model focuses on the dynamic interplay between three processes: selection, optimization, and compensation. The model is universal in its basic features, but at the same time emphasizes individual variations in phenotypic manifestation. PMID:1780400

  16. Acetylcholinesterase: an enzymatic marker of human red blood cell aging.

    PubMed

    Prall, Y G; Gambhir, K K; Ampy, F R

    1998-01-01

    The purpose of this investigation was to determine whether acetylcholinesterase (AChE) can be used as a marker of cell aging in human red blood cells (RBCs). This study used consented subjects; both males and females in an age range of 21-42 years. The blood samples (8-9 mL) were drawn in tubes containing sodium heparin or EDTA as anticoagulants. To avoid contamination with other cells, (lymphocytes, monocytes and reticulocytes), RBCs were purified (PRBC) by Hypaque-Ficoll gradient technique. The PRBCs were subfractionated into young (y) (1.08-1.09), mid (m) (1.09-1.11) and old (o) (1.11-1.12) percoll density (g/mL) fractions using a discontinuous percoll gradient. The mean +/- 1 SD AChE per gram hemoglobin (U/g Hgb) activities in whole blood (WB) purified human red blood cells (PRBCs), young human red blood cells (y-RBCs), mid age human red blood cells (m-RBCs) and old human red blood cells (o-RBCs) were 27.4 +/- 2.98, 26.0 +/- 2.33, 25.5 +/- 1.64, 20.3 +/- 3.84, 14.6 +/- 3.42 in males and 26.3 +/- 4.44, 24.8 /- 4.83, 26.4 +/- 4.59, 24.0 +/- 5.50 and 12.4 +/- 7.09 in females respectively. Although there was variation in the data, the results indicated that old human red blood cells showed significantly (p<.05) lower AChE activity compared to young human red blood cells of both sexes. These preliminary but novel observations suggest that AChE can be an excellent enzymatic marker for RBC aging in man. PMID:9698047

  17. Engineered human vascularized constructs accelerate diabetic wound healing.

    PubMed

    Shen, Yu-I; Cho, Hongkwan; Papa, Arianne E; Burke, Jacqueline A; Chan, Xin Yi; Duh, Elia J; Gerecht, Sharon

    2016-09-01

    Stem cell-based therapy is emerging as a promising approach for chronic diabetic wounds, but strategies for optimizing both cellular differentiation and delivery remain as major obstacles. Here, we study bioengineered vascularized constructs as a therapeutic modality for diabetic wound healing. We developed a wound model in immunodeficient rodent and treated it with engineered vascularized constructs from endothelial progenitors or early vascular cells-derived from human induced pluripotent stem cells (hiPSCs) reprogrammed either from healthy donor or type-1 diabetic patient. We found that all vascularized constructs expedited wound closure and reperfusion, with endothelial progenitor constructs having the earliest maximum closure rate followed closely by healthy and diabetic hiPSC-derivative constructs. This was accompanied by rapid granulation layer formation and regression in all vascularized construct groups. Macrophage infiltration into the hydrogel matrix occurred during early stages of healing, seeming to facilitate rapid neovascularization of the wound that could then better persist in the vascularized constructs. Blood perfusion of the human vasculature could be detected after three days, indicating rapid integration with the host vasculature. Overall, we propose a potential therapeutic strategy using allograft or autologous vascularized constructs to treat type-1 diabetic wounds. This approach highlights the unprecedented prospects of designing patient-specific stem cell therapy. PMID:27328431

  18. Variations in Human Capital Investment Activity by Age.

    ERIC Educational Resources Information Center

    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…

  19. Age-dependent changes in lipid peroxide levels in peripheral organs, but not in brain, in senescence-accelerated mice.

