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Sample records for accelerated human ageing

  1. Obesity accelerates epigenetic aging of human liver.

    PubMed

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

    2014-10-28

    Because of the dearth of biomarkers of aging, it has been difficult to test the hypothesis that obesity increases tissue age. Here we use a novel epigenetic biomarker of aging (referred to as an "epigenetic clock") to study the relationship between high body mass index (BMI) and the DNA methylation ages of human blood, liver, muscle, and adipose tissue. A significant correlation between BMI and epigenetic age acceleration could only be observed for liver (r = 0.42, P = 6.8 × 10(-4) in dataset 1 and r = 0.42, P = 1.2 × 10(-4) in dataset 2). On average, epigenetic age increased by 3.3 y for each 10 BMI units. The detected age acceleration in liver is not associated with the Nonalcoholic Fatty Liver Disease Activity Score or any of its component traits after adjustment for BMI. The 279 genes that are underexpressed in older liver samples are highly enriched (1.2 × 10(-9)) with nuclear mitochondrial genes that play a role in oxidative phosphorylation and electron transport. The epigenetic age acceleration, which is not reversible in the short term after rapid weight loss induced by bariatric surgery, may play a role in liver-related comorbidities of obesity, such as insulin resistance and liver cancer. PMID:25313081

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

    PubMed

    Dreesen, Oliver; Stewart, Colin L

    2011-09-01

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

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

    PubMed

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

    2015-09-01

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

  4. Dicarbonyl-induced accelerated aging in vitro in human skin fibroblasts.

    PubMed

    Sejersen, Henrik; Rattan, Suresh I S

    2009-04-01

    Dicarbonyls glyoxal (GO) and methylglyoxal (MGO) produced during the autoxidation of reducing sugars are a source of macromolecular damage in cells. Since an accumulation of damaged macromolecules is a universal characteristic of aging, we have tested whether GO and MGO which cause oxidative damage to proteins and other macromolecules can bring about accelerated aging in normal human skin fibroblasts in vitro. A treatment of cells with 1.0 mM GO or 400 microM MGO leads to the appearance of senescent phenotype within 3 days, as judged by the following criteria: morphological phenotype, irreversible growth arrest and G2 arrest, increased senescence-associated beta-galactosidase (SABG) activity, increased H2O2 level, increased Nxi-(carboxymethyl)-lysine (CML) protein level, and altered activities of superoxide dismutase and catalase antioxidant enzymes. This experimental model of accelerated cellular aging in vitro can be useful for studies on testing the effects of various physical, chemical and biological conditions, including natural and synthetic molecules, for the modulation of aging.

  5. 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

  6. 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

  7. 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

  8. Cytomegalovirus infection accelerates epigenetic aging.

    PubMed

    Kananen, Laura; Nevalainen, Tapio; Jylhävä, Juulia; Marttila, Saara; Hervonen, Antti; Jylhä, Marja; Hurme, Mikko

    2015-12-01

    Epigenetic mechanisms such as DNA methylation (DNAm) have a central role in the regulation of gene expression and thereby in cellular differentiation and tissue homeostasis. It has recently been shown that aging is associated with profound changes in DNAm. Several of these methylation changes take place in a clock-like fashion, i.e. correlating with the calendar age of an individual. Thus, the epigenetic clock based on these kind of DNAm changes could provide a new biomarker for human aging process, i.e. being able to separate the calendar and biological age. Information about the correlation of the time indicated by this clock to the various aspects of immunosenescence is still missing. As chronic cytomegalovirus (CMV) infection is probably one of the major driving forces of immunosenescence, we now have analyzed the correlation of CMV seropositivity with the epigenetic age in the Vitality 90+cohort 1920 (122 nonagenarians and 21 young controls, CMV seropositivity rates 95% and 57%, respectively). The data showed that CMV seropositivity was associated with a higher epigenetic age in both of these age groups (median 26.5 vs. 24.0 (p < 0.02,Mann–Whitney U-test) in the young controls and 76.0 vs. 70.0 (p < 0.01) in the nonagenarians). Thus, these data provide a new aspect to the CMV associated pathological processes. PMID:26485162

  9. 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.

  10. 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.

  11. Accelerated epigenetic aging in Down syndrome

    PubMed Central

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

    2015-01-01

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

  12. Accelerated epigenetic aging in Down syndrome.

    PubMed

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

    2015-06-01

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

  13. Accelerated aging test on LEDs life estimation

    NASA Astrophysics Data System (ADS)

    Dong, Yi; Zhang, Shu-sheng; Du, Jiang-qi

    2011-11-01

    Light-emitting diodes(LEDs) have become very attractive in different application field such as Solid State Lighting, automotive and street lights, due to their long operative lifetime, lower energy consumption etc. This paper mainly introduces the accelerated aging test, we focus our attention on the study of a life model for LEDs by relating the time to failure with the supplying condition. The constant accelerated aging experiments were firstly performed on LED samples. Process the experiment data by exploiting the degradation of LED optical power formula and degradation coefficient. Finally, the average lifetime of the samples under normal conditions was calculated via using numerical analytical method. According to data, analysis the test result and the failure mechanism of LED, provide the technical basis to improve product design and quality assurance.

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

    PubMed

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

    2014-06-01

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

  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. 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

  18. Biodemography of human ageing

    PubMed Central

    Vaupel, James W.

    2014-01-01

    Human senescence has been delayed by a decade. This finding, documented in 1994 and bolstered since, is a fundamental discovery about the biology of human ageing, and one with profound implications for individuals, society and the economy. Remarkably, the rate of deterioration with age seems to be constant across individuals and over time: it seems that death is being delayed because people are reaching old age in better health. Research by demographers, epidemiologists and other biomedical researchers suggests that further progress is likely to be made in advancing the frontier of survival — and healthy survival — to even greater ages. PMID:20336136

  19. 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.

  20. 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.

  1. Accelerated aging of EPDM and butyl elastomers

    SciTech Connect

    Wilson, M.H.

    1996-06-01

    This study was composed of three parts: a post cure study to optimize final properties of an ethylene-propylene-diene (EPDM) formulation, an accelerated aging study to compare the stress relaxation behavior of a butyl and an EPDM elastomer under compression, and a cursory evaluation of a new 70 Shore A EPDM. The optimum postcure for the EPDM was found to be 2 to 4 hours at 182{degrees}C in a vacuum. The EPDM was also shown to have superior aging characteristics compared to the butyl and is recommended for use instead of the butyl material. The physical properties for new 70 Shore A EPDM are satisfactory, and the stress relaxation behavior was only slightly inferior to the other EPDM.

  2. 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.

  3. 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)

  4. Accelerated aging of polymer composite bridge materials

    NASA Astrophysics Data System (ADS)

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

    1999-05-01

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

  5. Accelerated Aging of Polymer Composite Bridge Materials

    SciTech Connect

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

    1999-03-01

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

  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. 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

  8. Kinematics of transition during human accelerated sprinting

    PubMed Central

    Nagahara, Ryu; Matsubayashi, Takeo; Matsuo, Akifumi; Zushi, Koji

    2014-01-01

    ABSTRACT This study investigated kinematics of human accelerated sprinting through 50 m and examined whether there is transition and changes in acceleration strategies during the entire acceleration phase. Twelve male sprinters performed a 60-m sprint, during which step-to-step kinematics were captured using 60 infrared cameras. To detect the transition during the acceleration phase, the mean height of the whole-body centre of gravity (CG) during the support phase was adopted as a measure. Detection methods found two transitions during the entire acceleration phase of maximal sprinting, and the acceleration phase could thus be divided into initial, middle, and final sections. Discriminable kinematic changes were found when the sprinters crossed the detected first transition—the foot contacting the ground in front of the CG, the knee-joint starting to flex during the support phase, terminating an increase in step frequency—and second transition—the termination of changes in body postures and the start of a slight decrease in the intensity of hip-joint movements, thus validating the employed methods. In each acceleration section, different contributions of lower-extremity segments to increase in the CG forward velocity—thigh and shank for the initial section, thigh, shank, and foot for the middle section, shank and foot for the final section—were verified, establishing different acceleration strategies during the entire acceleration phase. In conclusion, there are presumably two transitions during human maximal accelerated sprinting that divide the entire acceleration phase into three sections, and different acceleration strategies represented by the contributions of the segments for running speed are employed. PMID:24996923

  9. Accelerated ageing: from mechanism to therapy through animal models.

    PubMed

    Osorio, Fernando G; Obaya, Alvaro J; López-Otín, Carlos; Freije, José M P

    2009-02-01

    Ageing research benefits from the study of accelerated ageing syndromes such as Hutchinson-Gilford progeria syndrome (HGPS), characterized by the early appearance of symptoms normally associated with advanced age. Most HGPS cases are caused by a mutation in the gene LMNA, which leads to the synthesis of a truncated precursor of lamin A known as progerin that lacks the target sequence for the metallopotease FACE-1/ZMPSTE24 and remains constitutively farnesylated. The use of Face-1/Zmpste24-deficient mice allowed us to demonstrate that accumulation of farnesylated prelamin A causes severe abnormalities of the nuclear envelope, hyper-activation of p53 signalling, cellular senescence, stem cell dysfunction and the development of a progeroid phenotype. The reduction of prenylated prelamin A levels in genetically modified mice leads to a complete reversal of the progeroid phenotype, suggesting that inhibition of protein farnesylation could represent a therapeutic option for the treatment of progeria. However, we found that both prelamin A and its truncated form progerin can undergo either farnesylation or geranylgeranylation, revealing the need of targeting both activities for an efficient treatment of HGPS. Using Face-1/Zmpste24-deficient mice as model, we found that a combination of statins and aminobisphosphonates inhibits both types of modifications of prelamin A and progerin, improves the ageing-like symptoms of these mice and extends substantially their longevity, opening a new therapeutic possibility for human progeroid syndromes associated with nuclear-envelope defects. We discuss here the use of this and other animal models to investigate the molecular mechanisms underlying accelerated ageing and to test strategies for its treatment.

  10. Loss of epidermal hypoxia-inducible factor-1α accelerates epidermal aging and affects re-epithelialization in human and mouse.

    PubMed

    Rezvani, Hamid Reza; Ali, Nsrein; Serrano-Sanchez, Martin; Dubus, Pierre; Varon, Christine; Ged, Cécile; Pain, Catherine; Cario-André, Muriel; Seneschal, Julien; Taïeb, Alain; de Verneuil, Hubert; Mazurier, Frédéric

    2011-12-15

    In mouse and human skin, HIF-1α is constitutively expressed in the epidermis, mainly in the basal layer. HIF-1α has been shown to have crucial systemic functions: regulation of kidney erythropoietin production in mice with constitutive HIF-1α epidermal deletion, and hypervascularity following epidermal HIF-1α overexpression. However, its local role in keratinocyte physiology has not been clearly defined. To address the function of HIF-1α in the epidermis, we used the mouse model of HIF-1α knockout targeted to keratinocytes (K14-Cre/Hif1a(flox/flox)). These mice had a delayed skin phenotype characterized by skin atrophy and pruritic inflammation, partly mediated by basement membrane disturbances involving laminin-332 (Ln-332) and integrins. We also investigated the relevance of results of studies in mice to human skin using reconstructed epidermis and showed that HIF-1α knockdown in human keratinocytes impairs the formation of a viable reconstructed epidermis. A diminution of keratinocyte growth potential, following HIF-1α silencing, was associated with a decreased expression of Ln-322 and α6 integrin and β1 integrin. Overall, these results indicate a role of HIF-1α in skin homeostasis especially during epidermal aging.

  11. 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.

  12. 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.

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

    PubMed

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

    2016-04-21

    In this issue of Molecular Cell, Gross et al. (2016) find a CpG DNA methylation signature in blood cells of patients with chronic well-controlled HIV infection that correlates with accelerated aging. PMID:27105110

  14. Skin mirrors human aging.

    PubMed

    Nikolakis, Georgios; Makrantonaki, Evgenia; Zouboulis, Christos C

    2013-12-01

    Abstract Aged skin exhibits disturbed lipid barrier, angiogenesis, production of sweat, immune functions, and calcitriol synthesis as well as the tendency towards development of certain benign or malignant diseases. These complex biological processes comprise endogenous and exogenous factors. Ethnicity also markedly influences the phenotype of skin aging. The theories of cellular senescence, telomere shortening and decreased proliferative capacity, mitochondrial DNA single mutations, the inflammation theory, and the free radical theory try to explain the biological background of the global aging process, which is mirrored in the skin. The development of advanced glycation end-products and the declining hormonal levels are major factors influencing intrinsic aging. Chronic photodamage of the skin is the prime factor leading to extrinsic skin aging. The deterioration of important skin functions, due to intrinsic and extrinsic aging, leads to clinical manifestations, which mirror several internal age-associated diseases such as diabetes, arterial hypertension and malignancies.

  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. 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

    2015-01-19

    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.

  17. 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

  18. 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

  19. Fluorescence intensity of resin composites and dental tissues before and after accelerated aging: a comparative study.

    PubMed

    Takahashi, Marcos Kenzo; Vieira, Sergio; Rached, Rodrigo Nunes; de Almeida, Janaina Bertoncelo; Aguiar, Marcelo; de Souza, Evelise Machado

    2008-01-01

    This study quantitatively evaluated the fluorescence intensity of resin composites with different opacities and translucencies and determined changes in fluorescence after accelerated aging, using human enamel and dentin as controls. Six microhybrid and nanofilled composites, each in three different shades, were tested. Ten sound human incisors were used to obtain enamel and dentin specimens separately. Fluorescence measurements were obtained with a fluorescence spectrophotometer before (baseline) and after accelerated aging at 150 kJ energy for 120 hours. One-way analysis of variance (ANOVA) and Games-Howell multiple comparison tests were performed at a significance level of 0.05. Student's t-test was also used for comparison before and after aging. At baseline, there was no statistically significant difference (p>0.05) between the fluorescence intensity of dentin and any of the shades of Charisma or Opallis, Esthet-X dentin shade or Vit-l-escence enamel, or the translucent shades. After accelerated aging, all shades of the 4 Seasons, enamel and the translucent shades of Esthet-X had fluorescence intensities statistically similar to that of aged dentin (p>0.05). A significant reduction in fluorescence after aging (p<0.05) was observed for all the materials, except for human enamel and translucent Filtek Supreme XT. Accelerated aging reduced fluorescence in most of the composites evaluated.

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2000-03-01

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

  9. 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

  10. Accelerated optical polymer aging studies for LED luminaire applications

    NASA Astrophysics Data System (ADS)

    Estupiñán, Edgar; Wendling, Peter; Kostrun, Marijan; Garner, Richard

    2013-09-01

    There is a need in the lighting industry to design and implement accelerated aging methods that accurately simulate the aging process of LED luminaire components. In response to this need, we have built a flexible and reliable system to study the aging characteristics of optical polymer materials, and we have employed it to study a commercially available LED luminaire diffuser made of PMMA. The experimental system consists of a "Blue LED Emitter" and a working surface. Both the temperatures of the samples and the optical powers of the LEDs are appropriately characterized in the system. Several accelerated aging experiments are carried out at different temperatures and optical powers over a 90 hour period and the measured transmission values are used as inputs to a degradation model derived using plausibility arguments. This model seems capable of predicting the behavior of the material as a function of time, temperature and optical power. The model satisfactorily predicts the measured transmission values of diffusers aged in luminaires at two different times and thus can be used to make application recommendations for this material. Specifically, at 35000 hours (the manufacturer's stated life of the luminaire) and at the typical operational temperature of the diffuser, the model predicts a transmission loss of only a few percent over the original transmission of the material at 450 nm, which renders this material suitable for this application.

  11. 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.

  12. [Human bioaging acceleration as Chernobyl radiation consequence].

    PubMed

    Neĭfakh, E A; Liuman, G K

    2013-01-01

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

  13. 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

  14. Accelerated epigenetic aging in brain is associated with pre-mortem HIV-associated neurocognitive disorders.

    PubMed

    Levine, Andrew J; Quach, Austin; Moore, David J; Achim, Cristian L; Soontornniyomkij, Virawudh; Masliah, Eliezer; Singer, Elyse J; Gelman, Benjamin; Nemanim, Natasha; Horvath, Steve

    2016-06-01

    HIV infection leads to age-related conditions in relatively young persons. HIV-associated neurocognitive disorders (HAND) are considered among the most prevalent of these conditions. To study the mechanisms underlying this disorder, researchers need an accurate method for measuring biological aging. Here, we apply a recently developed measure of biological aging, based on DNA methylation, to the study of biological aging in HIV+ brains. Retrospective analysis of tissue bank specimens and pre-mortem data was carried out. Fifty-eight HIV+ adults underwent a medical and neurocognitive evaluation within 1 year of death. DNA was obtained from occipital cortex and analyzed with the Illumina Infinium Human Methylation 450K platform. Biological age determined via the epigenetic clock was contrasted with chronological age to obtain a measure of age acceleration, which was then compared between those with HAND and neurocognitively normal individuals. The HAND and neurocognitively normal groups did not differ with regard to demographic, histologic, neuropathologic, or virologic variables. HAND was associated with accelerated aging relative to neurocognitively normal individuals, with average relative acceleration of 3.5 years. Age acceleration did not correlate with pre-mortem neurocognitive functioning or HAND severity. This is the first study to demonstrate that the epigenetic age of occipital cortex samples is associated with HAND status in HIV+ individuals pre-mortem. While these results suggest that the increased risk of a neurocognitive disorder due to HIV might be mediated by an epigenetic aging mechanism, future studies will be needed to validate the findings and dissect causal relationships and downstream effects. PMID:26689571

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. Accelerated aging for testing polymeric biomaterials and medical devices.

    PubMed

    Hukins, D W L; Mahomed, A; Kukureka, S N

    2008-12-01

    Elevated temperature is frequently used to accelerate the aging process in polymers that are associated with medical devices and other applications. A common approach is to assume that the rate of aging is increased by a factor of 2(DeltaT/10), where DeltaT is the temperature increase. This result is a mathematical expression of the empirical observation that increasing the temperature by about 10 degrees C roughly doubles the rate of many polymer reactions. It is equivalent to assuming that the aging process is a first order chemical reaction with an activation energy of 10R/log(e)2, where R is the universal gas constant. A better approach would be to determine the activation energy for the process being considered but this is not always practicable. The simple approach does not depend on the temperature increase, provided that it is not so great that it initiates any physical or chemical process that is unlikely to be involved in normal aging. If a temperature increment theta were to increase a given polymer reaction rate n times, then an elevated temperature would increase the rate of aging by a factor of n(DeltaT/theta).

  1. 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.

  2. 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

  3. 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

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

    PubMed

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

    2016-02-25

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

  5. Ultraweak chemiluminescence of rice seeds during accelerated aging

    NASA Astrophysics Data System (ADS)

    Chen, Wenli; Xing, Da; He, Yonghong

    2002-04-01

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

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

    NASA Astrophysics Data System (ADS)

    Tavlet, Marc

    1997-08-01

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

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

    PubMed Central

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

    2009-01-01

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

  8. 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.

  9. GenAge: a genomic and proteomic network map of human ageing.

    PubMed

    de Magalhães, João Pedro; Toussaint, Olivier

    2004-07-30

    The aim of this work was to provide an overview of the genetics of human ageing to gain novel insights about the mechanisms involved. By incorporating findings from model organisms to humans, such as mutations that either delay or accelerate ageing in mice, we constructed the gene networks previously related to ageing: namely, the network related to DNA metabolism and the network involving the GH/IGF-1 axis. Gathering data about the interacting partners of these proteins allowed us to suggest the involvement in ageing of a number of proteins through a "guilt-by-association" methodology. To organize our data, we developed the first curated database of genes related to human ageing: GenAge. With over 200 entries, GenAge may serve as a reference database of genes related to human ageing. Moreover, we rendered the first proteomic network map of human ageing, which suggests a relationship between the genetics of development and the genetics of ageing. Our work serves as a framework upon which a systems-biology understanding of ageing can be developed. GenAge is freely available for academic purposes at: http://genomics.senescence.info/genes/.

  10. [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

  11. 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

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

    PubMed

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

    2014-11-01

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

  13. 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.

  14. 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.

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

    PubMed

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

    2013-06-01

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

  16. Accelerated changes in white matter microstructure during aging: a longitudinal diffusion tensor imaging study.

    PubMed

    Sexton, Claire E; Walhovd, Kristine B; Storsve, Andreas B; Tamnes, Christian K; Westlye, Lars T; Johansen-Berg, Heidi; Fjell, Anders M

    2014-11-12

    It is well established that human brain white matter structure changes with aging, but the timescale and spatial distribution of this change remain uncertain. Cross-sectional diffusion tensor imaging (DTI) studies indicate that, after a period of relative stability during adulthood, there is an accelerated decline in anisotropy and increase in diffusivity values during senescence; and, spatially, results have been discussed within the context of several anatomical frameworks. However, inferring trajectories of change from cross-sectional data can be challenging; and, as yet, there have been no longitudinal reports of the timescale and spatial distribution of age-related white matter change in healthy adults across the adult lifespan. In a longitudinal DTI study of 203 adults between 20 and 84 years of age, we used tract-based spatial statistics to characterize the pattern of annual change in fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity and examined whether there was an acceleration of change with age. We found extensive and overlapping significant annual decreases in fractional anisotropy, and increases in axial diffusivity, radial diffusivity, and mean diffusivity. Spatially, results were consistent with inferior-to-superior gradients of lesser-to-greater vulnerability. Annual change increased with age, particularly within superior regions, with age-related decline estimated to begin in the fifth decade. Charting white matter microstructural changes in healthy aging provides essential context to clinical studies, and future studies should compare age trajectories between healthy participants and at-risk populations and also explore the relationship between DTI rates of change and cognitive decline.

  17. 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

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

    PubMed Central

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

    2012-01-01

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

  19. Muscle sympathetic outflow during horizontal linear acceleration in humans.

    PubMed

    Cui, J; Iwase, S; Mano, T; Katayama, N; Mori, S

    2001-08-01

    To elucidate the effects of linear acceleration on muscle sympathetic nerve activity (MSNA) in humans, 16 healthy men were tested in a linear accelerator. Measurements of MSNA, electrocardiogram, blood pressure, and thoracic impedance were undertaken during linear acceleration. Sinusoidal linear acceleration with peak values at +/-0.10, +/-0.15, and +/-0.20 G was applied in anteroposterior (+/-G(x), n = 10) or lateral (+/-G(y), n = 6) directions. The total activity and burst rate of MSNA decreased significantly during forward, backward, left, or right linear accelerations. The total activity of MSNA decreased to 50.5 +/- 6.9, 52.5 +/- 4.4, 71.2 +/- 9.6, and 67.6 +/- 8.2% from the baselines (100%) during linear accelerations with peak values at +/-0.20 G in the four directions, respectively. These results suggest that dynamic stimulation of otolith organs in horizontal directions in humans might inhibit MSNA directly in order to quickly redistribute blood to muscles during postural reflexes induced by passive movement, which supports the concept that the vestibular system contributes to sympathetic regulation in humans.

  20. 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

  1. [Aging of the human testis].

    PubMed

    Sibert, Louis; Lacarrière, Emeric; Safsaf, Athmane; Rives, Nathalie

    2014-02-01

    The morphological and histological changes related to testicular aging are: volume decrease, arteriolar sclerosis, degeneration of Leydig cells and Sertoli, depletion of germ cells and thickening of the tunica albuginea testis. The participation in testicular androgen decline in aging is related to the decrease in the number of Leydig cells associated with alterations in the functioning of the hypothalamic-pituitary axis Sperm volume, concentration and total number, motility and morphology of sperm decrease with aging male. The interindividual variability of sperm parameters, the variability of methodologies for data collection and selection of patients must be careful in interpreting the published results. Overall, the quality of sperm decreases progressively with age, without any age limit that can be individualized. Alterations of spermatogenesis do not seem significantly compromising fertility in the elderly. The clinical impact of testicular aging implies androgen production decrease and diseases associated with aging.

  2. 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

  3. 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.

  4. [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.

  5. [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

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

    USGS Publications Warehouse

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

    1984-01-01

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

  7. 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

  8. Functionality, growth and accelerated aging of tissue engineered living autologous vascular grafts.

    PubMed

    Kelm, Jens M; Emmert, Maximilian Y; Zürcher, Armin; Schmidt, Dörthe; Begus Nahrmann, Yvonne; Rudolph, Karl L; Weber, Benedikt; Brokopp, Chad E; Frauenfelder, Thomas; Leschka, Sebastian; Odermatt, Bernhard; Jenni, Rolf; Falk, Volkmar; Zünd, Gregor; Hoerstrup, Simon P

    2012-11-01

    Living autologous tissue engineered vascular-grafts (TEVGs) with growth-capacity may overcome the limitations of contemporary artificial-prostheses. However, the multi-step in vitro production of TEVGs requires extensive ex vivo cell-manipulations with unknown effects on functionality and quality of TEVGs due to an accelerated biological age of the cells. Here, the impact of biological cell-age and tissue-remodeling capacity of TEVGs in relation to their clinical long-term functionality are investigated. TEVGs were implanted as pulmonary-artery (PA) replacements in juvenile sheep and followed for up to 240 weeks (∼4.5years). Telomere length and telomerase activity were compared amongst TEVGs and adjacent native tissue. Telomerase-activity of in vitro expanded autologous vascular-cells prior to seeding was <5% as compared to a leukemic cell line, indicating biological-aging associated with decreasing telomere-length with each cellular-doubling. Up to 100 weeks, the cells in the TEVGs had consistently shorter telomeres compared to the native counterpart, whereas no significant differences were detectable at 240 weeks. Computed tomography (CT) analysis demonstrated physiological wall-pressures, shear-stresses, and flow-pattern comparable to the native PA. There were no signs of degeneration detectable and continuous native-analogous growth was confirmed by vessel-volumetry. TEVGs exhibit a higher biological age compared to their native counterparts. However, despite of this tissue engineering technology related accelerated biological-aging, growth-capacity and long-term functionality was not compromised. To the contrary, extensive in-vivo remodeling processes with substantial endogenous cellular turnover appears to result in "TEVG rejuvenation" and excellent clinical performance. As these large-animal results can be extrapolated to approximately 20 human years, this study suggests long-term clinical-safety of cardiovascular in vitro tissue engineering and may

  9. 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

  10. 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.

  11. Melatonin and human skin aging

    PubMed Central

    Kleszczynski, Konrad; Fischer, Tobias W.

    2012-01-01

    Like the whole organism, skin follows the process of aging during life-time. Additional to internal factors, several environmental factors, such as solar radiation, considerably contribute to this process. While fundamental mechanisms regarding skin aging are known, new aspects of anti-aging agents such as melatonin are introduced. Melatonin is a hormone produced in the glandula pinealis that follows a circadian light-dependent rhythm of secretion. It has been experimentally implicated in skin functions such as hair cycling and fur pigmentation, and melatonin receptors are expressed in many skin cell types including normal and malignant keratinocytes, melanocytes and fibroblasts. It possesses a wide range of endocrine properties as well as strong antioxidative activity. Regarding UV-induced solar damage, melatonin distinctly counteracts massive generation of reactive oxygen species, mitochondrial and DNA damage. Thus, there is considerable evidence for melatonin to be an effective anti-skin aging compound, and its various properties in this context are described in this review. PMID:23467217

  12. Ageing of the human hypothalamus.

    PubMed

    Swaab, D F

    1995-01-01

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

  13. Can accelerated aqueous aging simulate in vivo oxidation of gamma-sterilized UHMWPE?

    PubMed

    Mazzucco, Daniel C; Dumbleton, John; Kurtz, Steven M

    2006-10-01

    Oxidation of ultrahigh molecular weight polyethylene (UHMWPE) gamma-sterilized arthroplasty components occurs in vivo. Though accelerated in vitro protocols have been developed to test the relative oxidation resistance of various types of UHMWPE, it is desirable to develop an accelerated aging protocol that more closely approximates the in vivo environment. The goal of this study was to investigate the effects of temperature, solute, and oxygen partial pressure in aqueous media on the oxidation of gamma-sterilized UHMWPE, as the basis for the development of improved accelerated aging protocols. The accelerated oxidation behavior of gamma-sterilized GUR 1150 was studied at 60 and 70 degrees C in an open vessel filled with distilled water or PBS in equilibrium with a controlled partial pressure of oxygen. The extent of oxidation was assessed using standardized mechanical and chemical evaluation techniques (small punch and Fourier transform infrared spectroscopy). Accelerated oxidation of UHMWPE was achieved in aqueous environments; however, both clinically relevant and nonrelevant oxidation species (e.g., aldehydes) were observed for long aging times at 60 degrees C, and for all aging times at 70 degrees C. These findings point the way to the development of an accelerated aging protocol. The current data, considered in conjunction with real-time aging studies, suggest that a temperature between body temperature and 60 degrees C may accelerate oxidative degradation without altering the oxidative patterns encountered in vivo.

  14. Accelerated aging of extruded dielectric power cables. Part 1; Control and monitoring methodology

    SciTech Connect

    Walton, M.S.; Smith, J.T. III ); Thue, W.A. )

    1992-04-01

    In accelerated cable life testing of power cables, cable samples are usually subjected to elevated voltages and temperatures in the presence of water in order to promote aging of the insulation and premature failures through the treeing mechanism. Failure to accurately control and monitor these accelerating facts can have adverse effects on test results and can lead to erroneous conclusions. In this paper, a new and improved accelerated cable life test is described. Through the use of programmable logic controllers (PLCs), very precise and consistent control of the accelerated aging process has been achieved. A computer has been utilized to make continuous real-time data acquisition and storage to key operating parameters possible. This precise control of monitoring methodology has permitted the study of the synergistic effects of voltage and temperature on the accelerated aging of full-sized cables in the laboratory.

  15. 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

  16. 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.

  17. Caveolin-1 and Accelerated Host Aging in the Breast Tumor Microenvironment

    PubMed Central

    Mercier, Isabelle; Camacho, Jeanette; Titchen, Kanani; Gonzales, Donna M.; Quann, Kevin; Bryant, Kelly G.; Molchansky, Alexander; Milliman, Janet N.; Whitaker-Menezes, Diana; Sotgia, Federica; Jasmin, Jean-François; Schwarting, Roland; Pestell, Richard G.; Blagosklonny, Mikhail V.; Lisanti, Michael P.

    2013-01-01

    Increasing chronological age is the most significant risk factor for human cancer development. To examine the effects of host aging on mammary tumor growth, we used caveolin (Cav)-1 knockout mice as a bona fide model of accelerated host aging. Mammary tumor cells were orthotopically implanted into these distinct microenvironments (Cav-1+/+ versus Cav-1−/− age-matched young female mice). Mammary tumors grown in a Cav-1–deficient tumor microenvironment have an increased stromal content, with vimentin-positive myofibroblasts (a marker associated with oxidative stress) that are also positive for S6-kinase activation (a marker associated with aging). Mammary tumors grown in a Cav-1–deficient tumor microenvironment were more than fivefold larger than tumors grown in a wild-type microenvironment. Thus, a Cav-1–deficient tumor microenvironment provides a fertile soil for breast cancer tumor growth. Interestingly, the mammary tumor-promoting effects of a Cav-1–deficient microenvironment were estrogen and progesterone independent. In this context, chemoprevention was achieved by using the mammalian target of rapamycin (mTOR) inhibitor and anti-aging drug, rapamycin. Systemic rapamycin treatment of mammary tumors grown in a Cav-1–deficient microenvironment significantly inhibited their tumor growth, decreased their stromal content, and reduced the levels of both vimentin and phospho-S6 in Cav-1–deficient cancer-associated fibroblasts. Since stromal loss of Cav-1 is a marker of a lethal tumor microenvironment in breast tumors, these high-risk patients might benefit from treatment with mTOR inhibitors, such as rapamycin or other rapamycin-related compounds (rapalogues). PMID:22698676

  18. Age peculiarities of human motor control in aging.

    PubMed

    Mankovsky, N B; Mints, A Y; Lisenyuk, V P

    1982-01-01

    A clinicophysiological investigation of motor control was carried out in 199 apparently healthy, socially active elderly (aged 60-69 years) and long-living (90 years and over) subjects in order to establish the peculiarities of the motor sphere specific to age-related changes of the nervous system. Analyzing the experimentally induced state of readiness (intention) before a spontaneous movement, we found an increase with age in the latent period of the muscle intentional activity (IA) parallel to an increase in the latent period of the spontaneous movement, a decrease in IA amplitude with more frequent structural deviations of the EMG in the prestarting period and a reduction of the required IA selectiveness. The described changes in the organization of readiness for a spontaneous movement seemed to be related with age impairment of supraspinal (mainly corticospinal) influences and may be used for an explanation of a number of clinical peculiarities of human motor control in late ontogenesis.

  19. 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.

  20. Accelerated heat-aging studies on fluororubber in various media

    NASA Technical Reports Server (NTRS)

    Kalfayan, S. H.; Silver, R. H.; Liu, S. S.

    1976-01-01

    Heat-aging studies were conducted on fluororubber (copolymers of vinylidene fluoride and perfluoropropylene) using N,N-dicinnamylidene-1,6-hexanediamine, a Schiff's base of 1,6-hexanediamine, and MgO as acid acceptor. The principal technique employed was chemical stress relaxation for determining network changes brought about in the heat-aged fluororubber. This technique was backed up by swelling measurements, gel permeation chromatography, and IR spectroscopy. Stress relaxation curves are plotted for a wide range of variation in parameters (time, crosslinking density, state of curing, temperature, intermittent and continuous relaxation).

  1. 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.

  2. Anti-Muscarinic Adjunct Therapy Accelerates Functional Human Oligodendrocyte Repair

    PubMed Central

    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.

    2015-01-01

    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

  3. Low intensity laser therapy accelerates muscle regeneration in aged rats

    PubMed Central

    Vatansever, Fatma; Rodrigues, Natalia C.; Assis, Livia L.; Peviani, Sabrina S.; Durigan, Joao L.; Moreira, Fernando M.A.; Hamblin, Michael R.; Parizotto, Nivaldo A.

    2013-01-01

    Background Elderly people suffer from skeletal muscle disorders that undermine their daily activity and quality of life; some of these problems can be listed as but not limited to: sarcopenia, changes in central and peripheral nervous system, blood hypoperfusion, regenerative changes contributing to atrophy, and muscle weakness. Determination, proliferation and differentiation of satellite cells in the regenerative process are regulated by specific transcription factors, known as myogenic regulatory factors (MRFs). In the elderly, the activation of MRFs is inefficient which hampers the regenerative process. Recent studies found that low intensity laser therapy (LILT) has a stimulatory effect in the muscle regeneration process. However, the effects of this therapy when associated with aging are still unknown. Objective This study aimed to evaluate the effects of LILT (λ=830 nm) on the tibialis anterior (TA) muscle of aged rats. Subjects and methods The total of 56 male Wistar rats formed two population sets: old and young, with 28 animals in each set. Each of these sets were randomly divided into four groups of young rats (3 months of age) with n=7 per group and four groups of aged rats (10 months of age) with n=7 per group. These groups were submitted to cryoinjury + laser irradiation, cryoinjury only, laser irradiation only and the control group (no cryoinjury/no laser irradiation). The laser treatment was performed for 5 consecutive days. The first laser application was done 24 h after the injury (on day 2) and on the seventh day, the TA muscle was dissected and removed under anesthesia. After this the animals were euthanized. Histological analyses with toluidine blue as well as hematoxylin-eosin staining (for counting the blood capillaries) were performed for the lesion areas. In addition, MyoD and VEGF mRNA was assessed by quantitative polymerase chain reaction. Results The results showed significant elevation (p<0.05) in MyoD and VEGF genes expression levels

  4. [Age and aging as incomplete architecture of human ontogenesis].

    PubMed

    Baltes, P B

    1999-12-01

    The focus is on the basic biological-genetic and social-cultural architecture of human development across the life span. The starting point is the frame provided by past evolutionary forces. A first conclusion is that for modern times and the relative brevity of the time windows involved in modernity, further change in human functioning is primarily dependent on the evolution of new cultural forms of knowledge rather than evolution-based changes in the human genome. A second conclusion concerns the general architecture of the life course. Three governing lifespan developmental principles coexist. First, because long-term evolutionary selection evince a negative age correlation, genome-based plasticity and biological potential decrease with age. Second, for growth aspects of human development to extend further into the life span, culture-based resources are required at ever increasing levels. Third, because of age-related losses in biological plasticity and negative effects associated with some principles of learning (e.g., negative transfer), the efficiency of culture is reduced as lifespan development unfolds. Joint application of these principles suggests that the lifespan architecture becomes more and more incomplete with age. Three examples are given to illustrate the implications of the lifespan architecture outlined. The first is a general theory of development involving the orchestration of three component processes and their age-related dynamics: Selection, optimization, and compensation. The second example is theory and research on lifespan intelligence that distinguishes between the biology-based mechanics and culture-based pragmatics of intelligence and specifies distinct age gradients for the two categories of intellectual functioning. The third example considers the goal of evolving a positive biological and cultural scenario for the last phase of life (fourth age). Because of the general lifespan architecture outlined, this objective becomes

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

    PubMed

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

    2015-01-01

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

  6. Interlaboratory reproducibility of standard accelerated aging methods for oxidation of UHMWPE.

    PubMed

    Kurtz, S M; Muratoglu, O K; Buchanan, F; Currier, B; Gsell, R; Greer, K; Gualtieri, G; Johnson, R; Schaffner, S; Sevo, K; Spiegelberg, S; Shen, F W; Yau, S S

    2001-07-01

    During accelerating aging, experimental uncertainty may arise due to variability in the oxidation process, or due to limitations in the technique that is ultimately used to measure oxidation. The purpose of the present interlaboratory study was to quantify the repeatability and reproducibility of standard accelerated aging methods for ultra-high molecular weight polyethylene (UHMWPE). Sections (200 microm thick) were microtomed from the center of an extruded rod of GUR 4150 HP, gamma irradiated in air or nitrogen, and circulated to 12 institutions in the United States and Europe for characterization of oxidation before and after accelerated aging. Specimens were aged for 3 weeks at 80 degrees C in an air circulating oven or for 2 weeks at 70 degrees C in an oxygen bomb (maintained at 503 kPa (5 atm.) of O2) in accordance with the two standard protocols described in ASTM F 2003-00. FTIR spectra were collected from each specimen within 24 h of the start and finish of accelerated aging, and oxidation indices were calculated by normalizing the peak area of the carbonyl region by the reference peak areas at 1370 or 2022 cm(-1). The mean relative interlaboratory uncertainty of the oxidation data was 78.5% after oven aging and 129.1% after bomb aging. The oxidation index measurement technique was not found to be a significant factor in the reproducibility. Comparable relative intrainstitutional uncertainty was observed after oven aging and bomb aging. For both aging methods, institutions successfully discriminated between air-irradiated and control specimens. However, the large interinstitutional variation suggests that absolute performance standards for the oxidation index of UHMWPE after accelerated aging may not be practical at the present time.

  7. 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

  8. Physical Property Changes in Plutonium from Accelerated Aging using Pu-238 Enrichment

    SciTech Connect

    Chung, B W; Choi, B W; Saw, C K; Thompson, S R; Woods, C H; Hopkins, D J; Ebbinghaus, B B

    2006-12-20

    We present changes in volume, immersion density, and tensile properties observed from accelerated aged plutonium alloys. Accelerated alloys (or spiked alloys) are plutonium alloys enriched with approximately 7.5 weight percent of the faster-decaying {sup 238}Pu to accelerate the aging process by approximately 17 times the rate of unaged weapons-grade plutonium. After sixty equivalent years of aging on spiked alloys, the dilatometry shows the samples at 35 C have swelled in volume by 0.15 to 0.17 % and now exhibit a near linear volume increase due to helium in-growth. The immersion density of spiked alloys shows a decrease in density, similar normalized volumetric changes (expansion) for spiked alloys. Tensile tests show increasing yield and engineering ultimate strength as spiked alloys are aged.

  9. 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

  10. 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.

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

    PubMed

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

    2010-10-01

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

  12. 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

  13. 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.

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

    PubMed Central

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

    2008-01-01

    LMNA mutations are responsible for a variety of genetic disorders, including muscular dystrophy, lipodystrophy, and certain progeroid syndromes, notably Hutchinson-Gilford Progeria. Although a number of clinical features of these disorders are suggestive of accelerated aging, it is not known whether cells derived from these patients exhibit cellular phenotypes associated with accelerated aging. We examined a series of isogenic skin fibroblast lines transfected with LMNA constructs bearing known pathogenic point mutations or deletion mutations found in progeroid syndromes. Fibroblasts overexpressing mutant lamin A exhibited accelerated rates of loss of telomeres and shortened replicative lifespans, in addition to abnormal nuclear morphology. To our surprise, these abnormalities were also observed in lines overexpressing wild-type lamin A. Copy number variants are common in human populations; those involving LMNA, whether arising meiotically or mitotically, might lead to progeroid phenotypes. In an initial pilot study of 23 progeroid cases without detectible WRN or LMNA mutations, however, no cases of altered LMNA copy number were detected. Nevertheless, our findings raise a hypothesis that changes in lamina organization may cause accelerated telomere attrition, with different kinetics for overexpession of wild-type and mutant lamin A, which leads to rapid replicative senescence and progroid phenotypes. PMID:17870066

  15. 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

  16. Degradation of mechanical behavior in UHMWPE after natural and accelerated aging.

    PubMed

    Edidin, A A; Jewett, C W; Kalinowski, A; Kwarteng, K; Kurtz, S M

    2000-07-01

    Ultra-high molecular weight polyethylene (UHMWPE) is known to degrade during natural (shelf) aging following gamma irradiation in air, but the mechanical signature of degradation remains poorly understood. Accelerated aging methods have been developed to reproduce the natural aging process as well as to precondition total joint replacement components prior to joint simulator wear testing. In this study, we compared the mechanical behavior of naturally (shelf) aged and accelerated aged tibial inserts using a previously validated miniature specimen testing technique known as the small punch test. Tibial inserts made-of GUR 1120 and sterilized with 25 to 40 kGy of gamma radiation (in air) in 1988, 1993, and 1997 were obtained; a subset of the 1997 implants were subjected to 4 weeks of accelerated aging in air at 80 degrees C. To determine the spatial variation of mechanical properties within each insert, miniature disk shaped specimens were machined from the surface and subsurface regions of the inserts. Analysis of variance of the test data showed that aging significantly affected the small punch test measures of elastic modulus, initial load, ultimate load, ultimate displacement, and work to failure. The accelerated aging protocol was unable to reproduce the spatial mechanical profile seen in shelf aged components, but it did mechanically degrade the surface of GUR 1120 tibial components to an extent comparable to that seen after 10 years of natural aging. Test specimens showed a fracture morphology consistent with the decreased ductility and toughness which was corroborated by the small punch test metrics of this study. Our data support the hypothesis that UHMWPE undergoes a spatially nonuniform change towards a less ductile (more brittle) mechanical behavior after gamma irradiation in air and shelf aging.

  17. Effect of water load in human body systems upon tolerance to +Gz acceleration.

    PubMed

    Gembicka, D

    1989-01-01

    A possible improvement of +Gz acceleration tolerance, obtained in human subjects through administering specific volumes of water, viz. 7, 14 and 21 ml/kg body weight, to be drunk immediately before centrifuge examination in order to increase the volume of plasma, thus increasing the circulating blood volume, was the starting-point for this work. Two hundred healthy male subjects, aged 19.9 +/- 0.9, were classified in 4 main groups and 2 supplementary groups for examination. It was found that the water intake in volumes of 14 ml/kg body weight produced a significant mean increase in the acceleration tolerance of 0.8 G, and that of 21 ml/kg body weight improved acceleration tolerance by 1.1 G on the average. The increase tolerance to acceleration was maintained throughout a period of about 30 minutes (for 14 ml/kg body weight) up to approximately 50 minutes (for 21 ml/kg body weight). The favourable effect of water load in the body systems upon +Gz acceleration tolerance was probably due to the increase of plasma volume (by 5.24% and 6.98% for 14 and 21 ml/kg body weight, respectively). PMID:2485611

  18. 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

  19. Effects of fibers on the color change and stability of resin composites after accelerated aging.

    PubMed

    Tuncdemir, Ali Riza; Aykent, Filiz

    2012-01-01

    Composite resins were reinforced with glass and polyethylene fibers in this study, and the effect of fiber reinforcement on the color change of composite resins was investigated. After accelerated aging, the effect of fiber reinforcement on the color stability of composite resins was also examined. There were three experimental groups (n=12 disks per group): non-fiber-reinforced composite (non-FRC control), polyethylene fiber (Ribbond-THM)-reinforced composite, and glass fiber (everstick NET)-reinforced composite. According to the critical remarks of color change of National Bureau of Standarts (NSB), glass fiber-reinforced anterior composites showed trace color change and polyethylene-fiber reinforced composites showed slight color change before accelerated aging. After accelerated aging, both control and fiber-reinforced composite groups showed noticeable color change. It was concluded that both the types of fiber reinforcement and composite resin influenced the color change of fiber-reinforced composite resins.