    PubMed

    Matsugo, S; Kitagawa, T; Minami, S; Esashi, Y; Oomura, Y; Tokumaru, S; Kojo, S; Matsushima, K; Sasaki, K

    2000-01-01

    The tissue concentration of lipid peroxides was determined in the brain, heart, liver, lung and kidney of accelerated senescence-prone (SAMP-8) and -resistant (SAMR-1) mice at 3, 6 and 9 months of age by a method involving chemical derivatization and high performance liquid chromatography. The level of lipid peroxides in the brain did not show an age-dependent change, but at each age the brain level of lipid peroxides was significantly higher in SAMP-8 than in SAMR-1. In contrast, the lipid peroxide levels in the peripheral organs showed increases with aging in both strains, and they were significantly higher in SAMP-8 than in SAMR-1 at both 3 and 6 months of age (except at 3 months of age in the kidney). These results suggest that increased oxidative stress in the brain and peripheral organs is a cause of the senescence-related degeneration and impairments seen in SAMP-8. PMID:10643812

  20. The Laboratory Rat: Relating Its Age With Human's

    PubMed Central

    Sengupta, Pallav

    2013-01-01

    By late 18th or early 19th century, albino rats became the most commonly used experimental animals in numerous biomedical researches, as they have been recognized as the preeminent model mammalian system. But, the precise correlation between age of laboratory rats and human is still a subject of debate. A number of studies have tried to detect these correlations in various ways, But, have not successfully provided any proper association. Thus, the current review attempts to compare rat and human age at different phases of their life. The overall findings indicate that rats grow rapidly during their childhood and become sexually mature at about the sixth week, but attain social maturity 5-6 months later. In adulthood, every day of the animal is approximately equivalent to 34.8 human days (i.e., one rat month is comparable to three human years). Numerous researchers performed experimental investigations in albino rats and estimated, in general, while considering their entire life span, that a human month resembles every-day life of a laboratory rat. These differences signify the variations in their anatomy, physiology and developmental processes, which must be taken into consideration while analyzing the results or selecting the dose of any research in rats when age is a crucial factor. PMID:23930179

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

    PubMed Central

    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

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

    PubMed

    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. PMID:25902704

  3. Simulation analysis for effects of bone loss on acceleration tolerance of human lumbar vertebra

    NASA Astrophysics Data System (ADS)

    Ma, Honglei; Zhang, Feng; Zhu, Yu; Xiao, Yanhua; Wazir, Abrar

    2014-02-01

    The purpose of the present study was to analyze and predict the changes in acceleration tolerance of human vertebra as a result of bone loss caused by long-term space flight. A human L3-L4 vertebra FEM model was constructed, in which the cancellous bone was separated, and surrounding ligaments were also taken into account. The simulation results demonstrated that bone loss has more of an effect on the acceleration tolerance in x-direction. The results serve to aid in the creation of new acceleration tolerance standards, ensuring astronauts return home safely after long-term space flight. This study shows that more attention should be focused on the bone degradation of crew members and to create new protective designs for space capsules in the future.

  4. Pathogenesis of Age-Related Bone Loss in Humans

    PubMed Central

    2013-01-01

    Background. Although data from rodent systems are extremely useful in providing insights into possible mechanisms of age-related bone loss, concepts evolving from animal models need to ultimately be tested in humans. Methods. This review provides an update on mechanisms of age-related bone loss in humans based on the author’s knowledge of the field and focused literature reviews. Results. Novel imaging, experimental models, biomarkers, and analytic techniques applied directly to human studies are providing new insights into the patterns of bone mass acquisition and loss as well as the role of sex steroids, in particular estrogen, on bone metabolism and bone loss with aging in women and men. These studies have identified the onset of trabecular bone loss at multiple sites that begins in young adulthood and remains unexplained, at least based on current paradigms of the mechanisms of bone loss. In addition, estrogen appears to be a major regulator of bone metabolism not only in women but also in men. Studies assessing mechanisms of estrogen action on bone in humans have identified effects of estrogen on RANKL expression by several different cell types in the bone microenvironment, a role for TNF-α and IL-1β in mediating effects of estrogen deficiency on bone, and possible regulation of the Wnt inhibitor, sclerostin, by estrogen. Conclusions. There have been considerable advances in our understanding of age-related bone loss in humans. However, there are also significant gaps in knowledge, particularly in defining cell autonomous changes in bone in human studies to test or validate concepts emerging from studies in rodents. Decision Editor: Luigi Ferrucci, MD, PhD PMID:22923429