  20. 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

  1. Human ageing and the sympathoadrenal system.

    PubMed

    Seals, D R; Esler, M D

    2000-11-01

    Over the past three decades the changes in sympathoadrenal function that occur with age in healthy adult humans have been systematically studied using a combination of neurochemical, neurophysiological and haemodynamic experimental approaches. The available experimental evidence indicates that tonic whole-body sympathetic nervous system (SNS) activity increases with age. The elevations in SNS activity appear to be region specific, targeting skeletal muscle and the gut, but not obviously the kidney. The SNS tone of the heart is increased, although this appears to be due in part to reduced neuronal reuptake of noradrenaline (norepinephrine). In contrast to SNS activity, tonic adrenaline (epinephrine) secretion from the adrenal medulla is markedly reduced with age. This is not reflected in plasma adrenaline concentrations because of reduced plasma clearance. Despite widely held beliefs to the contrary, sympathoadrenal responsiveness to acute stress is not exaggerated with age in healthy adults. Indeed, adrenaline release in response to acute stress is substantially attenuated in older men. The mechanisms underlying the age-associated increases in SNS activity have not been established, but our preliminary data are consistent with increased subcortical central nervous system (CNS) sympathetic drive. These changes in sympathoadrenal function with advancing age may have a number of important physiological and pathophysiological consequences for human health and disease. PMID:11060120

  2. Cardiovascular Aging: Perspectives From Humans to Rodents.

    PubMed

    Lakatta, Edward G.

    1998-11-01

    In order to define and target the specific characteristics of cardiovascular aging that render aging as a risk factor for diseases (such as atherosclerosis, hypertension, stroke, and heart failure) that reach epidemic proportions among older individuals, it is essential to develop quantitative information on age-associated alterations in cardiovascular structure and function in health. A sustained effort, over the past two decades, has been applied to characterize the multiple effects of aging on health in cardiovascular structure and function in a single study population (BLSA). In these studies, community-dwelling, volunteer participants are rigorously screened to detect both clinical and occult cardiovascular disease and characterized with respect to lifestyle (e.g., exercise habits), in an attempt to deconvolute interactions among lifestyle, cardiovascular disease, and the aging process in health. Some specific changes in resting cardiovascular structure and function and cardiovascular reserve capacity that occur with advancing age in these healthy humans have been identified and are presented here. These observations in humans are extended by relevant experiments from animal models to provide possible mechanistic insight.

  3. 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.

  4. 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

  5. Noncoding Transcriptional Landscape in Human Aging.

    PubMed

    Costa, Marina C; Leitão, Ana Lúcia; Enguita, Francisco J

    2016-01-01

    Aging is a universal phenomenon in metazoans, characterized by a general decline of the organism physiology associated with an increased risk of mortality and morbidity. Aging of an organism correlates with a decline in function of its cells, as shown for muscle, immune, and neuronal cells. As the DNA content of most cells within an organism remains largely identical throughout the life span, age-associated transcriptional changes must be achieved by epigenetic mechanisms. However, how aging may impact on the epigenetic state of cells is only beginning to be understood. In light of a growing number of studies demonstrating that noncoding RNAs can provide molecular signals that regulate expression of protein-coding genes and define epigenetic states of cells, we hypothesize that noncoding RNAs could play a direct role in inducing age-associated profiles of gene expression. In this context, the role of long noncoding RNAs (lncRNAs) as regulators of gene expression might be important for the overall transcriptional landscape observed in aged human cells. The possible functions of lncRNAs and other noncoding RNAs, and their roles in the regulation of aging-related cellular pathways will be analyzed.

  6. Evolution of morphology in UHMWPE following accelerated aging: the effect of heating rates.

    PubMed

    Kurtz, S M; Pruitt, L A; Crane, D J; Edidin, A A

    1999-07-01

    Accelerated aging methods are used to evaluate the oxidative stability of UHMWPE components for total joint replacements. In this study, we traced the evolution of the crystalline morphology during accelerated thermal aging of UHMWPE in air with the intent of explaining previous, counterintuitive heating rate effects. GUR4150HP extruded rod stock material was machined into miniature (0.5 mm thick) specimens that were either gamma irradiated in air or in nitrogen (27 +/- 3 kGy) or left unirradiated (control). Accelerated aging in an air furnace (at 80 degrees C, atmospheric pressure) was performed on half of the test samples at a heating rate of 0.1 degrees C/min and at 5 degrees C/min for the remaining half. Although the initial heating rate, as measured by changes in density, did influence the absolute degradation rate by up to 214%, the heating rate effect did not appear to influence the relative ranking of UHMWPE in terms of its oxidative stability. The heating rate effect is more consistent with a kinetic mechanism of the oxidation process than it is with a previously hypothesized diffusion mechanism. UHMWPE morphology, as characterized using a transmission electron microscope (TEM), demonstrated considerable rearrangement of the crystalline regions as a result of the accelerated aging. The stacking of the lamellae observed after accelerated aging was not consistent with the morphology of naturally aged UHMWPE components. The observed differences in crystalline morphology likely result from the enhanced mobility of the polymer chains due to thermal aging and may be analogous to an annealing process.

  7. 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.

  8. A methodology for examining the plausibility of accelerated aging protocols for UHMWPE components.

    PubMed

    Lewis, G; Nyman, J S; Trieu, H H

    1998-01-01

    In light of the time-intensive nature of using real-time shelf-aged specimens in research into property changes of ultra-high-molecular-weight polyethylene (UHMWPE), accelerated thermal diffusion oxidative aging (usually referred to as accelerated aging) is frequently resorted to. A number of such aging protocols have been reported in the literature, with various claims for their producing changes in the properties of the polymer being the same as or similar to those seen in real-time shelf-aged samples. The thrust of the present work is the presentation of a methodology for examining such claims. The methodology is applied to six properties (% crystallinity, melting temperature, oxidation index, ultimate tensile strength, ultimate tensile elongation, and tensile toughness) of 4150HP UHMWPE grade, sterilized using six different methods, prior to and following the use of a specific accelerated aging protocol (oxygen gas at 70 degrees C and 507 kPa pressure; 14 d.). These six properties have been identified in the literature as being strongly correlated with the clinical wear of UHMWPE articular components. It is shown that the claim for the protocol used in the present work (in terms of the simulated equivalent shelf aging time) is plausible. It needs to be emphasized, however, that this conclusion is tentative given the paucity of the relevant literature results that are currently available and which are vital to the application of the methodology.

  9. Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.

    PubMed

    Doan, Ryan N; Bae, Byoung-Il; Cubelos, Beatriz; Chang, Cindy; Hossain, Amer A; Al-Saad, Samira; Mukaddes, Nahit M; Oner, Ozgur; Al-Saffar, Muna; Balkhy, Soher; Gascon, Generoso G; Nieto, Marta; Walsh, Christopher A

    2016-10-01

    Comparative analyses have identified genomic regions potentially involved in human evolution but do not directly assess function. Human accelerated regions (HARs) represent conserved genomic loci with elevated divergence in humans. If some HARs regulate human-specific social and behavioral traits, then mutations would likely impact cognitive and social disorders. Strikingly, rare biallelic point mutations-identified by whole-genome and targeted "HAR-ome" sequencing-showed a significant excess in individuals with ASD whose parents share common ancestry compared to familial controls, suggesting a contribution in 5% of consanguineous ASD cases. Using chromatin interaction sequencing, massively parallel reporter assays (MPRA), and transgenic mice, we identified disease-linked, biallelic HAR mutations in active enhancers for CUX1, PTBP2, GPC4, CDKL5, and other genes implicated in neural function, ASD, or both. Our data provide genetic evidence that specific HARs are essential for normal development, consistent with suggestions that their evolutionary changes may have altered social and/or cognitive behavior. PAPERCLIP.

  10. 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.

  11. Effect of an accelerated aging protocol on viscoelastic properties of UHMWPE.

    PubMed

    Lewis, Gladius

    2002-01-01

    The values of two viscoelastic properties (storage modulus and loss angle) of four sets of ultra-high-molecular-weight polyethylene specimens were obtained. Two sets comprised specimens that had been sterilized (using gamma radiation in air or ethylene oxide gas) while the other two sets comprised specimens that were sterilized and then exposed to an accelerated aging protocol that, in the literature, has been proposed as simulating 5 years of real-time shelf aging. An analysis of the present results from the four specimen sets and those obtained, in a previous study by the present author, on specimens machined from real-time shelf aged tibial inserts suggests that the claim made for the accelerated aging protocol may be conservative.

  12. Exposure to light at night accelerates aging and spontaneous uterine carcinogenesis in female 129/Sv mice

    PubMed Central

    Popovich, Irina G.; Zabezhinski, Mark A.; Panchenko, Andrei V.; Piskunova, Tatiana S.; Semenchenko, Anna V.; Tyndyk, Maragriata L.; Yurova, Maria N.; Anisimov, Vladimir N.

    2013-01-01

    The effect of the constant illumination on the development of spontaneous tumors in female 129/Sv mice was investigated. Forty-six female 129/Sv mice starting from the age of 2 mo were kept under standard light/dark regimen [12 h light (70 lx):12hr dark; LD, control group], and 46 of 129/Sv mice were kept under constant illumination (24 h a day, 2,500 lx, LL) from the age of 5 mo until to natural death. The exposure to the LL regimen significantly accelerated body weight gain, increased body temperature as well as acceleration of age-related disturbances in estrous function, followed by significant acceleration of the development of the spontaneous uterine tumors in female 129/Sv mice. Total tumor incidence as well as a total number of total or malignant tumors was similar in LL and LD group (p > 0.05). The mice from the LL groups survived less than those from the LD group (χ2 = 8.5; p = 0.00351, log-rank test). According to the estimated parameters of the Cox’s regression model, constant light regimen increased the relative risk of death in female mice compared with the control (LD) group (p = 0.0041). The data demonstrate in the first time that the exposure to constant illumination was followed by the acceleration of aging and spontaneous uterine tumorigenesis in female 129/Sv mice. PMID:23656779

  13. Effect ofartificial accelerated aging on color stability and surface roughness of indirect composites.

    PubMed

    Zanin, Fabíola Rejane; Garcia, Lucas da Fonseca Roberti; Casemiro, Luciana Assirati; Pires-de-Souza, Fernanda de Carvalho Panzeri

    2008-03-01

    Direct and indirect composite resins have different forms of polymerization. Some materials require a post-cure system associating light and heat enhancing clinical properties. This study assessed the changes in color and surface roughness of three indirect composite resins after accelerated aging. Twelve specimens (15 x 2 mm) were obtained for each tested material. Subsequently, the first measurements for roughness tests and colorimetric spectrophotometry (CIE L*a*b* scale) were performed. Specimens were subject to accelerated aging for 384 hours. New measurements were then performed to evaluate the resulting change. Accelerated aging produced color change and increased surface roughness in all composite resins. Solidex resin showed color changes above the clinically accepted value (DeltaE = 4.31 +/- 0.22), and roughness values (Ra = 0.088 +/- 0.008 microm) statistically lower than that of Artglass (Ra = 0.141 +/- 0.026 microm) and Targis (Ra = 0.124 +/- 0.02 microm) (p<0.001). All the indirect resins tested showed color change and increased roughness after accelerated aging. Solidex showed color stability above a quantitative level considered clinically acceptable and lower roughness values compared to the other resins.

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

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

  15. 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

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

    PubMed Central

    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

  17. 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

  18. 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.

  19. 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.

  20. Prediction of brain age suggests accelerated atrophy after traumatic brain injury

    PubMed Central

    Cole, James H; Leech, Robert; Sharp, David J

    2015-01-01

    Objective The long-term effects of traumatic brain injury (TBI) can resemble observed in normal ageing, suggesting that TBI may accelerate the ageing process. We investigate this using a neuroimaging model that predicts brain age in healthy individuals and then apply it to TBI patients. We define individuals' differences in chronological and predicted structural "brain age," and test whether TBI produces progressive atrophy and how this relates to cognitive function. Methods A predictive model of normal ageing was defined using machine learning in 1,537 healthy individuals, based on magnetic resonance imaging–derived estimates of gray matter (GM) and white matter (WM). This ageing model was then applied to test 99 TBI patients and 113 healthy controls to estimate brain age. Results The initial model accurately predicted age in healthy individuals (r * 0.92). TBI brains were estimated to be "older," with a mean predicted age difference (PAD) between chronological and estimated brain age of 4.66 years (±10.8) for GM and 5.97 years (±11.22) for WM. This PAD predicted cognitive impairment and correlated strongly with the time since TBI, indicating that brain tissue loss increases throughout the chronic postinjury phase. Interpretation TBI patients' brains were estimated to be older than their chronological age. This discrepancy increases with time since injury, suggesting that TBI accelerates the rate of brain atrophy. This may be an important factor in the increased susceptibility in TBI patients for dementia and other age-associated conditions, motivating further research into the age-like effects of brain injury and other neurological diseases. PMID:25623048

  1. 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.

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

    PubMed

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

    2016-02-01

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

  3. Effect of accelerated aging on the microhardness and color stability of flexible resins for dentures.

    PubMed

    Goiato, Marcelo Coelho; Santos, Daniela Micheline dos; Haddad, Marcela Filie; Pesqueira, Aldiéris Alves

    2010-01-01

    Acrylic resins have been widely used due to their acceptable esthetics and desirable characteristics such as easy handling, good thermal conductivity, low permeability to oral fluids and color stability. Flexible resins were introduced on the market as an alternative to the use of conventional acrylic resins in the construction of complete and partial removable dentures. Although these resins present advantages in terms of esthetics and comfort, studies assessing chromatic and microhardness alterations of these materials are still scarce in the related literature. The aim of this study was to evaluate the chromatic and microhardness alterations of two commercial brands of flexible resins in comparison to the conventional resin Triplex when submitted to accelerated aging. The resins were manipulated according to manufacturers' instructions and inserted into a silicone matrix to obtain 21 specimens divided into 3 groups: Triplex, Ppflex and Valplast. Triplex presented the highest microhardness value (p < 0.05) for all the aging periods, which was significantly different from that of the other resins, followed by the values of Valplast and Ppflex. Comparison between the flexible resins (Ppflex and Valplast) revealed a statistically significant difference (p < 0.05) as regards color. The flexible resin Ppflex and the conventional resin Triplex presented no statistically significant difference (p < 0.05) as regards aging. The accelerated aging significantly increased the microhardness values of the resins, with the highest values being observed for Triplex. Valplast presented the greatest chromatic alteration after accelerated aging. PMID:20339724

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

    PubMed

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

    2009-04-01

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

  5. Evidence of accelerated aging among African Americans and its implications for mortality.

    PubMed

    Levine, M E; Crimmins, E M

    2014-10-01

    Blacks experience morbidity and mortality earlier in the life course compared to whites. Such premature declines in health may be indicative of an acceleration of the aging process. The current study uses data on 7644 black and white participants, ages 30 and above, from the third National Health and Nutrition Examination Survey, to compare the biological ages of blacks and whites as indicated from a combination of ten biomarkers and to determine if such differences in biological age relative to chronological age account for racial disparities in mortality. At a specified chronological age, blacks are approximately 3 years older biologically than whites. Differences in biological age between blacks and whites appear to increase up until ages 60-65 and then decline, presumably due to mortality selection. Finally, differences in biological age were found to completely account for higher levels of all-cause, cardiovascular and cancer mortality among blacks. Overall, these results suggest that being black is associated with significantly higher biological age at a given chronological age and that this is a pathway to early death both overall and from the major age-related diseases.

  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. 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

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

    PubMed Central

    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

  9. 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.

  10. 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.

  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. Preserving humanity in an age of technology.

    PubMed

    Mann, R E

    1992-03-01

    Preserving humanity in the present technological age can be a challenge for all health care workers, but perhaps particularly for staff working within an intensive care environment. This article highlights some of the potential effects of such technology on staff, patients and relatives, particularly bringing to light some of the disadvantages brought about by the use of such technology. Areas considered include the role of nurses within a technological environment, patients' and relatives' reactions to technology, the potential effect on autonomy and responsibility for both patients and nurses, economic issues, and finally ethical and moral issues raised by the advent of further technology. Despite many positive contributions to nursing care which arise from the use of technology, there are disadvantages attributed to technology which have only been mentioned superficially in previous literature on this subject. The question arises as to whether nurses are able to balance preserving the humanity of patients with the extensive use of technology in an intensive care environment today.

  13. 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

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

    PubMed

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

    2015-06-01

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

  15. 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

  16. 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.

  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. 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.

  19. 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.

  20. Dynamic changes of DNA epigenetic marks in mouse oocytes during natural and accelerated aging.

    PubMed

    Qian, Yan; Tu, Jiajie; Tang, Nelson Leung Sang; Kong, Grace Wing Shan; Chung, Jacqueline Pui Wah; Chan, Wai-Yee; Lee, Tin-Lap

    2015-10-01

    Aging is a complex time-dependent biological process that takes place in every cell and organ, eventually leading to degenerative changes that affect normal biological functions. In the past decades, the number of older parents has increased significantly. While it is widely recognized that oocyte aging poses higher birth and reproductive risk, the exact molecular mechanisms remain largely elusive. DNA methylation of 5-cytosine (5mC) and histone modifications are among the key epigenetic mechanisms involved in critical developmental processes and have been linked to aging. However, the impact of oocyte aging on DNA demethylation pathways has not been examined. The recent discovery of Ten-Eleven-Translocation (TET) family proteins, thymine DNA glycosylase (TDG) and the demethylation intermediates 5hmC, 5fC and 5caC has provided novel clues to delineate the molecular mechanisms in DNA demethylation. In this study, we examined the cellular level of modified cytosines (5mC, 5hmC, 5fC and 5caC) and Tet/Tdg expression in oocytes obtained from natural and accelerated oocyte aging conditions. Here we show all the DNA demethylation marks are dynamically regulated in both aging conditions, which are associated with Tet3 over-expression and Tdg repression. Such an aberrant expression pattern was more profound in accelerated aging condition. The results suggest that DNA demethylation may be actively involved in oocyte aging and have implications for development of potential drug targets to rejuvenate aging oocytes. This article is part of a Directed Issue entitled: Epigenetics dynamics in development and disease.

  1. 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

  2. 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.

  3. Declining expression of a single epithelial cell-autonomous gene accelerates age-related thymic involution

    PubMed Central

    Sun, Liguang; Guo, Jianfei; Brown, Robert; Amagai, Takashi; Zhao, Yong; Su, Dong-Ming

    2010-01-01

    SUMMARY Age-related thymic involution may be triggered by gene expression changes in lymphohematopoietic and/or non-hematopoietic thymic epithelial cells (TECs). The role of epithelial cell-autonomous gene FoxN1 may be involved in the process, but it is still a puzzle due to shortage of evidence from gradual loss-of-function and exogenous gain-of-function studies. Using our recently generated loxP-floxed-FoxN1(fx) mouse carrying the ubiquitous CreERT (uCreERT) transgene with a low dose of spontaneous activation, which causes gradual FoxN1 deletion with age, we found that the uCreERT-fx/fx mice showed an accelerated age-related thymic involution due to progressive loss of FoxN1+ TECs. The thymic aging phenotypes were clearly observable as early as at 3–6 months of age, resembling the naturally aged (18–22-month-old) murine thymus. By intrathymically supplying aged wild-type mice with exogenous FoxN1-cDNA, thymic involution and defective peripheral CD4+ T-cell function could be partially rescued. The results support the notion that decline of a single epithelial cell-autonomous gene FoxN1 levels with age causes primary deterioration in TECs followed by impairment of the total postnatal thymic microenvironment, and potentially triggers age-related thymic involution in mice. PMID:20156205

  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.

  5. 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.

  6. 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.

  7. 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.

  8. Sod2 haploinsufficiency does not accelerate aging of telomere dysfunctional mice.

    PubMed

    Guachalla, Luis Miguel; Ju, Zhenyu; Koziel, Rafal; von Figura, Guido; Song, Zhangfa; Fusser, Markus; Epe, Bernd; Jansen-Durr, Pidder; Rudolph, K Lenhard

    2009-03-05

    Telomere shortening represents a causal factor of cellular senescence. At the same time, several lines of evidence indicate a pivotal role of oxidative DNA damage for the aging process in vivo. A causal connection between the two observations was suggested by experiments showing accelerated telomere shorting under conditions of oxidative stress in cultured cells, but has never been studied in vivo. We therefore have analysed whether an increase in mitochondrial derived oxidative stress in response to heterozygous deletion of superoxide dismutase (Sod2(+/-)) would exacerbate aging phenotypes in telomere dysfunctional (mTerc(-/-)) mice. Heterozygous deletion of Sod2 resulted in reduced SOD2 protein levels and increased oxidative stress in aging telomere dysfunctional mice, but this did not lead to an increase in basal levels of oxidative nuclear DNA damage, an accumulation of nuclear DNA breaks, or an increased rate of telomere shortening in the mice. Moreover, heterozygous deletion of Sod2 did not accelerate the depletion of stem cells and the impairment in organ maintenance in aging mTerc(-/-) mice. In agreement with these observations, Sod2 haploinsufficiency did not lead to a further reduction in lifespan of mTerc(-/-) mice. Together, these results indicate that a decrease in SOD2-dependent antioxidant defence does not exacerbate aging in the context of telomere dysfunction.

  9. 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.

  10. 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

  11. Tooth loss early in life accelerates age-related bone deterioration in mice.

    PubMed

    Kurahashi, Minori; Kondo, Hiroko; Iinuma, Mitsuo; Tamura, Yasuo; Chen, Huayue; Kubo, Kin-ya

    2015-01-01

    Both osteoporosis and tooth loss are health concerns that affect many older people. Osteoporosis is a common skeletal disease of the elderly, characterized by low bone mass and microstructural deterioration of bone tissue. Chronic mild stress is a risk factor for osteoporosis. Many studies showed that tooth loss induced neurological alterations through activation of a stress hormone, corticosterone, in mice. In this study, we tested the hypothesis that tooth loss early in life may accelerate age-related bone deterioration using a mouse model. Male senescence-accelerated mouse strain P8 (SAMP8) mice were randomly divided into control and toothless groups. Removal of the upper molar teeth was performed at one month of age. Bone response was evaluated at 2, 5 and 9 months of age. Tooth loss early in life caused a significant increase in circulating corticosterone level with age. Osteoblast bone formation was suppressed and osteoclast bone resorption was activated in the toothless mice. Trabecular bone volume fraction of the vertebra and femur was decreased in the toothless mice with age. The bone quality was reduced in the toothless mice at 5 and 9 months of age, compared with the age-matched control mice. These findings indicate that tooth loss early in life impairs the dynamic homeostasis of the bone formation and bone resorption, leading to reduced bone strength with age. Long-term tooth loss may have a cumulative detrimental effect on bone health. It is important to take appropriate measures to treat tooth loss in older people for preventing and/or treating senile osteoporosis.

  12. The role of cellular senescence in Werner syndrome: toward therapeutic intervention in human premature aging.

    PubMed

    Davis, Terence; Wyllie, Fiona S; Rokicki, Michal J; Bagley, Mark C; Kipling, David

    2007-04-01

    Werner syndrome (WS) is a premature aging disorder used as a model of normal human aging. WS individuals have several characteristics of normal aging, such as cataracts, hair graying, and skin aging, but manifest these at an early age. Additionally, WS individuals have high levels of inflammatory diseases, such as atherosclerosis and type 2 diabetes. The in vivo aging in WS is associated with accelerated aging of fibroblasts in culture. The cause of the accelerated senescence is not understood, but may be due to the genomic instability that is a hallmark of WS. Genome instability results in activation of stress kinases, such as p38, and the p38-specific inhibitor SB203580, prevents the accelerated senescence seen in WS fibroblasts. However, oxidative damage plays a role, as low oxygen conditions and antioxidant treatment revert some of the accelerated senescence phenotype. The effects of oxidative stress appear to be suppressible by SB203580; however, it does not appear to be transduced by p38. As SB203580 is known to inhibit other kinases in addition to p38, this suggests that more than one kinase pathway is involved. The recent development of p38 inhibitors with different binding properties, specificities, and oral bioavailability, and of new potent and selective inhibitors of JNK and MK2, will make it possible to dissect the roles of various kinase pathways in the accelerated senescence of WS cells. If this accelerated senescence is reflective of WS aging in vivo, these kinase inhibitors may well form the basis of antiaging therapies for individuals with WS.

  13. 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.

  14. "Accelerating aging" chemotherapy on aged animals: protective effect from nutraceutical modulation.

    PubMed

    Marotta, Francesco; Harada, Masatoshi; Minelli, Emilio; Ono-Nita, Suzanne K; Marandola, Paulo

    2008-04-01

    The aim of this study was to test a novel phytocompound in an experimental model of antitumor-induced immunosuppression. Five groups of mice were considered: young (Y) and aged (A) that were given intraperitoneally 10 doses of cyclophosphamide (CPX, 25mg/kg/bw) or CPX plus (150 mg/kg/bw) of the nutraceutical DTS (Denshichi-Tochiu-Sen), and control. After sacrifice, macrophage chemotaxis and serum levels of IFN-gamma, IL-2, and GM-CSF were determined. Liver and urinary bladder were examined histologically, as were the liver and kidney for redox enzymes. CPX significantly decreased macrophage chemotaxis and all cytokines (p < 0.05, A > Y). DTS restored macrophage function and cytokine concentration (p < 0.001) and partly improved the necro-inflammatory score and substance P receptor expression in the bladder and the redox status in liver and kidney (p < 0.05). Such data suggest that DTS effectively prevents CPX-induced immune suppression and oxidative-inflammatory damage, which are particularly enhanced in aged organisms.

  15. Collagens in the aged human macula.

    PubMed

    Marshall, G E; Konstas, A G; Reid, G G; Edwards, J G; Lee, W R

    1994-03-01

    Immunogold cytochemistry was used to investigate the fine structural distribution of collagen types I-VI in Bruch's membrane and choroid of the aged human macula. Macular tissue was obtained from ten eyes, and processed for cryoultramicrotomy and London Resin white embedding. Striated collagen fibrils within the inner and outer collagenous layers were found to contain collagen types I, III and V. In addition, type V collagen was also present in the basement membrane of the choriocapillaris. Gross thickening of the choriocapillaris basement membrane was attributed to the deposition of type IV collagen. However, type IV collagen appeared to be absent from the basement membrane of the retinal pigment epithelium. The interesting location of type VI collagen on the choroidal side of the choriocapillaris suggested that its function is to anchor the choriocapillaris onto the choroid. The collagens studied were absent from fibrous banded material, long-spacing collagen, the elastic layer and amorphous granular material. It was concluded that, of the collagen types studied, only the deposition of type IV collagen contributes to the age-related thickening of Bruch's membrane.

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

    PubMed

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

    2008-01-01

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

  17. Accelerated long-term forgetting in aging and intra-sleep awakenings

    PubMed Central

    Mary, Alison; Schreiner, Svenia; Peigneux, Philippe

    2013-01-01

    The architecture of sleep and the functional neuroanatomical networks subtending memory consolidation processes are both modified with aging, possibly leading to accelerated forgetting in long-term memory. We investigated associative learning and declarative memory consolidation processes in 16 young (18–30 years) and 16 older (65–75 years) healthy adults. Performance was tested using a cued recall procedure at the end of learning (immediate recall), and 30 min and 7 days later. A delayed recognition test was also administered on day 7. Daily sleep diaries were completed during the entire experiment. Results revealed a similar percentage of correct responses at immediate and 30-min recall in young and older participants. However, recall was significantly decreased 7 days later, with an increased forgetting in older participants. Additionally, intra-sleep awakenings were more frequent in older participants than young adults during the seven nights, and were negatively correlated with delayed recall performance on day 7 in the older group. Altogether, our results suggest a decline in verbal declarative memory consolidation processes with aging, eventually leading to accelerated long-term forgetting indicating that increased sleep fragmentation due to more frequent intra-sleep awakenings in older participants contribute to the reported age-related decline in long-term memory retrieval. Our results highlight the sensitivity of long-term forgetting measures to evidence consolidation deficits in healthy aging. PMID:24137151

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

    PubMed

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

    2013-01-01

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

  19. Hardness evaluation of prosthetic silicones containing opacifiers following chemical disinfection and accelerated aging.

    PubMed

    Goiato, Marcelo Coelho; Haddad, Marcela Filié; Santos, Daniela Micheline dos; Pesqueira, Aldiéris Alves; Moreno, Amália

    2010-01-01

    We evaluated the effects of disinfection and aging on the hardness of silicones containing opacifiers and intended for use in facial prosthetics. A total of 90 samples were produced using a cylindrical metal mold 3 mm in height and 30 mm in diameter. The samples were fabricated from Silastic MDX 4-4210 silicone in three groups: GI contained no opacifier, GII contained barium sulfate (Ba), and GIII contained titanium dioxide (Ti). The samples were disinfected using effervescent tablets (Ef), neutral soap (Ns), or 4% chlorhexidine (Cl) 3 times a week for 60 days. After this period the samples underwent 1,008 hours of accelerated aging. The hardness was measured using a durometer immediately following the disinfection period and after 252, 504, and 1,008 hours of aging. The data were statistically analyzed using 3-way ANOVA and the Tukey test (p < .05). The GIII group exhibited the greatest variation in hardness regardless of elapsed time. All groups displayed greater hardness after 1,008 hours of accelerated aging independent of disinfectant type. All of the hardness values were within the clinically acceptable range.

  20. 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

  1. 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

  2. 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

  3. Colour stability, opacity and cross-link density of composites submitted to accelerated artificial aging.

    PubMed

    Mundim, Fabrício Mariano; Pires-de-Souza, Fernanda de Carvalho Panzeri; Garcia, Lucas da Fonseca Roberti; Consani, Simonides

    2010-06-01

    The study evaluated the influence of accelerated artificial aging on colour stability, opacity and cross-link density of resin-based composites (RBCs). Seven specimens were obtained of five RBCs (Heliomolar, 4 Seasons, Tetric Evo Ceram, SR Adoro), which were submitted to colour stability and opacity analysis and cross-link density evaluation. All tests were performed before and after aging. After statistical analysis (one-way ANOVA; Tukey; p<0.05), it was observed that QuiXfil and SR Adoro presented colour alteration values above those that are clinically acceptable (deltaE=5.77 and 4.34 respectively) and the variation in opacity was lowest for SR Adoro. There was an increase in the cross-link density of all studied materials after aging.

  4. The effect of accelerated aging on color stability of denture liners.

    PubMed

    Anil, N; Hekimoglu, C; Sahin, S

    1998-09-01

    The objective of the present study was to determine the color changes resulting from the aging process in two cold and three hot curing soft liners and two hard liners. Seven samples were fabricated for each material. The initial color measurements were made with a UV-Visible Recording Spectrophotometer. The samples were then placed in an accelerated aging chamber to simulate the aging process. The color of the samples was then measured again with a colorimeter, and the color changes (delta E) were calculated. The critical mark of color change (delta E) has been quantified by the NBS. It was concluded that cold curing soft liners were not color-stable, and that hot curing soft liners and hard liners had similar color durability. These results suggest that colorants used in cold curing soft liners must be reinforced.

  5. 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

  6. 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.

  7. 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

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

    NASA Astrophysics Data System (ADS)

    Tang, Xiaping; Chevalier, Roger A.

    2016-06-01

    Recent gamma-ray observations show that middle aged supernova remnants (SNRs) interacting with molecular clouds (MCs) can be sources of both GeV and TeV emission. Based on the MC association, two scenarios have been proposed to explain the observed gamma-ray emission. In one, energetic cosmic ray (CR) particles escape from the SNR and then illuminate nearby MCs, producing gamma-ray emission, while the other involves direct interaction between the SNR and MC. In the direct interaction scenario, re-acceleration of pre-existing CRs in the ambient medium is investigated while particles injected from the thermal pool are neglected in view of the slow shock speeds in middle aged SNRs. However, standard diffusive shock acceleration (DSA) theory produces a steady state particle spectrum that is too flat compared to observations, which suggests that the high energy part of the observed spectrum has not yet reached a steady state. We derive a time dependent DSA solution in the test particle limit for re-acceleration of pre-existing CRs case and show that it is capable of reproducing the observed gamma-ray emission in SNRs like IC 443 and W44, in the context of a MC interaction model. We also provide a simple physical picture to understand the time dependent DSA spectrum. A spatially averaged diffusion coefficient around the SNR can be estimated through fitting the gamma-ray spectrum. The spatially averaged diffusion coefficient in middle aged SNRs like IC 443 and W44 is estimated to be ~10^(25) cm^2/s at ~ 1GeV, which is between the Bohm limit and interstellar value.

  9. Length velocity acceleration at 9 months of age in a representative birth cohort of Dutch infants.

    PubMed

    Van den Broeck, J; Brand, R; Massa, G; Herngreen, W P; Wit, J M

    2000-01-01

    According to the ICP (infancy-childhood-puberty) growth model, statural growth can be divided into three partially superimposed components assumed to represent different physiologic mechanisms. This model predicts a sudden acceleration of length velocity (LV) at the onset of the childhood component around 9 months. The existence of such an infancy-childhood growth spurt has not yet been firmly corroborated by epidemiological studies. In the present study length measurements were made at the target ages of 1, 3, 6, 9, 12, 15, 18 and 24 months in a birth cohort of 2034 infants. In order to check whether length growth showed a continuous smooth pattern, different mathematical models were fitted to the individual growth curves. The models included Count and Guo functions, 5th order polynomial and combinations of 5th order polynomial with the logarithmic term of the Count function and the square root term of the Guo function. We showed that in boys and girls there is a small but systematic lack of fit of the mathematical modeling, due to a sudden acceleration of LV around 9 months. In addition there was an increase in variation of attained length at this age. Comparison of unbalanced ANOVA models with and without addition of dummy variables for the target ages confirmed that there was an acceleration around 9 months that, if corrected for, leads to a significantly improved model fit (likelihood ratio test p < 0.0001). In absolute terms of LV, the misfit at 9 months was not greater than 0.5 cm/year on average. We conclude that the results of this study support the existence of a late infancy growth spurt. In our opinion, however, the magnitude of the phenomenon does not legitimate construction and use of discontinuous growth references such as the ICP reference.

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

    PubMed Central

    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

    2013-01-01

    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

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

    PubMed

    Kiecolt-Glaser, Janice K; Wilson, Stephanie J

    2016-09-01

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

  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. Skeletal Involution by Age-associated Oxidative Stress and Its Acceleration by Loss of Sex Steroids*

    PubMed Central

    Almeida, Maria; Han, Li; Martin-Millan, Marta; Plotkin, Lilian I.; Stewart, Scott A.; Roberson, Paula K.; Kousteni, Stavroula; O’Brien, Charles A.; Bellido, Teresita; Parfitt, A. Michael; Weinstein, Robert S.; Jilka, Robert L.; Manolagas, Stavros C.

    2011-01-01

    Both aging and loss of sex steroids have adverse effects on skeletal homeostasis, but whether and how they may influence each others negative impact on bone remains unknown. We report herein that both female and male C57BL/6 mice progressively lost strength (as determined by load-to-failure measurements) and bone mineral density in the spine and femur between the ages of 4 and 31 months. These changes were temporally associated with decreased rate of remodeling as evidenced by decreased osteoblast and osteoclast numbers and decreased bone formation rate; as well as increased osteoblast and osteocyte apoptosis, increased reactive oxygen species levels, and decreased glutathione reductase activity and a corresponding increase in the phosphorylation of p53 and p66shc, two key components of a signaling cascade that are activated by reactive oxygen species and influences apoptosis and lifespan. Exactly the same changes in oxidative stress were acutely reproduced by gonadectomy in 5-month-old females or males and reversed by estrogens or androgens in vivo as well as in vitro.We conclude that the oxidative stress that underlies physiologic organismal aging in mice may be a pivotal pathogenetic mechanism of the age-related bone loss and strength. Loss of estrogens or androgens accelerates the effects of aging on bone by decreasing defense against oxidative stress. PMID:17623659

  15. 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.

  16. Impulse noise exposure in early adulthood accelerates age-related hearing loss.

    PubMed

    Xiong, Min; Yang, Chuanhong; Lai, Huangwen; Wang, Jian

    2014-06-01

    The aim of this study was to investigate the influence of impulse noise on age-related hearing loss. The study consisted of two groups. Each group contained 109 men. Group I comprised veterans with normal hearing at the end of 1979 sino-vietnamese war. All these veterans were randomly selected from Guangzhou Military Command. Group II were men with no military experience randomly chosen from the health examination center of Guangzhou General Hospital of Guangzhou Military Command. Pure-tone thresholds of these two groups were measured and compared. The pure-tone thresholds of Group I were poorer than those of Group II at the frequencies of 4, 6 and 8 kHz. Thus, impulse noise accelerates age-related hearing loss.

  17. 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.

  18. 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.

  19. 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.

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

    PubMed

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

    2010-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

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

    PubMed

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

    2015-06-01

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

  3. Analysis of blood flow through a model of the human arterial system under periodic body acceleration.

    PubMed

    Sud, V K; Sekhon, G S

    1986-01-01

    The human system may be subjected to a body acceleration deliberated for example by making subjects lie down on vibrating tables or more frequently unintentionally, for example during travel in water and land or in air and space. The present study is concerned with the effects of externally imposed body accelerations on blood flow in a branched system of arteries. A finite-element model of flow in the arterial system subject to periodic body accelerations is presented. Computational results on the flow rates through selected arteries and the corresponding inlet and outlet pressures under different conditions (magnitude, frequency and direction) of applied acceleration are presented.

  4. 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

  5. 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

  6. 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

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

    PubMed

    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

    2014-04-01

    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.

  8. Olfactory phenotypic expression unveils human aging.

    PubMed

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

    2016-04-12

    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

  9. 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

  10. 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

  11. 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.

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

    PubMed Central

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

    2015-01-01

    Werner syndrome (WS) is a premature aging disorder caused by WRN protein deficiency. Here, we report on the generation of a human WS model in human embryonic stem cells (ESCs). Differentiation of WRN-null ESCs to mesenchymal stem cells (MSCs) recapitulates features of premature cellular aging, a global loss of H3K9me3, and changes in heterochromatin architecture. We show that WRN associates with heterochromatin proteins SUV39H1 and HP1α and nuclear lamina-heterochromatin anchoring protein LAP2β. Targeted knock-in of catalytically inactive SUV39H1 in wild-type MSCs recapitulates accelerated cellular senescence, resembling WRN-deficient MSCs. Moreover, decrease in WRN and heterochromatin marks are detected in MSCs from older individuals. Our observations uncover a role for WRN in maintaining heterochromatin stability and highlight heterochromatin disorganization as a potential determinant of human aging. PMID:25931448

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-10-01

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

  15. Accelerated aging of extruded dielectric power cables. Part 2; Life testing of 15 kV XLPE-insulated cables

    SciTech Connect

    Bernstein, B.S.; Thue, W.A. ); Walton, M.D.; Smith J.T. III )

    1992-04-01

    Attempts to successfully use accelerated aging tests to quantify the life of medium voltage power cables in service have been elusive. This paper describes preliminary results in which 15 kV XLPE cables were subjected to accelerated aging tests under a variety of controlled voltage stress and thermal load cycle conditions, with loss of life being calculated for each set of conditions in terms of the geometric mean time to failure (GMTF). In this paper the relative influence of voltage stress and load cycle temperature are discussed. This work is part of a broad effort that also involves studies with EPR-insulated cables, accelerated aging of cables from the same manufacturing run that are direct buried at the manufacturer's site, and also aging of these cables under normal operating conditions at four United States utilities.

  16. Density Changes in Plutonium Observed from Accelerated Aging using Pu-238 Enrichment

    SciTech Connect

    Chung, B W; Thompson, S R; Woods, C H; Hopkins, D J; Gourdin, W H; Ebbinghaus, B B

    2003-12-19

    Plutonium, because of its radioactive nature, ages from the ''inside out'' by means of self-irradiation damage and thus produces Frankel-type defects (vacancies and self-interstitial atoms) and defect clusters. The self-irradiation damage in Plutonium-239 occurs mainly by {alpha}-particle decay, where most of the damage comes from the U-235 recoil nucleus. The defects resulting from the residual lattice damage and helium in-growth could result in microstructural and physical property changes. Because these self-irradiation effects would normally require decades to measure, with a fraction (7.5 wt%) of Pu-238 is added to the reference plutonium alloy thus accelerating the aging process by approximately 18 times the normal rate. By monitoring the properties of the Pu-238 spiked alloy over a period of about 3.5 years, the properties of plutonium in storage can be projected for periods up to about 60 years. This paper presents density and volume changes observed from the immersion density and dilatometry measurements equivalent to aging the reference plutonium alloys to nine years.

  17. Disparity between online and offline tests in accelerated aging tests of LED lamps under electric stress.

    PubMed

    Wang, Yao; Jing, Lei; Ke, Hong-Liang; Hao, Jian; Gao, Qun; Wang, Xiao-Xun; Sun, Qiang; Xu, Zhi-Jun

    2016-09-20

    The accelerated aging tests under electric stress for one type of LED lamp are conducted, and the differences between online and offline tests of the degradation of luminous flux are studied in this paper. The transformation of the two test modes is achieved with an adjustable AC voltage stabilized power source. Experimental results show that the exponential fitting of the luminous flux degradation in online tests possesses a higher fitting degree for most lamps, and the degradation rate of the luminous flux by online tests is always lower than that by offline tests. Bayes estimation and Weibull distribution are used to calculate the failure probabilities under the accelerated voltages, and then the reliability of the lamps under rated voltage of 220 V is estimated by use of the inverse power law model. Results show that the relative error of the lifetime estimation by offline tests increases as the failure probability decreases, and it cannot be neglected when the failure probability is less than 1%. The relative errors of lifetime estimation are 7.9%, 5.8%, 4.2%, and 3.5%, at the failure probabilities of 0.1%, 1%, 5%, and 10%, respectively. PMID:27661576

  18. 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

  19. ACCELERATED-AGING OF SHIPPING PACKAGE O-RINGS FOR PU STORAGE

    SciTech Connect

    Hoffman, E

    2008-01-10

    The Savannah River Site (SRS) is storing surplus plutonium (Pu) materials in the K-Area Materials Storage (KAMS) facility. The Pu materials are packaged per the DOE 3013 Standard. The nested, welded 300 series stainless steel 3013 containers are transported to KAMS in Type B shipping packages and subsequently stored in the same packages. These type B shipping packages consist of double containment vessels sealed with dual O-rings. The O-ring compound is Parker Seals V0835-75, based on Viton{reg_sign} GLT fluoroelastomer. This work evaluates the performance of the V0835-75 O-rings at accelerated-aging conditions. The results will be used to develop a lifetime prediction model for O-rings in KAMS.

  20. 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.

  1. 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…

  2. 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

  3. Human neurologic function and the aging process.

    PubMed

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

    1980-01-01

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

  4. 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.

  5. The Werner syndrome. A model for the study of human aging.

    PubMed

    Nehlin, J O; Skovgaard, G L; Bohr, V A

    2000-06-01

    Human aging is a complex process that leads to the gradual deterioration of body functions with time. Various models to approach the study of aging have been launched over the years such as the genetic analysis of life span in the yeast S. cerevisiae, the worm C. elegans, the fruitfly, and mouse, among others. In human models, there have been extensive efforts using replicative senescence, the study of centenerians, comparisons of young versus old at the organismal, cellular, and molecular levels, and the study of premature aging syndromes to understand the mechanisms leading to aging. One good model for studying human aging is a rare autosomal recessive disorder known as the Werner syndrome (WS), which is characterized by accelerated aging in vivo and in vitro. A genetic defect implicated in WS was mapped to the WRN locus. Mutations in this gene are believed to be associated, early in adulthood, with clinical symptoms normally found in old individuals. WRN functions as a DNA helicase, and recent evidence, summarized in this review, suggests specific biochemical roles for this multifaceted protein. The interaction of WRN protein with RPA (replication protein A) and p53 will undoubtedly direct efforts to further dissect the genetic pathway(s) in which WRN protein functions in DNA metabolism and will help to unravel its contribution to the human aging process.

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

  7. 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.

  8. 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

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

    PubMed

    Somel, Mehmet; Rohlfs, Rori; Liu, Xiling

    2014-12-01

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

  10. [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

  11. 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

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

    PubMed

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

    2007-08-01

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

  13. Oxidative stress in aging human skin.

    PubMed

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

    2015-04-21

    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.

  14. 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

  15. [Biofunctional age diagnosis in humans. Potentials and limits].

    PubMed

    Pöthig, D; Gerdes, W; Viol, M; Wagner, P; Simm, A

    2011-06-01

    The demand and requirements for valid, practicable, and reliable procedures for age diagnosis are increasing worldwide. In contrast, few studies and only a small number of procedures exist. The authors review the theoretical and methodological requirements for the development of models for age diagnostics. They describe the fundamentals for further studies, based on an analysis of current gerontological research in this area. A following publication will report the valid systems measuring vitality and biofunctional age(ing) of human beings. PMID:21505938

  16. DNA-related pathways defective in human premature aging.

    PubMed

    Bohr, Vilhelm A

    2002-05-07

    One of the major issues in studies on aging is the choice of biological model system. The human premature aging disorders represent excellent model systems for the study of the normal aging process, which occurs at a much earlier stage in life in these individuals than in normals. The patients with premature aging also get the age associated diseases at an early stage in life, and thus age associated disease can be studied as well. It is thus of great interest to understand the molecular pathology of these disorders.