  5. Total body potassium in aging humans: A longitudinal study

    SciTech Connect

    Flynn, M.A.; Nolph, G.B.; Baker, A.S.; Martin, W.M.; Krause, G. )

    1989-10-01

    Total body potassium (TBK) data calculated from longitudinal measurements over 18 y of 40K by whole-body counting of 564 male and 61 female healthy humans in a 2-pi liquid scintillation counter show little change in females younger than 50 y compared with males of those ages. Males show less TBK from 41 y onward as they age, with most rapid rate of loss between 41 and 60 y. Females have a rapid loss of TBK when they are older than 60 y; the loss is at a greater rate than that of males. Percent total body fat calculated from total body weight and lean body mass (LBM) derived from TBK document greater adiposity in females at all ages except ages 51-60 y when females are similar to males in change in percent fat per year per centimeter.

  6. Characterizing healthy samples for studies of human cognitive aging

    PubMed Central

    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 interpret studies. This paper addresses important factors in study design, patient demographics, co-morbid and incipient medical conditions, and assessment instruments that will allow researchers to optimize the characterization of healthy participants and produce meaningful and generalizable research outcomes from studies of cognitive aging. Application of knowledge from well-designed studies should be useful in clinical settings to facilitate the earliest possible recognition of disease and guide appropriate interventions to best meet the needs of the affected individual and public health priorities. PMID:22988440

  7. A network model of human aging: Limits, errors, and information

    NASA Astrophysics Data System (ADS)

    Farrell, Spencer; Mitnitski, Arnold; Rockwood, Kenneth; Rutenberg, Andrew

    The Frailty Index (FI) quantifies human aging using the fraction of accumulated age-related deficits. The FI correlates strongly with mortality and accumulates non-linearly and stochastically with age. Clinical data shows a nearly universal limit of FI <= 0 . 7 . We computationally model an aging population using a network model of interacting deficits. Deficits damage and repair at rates that depend upon the average damage of connected nodes. The model is parametrized to fit clinical data. We find that attribution errors, especially false negative, allow the model to recover the frailty limit. Mutual information allows us to assess how well the FI can predict mortality. Mutual information provides a non-parametric measure of how the FI predicts mortality. We find that attribution errors have a small effect on the mutual information when many deficits are included in the model. The mutual information of our model and of the clinical data are comparable.

  8. Survivin expression increases during aging and enhances the resistance of aged human fibroblasts to genotoxic stress.

    PubMed

    Al-Khalaf, Huda H; Aboussekhra, Abdelilah

    2013-06-01

    Survivin, an important anti-apoptotic protein, is highly expressed in most cancers, which generally arise in cells of older individuals. We have shown here accumulation of survivin and phospho-survivin in aged normal human skin fibroblasts and mice organs. This age-related accumulation of survivin was due to protein stabilization through association with the molecular chaperone Hsp90 protein, which was also up-regulated during aging. Interestingly, Hsp90 binds preferentially to phospho-survivin, which explains its higher stability. In addition, we provide clear evidence that aged cells exhibit apoptosis resistance when challenged with UV light, cisplatin, γ-rays or H2O2 as compared to their younger counterparts. In response to γ-rays and H2O2, the levels of Bcl-2 and both forms of survivin were up-regulated in old cells, but not in their corresponding young ones. This repression of survivin and phospho-survivin in young cells is p53 dependent. Importantly, survivin inhibition/down-regulation with flavopiridol or specific shRNAs increased the apoptotic response of old fibroblasts to various genotoxic agents, and restored the pro-apoptotic Bax/Bcl2 ratio and the increase in the levels of cleaved caspase-3 and PARP in old cells. These results show the role of survivin in the age-dependent resistance of human fibroblasts, and provide new insights into the molecular mechanisms that underlie the complex relationship between aging, apoptosis, and cancer. PMID:22252435

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

    PubMed

    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 (P<0.1) in rAAV-GFP-treated rats (13.5 months old) compared to baseline control rats (9 months old). Significant differences in cancellous bone or biomarkers of bone turnover were not detected between rAAV-Leptin 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. PMID:26487675

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

    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