  17. Age-related differences in acceleration, maximum running speed, and repeated-sprint performance in young soccer players.

    PubMed

    Mendez-Villanueva, Alberto; Buchheit, Martin; Kuitunen, Sami; Douglas, Andrew; Peltola, Esa; Bourdon, Pitre

    2011-03-01

    We investigated age-related differences in the relationships among acceleration, maximum running speed, and repeated-sprint performance in 61 highly trained young male soccer players (Under 14, n = 14; Under 16, n = 22; Under 18, n = 25). We also examined the possible influence of anthropometry (stature, body mass, fat-free mass) and biological maturation (age at peak height velocity) on performance in those three sprint-running qualities. Players were tested for 10-m sprint (acceleration), flying 20-m sprint (maximum running speed), and 10 × 30-m sprint (repeated-sprint performance) times. Correlations between acceleration, maximum running speed, and repeated-sprint performance were positive and large to almost perfect (r = 0.55-0.96), irrespective of age group. There were age-based differences both in absolute performance in the three sprint-running qualities (Under 18 > Under 16 > Under 14; P < 0.001) and when body mass and fat-free mass were statistically controlled (P < 0.05). In contrast, all between-group differences disappeared after adjustment for age at peak height velocity (P > 0.05). The large correlations among acceleration, maximum running speed, and repeated-sprint performance in all age groups, as well as the disappearance of between-group differences when adjusted for estimated biological maturity, suggest that these physical qualities in young highly trained soccer players might be considered as a general quality, which is likely to be related to qualitative adaptations that accompany maturation.

  18. 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...

  19. 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

  20. 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

  1. 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.

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

    PubMed

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

    2012-01-01

    The aim of this study was to evaluate the color stability of composites subjected to different periods of accelerated artificial aging (AAA). A polytetrafluorethylene matrix (10 x 2 mm) was used to fabricate 24 test specimens of three different composites (n=8): Tetric Ceram (Ivoclar/Vivadent); Filtek P90 and Z250 (3M ESPE), shade A3. After light activation for 20 s (FlashLite 1401), polishing and initial color readout (Spectrophotometer PCB 687; BYK Gardner), the test specimens were subjected to AAA (C-UV; Comexim), in 8-h cycles: 4 h exposure to UV-B rays at 50°C and 4 h condensation at 50°C. At the end of each cycle, color readouts were taken and the test ended when the mean value of ΔE attained a level ≥3.30. Tetric Ceram presented alteration in ΔE equal to 3.33 in the first aging cycle. For Filtek P90 and Z250, two (ΔE=3.60) and four (ΔE=3.42) AAA cycles were necessary. After each cycle, there was a reduction of luminosity in all the samples (ΔL). It was concluded that a short period of AAA was sufficient to promote clinically unacceptable color alteration in composites, and that this alteration was material-dependent. PMID:23306237

  3. The effect of accelerated ageing on performance properties of addition type silicone biomaterials.

    PubMed

    Stathi, K; Tarantili, P A; Polyzois, G

    2010-05-01

    The UV-protection provided to addition type silicone elastomers by various colorants, such as conventional dry earth pigments, as well as the so called "functional or reactive" pigments, was investigated. Moreover, the effect of a UV light absorber and a silica filler was also explored. Under the experimental parameters of this work, the exposure of silicone to UV radiation resulted in some changes of the IR absorbance, thermal decomposition after 400 degrees C, T(g) and tensile properties, whereas the storage modulus of samples was not affected. The obtained spectroscopic data, as well as the results of TGA and storage modulus, were interpreted by assuming that chain scission takes place during aging, whereas the improvement of tensile strength allows the hypothesis of a post-curing process, initiated by UV radiation. Therefore, the increase of T(g) could partly be due to the above reason and, furthermore, to the contribution of a rearrangement of chain fragments within the free volume of the elastomeric material. Regarding the evaluation of various coloring agents used in this work, the obtained results show that dry pigments are more sensitive to accelerated ageing conditions in comparison with functional liquid pigments. Moreover, the hydrophobic character of silicone matrix is enhanced, with the addition of this type pigments because of the vinyl functional silanes groups present in their chemical structure. Finally, it should be noted that the incorporation of silica nanofiller did not seem to prevent the silicone elastomer from degradation upon UV irradiation, but showed a significant reinforcing effect.

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

    PubMed

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

    2012-01-01

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

  5. Density Changes in Plutonium Observed from Accelerated Aging Using Pu-238 Enrichment

    SciTech Connect

    Chung, B W; Thompson, S R; Woods, C H; Hopkins, D J; Gourdin, W H; Ebbinghaus, B B

    2005-10-19

    In support of Stockpile Stewardship activities, accelerated aging tests on a plutonium alloy enriched with 7.3 atomic percentage of {sup 238}Pu is underway using dilatometry at 35, 50, and 65 C and immersion density measurements of material stored at 50 C. Changes in density are expected from radiation damage in the lattice and helium in-growth. After twenty-five equivalent years of aging, the dilatometry data shows that the alloys at 35 C have expanded in volume by 0.11% to 0.12% and have started to exhibit a near linear expansion behavior primarily caused by the helium accumulation. The average He-to-vacancy ratio from tested specimens was determined to be around 2.3. The model for the lattice damage and helium in-growth accurately represents the volume swelling at 35 C. The density converted from the dilatometry corresponds well to the decreasing density trend of reference plutonium alloys as a function of time.

  6. Density changes in plutonium observed from accelerated aging using Pu-238 enrichment

    NASA Astrophysics Data System (ADS)

    Chung, B. W.; Thompson, S. R.; Woods, C. H.; Hopkins, D. J.; Gourdin, W. H.; Ebbinghaus, B. B.

    2006-09-01

    In support of Stockpile Stewardship activities, accelerated aging tests on a plutonium alloy enriched with 7.3 at.% of 238Pu is underway using dilatometry at 35, 50, and 65 °C and immersion density measurements of materials stored at 50 °C. Changes in density are expected from radiation damage in the lattice and helium in-growth. After 25 equivalent years of aging, the dilatometry data shows that the alloys at 35 °C have expanded in volume by 0.11-0.12% and have started to exhibit a near linear expansion behavior primarily caused by the helium accumulation. The average He-to-vacancy ratio from tested specimens was determined to be around 2.55. The model for the lattice damage and helium in-growth accurately represents the volume swelling at 35 °C. The density converted from the dilatometry corresponds well to the decreasing density trend of reference plutonium alloys as a function of time.

  7. [Proteoglycan in Bruch's membrane of senescence accelerated mouse: localization and age-related changes].

    PubMed

    Takada, Y; Ohkuma, H; Ogata, N; Matsushima, M; Sugasawa, K; Uyama, M

    1994-05-01

    We demonstrated the distribution of sulfated proteoglycans in Bruch's membrane of Senescence Accelerated Mouse histochemically and ultrastructurally using cuprolinic blue in conjunction with specific enzyme treatments and nitrous acid digestion. Two kinds of proteoglycan filaments were observed in the inner and outer collagenous layers, i.e., small collagen fibril-associated filaments (11 nm in average length), and large filaments (32 nm in average length). Intermediate size filaments (25 nm in average length) were seen in the basement membranes of the retinal pigment epithelium and choriocapillaris. Chondroitinase AC treatment eliminated the staining of filaments in the collagenous layers (chondroitin sulfate). Chondroitinase ABC treatment also eliminated the staining of filaments in the collagenous layers (chondroitin sulfate and dermatan sulfate). Nitrous acid eliminated the staining of filaments in both basement membranes (heparan sulfate). Proteoglycans containing chondroitin sulfate and dermatan sulfate were associated uniquely with collagen fibrils. Heparan sulfate proteoglycans were associated with the basement membranes of the pigment epithelium and choriocapillaris. With aging, the thickness of the basement membrane of the choriocapillaris and the staining of the filaments in the basement membranes of the pigment epithelium and choriocapillaris (heparan sulfate proteoglycans) increased. Collagen fibers became disarranged and the staining of both filaments in the collagenous layers decreased. The results of the staining characteristics probably reflect the aging of Bruch's membrane.

  8. 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

  9. 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

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

    PubMed Central

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

    2010-01-01

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

  11. A golden age of human pigmentation genetics.

    PubMed

    Sturm, Richard A

    2006-09-01

    The zebrafish golden mutation is characterized by the production of small and irregular-shaped melanin granules, resulting in a lightening of the pigmented lateral stripes of the animal. The recent positional cloning and localization of the golden gene, combined with genotype-phenotype correlations of alleles of its human orthologue (SLC24A5) in African-American and African-Caribbean populations, provide insights into the genetic and molecular basis of human skin colour. SLC24A5 promotes melanin deposition through maturation of the melanosome, highlighting the importance of ion-exchange in the function of this organelle.

  12. Biochemical markers of aging for longitudinal studies in humans.

    PubMed

    Engelfriet, Peter M; Jansen, Eugène H J M; Picavet, H Susan J; Dollé, Martijn E T

    2013-01-01

    Much progress has been made in the past decades in unraveling the mechanisms that are responsible for aging. The discovery that particular gene mutations in experimental species such as yeast, flies, and nematodes are associated with longevity has led to many important insights into pathways that regulate aging processes. However, extrapolating laboratory findings in experimental species to knowledge that is valid for the complexity of human physiology remains a major challenge. Apart from the restricted experimental possibilities, studying aging in humans is further complicated by the development of various age-related diseases. The availability of a set of biomarkers that really reflect underlying aging processes would be of much value in disentangling age-associated pathology from specific aging mechanisms. In this review, we survey the literature to identify promising biochemical markers of aging, with a particular focus on using them in longitudinal studies of aging in humans that entail repeated measurements on easily obtainable material, such as blood samples. Our search strategy was a 2-pronged approach, one focused on general mechanisms of aging and one including studies on clinical biomarkers of age-related diseases.

  13. Biochemical Markers of Aging for Longitudinal Studies in Humans

    PubMed Central

    Engelfriet, Peter M.; Jansen, Eugène H. J. M.; Picavet, H. Susan J.; Dollé, Martijn E. T.

    2013-01-01

    Much progress has been made in the past decades in unraveling the mechanisms that are responsible for aging. The discovery that particular gene mutations in experimental species such as yeast, flies, and nematodes are associated with longevity has led to many important insights into pathways that regulate aging processes. However, extrapolating laboratory findings in experimental species to knowledge that is valid for the complexity of human physiology remains a major challenge. Apart from the restricted experimental possibilities, studying aging in humans is further complicated by the development of various age-related diseases. The availability of a set of biomarkers that really reflect underlying aging processes would be of much value in disentangling age-associated pathology from specific aging mechanisms. In this review, we survey the literature to identify promising biochemical markers of aging, with a particular focus on using them in longitudinal studies of aging in humans that entail repeated measurements on easily obtainable material, such as blood samples. Our search strategy was a 2-pronged approach, one focused on general mechanisms of aging and one including studies on clinical biomarkers of age-related diseases. PMID:23382477

  14. 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)

  15. Aging as accelerated accumulation of somatic variants: whole-genome sequencing of centenarian and middle-aged monozygotic twin pairs.

    PubMed

    Ye, Kai; Beekman, Marian; Lameijer, Eric-Wubbo; Zhang, Yanju; Moed, Matthijs H; van den Akker, Erik B; Deelen, Joris; Houwing-Duistermaat, Jeanine J; Kremer, Dennis; Anvar, Seyed Yahya; Laros, Jeroen F J; Jones, David; Raine, Keiran; Blackburne, Ben; Potluri, Shobha; Long, Quan; Guryev, Victor; van der Breggen, Ruud; Westendorp, Rudi G J; 't Hoen, Peter A C; den Dunnen, Johan; van Ommen, Gert Jan B; Willemsen, Gonneke; Pitts, Steven J; Cox, David R; Ning, Zemin; Boomsma, Dorret I; Slagboom, P Eline

    2013-12-01

    It has been postulated that aging is the consequence of an accelerated accumulation of somatic DNA mutations and that subsequent errors in the primary structure of proteins ultimately reach levels sufficient to affect organismal functions. The technical limitations of detecting somatic changes and the lack of insight about the minimum level of erroneous proteins to cause an error catastrophe hampered any firm conclusions on these theories. In this study, we sequenced the whole genome of DNA in whole blood of two pairs of monozygotic (MZ) twins, 40 and 100 years old, by two independent next-generation sequencing (NGS) platforms (Illumina and Complete Genomics). Potentially discordant single-base substitutions supported by both platforms were validated extensively by Sanger, Roche 454, and Ion Torrent sequencing. We demonstrate that the genomes of the two twin pairs are germ-line identical between co-twins, and that the genomes of the 100-year-old MZ twins are discerned by eight confirmed somatic single-base substitutions, five of which are within introns. Putative somatic variation between the 40-year-old twins was not confirmed in the validation phase. We conclude from this systematic effort that by using two independent NGS platforms, somatic single nucleotide substitutions can be detected, and that a century of life did not result in a large number of detectable somatic mutations in blood. The low number of somatic variants observed by using two NGS platforms might provide a framework for detecting disease-related somatic variants in phenotypically discordant MZ twins. PMID:24182360

  16. 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

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

    PubMed

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

    2016-01-01

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

  18. 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.

  19. 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.

  20. HEAT WAVES, AGING, AND HUMAN CARDIOVASCULAR HEALTH

    PubMed Central

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

    2014-01-01

    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 is 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, as well as 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 due to 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 increases the extent of future untoward health outcomes. PMID:24598696

  1. 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.

  2. Age-related differences in human skin proteoglycans

    PubMed Central

    Carrino, David A; Calabro, Anthony; Darr, Aniq B; Dours-Zimmermann, Maria T; Sandy, John D; Zimmermann, Dieter R; Sorrell, J Michael; Hascall, Vincent C; Caplan, Arnold I

    2011-01-01

    Previous work has shown that versican, decorin and a catabolic fragment of decorin, termed decorunt, are the most abundant proteoglycans in human skin. Further analysis of versican indicates that four major core protein species are present in human skin at all ages examined from fetal to adult. Two of these are identified as the V0 and V1 isoforms, with the latter predominating. The other two species are catabolic fragments of V0 and V1, which have the amino acid sequence DPEAAE as their carboxyl terminus. Although the core proteins of human skin versican show no major age-related differences, the glycosaminoglycans (GAGs) of adult skin versican are smaller in size and show differences in their sulfation pattern relative to those in fetal skin versican. In contrast to human skin versican, human skin decorin shows minimal age-related differences in its sulfation pattern, although, like versican, the GAGs of adult skin decorin are smaller than those of fetal skin decorin. Analysis of the catabolic fragments of decorin from adult skin reveals the presence of other fragments in addition to decorunt, although the core proteins of these additional decorin catabolic fragments have not been identified. Thus, versican and decorin of human skin show age-related differences, versican primarily in the size and the sulfation pattern of its GAGs and decorin in the size of its GAGs. The catabolic fragments of versican are detected at all ages examined, but appear to be in lower abundance in adult skin compared with fetal skin. In contrast, the catabolic fragments of decorin are present in adult skin, but are virtually absent from fetal skin. Taken together, these data suggest that there are age-related differences in the catabolism of proteoglycans in human skin. These age-related differences in proteoglycan patterns and catabolism may play a role in the age-related changes in the physical properties and injury response of human skin. PMID:20947661

  3. DeltaNp63alpha overexpression induces downregulation of Sirt1 and an accelerated aging phenotype in the mouse.

    PubMed

    Sommer, Matthias; Poliak, Nina; Upadhyay, Sunil; Ratovitski, Edward; Nelkin, Barry D; Donehower, Lawrence A; Sidransky, David

    2006-09-01

    p63 is highly expressed in the skin and appears to be an early marker of keratinocyte differentiation. To examine the role of p63 in vivo, we generated transgenic mice that overexpress deltaNp63alpha in the skin. These mice exhibited an accelerated aging phenotype in the skin characterized by striking wound healing defects, decreased skin thickness, decreased subcutaneous fat tissue, hair loss, and decreased cell proliferation. The accelerated skin aging was accompanied by a dramatic decrease in longevity of the mice. We found that aging in deltaNp63alpha transgenic mice and other mouse models correlated with levels of Sirt1, a mammalian SIR2 orthologue thought to extend the lifespan in lower species. Moreover, increased deltaNp63alpha expression induced cellular senescence that was rescued by Sirt1. Our data suggest that deltaNp63alpha levels may affect aging in mammals, at least in part, through regulation of Sirt1.

  4. 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

  5. Looking for disease being a model of human aging

    PubMed Central

    Hausmanowa-Petrusewicz, I; Madej-Pilarczyk, A

    2007-01-01

    Summary This paper is a part of an introduction to authors’ study on systemic laminopathies and their role in human aging. Of special interest is progeria – a type of systemic laminopathy associated usually with mutation 1824 C > T and presenting phenotype of preliminary aging. The authors analyse the differences between the progeria and other syndrome of preliminary aging – Werner’s syndrome. PMID:18421896

  6. Translating human simulation technologies to veterinary surgical training: accelerating adoption.

    PubMed

    Stredney, Don; Hittle, Brad; Collidas, Jared; McLoughlin, Mary Ann

    2008-01-01

    Through the reduction of live animal use in teaching surgical technique, the opportunities to deliberately study complex regional anatomy and practice surgical technique have decreased. With reduced exposure, there is concern some individuals are graduating without the requisite knowledge and proficiency to perform adequate surgical techniques. Ultimately, animals may unnecessarily suffer due to morbidities from limited or poor surgical competencies. We have translated developments derived from the human surgical simulation field for application to veterinary surgical training. We present our work on intuitive software for learning regional anatomy, surgical simulations, and on several limiting factors that impede the validation and adoption of simulation technologies for use by the veterinarian surgical community.

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

    PubMed

    Pretorius, E

    2010-03-01

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

  8. Increased ghrelin signaling prolongs survival in mouse models of human aging through activation of sirtuin1

    PubMed Central

    Fujitsuka, N; Asakawa, A; Morinaga, A; Amitani, M S; Amitani, H; Katsuura, G; Sawada, Y; Sudo, Y; Uezono, Y; Mochiki, E; Sakata, I; Sakai, T; Hanazaki, K; Yada, T; Yakabi, K; Sakuma, E; Ueki, T; Niijima, A; Nakagawa, K; Okubo, N; Takeda, H; Asaka, M; Inui, A

    2016-01-01

    Caloric restriction (CR) is known to retard aging and delay functional decline as well as the onset of diseases in most organisms. Ghrelin is secreted from the stomach in response to CR and regulates energy metabolism. We hypothesized that in CR ghrelin has a role in protecting aging-related diseases. We examined the physiological mechanisms underlying the ghrelin system during the aging process in three mouse strains with different genetic and biochemical backgrounds as animal models of accelerated or normal human aging. The elevated plasma ghrelin concentration was observed in both klotho-deficient and senescence-accelerated mouse prone/8 (SAMP8) mice. Ghrelin treatment failed to stimulate appetite and prolong survival in klotho-deficient mice, suggesting the existence of ghrelin resistance in the process of aging. However, ghrelin antagonist hastened death and ghrelin signaling potentiators rikkunshito and atractylodin ameliorated several age-related diseases with decreased microglial activation in the brain and prolonged survival in klotho-deficient, SAMP8 and aged ICR mice. In vitro experiments, the elevated sirtuin1 (SIRT1) activity and protein expression through the cAMP–CREB pathway was observed after ghrelin and ghrelin potentiator treatment in ghrelin receptor 1a-expressing cells and human umbilical vein endothelial cells. Furthermore, rikkunshito increased hypothalamic SIRT1 activity and SIRT1 protein expression of the heart in the all three mouse models of aging. Pericarditis, myocardial calcification and atrophy of myocardial and muscle fiber were improved by treatment with rikkunshito. Ghrelin signaling may represent one of the mechanisms activated by CR, and potentiating ghrelin signaling may be useful to extend health and lifespan. PMID:26830139

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

    PubMed

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

    2014-07-01

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

  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. Composites Associated with Pulp-Protection Material: Color-Stability Analysis after Accelerated Artificial Aging

    PubMed Central

    Cruvinel, Diogo Rodrigues; Garcia, Lucas da Fonseca Roberti; Consani, Simonides; de Carvalho Panzeri Pires-de-Souza, Fernanda

    2010-01-01

    Objectives: This study assessed the color stability of two composites associated with two pulp protectors submitted to accelerated artificial aging (AAA). Methods: 60 test specimens were made with 0.5 mm of protection material (calcium hydroxide - CH or glass ionomer cement - GIC) and 2.5 mm of restoration material (Concept or QuixFil) and divided into 3 groups (n=10) according to the type of protection material/composite, and the control group (no protection). After polishing, color readings were obtained with a spectrophotometer (PCB 6807 Byk Gardner) before and after AAA for 384 hours, and L*, a*, and b* coordinates and total color variation (ΔE) were analyzed (2-way ANOVA, Bonferroni, α=05). Results: Composites placed on CH presented lower L* levels than those on GIC, which presented higher L* values than the control group and lower b* values than those of the CH group. The Concept composite presented higher ΔE levels for all groups, differing statistically from QuixFil, except when placed on GIC. Conclusions: It was concluded that the protection material could affect the color stability and AAA is a factor that enhances this effect, depending on the type of composite used. PMID:20046473

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

    PubMed

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

    2013-01-01

    The aim of this study was to investigate the influence of accelerated artificial aging (AAA) on the microstructure and mechanical properties of the Filtek Z250, Filtek Supreme, 4 Seasons, Herculite, P60, Tetric Ceram, Charisma and Filtek Z100. composite resins. The composites were characterized by Fourier-transform Infrared spectroscopy (FTIR) and thermal analyses (Differential Scanning Calorimetry - DSC and Thermogravimetry - TG). The microstructure of the materials was examined by scanning electron microscopy. Surface hardness and compressive strength data of the resins were recorded and the mean values were analyzed statistically by ANOVA and Tukey's test (α=0.05). The results showed significant differences among the commercial brands for surface hardness (F=86.74, p<0.0001) and compressive strength (F=40.31, p<0.0001), but AAA did not affect the properties (surface hardness: F=0.39, p=0.53; compressive strength: F=2.82, p=0.09) of any of the composite resins. FTIR, DSC and TG analyses showed that resin polymerization was complete, and there were no differences between the spectra and thermal curve profiles of the materials obtained before and after AAA. TG confirmed the absence of volatile compounds and evidenced good thermal stability up to 200 °C, and similar amounts of residues were found in all resins evaluated before and after AAA. The AAA treatment did not significantly affect resin surface. Therefore, regardless of the resin brand, AAA did not influence the microstructure or the mechanical properties.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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…

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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

  4. Increased mobilization of aged carbon to rivers by human disturbance

    NASA Astrophysics Data System (ADS)

    Butman, David E.; Wilson, Henry F.; Barnes, Rebecca T.; Xenopoulos, Marguerite A.; Raymond, Peter A.

    2015-02-01

    Approximately 8% of anthropogenic carbon dioxide emissions are estimated to come from land-use change, but this estimate excludes fluxes of terrestrial carbon to aquatic ecosystems from human disturbance. Carbon fluxes from land to rivers have probably increased by 0.1 to 0.2 petagrams of carbon per year as a result of disturbances such as deforestation, agricultural intensification and the injection of human wastewater. Most dissolved organic carbon in rivers originates from young organic carbon from soils and vegetation, but aged carbon removed from the modern carbon cycle is also exported in many systems. Here we analyse a global data set of radiocarbon ages of riverine dissolved organic carbon and spatial data on land cover, population and environmental variables. We find that the age of dissolved organic carbon in rivers increases with population density and the proportion of human-dominated landscapes within a watershed, and decreases with annual precipitation. We reason that disturbance reintroduces aged soil organic matter into the modern carbon cycle, although fossil carbon in fertilizer or petroleum products may also be a source of aged carbon in disturbed watersheds. The total export from the terrestrial environment to freshwater systems remains unknown; nevertheless, our results suggest that 3-9% of dissolved organic carbon in rivers is aged carbon mobilized by human disturbance.

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

    PubMed

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

    2014-06-01

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

  6. 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.

  7. 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.

  8. Electrical properties of human skin as aging biomarkers.

    PubMed

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

    2014-09-01

    A non-invasive bioimpedance spectroscopy (BIS) and Cole-Cole impedance model parameters (R0, R∞, τ and α) were used to analyze electrical properties of intact and stripped human skin for both gender subjects divided into younger and older age groups. R0, R∞ and τ significantly increased while α significantly decreased with age in stripped skin for both genders (p<0.031). Using pooled data with respect to age, gender and skin stripping, R0, R∞ and τ values were shown to increase with age (p<0.0034), R0, τ and α were different between genders (p<0.024) and R0, R∞ and τ decreased with skin stripping (p<0.000008). All of four Cole-Cole parameters were age dependent with specific differences observed for genders and intact and stripped skin layers. Therefore, Cole-Cole parameters, obtained by non-invasive BIS measurements, are a new type of age dependent biomarkers.

  9. 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

  10. The effect of summation of contraction on acceleration signals in human skeletal muscle.

    PubMed

    Ohta, Yoichi; Shima, Norihiro; Yabe, Kyonosuke

    2010-10-01

    The purpose of this study was to determine the effects of summation of contraction on acceleration signals in human skeletal muscle. The torque parameters of dorsiflexion and acceleration signals in the tibialis anterior muscle were measured during evoked isometric contractions. In an examination of two-pulse trains with different inter-pulse intervals, the torque and accelerometer responses to inter-pulse intervals of 10-100 ms were recorded. In an investigation of the effects of different numbers of stimuli, the torque and accelerometer responses to 1-8 pulses with a constant inter-pulse interval of 10 ms were recorded. The present study found that there was a difference in acceleration amplitude between the single-pulse and two-pulse trains with an inter-pulse interval of 10 ms but not two-pulse trains with an inter-pulse interval of 20 ms or more. In the investigation of different numbers of stimuli, we found a similar MMG amplitude across 2-8 pulses. Moreover, we observed that the maximal time to the peak acceleration signal was approximately 27 ms. In a comparison of torque parameters with acceleration signals, the present study clearly shows that acceleration amplitude is poorly correlated to changes in force parameters when the inter-pulse interval or the number of stimuli are increased. These results suggest that the absence of associated changes in acceleration peak is due to the long interval for the subsequent pulses relative to the time at which acceleration peak is achieved ( approximately 27 ms). These findings will provide useful information concerning the method for assessing summation of contraction with an accelerometer.

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

    PubMed Central

    Fernandez-Twinn, Denise S.; Chen, Jian Hua; Hargreaves, Iain P.; Neergheen, Viruna; Aiken, Catherine E.; Ozanne, Susan E.

    2016-01-01

    ABSTRACT ‘Developmental programming’, which occurs as a consequence of suboptimal in utero and early environments, can be associated with metabolic dysfunction in later life, including an increased incidence of cardiovascular disease and type 2 diabetes, and predisposition of older men to sarcopenia. However, the molecular mechanisms underpinning these associations are poorly understood. Many conditions associated with developmental programming are also known to be associated with the aging process. We therefore utilized our well-established rat model of low birth weight and accelerated postnatal catch-up growth (termed ‘recuperated’) in this study to establish the effects of suboptimal maternal nutrition on age-associated factors in skeletal muscle. We demonstrated accelerated telomere shortening (a robust marker of cellular aging) as evidenced by a reduced frequency of long telomeres (48.5-8.6 kb) and an increased frequency of short telomeres (4.2-1.3 kb) in vastus lateralis muscle from aged recuperated offspring compared to controls. This was associated with increased protein expression of the DNA-damage-repair marker 8-oxoguanine-glycosylase (OGG1) in recuperated offspring. Recuperated animals also demonstrated an oxidative stress phenotype, with decreased citrate synthase activity, increased electron-transport-complex activities of complex I, complex II-III and complex IV (all markers of functional mitochondria), and increased xanthine oxidase (XO), p67phox and nuclear-factor kappa-light-chain-enhancer of activated B-cells (NF-κB). Recuperated offspring also demonstrated increased antioxidant defense capacity, with increased protein expression of manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), catalase and heme oxygenase-1 (HO1), all of which are known targets of NF-κB and can be upregulated as a consequence of oxidative stress. Recuperated offspring also had a pro-inflammatory phenotype, as evidenced by

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

    PubMed

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

    2014-01-01

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

  13. Experimental Induction of Type 2 Diabetes in Aging-Accelerated Mice Triggered Alzheimer-Like Pathology and Memory Deficits

    PubMed Central

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

    2014-01-01

    Alzheimer’s disease (AD) is an age-dependent neurodegenerative disease constituting ~95% of late-onset non-familial/sporadic AD, and only ~5% accounting for early-onset familial AD. Availability of a pertinent model representing sporadic AD is essential for testing candidate therapies. Emerging evidence indicates a causal link between diabetes and AD. People with diabetes are >1.5-fold more likely to develop AD. Senescence-accelerated mouse model (SAMP8) of accelerated aging displays many features occurring early in AD. Given the role played by diabetes in the pre-disposition of AD, and the utility of SAMP8 non-transgenic mouse model of accelerated aging, we examined if high fat diet-induced experimental type 2 diabetes in SAMP8 mice will trigger pathological aging of the brain. Results showed that compared to non-diabetic SAMP8 mice, diabetic SAMP8 mice exhibited increased cerebral amyloid-β, dysregulated tau-phosphorylating glycogen synthase kinase 3β, reduced synaptophysin immunoreactivity, and displayed memory deficits, indicating Alzheimer-like changes. High fat diet-induced type 2 diabetic SAMP8 mice may represent the metabolic model of AD. PMID:24121970

  14. 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.

  15. 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.

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

    PubMed

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

    2015-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Eiband, A. Martin

    1959-01-01

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

  18. Multi-Directional Sprinting and Acceleration Phase in Basketball and Handball Players Aged 14 and 15 Years.

    PubMed

    Popowczak, Marek; Rokita, Andrzej; Struzik, Artur; Cichy, Ireneusz; Dudkowski, Andrzej; Chmura, Paweł

    2016-10-01

    An important role in handball and basketball is played by ability to accelerate and ability to repeat multiple sprints. The aim of the study was to assess level of ability in multi-directional sprinting and running time over the first 5 m of the 30 m sprint in 93 basketball and handball players (46 boys and 47 girls) aged 14 to 15 years. The attempts were also made to find the relationships between the time of a 5-m run to evaluate initial acceleration phase and multi-directional sprinting evaluated using Five-Time Shuttle Run To Gates Test Statistical analysis revealed no important differences in times of 5-m runs and times of multi-directional sprinting between groups with different ages, genders, and sports specialties. Furthermore, no significant correlations were found based on Spearman's rank correlation coefficient between times of 5-m run and multi-directional sprinting in the most of subgroups studied.

  19. 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

  20. 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.

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

    PubMed

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

    2016-05-01

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

  2. Interjoint dynamic interaction during constrained human quiet standing examined by induced acceleration analysis.

    PubMed

    Sasagawa, Shun; Shinya, Masahiro; Nakazawa, Kimitaka

    2014-01-01

    Recent studies have demonstrated that human quiet standing is a multijoint movement, whereby the central nervous system (CNS) is required to deal with dynamic interactions among the joints to achieve optimal motor performance. The purpose of this study was to investigate how the CNS deals with such interjoint interaction during quiet standing by examining the relationship between the kinetics (torque) and kinematics (angular acceleration) within the multi-degree of freedom system. We modeled quiet standing as a double-link inverted pendulum involving both ankle and hip joints and conducted an "induced acceleration analysis." We found that the net ankle and hip torques induced angular accelerations of comparable magnitudes to the ankle (3.8 ± 1.4°/s(2) and 3.3 ± 1.2°/s(2)) and hip (9.1 ± 3.2°/s(2) and 10.5 ± 3.5°/s(2)) joints, respectively. Angular accelerations induced by the net ankle and hip torques were modulated in a temporally antiphase pattern to one another in each of the two joints. These quantitative and temporal relationships allowed the angular accelerations induced by the two net torques to countercompensate one another, thereby substantially (∼70%) reducing the resultant angular accelerations of the individual joints. These results suggest that, by taking advantage of the interjoint interaction, the CNS prevents the net torques from producing large amplitudes of the resultant angular accelerations when combined with the kinematic effects of all other torques in the chain.

  3. Interjoint dynamic interaction during constrained human quiet standing examined by induced acceleration analysis.

    PubMed

    Sasagawa, Shun; Shinya, Masahiro; Nakazawa, Kimitaka

    2014-01-01

    Recent studies have demonstrated that human quiet standing is a multijoint movement, whereby the central nervous system (CNS) is required to deal with dynamic interactions among the joints to achieve optimal motor performance. The purpose of this study was to investigate how the CNS deals with such interjoint interaction during quiet standing by examining the relationship between the kinetics (torque) and kinematics (angular acceleration) within the multi-degree of freedom system. We modeled quiet standing as a double-link inverted pendulum involving both ankle and hip joints and conducted an "induced acceleration analysis." We found that the net ankle and hip torques induced angular accelerations of comparable magnitudes to the ankle (3.8 ± 1.4°/s(2) and 3.3 ± 1.2°/s(2)) and hip (9.1 ± 3.2°/s(2) and 10.5 ± 3.5°/s(2)) joints, respectively. Angular accelerations induced by the net ankle and hip torques were modulated in a temporally antiphase pattern to one another in each of the two joints. These quantitative and temporal relationships allowed the angular accelerations induced by the two net torques to countercompensate one another, thereby substantially (∼70%) reducing the resultant angular accelerations of the individual joints. These results suggest that, by taking advantage of the interjoint interaction, the CNS prevents the net torques from producing large amplitudes of the resultant angular accelerations when combined with the kinematic effects of all other torques in the chain. PMID:24089399

  4. Secular trend of the age at menarche of Japanese girls with special regard to the secular acceleration of the age at peak height velocity.

    PubMed

    Hoshi, H; Kouchi, M

    1981-12-01

    An attempt is made to clarify the special characteristics of the secular trend of the menarchial age in Japan. The relationships with the precocious appearance of the age at peak high velocity, another exemplification of the maturity acceleration, is also reviewed. This research on menarche was conducted in 1979-1980 on 284 school girls born between 1961 and 1966. The girls were healthy, of middle socioeconomic class, and grew up and lived in Tokyo and its outskirts. A questionnaire was given to each subject who was requested to answer after referring to her diary, mother's or sister's records, or any other writing about her menarche. If none of these was available, they were asked to provide an event which occurred soon before or after the menarche. The arithmetic mean of the age at menarche was 12.40 years with a range of 9.63 to 15.44 years. In 1958 research was conducted on the menarche of 309 girls in the same school, and the mean menarchial age was reported to be 13.27 years with a range of 10.83 to 16.92 years. The rate of acceleration during these 21 years was 4.4 months/decade. Mean menarchial ages obtained in 157 studies ever reported in Japan were plotted against the year of publication. No definite tendency was apparent until a gradual change toward earlier menstruation began in about 1920. In the next 20 years the average decreased from 15.0 to 14.2 years of age. The rate of decrease during the 1920-1940 period was about 4 months/decade. Due to World War 2, a retardation of menarche began in 1941 and reached a peak of about 15.0 years of age in 1950-1952, after which the trend changed into one of rapid acceleration. It is believed that the age at peak height velocity (PHV) is highly correlated with menarche age. The correlation coefficient is reported to be 0.71 by Nicholson and Hanly (1953), 0.93 by Deming (1957) and 0.77 by the author's of this study based on the present subjects. Thus it can be reasonably assumed that the secular trend of menarche

  5. A 32-Channel Head Coil Array with Circularly Symmetric Geometry for Accelerated Human Brain Imaging

    PubMed Central

    Chu, Ying-Hua; Hsu, Yi-Cheng; Keil, Boris; Kuo, Wen-Jui; Lin, Fa-Hsuan

    2016-01-01

    The goal of this study is to optimize a 32-channel head coil array for accelerated 3T human brain proton MRI using either a Cartesian or a radial k-space trajectory. Coils had curved trapezoidal shapes and were arranged in a circular symmetry (CS) geometry. Coils were optimally overlapped to reduce mutual inductance. Low-noise pre-amplifiers were used to further decouple between coils. The SNR and noise amplification in accelerated imaging were compared to results from a head coil array with a soccer-ball (SB) geometry. The maximal SNR in the CS array was about 120% (1070 vs. 892) and 62% (303 vs. 488) of the SB array at the periphery and the center of the FOV on a transverse plane, respectively. In one-dimensional 4-fold acceleration, the CS array has higher averaged SNR than the SB array across the whole FOV. Compared to the SB array, the CS array has a smaller g-factor at head periphery in all accelerated acquisitions. Reconstructed images using a radial k-space trajectory show that the CS array has a smaller error than the SB array in 2- to 5-fold accelerations. PMID:26909652

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

    PubMed Central

    Nunn, Alistair VW; Bell, Jimmy D; Guy, Geoffrey W

    2009-01-01

    determines functional longevity, a rather more descriptive term for the metabolic syndrome is the 'lifestyle-induced metabolic inflexibility and accelerated ageing syndrome'. Ultimately, thriftiness is good for us as long as we have hormetic stimuli; unfortunately, mankind is attempting to remove all hormetic (stressful) stimuli from his environment. PMID:19371409

  7. U. S. -French Cooperative Research Program: U. S. test results for cable insulation and jacket materials at the completion of accelerated aging

    SciTech Connect

    Bustard, L.D.

    1984-01-01

    Eight different U.S. insulation and jacket products have been accelerated aged at Sandia. The experimental variables included: (1) sequential versus simultaneous accelerated aging exposures; (2) the order of the sequential exposures; and (3) ambient versus 70/sup 0/C irradiation temperatures during sequential aging exposures. We observed that the irradiation temperature (70/sup 0/C or ambient) was secondary in importance to the choice of sequence for thermal and radiation aging. For most materials studied (except TEFZEL) the irradiation then thermal aging sequence was as severe or more severe than the thermal then irradiation aging sequence.

  8. Age-dependent fatigue behaviour of human cortical bone.

    PubMed

    Diab, T; Sit, S; Kim, D; Rho, J; Vashishth, D

    2005-01-01

    Despite a general understanding that bone quality contributes to skeletal fragility, very little information exits on the age-dependent fatigue behavior of human bone. In this study four-point bending fatigue tests were conducted on aging bone in conjunction with the analysis of stiffness loss and preliminary investigation of nanoindentation based measurements of local tissue stiffness and histological evaluation of resultant tensile and compressive damage to identify the damage mechanism responsible for the increase in age-related bone fragility. The results obtained show that there is an exponential decrease in fatigue life with age, and old bone exhibits different modulus degradation profiles than young bone. In addition, this study provides preliminary evidence indicating that during fatigue loading, younger bone formed diffuse damage, lost local tissue stiffness on the tensile side. Older bone, in contrast, formed linear microcracks lost local tissue stiffness on the compressive side. Thus, the propensity of aging human bone to form more linear microcracks than diffuse damage may be a significant contributor to bone quality, and age related fragility in bone.

  9. Aging and the human vestibular nuclei: morphometric analysis.

    PubMed

    Alvarez, J C; Díaz, C; Suárez, C; Fernández, J A; González del Rey, C; Navarro, A; Tolivia, J

    2000-04-14

    The data concerning the effects of age on the brainstem are scarce and few works are devoted to the human vestibular nuclear complex. The study of the effects of aging in the vestibular nuclei could have clinical interest due to the high prevalence of balance control and gait problems in the elderly. We have used in this work eight human brainstems of different ages sectioned and stained by the formaldehyde-thionin technique. The neuron's profiles were drawn with a camera lucida and Abercrombie's method was used to estimate the total number of neurons. The test of Kolmogorov-Smirnov with the correction of Lilliefors was used to evaluate the fit of our data to a normal distribution and a regression analysis was done to determine if the variation of our data with age was statistically significant. Aging does not affect the volume or length of the vestibular nuclear complex. Our results clearly show that neuronal loss occurs with aging in the descending (DVN), medial (MVN), and lateral (LVN) vestibular nuclei, but not in the superior (SVN). There are changes in the proportions of neurons of different sizes but they are not statistically significant. The neuronal loss could be related with the problems that elderly people have to compensate unilateral vestibular lesions and the alterations of the vestibulospinal reflexes. The preservation of SVN neurons can explain why vestibulo-ocular reflexes are compensated after unilateral vestibular injuries.

  10. 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

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

    NASA Technical Reports Server (NTRS)

    Maas, E. F.; Huebner, W. P.; Seidman, S. H.; Leigh, R. J.

    1989-01-01

    The horizontal vestibulo-ocular reflex (VOR) during transient, high-acceleration (1900-7100 deg/sec-squared) head rotations was studied in four human subjects. Such stimuli perturbed the angle of gaze and caused illusory movement of a viewed target (oscillopsia). The disturbance of gaze could be attributed to the latency of the VOR (which ranged from 6-15 ms) and inadequate compensatory eye rotations (median VOR gain ranged from 0.61-0.83).

  12. Optimizing the science of drug development: opportunities for better candidate selection and accelerated evaluation in humans.

    PubMed

    Lesko, L J; Rowland, M; Peck, C C; Blaschke, T F

    2000-08-01

    Two international meetings were convened in 1998 to review the current science of drug development and the potential opportunities to optimize the evaluation of new drugs in humans. This report represents a synopsis of these meetings, and focuses on the current state of knowledge pertaining to drug development, future scientific and technical needs, and the relative merits of various strategies intended to accelerate the clinical development of drugs. PMID:10934664

  13. 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

  14. 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.

  15. 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

  16. Uniquely human self-control begins at school age.

    PubMed

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

    2015-11-01

    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 resist an impulse for immediate gratification, repeat a previously successful action, attend to a distracting noise, and quit in the face of repeated failure. Six-year-old children were more skillful than either 3-year-olds or chimpanzees at controlling their impulses. These results suggest that humans' most fundamental skills of self-control - as part of the overall decision-making process - are a part of their general great ape heritage, and that their species-unique skills of self-control begin at around the age at which many children begin formal schooling.

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

    PubMed

    Menapace, Ilaria; Masad, Eyad

    2016-09-01

    This paper presents findings on the evolution of the surface microstructure of two asphalt binders, one unmodified and one polymer modified, directly exposed to aging agents with increasing durations. The aging is performed using an accelerated weathering tester, where ultraviolet radiation, oxygen and an increased temperature are applied to the asphalt binder surface. Ultraviolet and dark cycles, which simulated the succession of day and night, alternated during the aging process, and also the temperature varied, which corresponded to typical summer day and night temperatures registered in the state of Qatar. Direct aging of an exposed binder surface is more effective in showing microstructural modifications than previously applied protocols, which involved the heat treatment of binders previously aged with standardized methods. With the new protocol, any molecular rearrangements in the binder surface after aging induced by the heat treatment is prevented. Optical photos show the rippling and degradation of the binder surface due to aging. Microstructure images obtained by means of atomic force microscopy show gradual alteration of the surface due to aging. The original relatively flat microstructure was substituted with a profoundly different microstructure, which significantly protrudes from the surface, and is characterized by various shapes, such as rods, round structures and finally 'flower' or 'leaf' structures. PMID:27059404

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

    PubMed

    Menapace, Ilaria; Masad, Eyad

    2016-09-01

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

  19. Issues on human acceleration tolerance after long-duration space flights

    NASA Technical Reports Server (NTRS)

    Kumar, K. Vasantha; Norfleet, William T.

    1992-01-01

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

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

    PubMed

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

    2016-05-19

    Humans are distinguished from the other living apes in having larger brains and an unusual life history that combines high reproductive output with slow childhood growth and exceptional longevity. This suite of derived traits suggests major changes in energy expenditure and allocation in the human lineage, but direct measures of human and ape metabolism are needed to compare evolved energy strategies among hominoids. Here we used doubly labelled water measurements of total energy expenditure (TEE; kcal day(-1)) in humans, chimpanzees, bonobos, gorillas and orangutans to test the hypothesis that the human lineage has experienced an acceleration in metabolic rate, providing energy for larger brains and faster reproduction without sacrificing maintenance and longevity. In multivariate regressions including body size and physical activity, human TEE exceeded that of chimpanzees and bonobos, gorillas and orangutans by approximately 400, 635 and 820 kcal day(-1), respectively, readily accommodating the cost of humans' greater brain size and reproductive output. Much of the increase in TEE is attributable to humans' greater basal metabolic rate (kcal day(-1)), indicating increased organ metabolic activity. Humans also had the greatest body fat percentage. An increased metabolic rate, along with changes in energy allocation, was crucial in the evolution of human brain size and life history. PMID:27144364

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

    PubMed Central

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

    2016-01-01

    Humans are distinguished from the other living apes in having larger brains and an unusual life history that combines high reproductive output with slow childhood growth and exceptional longevity1. This suite of derived traits suggests major changes in energy expenditure and allocation in the human lineage, but direct measures of human and ape metabolism are needed to compare evolved energy strategies among hominoids. Here we used doubly labelled water measurements of total energy expenditure (TEE; kcal day−1) in humans, chimpanzees, bonobos, gorillas and orangutans to test the hypothesis that the human lineage has experienced an acceleration in metabolic rate, providing energy for larger brains and faster reproduction without sacrificing maintenance and longevity. In multivariate regressions including body size and physical activity, human TEE exceeded that of chimpanzees and bonobos, gorillas and orangutans by approximately 400, 635 and 820 kcal day−1, respectively, readily accommodating the cost of humans' greater brain size and reproductive output. Much of the increase in TEE is attributable to humans' greater basal metabolic rate (kcal day−1), indicating increased organ metabolic activity. Humans also had the greatest body fat percentage. An increased metabolic rate, along with changes in energy allocation, was crucial in the evolution of human brain size and life history. PMID:27144364

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

    PubMed

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

    2016-05-04

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

  3. 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.

  4. 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.

  5. ISSLS PRIZE WINNER: INHIBITION OF NF-κB ACTIVITY AMELIORATES AGE-ASSOCIATED DISC DEGENERATION IN A MOUSE MODEL OF ACCELERATED AGING

    PubMed Central

    Nasto, Luigi A.; Seo, Hyoung-Yeon; Robinson, Andria R.; Tilstra, Jeremy S.; Clauson, Cheryl L.; Sowa, Gwendolyn A.; Ngo, Kevin; Dong, Qing; Pola, Enrico; Lee, Joon Y.; Niedernhofer, Laura J.; Kang, James D.; Robbins, Paul D.; Vo, Nam V.

    2012-01-01

    Study Design NF-κB activity was pharmacologically and genetically blocked in an accelerated aging mouse model to mitigate age-related disc degenerative changes. Objective To study the mediatory role of NF-κB signaling pathway in age-dependent intervertebral disc degeneration. Summary of Background Data Aging is a major contributor to intervertebral disc degeneration (IDD), but the molecular mechanism behind this process is poorly understood. NF-κB is a family of transcription factors which play a central role in mediating cellular response to damage, stress, and inflammation. Growing evidence implicates chronic NF-κB activation as a culprit in many aging-related diseases, but its role in aging-related IDD has not been adequately explored. We studied the effects of NF-κB inhibition on IDD using a DNA repair-deficient mouse model of accelerated aging (Ercc1-/Δ mice) previously been reported to exhibit age-related IDD. Methods Systemic inhibition of NF-κB activation was achieved either genetically by deletion of one allele of the NF-κB subunit p65 (Ercc1-/Δp65+/- mice) or pharmacologically by chronic intra-peritoneal administration of the Nemo Binding Domain (8K-NBD) peptide to block the formation of the upstream activator of NF-κB, IκB Inducible Kinase (IKK), in Ercc1-/Δ mice. Disc cellularity, total proteoglycan content and proteoglycan synthesis of treated mice and untreated controls were assessed. Results Decreased disc matrix proteoglycan content, a hallmark feature of IDD, and elevated disc NF-κB activity were observed in discs of progeroid Ercc1-/Δ mice and naturally aged wild-type compared to young WT mice. Systemic inhibition of NF-κB by the 8K-NBD peptide in Ercc1-/Δ mice increased disc proteoglycan synthesis and ameriolated loss disc cellularity and matrix proteoglycan. These results were confirmed genetically by using the p65 haploinsufficient Ercc1-/Δp65+/- mice. Conclusion These findings demonstrate that the IKK/NF-κB signaling pathway

  6. Methodology for designing accelerated aging tests for predicting life of photovoltaic arrays

    NASA Technical Reports Server (NTRS)

    Gaines, G. B.; Thomas, R. E.; Derringer, G. C.; Kistler, C. W.; Bigg, D. M.; Carmichael, D. C.

    1977-01-01

    A methodology for designing aging tests in which life prediction was paramount was developed. The methodology builds upon experience with regard to aging behavior in those material classes which are expected to be utilized as encapsulant elements, viz., glasses and polymers, and upon experience with the design of aging tests. The experiences were reviewed, and results are discussed in detail.

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

    PubMed Central

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

    2008-01-01

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

  8. Effects of aging on the mechanical behavior of human dentin.

    PubMed

    Arola, D; Reprogel, R K

    2005-06-01

    An experimental study on the mechanical behavior of human dentin and the influence of age was conducted. Beams with rectangular cross-section were sectioned from the coronal dentin of virgin extracted molars (N = 76) that were obtained from (N = 70) patients between 17 and 80 years of age. The beams were loaded in either quasi-static 4-point flexure or 4-point flexural fatigue to failure and the stiffness, strength and fatigue properties were evaluated. In characterizing the fatigue response the beams were divided into two age groups that were regarded as young (17 < or = age < or = 30, mean +/- std. dev. = 25 +/- 5 years) and old (50 < or = age < or = 80, mean +/- std. dev. = 64 +/- 9 years) dentin. Results from monotonic loading showed that both the flexural strength and strain to fracture of dentin decreased significantly with age. The fatigue life of dentin increased with a reduction in cyclic stress amplitude and the fatigue strength of young dentin was greater than that of old dentin at all cyclic stress amplitudes. The endurance strength of young dentin (at 10(7) cycles) was approximately 44 MPa, whereas the old dentin exhibited an endurance strength of approximately 23 MPa. Based on differences in the mechanical behavior and microscopic features of the fracture surfaces from the young and old specimens, aging appears to result in an increase in both the rate of damage initiation and propagation in dentin.

  9. Age-related acceleration of endothelial dysfunction and subclinical atherosclerosis in subjects with coronary artery lesions after Kawasaki disease.

    PubMed

    Noto, Nobutaka; Okada, Tomoo; Karasawa, Kensuke; Ayusawa, Mamoru; Sumitomo, Naokata; Harada, Kensuke; Mugishima, Hideo

    2009-04-01

    The objective of this study was to test the hypothesis that accelerated endothelial dysfunction and the development of premature atherosclerosis are associated with age in subjects with coronary artery lesions after Kawasaki disease (KD). A case-control study was performed at a university hospital that included 35 post-KD subjects across a wide age range (range, 8-42 years) without traditional cardiovascular risk factors and 35 age- and sex-matched healthy control subjects (Cont). Flow-mediated dilatation (FMD) of the brachial artery-induced by reactive hyperemia, intima media thickness (IMT), and elastic modulus (Ep) of the common carotid artery were compared between KD and Cont subjects assessed against age. KD subjects had slightly higher levels of body mass index, lipid profile, and HbA1c than Cont subjects, but the differences were not significant. The mean IMT (p < 0.001), age-adjusted percentage normal IMT (%N IMT; p < 0.0001), and Ep (p < 0.001) were significantly higher in KD than Cont subjects, and the peak FMD% (p < 0.01) was significantly lower in KD than Cont subjects. There were significant correlations between FMD% and age (r = -0.51 p < 0.0001), IMT and age (r = 0.68, p < 0.001), and Ep and age (r = 0.58, p < 0.01) in KD but not Cont subjects. When the difference in FMD% between KD and matched Cont subjects (DeltaFMD%) was plotted against age, no significant relationship was found, although significant correlations between DeltaIMT and age (r = 0.52, p < 0.01) as well as between DeltaEp and age (r = 0.46, p < 0.05) were observed. When we defined values that were +2.0 SD over the mean control values (i.e., %N IMT >or= 120% and/or Ep >or= 50 kPa) as markers of subclinical atherosclerosis, 15 subjects met the criteria. Subjects over the age of 22 years were more likely to have (OR = 16.54, p = 0.0001) subclinical atherosclerosis in this cohort. Our results suggest that endothelial dysfunction and the development of premature atherosclerosis were

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

    PubMed

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

    2009-08-11

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

  11. Reliability and Failure Modes of Solid-State Lighting Electrical Drivers Subjected to Accelerated Aging

    SciTech Connect

    Lall, Pradeep; Sakalaukus, Peter; Davis, Lynn

    2015-02-19

    An investigation of an off-the-shelf solid-state lighting device with the primary focus on the accompanied light-emitting diode (LED) electrical driver (ED) has been conducted. A set of 10 EDs were exposed to temperature humidity life testing of 85% RH and 85 C (85/85) without an electrical bias per the JEDEC standard JESD22-A101C in order to accelerate the ingress of moisture into the aluminum electrolytic capacitor (AEC) and the EDs in order to assess the reliability of the LED drivers for harsh environment applications. The capacitance and equivalent series resistance for each AEC inside the ED were measured using a handheld LCR meter as possible leading indications of failure. The photometric quantities of a single pristine light engine were monitored in order to investigate the interaction between the light engine and the EDs. These parameters were used in assessing the overall reliability of the EDs. In addition, a comparative analysis has been conducted between the 85/85 accelerated test data and a previously published high-temperature storage life accelerated test of 135°C. The results of the 85/85 acceleration test and the comparative analysis are presented in this paper.

  12. Reliability and Failure Modes of Solid-State Lighting Electrical Drivers Subjected to Accelerated Aging

    DOE PAGESBeta

    Lall, Pradeep; Sakalaukus, Peter; Davis, Lynn

    2015-02-19

    An investigation of an off-the-shelf solid-state lighting device with the primary focus on the accompanied light-emitting diode (LED) electrical driver (ED) has been conducted. A set of 10 EDs were exposed to temperature humidity life testing of 85% RH and 85 C (85/85) without an electrical bias per the JEDEC standard JESD22-A101C in order to accelerate the ingress of moisture into the aluminum electrolytic capacitor (AEC) and the EDs in order to assess the reliability of the LED drivers for harsh environment applications. The capacitance and equivalent series resistance for each AEC inside the ED were measured using a handheldmore » LCR meter as possible leading indications of failure. The photometric quantities of a single pristine light engine were monitored in order to investigate the interaction between the light engine and the EDs. These parameters were used in assessing the overall reliability of the EDs. In addition, a comparative analysis has been conducted between the 85/85 accelerated test data and a previously published high-temperature storage life accelerated test of 135°C. The results of the 85/85 acceleration test and the comparative analysis are presented in this paper.« less

  13. Telocytes and putative stem cells in ageing human heart.

    PubMed

    Popescu, Laurentiu M; Curici, Antoanela; Wang, Enshi; Zhang, Hao; Hu, Shengshou; Gherghiceanu, Mihaela

    2015-01-01

    Tradition considers that mammalian heart consists of about 70% non-myocytes (interstitial cells) and 30% cardiomyocytes (CMs). Anyway, the presence of telocytes (TCs) has been overlooked, since they were described in 2010 (visit www.telocytes.com). Also, the number of cardiac stem cells (CSCs) has not accurately estimated in humans during ageing. We used electron microscopy to identify and estimate the number of cells in human atrial myocardium (appendages). Three age-related groups were studied: newborns (17 days-1 year), children (6-17 years) and adults (34-60 years). Morphometry was performed on low-magnification electron microscope images using computer-assisted technology. We found that interstitial area gradually increases with age from 31.3 ± 4.9% in newborns to 41 ± 5.2% in adults. Also, the number of blood capillaries (per mm(2) ) increased with several hundreds in children and adults versus newborns. CMs are the most numerous cells, representing 76% in newborns, 88% in children and 86% in adults. Images of CMs mitoses were seen in the 17-day newborns. Interestingly, no lipofuscin granules were found in CMs of human newborns and children. The percentage of cells that occupy interstitium were (depending on age): endothelial cells 52-62%; vascular smooth muscle cells and pericytes 22-28%, Schwann cells with nerve endings 6-7%, fibroblasts 3-10%, macrophages 1-8%, TCs about 1% and stem cells less than 1%. We cannot confirm the popular belief that cardiac fibroblasts are the most prevalent cell type in the heart and account for about 20% of myocardial volume. Numerically, TCs represent a small fraction of human cardiac interstitial cells, but because of their extensive telopodes, they achieve a 3D network that, for instance, supports CSCs. The myocardial (very) low capability to regenerate may be explained by the number of CSCs, which decreases fivefold by age (from 0.5% to 0.1% in newborns versus adults).

  14. Vestibulosympathetic reflex during orthostatic challenge in aging humans

    NASA Technical Reports Server (NTRS)

    Monahan, Kevin D.; Ray, Chester A.

    2002-01-01

    Aging attenuates the increase in muscle sympathetic nerve activity (MSNA) and elicits hypotension during otolith organ engagement in humans. The purpose of the present study was to determine the neural and cardiovascular responses to otolithic engagement during orthostatic stress in older adults. We hypothesized that age-related impairments in the vestibulosympathetic reflex would persist during orthostatic challenge in older subjects and might compromise arterial blood pressure regulation. MSNA, arterial blood pressure, and heart rate responses to head-down rotation (HDR) performed with and without lower body negative pressure (LBNP) in prone subjects were measured. Ten young (27 +/- 1 yr) and 11 older subjects (64 +/- 1 yr) were studied prospectively. HDR performed alone elicited an attenuated increase in MSNA in older subjects (Delta106 +/- 28 vs. Delta20 +/- 7% for young and older subjects). HDR performed during simultaneous orthostatic stress increased total MSNA further in young (Delta53 +/- 15%; P < 0.05) but not older subjects (Delta-5 +/- 4%). Older subjects demonstrated consistent significant hypotension during HDR performed both alone (Delta-6 +/- 2 mmHg) and during LBNP (Delta-7 +/- 2 mmHg). These data provide experimental support for the concept that age-related impairments in the vestibulosympathetic reflex persist during orthostatic challenge in older adults. Furthermore, these findings are consistent with the concept that age-related alterations in vestibular function might contribute to altered orthostatic blood pressure regulation with age in humans.

  15. Strategies and Challenges in Clinical Trials Targeting Human Aging

    PubMed Central

    Newman, John C.; Milman, Sofiya; Hashmi, Shahrukh K.; Austad, Steve N.; Kirkland, James L.; Halter, Jeffrey B.

    2016-01-01

    Interventions that target fundamental aging processes have the potential to transform human health and health care. A variety of candidate drugs have emerged from basic and translational research that may target aging processes. Some of these drugs are already in clinical use for other purposes, such as metformin and rapamycin. However, designing clinical trials to test interventions that target the aging process poses a unique set of challenges. This paper summarizes the outcomes of an international meeting co-ordinated by the NIH-funded Geroscience Network to further the goal of developing a translational pipeline to move candidate compounds through clinical trials and ultimately into use. We review the evidence that some drugs already in clinical use may target fundamental aging processes. We discuss the design principles of clinical trials to test such interventions in humans, including study populations, interventions, and outcomes. As examples, we offer several scenarios for potential clinical trials centered on the concepts of health span (delayed multimorbidity and functional decline) and resilience (response to or recovery from an acute health stress). Finally, we describe how this discussion helped inform the design of the proposed Targeting Aging with Metformin study. PMID:27535968

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

    NASA Astrophysics Data System (ADS)

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

    2012-10-01

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

  17. Mechanisms of chemotherapy-induced human ovarian aging: double strand DNA breaks and microvascular compromise.

    PubMed

    Soleimani, Reza; Heytens, Elke; Darzynkiewicz, Zbigniew; Oktay, Kutluk

    2011-08-01

    The mechanism of chemotherapy-induced acceleration of ovarian aging is not fully understood. We used doxorubicin, a widely used cancer chemotherapeutic, in a variety of in vivo xenograft, and in vitro models to investigate the impact of chemotherapy-induced aging on the human ovary. Doxorubicin caused massive double-strand-DNA-breaks in primordial follicles, oocytes, and granulosa cells in a dose dependent fashion as revealed by accumulating γH2AX foci. This damage was associated with apoptotic oocyte death and resulted in the activation of ATM. It appeared that the repair response enabled a minor proportion of oocytes (34.7%) and granulosa cells (12.1%) to survive while the majority succumbed to apoptotic death. Paradoxically, inhibition of ATM by KU-55933 resulted in improved survival, probably via prevention of downstream activation of TAp63α. Furthermore, doxorubicin caused vascular and stromal damage in the human ovary, which might impair ovarian function both pre- and post-menopausally. Chemotherapy-induced premature ovarian aging appears to result from a complex process involving both the germ- and non-germ cell components of the ovary. These effects may have clinical implications in aging both for premenopausal and postmenopausal cancer survivors. PMID:21869459

  18. Effects of Age and Dysfunction on Human Meibomian Glands

    PubMed Central

    Nien, Chyong Jy; Massei, Salina; Lin, Gloria; Nabavi, Cameron; Tao, Jeremiah; Brown, Donald J.; Paugh, Jerry R.; Jester, James V.

    2015-01-01

    Objective To identify age-related changes in human meibomian glands that may be associated with meibomian gland dysfunction (MGD). Methods Excess eyelid tissue from 36 patients (age range, 18–95 years, 19 female, 17 male) who underwent canthoplasty procedures were used. Dermatologic history, age, and presence of MGD were recorded. Samples were frozen, sectioned, and stained with specific antibodies against peroxisome proliferator–activated receptor γ(PPARγ) to identify meibocyte differentiation, Ki67 nuclear antigen to identify cycling cells, and CD45 to identify inflammatory cell infiltration. Results Staining for PPARγ showed cytoplasmic and nuclear localization in the 2 youngest subjects (ages, 18 and 44 years). Older individuals (>60 years) showed predominantly nuclear staining, with cytoplasmic staining limited to the basal acinar cells in 17 of 31 subjects. The number of Ki67 positively stained basal cells were significantly elevated in the younger compared with older subjects based on linear regression analysis (r2= 0.35; P <.001). There was also a significant correlation between MG expression grade and CD45 cell infiltration (r =0.414; P =.05). Conclusions These results indicate that aging human meibomian glands show decreased meibocyte differentiation and cell cycling that is associated with the development of MGD. Findings also suggest that altered PPARγ signaling may lead to acinar atrophy and development of an age-related hyposecretory MGD. Clinical Relevance Meibomian gland dysfunction and evaporative dry eye are common age-related eyelid disorders. Understanding the underlying mechanism of MGD may lead to the development of novel therapeutic strategies to treat this disease. PMID:21482872

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

    PubMed

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

    2015-01-01

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

  20. Investigation of the effect of high +Gz accelerations on human cardiac function.

    PubMed

    Jamshidi, M; Ahmadian, M T

    2013-11-01

    This study investigates the effect of body acceleration on human cardiac function. Finite element analysis is conducted to simulate geometrical and mechanical properties of human heart. Heart geometrical modeling in three-dimension is performed by segmentation of cardiac MRI images. The nonlinear mechanical behavior of myocardium is modeled by Mooney-Rivlin, Polynomial, Ogden and Yeoh hyperelastic material models. Stress-strain curves of myocardial tissue are obtained from experimental compression tests on bovine heart samples. The experimental results are employed for the evaluation of material coefficients by the nonlinear least squares method. Among hyperelastic models, the Yeoh model presents the best fit with experimental stress-strain curve and is used for finite element simulation of heart tissue. Obtained material coefficients are implemented into the constructed heart model and nonlinear finite element analysis is performed for different levels of acceleration in upward direction of vertical axis of body during the rapid filling phase of cardiac cycle. Based on the finite element analysis, ventricular volume change, stress and deformation of heart model are evaluated. It is revealed that when the body is subjected to high accelerations, structural changes in the heart reduce blood supply to body up to 7.2% at +6G.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-01-01

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

  3. [Histological study on aging changes in the human tongue].

    PubMed

    Nakayama, M

    1991-04-01

    Dryness of the mouth, taste disturbance or misswallowing may appear due to physiological changes of tongue especially in old aged person. The purpose of this study is to investigate histological changes related to aging in the human tongue, qualitatively and quantitatively. The samples were collected from 100 autopsy-cases without any pathological changes consisting of 50 males and 50 females aged between 5 and 82. Five specimens (I-V) were obtained from each tongue by frontal section. Specimen I (anterior part of tongue), III (central part), V (posterior part) were studied. Each specimen with thickness of 4 microns were stained with Hematoxylin-Eosin and Alucian-Blue. Tongue mucosa, glands such as Blandin-Nuhn gland, von Ebner gland and those glands distributed in the root of tongue, and M. longitudinalis superior were observed histologically. The study was done quantitatively by I-BAS one picture analyzer manufactured by Zeiss Co. The results of this study are as following: 1) The epithelium of lingual mucosa The thickness of epithelium decreased with aging, rather prominent on dorsal part than the lateral. 2) lingual glands Acinar atrophy increased with aging, especially quickly in females. The atrophy of the acinus started from 40 years old in Blandin-nuhn gland and 30 in von Ebner gland. However, tongue root glandular atrophy was milder in comparison with the other two glands. 3) Lingual muscles Decrease in muscle fiber diameter with aging is also observed.

  4. Human microRNAs originated from two periods at accelerated rates in mammalian evolution.

    PubMed

    Iwama, Hisakazu; Kato, Kiyohito; Imachi, Hitomi; Murao, Koji; Masaki, Tsutomu

    2013-03-01

    MicroRNAs (miRNAs) are short, noncoding RNAs that modulate genes posttranscriptionally. Frequent gains and losses of miRNA genes have been reported to occur during evolution. However, little is known systematically about the periods of evolutionary origin of the present miRNA gene repertoire of an extant mammalian species. Thus, in this study, we estimated the evolutionary periods during which each of 1,433 present human miRNA genes originated within 15 periods, from human to platypus-human common ancestral branch and a class "conserved beyond theria," primarily using multiple genome alignments of 38 species, plus the pairwise genome alignments of five species. The results showed two peak periods in which the human miRNA genes originated at significantly accelerated rates. The most accelerated rate appeared in the period of the initial phase of hominoid lineage, and the second appeared shortly before Laurasiatherian divergence. Approximately 53% of the present human miRNA genes have originated within the simian lineage to human. In particular, approximately 28% originated within the hominoid lineage. The early phase of placental mammal radiation comprises approximately 28%, while no more than 15% of human miRNAs have been conserved beyond placental mammals. We also clearly showed a general trend, in which the miRNA expression level decreases as the miRNA becomes younger. Intriguingly, amid this decreasing trend of expression, we found one significant rise in the expression level that corresponded to the initial phase of the hominoid lineage, suggesting that increased functional acquisitions of miRNAs originated at this particular period. PMID:23171859

  5. Age and the transmittance of the human crystalline lens.

    PubMed Central

    Weale, R A

    1988-01-01

    1. Conflicting data both on the transmission of the human crystalline lens in the ultra-violet part of the spectrum and on its variation with age necessitate a re-examination of the subject. 2. Twenty-four excised lenses in the age range of 0-85 years were studied with a Perkin-Elmer spectrophotometer between 327 and 700 nm. 3. Some lenses were homogenized and the homogenates were similarly examined. 4. A systematic increase in absorbance with age was observed both in the visible and the ultra-violet parts of the spectrum. 5. An exponential function describes the data, facilitating comparison with, and prediction of, other values. 6. The absorbance of homogenized material was found to be predictable from that of intact lenses, and does not support the notion that mechanical trauma may account for high values in earlier studies. PMID:3411488

  6. Age-related changes in human vitreous structure.

    PubMed

    Sebag, J

    1987-01-01

    Changes in vitreous structure that occur with aging are important in the pathogenesis of vitreous liquefaction (synchisis senilis), vitreous detachment, and retinal disease. Vitreous morphology was studied in 59 human eyes post-mortem using dark-field horizontal slit illumination of the entire dissected vitreous. In many individuals younger than 30 years, the vitreous was homogeneous in structure. Middle-aged individuals had macroscopic fibers in the central vitreous, which coursed anteroposteriorly and inserted into the vitreous base and the vitreous cortex, posteriorly. During senescence, the vitreous volume was reduced, the vitreous body was collapsed (syneresis), and the fibers were thickened, tortuous, and surrounded by liquid vitreous. This sequence of age-related changes probably results from a progressive reorganization of the hyaluronic acid and collagen molecular networks. Characterization of the molecular events underlying these changes will elucidate the mechanisms of the phenomena of synchisis, syneresis, and detachment, and may provide methods with which to prevent or induce vitreous detachment prophylactically.

  7. Human mortality at very advanced age might be constant.

    PubMed

    Klemera, P; Doubal, S

    1997-11-01

    An attempt was made to identify the course of the mortality rate at the upper tail of human age. The only known data suitable for this purpose were published by Riggs and Millecchia (J.E. Riggs, R.J. Millecchia, Mech. Ageing Dev. 62 (1992) 191-199) and our analysis follows up their results. By means of mathematical elaboration it was proved that these data imply a constant mortality rate (approx. 25% per year) at ages above 113 years for men and above 116 years for women. Indirect arguments supporting the validity of the source data are discussed. Nevertheless, even if the source data are mistaken, we proved they cannot be the product of purely random errors and our results may contribute to the elucidation of the origin of those systematic errors. PMID:9379712

  8. Accelerated wound closure of pressure ulcers in aged mice by chitosan scaffolds with and without bFGF.

    PubMed

    Park, Chan J; Clark, Sherrie G; Lichtensteiger, Carol A; Jamison, Russell D; Johnson, Amy J Wagoner

    2009-07-01

    Pressure ulcers are a significant healthcare concern, especially for elderly populations. Our work served to ameliorate the chronicity of these ulcers by addressing ischemia-reperfusion injury mediated by neutrophils and the concomitant loss of vasculature in these wounds. To this end, chitosan scaffolds loaded with basic fibroblast growth factor (bFGF) contained in gelatin microparticles were developed and tested for clinical relevance in an aged mouse model. Pressure ulcers were induced in aged mice, and efficacy of treatment was assessed. On days 3 and 7, both chitosan and chitosan-bFGF scaffolds significantly accelerated wound closure compared to gauze control. By day 10, all wounds achieved similar closure. Delivery and angiogenic function of bFGF was verified through ELISA and histology. Elevated neutrophil levels were observed in chitosan and chitosan-bFGF groups. Since neutrophil elastase contributes to the proteolytic environments of pressure ulcers, the effect of chitosan on elastase was assessed. In vitro, chitosan inhibited elastase activity. In vivo, elastase protein levels in wounds were reduced with chitosan-bFGF scaffolds by day 10. These results suggest that chitosan is an effective material for growth factor delivery and can help to heal chronic ulcers. Collectively, our data show that chitosan-bFGF scaffolds are effective in accelerating wound closure of pressure ulcers in aged animals.

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

    NASA Astrophysics Data System (ADS)

    Lucas, Thomas J.

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

  10. Fractography evolution in accelerated aging of UHMWPE after gamma irradiation in air.

    PubMed

    Medel, F; Gómez-Barrena, E; García-Alvarez, F; Ríos, R; Gracia-Villa, L; Puértolas, J A

    2004-01-01

    We studied the fracture surface evolution of ultra high molecular weight polyethylene (UHMWPE) specimens, manufactured from GUR 1050 compression moulded sheets, after gamma sterilisation in air followed by different aging times after thermal treatment at 120 degrees C. Degradation profiles were obtained by FTIR and DSC measurements after 0, 7, 14, 24 and 36h aging. We observed by SEM the morphology patterns at these aging times, in surface fractographies after uniaxial tensile test of standardised samples. The results pointed out clear differences between short and long aging times. At shorter times, 7h, the behaviour was similar to non-degraded UHMWPE, exhibiting ductile behaviour. At longer times, 24-36h, this thermal protocol provided a highly degraded zone in the subsurface, similar to the white band found after gamma irradiation in air followed by natural aging, although closer to the surface, at 150-200mum. The microstructure of this oxidation zone, similarly found in gamma irradiated samples shelf-aged for 6-7 years, although with different distribution of microvoids, was formed by fibrils, associated with embrittlement of the oxidised UHMWPE. In addition, the evolution of the oxidation index, the enthalpy content, the mechanical parameters, and the depth of the oxidation front deduced from the fractographies versus aging time showed that a changing behaviour in the degradation rate appeared at intermediate aging times.

  11. Vertical accelerator device to apply loads simulating blast environments in the military to human surrogates.

    PubMed

    Yoganandan, Narayan; Pintar, Frank A; Schlick, Michael; Humm, John R; Voo, Liming; Merkle, Andrew; Kleinberger, Michael

    2015-09-18

    The objective of the study was to develop a simple device, Vertical accelerator (Vertac), to apply vertical impact loads to Post Mortem Human Subject (PMHS) or dummy surrogates because injuries sustained in military conflicts are associated with this vector; example, under-body blasts from explosive devices/events. The two-part mechanically controlled device consisted of load-application and load-receiving sections connected by a lever arm. The former section incorporated a falling weight to impact one end of the lever arm inducing a reaction at the other/load-receiving end. The "launch-plate" on this end of the arm applied the vertical impact load/acceleration pulse under different initial conditions to biological/physical surrogates, attached to second section. It is possible to induce different acceleration pulses by using varying energy absorbing materials and controlling drop height and weight. The second section of Vertac had the flexibility to accommodate different body regions for vertical loading experiments. The device is simple and inexpensive. It has the ability to control pulses and flexibility to accommodate different sub-systems/components of human surrogates. It has the capability to incorporate preloads and military personal protective equipment (e.g., combat helmet). It can simulate vehicle roofs. The device allows for intermittent specimen evaluations (x-ray and palpation, without changing specimen alignment). The two free but interconnected sections can be used to advance safety to military personnel. Examples demonstrating feasibilities of the Vertac device to apply vertical impact accelerations using PMHS head-neck preparations with helmet and booted Hybrid III dummy lower leg preparations under in-contact and launch-type impact experiments are presented.

  12. The Associative Changes in Scutellum Nuclear Content and Morphology with Viability Loss of Naturally Aged and Accelerated Aging Wheat (Triticum aestivum) Seeds

    PubMed Central

    Ahmed, Zaheer; Yang, Hui; Fu, Yong-Bi

    2016-01-01

    Timely prediction of seed viability loss over long-term storage represents a challenge in management and conservation of ex situ plant genetic resources. However, little attention has been paid to study the process of seed deterioration and seed aging signals under storage. An attempt was made here to investigate morphological and molecular changes in the scutellum and aleurone sections of naturally or artificially aged wheat seeds using TUNEL assay and DAPI staining. Twelve wheat genotypes or samples exposed to natural ageing (NA) or accelerated ageing (AA) were assayed and these samples had germination rates ranging from 11 to 93%. The assayed samples showed substantial changes in scutellum, but not aleurone. The nuclei observed in the majority of the scutellum cells of the NA seed samples of lower germination rates were longer in size and less visible, while the scutellum cell morphology or arrangement remained unchanged. In contrast, longer AA treatments resulted in the loss of scutellum cell structure, collapse of cell layers, and disappearance of honey comb arrangements. These nuclei and structural changes were consistent with the DNA assessments of nuclear alternations for the selected wheat samples. Interestingly, the sample seed germination loss was found to be associated with the reductions in the scutellum nuclear content and with the increases in the scutellum nuclei length to width ratio. These findings are significant for understanding the process of wheat seed deterioration and are also useful for searching for sensitive seed aging signals for developing tools to monitor seed viability under storage. PMID:27729925

  13. Microstructural modifications induced by accelerated aging and lipid absorption in remelted and annealed UHMWPEs for total hip arthroplasty.

    PubMed

    Puppulin, Leonardo; Zhu, Wenliang; Sugano, Nobuhiko; Pezzotti, Giuseppe

    2015-01-01

    Three types of commercially available ultra-high molecular weight polyethylene (UHMWPE) acetabular cups currently used in total hip arthroplasty have been studied by means of Raman micro-spectroscopy to unfold the microstructural modification induced by the oxidative degradation after accelerated aging with and without lipid absorption. The three investigated materials were produced by three different manufacturing procedures, as follows: irradiation followed by remelting, one-step irradiation followed by annealing, 3-step irradiation and annealing. Clear microstructural differences were observed in terms of phase contents (i.e. amorphous, crystalline and intermediate phase fraction). The three-step annealed material showed the highest crystallinity fraction in the bulk, while the remelted polyethylene is clearly characterized by the lowest content of crystalline phase and the highest content of amorphous phase. After accelerated aging either with or without lipids, the amount of amorphous phase decreased in all the samples as a consequence of the oxidation-induced recrystallization. The most remarkable variations of phase contents were detected in the remelted and in the single-step annealed materials. The presence of lipids triggered oxidative degradation especially in the remelted polyethylene. Such experimental evidence might be explained by the highest amount of amorphous phase in which lipids can be absorbed prior to accelerated aging. The results of these spectroscopic characterizations help to rationalize the complex effect of different irradiation and post-irradiation treatments on the UHMWPE microstructure and gives useful information on how significantly any single step of the manufacturing procedures might affect the oxidative degradation of the polymer.

  14. Quantitative proteomics analysis of specific protein expression and oxidative modification in aged senescence-accelerated-prone 8 mice brain.

    PubMed

    Poon, H F; Castegna, A; Farr, S A; Thongboonkerd, V; Lynn, B C; Banks, W A; Morley, J E; Klein, J B; Butterfield, D A

    2004-01-01

    The senescence-accelerated mouse (SAM) is a murine model of accelerated senescence that was established using phenotypic selection. The SAMP series includes nine substrains, each of which exhibits characteristic disorders. SAMP8 is known to exhibit age-dependent learning and memory deficits. In our previous study, we reported that brains from 12-month-old SAMP8 have greater protein oxidation, as well as lipid peroxidation, compared with brains from 4-month-old SAMP8 mice. In order to investigate the relation between age-associated oxidative stress on specific protein oxidation and age-related learning and memory deficits in SAMP8, we used proteomics to identify proteins that are expressed differently and/or modified oxidatively in aged SAMP8 brains. We report here that in 12 month SAMP8 mice brains the expressions of neurofilament triplet L protein, lactate dehydrogenase 2 (LDH-2), heat shock protein 86, and alpha-spectrin are significantly decreased, while the expression of triosephosphate isomerase (TPI) is increased compared with 4-month-old SAMP8 brains. We also report that the specific protein carbonyl levels of LDH-2, dihydropyrimidinase-like protein 2, alpha-spectrin and creatine kinase, are significantly increased in the brain of 12-month-old SAMP8 mice when compared with the 4-month-old SAMP8 brain. These findings are discussed in reference to the effect of specific protein oxidation and changes of expression on potential mechanisms of abnormal alterations in metabolism and neurochemicals, as well as to the learning and memory deficits in aged SAMP8 mice.

  15. Accelerated aging studies of UHMWPE. II. Virgin UHMWPE is not immune to oxidative degradation.

    PubMed

    Edidin, A A; Villarraga, M L; Herr, M P; Muth, J; Yau, S S; Kurtz, S M

    2002-08-01

    In Part I of this series, we showed that aging at elevated oxygen pressure is more successful at increasing the depth to which degradation occurs although it, too, generally causes greater degradation at the surface than at the subsurface. Therefore we hypothesized that thermal degradation alone, in the absence of free radicals, could be sufficient to artificially age UHMWPE in a manner analogous to natural aging. In the present study, virgin and air-irradiated UHMWPE (extruded GUR 1050 and compression-molded 1900) were aged up to 4 weeks at elevated oxygen pressure, and the mechanical behavior at the surface and subsurface was examined. All the materials were substantially degraded following 4 weeks of aging, but the spatial variations in the nonirradiated materials more closely mimicked the previously observed subsurface peak of degradation seen in naturally aged UHMWPE following irradiation in air. This aged material could provide a more realistic model for subsurface mechanical degradation, making it suitable for further mechanical testing in venues such as wear simulation.

  16. Accelerated aging phenotype in mice with conditional deficiency for mitochondrial superoxide dismutase in the connective tissue.

    PubMed

    Treiber, Nicolai; Maity, Pallab; Singh, Karmveer; Kohn, Matthias; Keist, Alexander F; Ferchiu, Florentina; Sante, Lea; Frese, Sebastian; Bloch, Wilhelm; Kreppel, Florian; Kochanek, Stefan; Sindrilaru, Anca; Iben, Sebastian; Högel, Josef; Ohnmacht, Michael; Claes, Lutz E; Ignatius, Anita; Chung, Jin H; Lee, Min J; Kamenisch, York; Berneburg, Mark; Nikolaus, Thorsten; Braunstein, Kerstin; Sperfeld, Anne-Dorte; Ludolph, Albert C; Briviba, Karlis; Wlaschek, Meinhard; Florin, Lore; Angel, Peter; Scharffetter-Kochanek, Karin

    2011-04-01

    The free radical theory of aging postulates that the production of mitochondrial reactive oxygen species is the major determinant of aging and lifespan. Its role in aging of the connective tissue has not yet been established, even though the incidence of aging-related disorders in connective tissue-rich organs is high, causing major disability in the elderly. We have now addressed this question experimentally by creating mice with conditional deficiency of the mitochondrial manganese superoxide dismutase in fibroblasts and other mesenchyme-derived cells of connective tissues in all organs. Here, we have shown for the first time that the connective tissue-specific lack of superoxide anion detoxification in the mitochondria results in reduced lifespan and premature onset of aging-related phenotypes such as weight loss, skin atrophy, kyphosis (curvature of the spine), osteoporosis and muscle degeneration in mutant mice. Increase in p16(INK4a) , a robust in vivo marker for fibroblast aging, may contribute to the observed phenotype. This novel model is particularly suited to decipher the underlying mechanisms and to develop hopefully novel connective tissue-specific anti-aging strategies.

  17. Analysis of Density Changes in Plutonium Observed from Accelerated Aging Using Pu-238 Enrichment

    SciTech Connect

    Chung, B W; Saw, C K; Thompson, S R; Quick, T M; Woods, C H; Hopkins, D J; Ebbinghaus, B B

    2006-07-11

    We present dimensional and density changes in an aging plutonium alloy enriched with 7.3 at.% of {sup 238}Pu and reference alloys of various ages. After 45 equivalent years of aging, the enriched alloys at 35 C have swelled in volume by 0.14 to 0.16% and now exhibit a near linear volume increase, without void swelling. Based on X-ray diffraction measurements, the lattice expansion by self-irradiation appears to be the primary cause for dimensional changes during the initial 2-3 years of aging. Following the initial transient, the density change is primarily cause by a constant helium in-growth rate as a result of {alpha}-particle decay.

  18. Ethylene propylene cable degradation during LOCA research tests: tensile properties at the completion of accelerated aging

    SciTech Connect

    Bustard, L.D.

    1982-05-01

    Six ethylene-propylene rubber (EPR) insulation materials were aged at elevated temperature and radiation stress exposures common in cable LOCA qualification tests. Material samples were subjected to various simultaneous and sequential aging simulations in preparation for accident environmental exposures. Tensile properties subsequent to the aging exposure sequences are reported. The tensile properties of some, but not all, specimens were sensitive to the order of radiation and elevated temperature stress exposure. Other specimens showed more severe degradation when simultaneously exposed to radiation and elevated temperature as opposed to the sequential exposure to the same stresses. Results illustrate the difficulty in defining a single test procedure for nuclear safety-related qualification of EPR elastomers. A common worst-case sequential aging sequence could not be identified.

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

    SciTech Connect

    Gilbertson, Robert D.; Patterson, Brian M.; Smith, Zachary

    2014-01-02

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

  20. Free radical entrapment and crystallinity of resin composites after accelerated aging as a function of the expiration date.

    PubMed

    D'Alpino, Paulo Henrique Perlatti; Vismara, Marcos Vinícius Gonçalves; González, Alejandra Hortencia Miranda; Graeff, Carlos Frederico de Oliveira

    2014-08-01

    This study evaluated the spin concentration and the crystallinity in different classifications of dental composites as a function of the material condition (new, aged and expired). Specimens were obtained according to the factors: composites: Filtek P60, Filtek Z250, Filtek Z350XT, and Filtek Silorane; and material conditions: new, aged, and expired. The syringe composites underwent an accelerated aging protocol (Arrhenius model). The magnetic properties of the composites were characterized using Electron Paramagnetic Resonance (EPR) and the concentration of spins (number of spins/mass) was calculated. The crystallinity of the composites tested was characterized with X-ray diffraction (XRD). Filtek P60 and Filtek Z250 presented similarities in terms of spin concentration and crystallinity, irrespective of the material condition. The aging protocol influenced the composite Filtek Z350XT that exhibited a significant increase in the spin concentration. Besides, lower intensity peaks of the organic matrix and amorphous silica were also observed for both aged and expired Filtek Z350XT. Although a significant lower spin concentration was observed for the silorane composite in comparison to that of the methacrylates, a decrease in the relative intensity of peaks of the amorphous region related to the organic components in the diffractograms was observed. The material conditions tested influence the crystallinity and the magnetic properties of the composites evaluated.

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

    PubMed

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

    2014-12-15

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

  2. Vestibular modulation of muscle sympathetic nerve activity during sinusoidal linear acceleration in supine humans

    PubMed Central

    Hammam, Elie; Bolton, Philip S.; Kwok, Kenny; Macefield, Vaughan G.

    2014-01-01

    The utricle and saccular components of the vestibular apparatus preferentially detect linear displacements of the head in the horizontal and vertical planes, respectively. We previously showed that sinusoidal linear acceleration in the horizontal plane of seated humans causes a pronounced modulation of muscle sympathetic nerve activity (MSNA), supporting a significant role for the utricular component of the otolithic organs in the control of blood pressure. Here we tested the hypothesis that the saccule can also play a role in blood pressure regulation by modulating lower limb MSNA. Oligounitary MSNA was recorded via tungsten microelectrodes inserted into the common peroneal nerve in 12 subjects, laying supine on a motorized platform with the head aligned with the longitudinal axis of the body. Slow sinusoidal linear accelerations-decelerations (peak acceleration ±4 mG) were applied in the rostrocaudal axis (which predominantly stimulates the saccule) and in the mediolateral axis (which also engages the utricle) at 0.08 Hz. The modulation of MSNA in the rostrocaudal axis (29.4 ± 3.4%) was similar to that in the mediolateral axis (32.0 ± 3.9%), and comparable to that obtained by stimulation of the utricle alone in seated subjects with the head vertical. We conclude that both the saccular and utricular components of the otolithic organs play a role in the control of arterial pressure during postural challenges. PMID:25346657

  3. Telocytes and putative stem cells in ageing human heart

    PubMed Central

    Popescu, Laurentiu M; Curici, Antoanela; Wang, Enshi; Zhang, Hao; Hu, Shengshou; Gherghiceanu, Mihaela

    2015-01-01

    Tradition considers that mammalian heart consists of about 70% non-myocytes (interstitial cells) and 30% cardiomyocytes (CMs). Anyway, the presence of telocytes (TCs) has been overlooked, since they were described in 2010 (visit http://www.telocytes.com). Also, the number of cardiac stem cells (CSCs) has not accurately estimated in humans during ageing. We used electron microscopy to identify and estimate the number of cells in human atrial myocardium (appendages). Three age-related groups were studied: newborns (17 days–1 year), children (6–17 years) and adults (34–60 years). Morphometry was performed on low-magnification electron microscope images using computer-assisted technology. We found that interstitial area gradually increases with age from 31.3 ± 4.9% in newborns to 41 ± 5.2% in adults. Also, the number of blood capillaries (per mm2) increased with several hundreds in children and adults versus newborns. CMs are the most numerous cells, representing 76% in newborns, 88% in children and 86% in adults. Images of CMs mitoses were seen in the 17-day newborns. Interestingly, no lipofuscin granules were found in CMs of human newborns and children. The percentage of cells that occupy interstitium were (depending on age): endothelial cells 52–62%; vascular smooth muscle cells and pericytes 22–28%, Schwann cells with nerve endings 6–7%, fibroblasts 3–10%, macrophages 1–8%, TCs about 1% and stem cells less than 1%. We cannot confirm the popular belief that cardiac fibroblasts are the most prevalent cell type in the heart and account for about 20% of myocardial volume. Numerically, TCs represent a small fraction of human cardiac interstitial cells, but because of their extensive telopodes, they achieve a 3D network that, for instance, supports CSCs. The myocardial (very) low capability to regenerate may be explained by the number of CSCs, which decreases fivefold by age (from 0.5% to 0.1% in newborns versus adults). PMID:25545142

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

    PubMed

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

    2007-05-01

    Imprinted genes are expressed in a parent-of-origin manner and are located in clusters throughout the genome. Aberrations in the expression of imprinted genes on human Chromosome 7 have been suggested to play a role in the etiologies of Russell-Silver Syndrome and autism. We describe the imprinting of KLF14, an intronless member of the Krüppel-like family of transcription factors located at Chromosome 7q32. We show that it has monoallelic maternal expression in all embryonic and extra-embryonic tissues studied, in both human and mouse. We examine epigenetic modifications in the KLF14 CpG island in both species and find this region to be hypomethylated. In addition, we perform chromatin immunoprecipitation and find that the murine Klf14 CpG island lacks allele-specific histone modifications. Despite the absence of these defining features, our analysis of Klf14 in offspring from DNA methyltransferase 3a conditional knockout mice reveals that the gene's expression is dependent upon a maternally methylated region. Due to the intronless nature of Klf14 and its homology to Klf16, we suggest that the gene is an ancient retrotransposed copy of Klf16. By sequence analysis of numerous species, we place the timing of this event after the divergence of Marsupialia, yet prior to the divergence of the Xenarthra superclade. We identify a large number of sequence variants in KLF14 and, using several measures of diversity, we determine that there is greater variability in the human lineage with a significantly increased number of nonsynonymous changes, suggesting human-specific accelerated evolution. Thus, KLF14 may be the first example of an imprinted transcript undergoing accelerated evolution in the human lineage. PMID:17480121

  5. Vasodilatory responsiveness to adenosine triphosphate in ageing humans

    PubMed Central

    Kirby, Brett S; Crecelius, Anne R; Voyles, Wyatt F; Dinenno, Frank A

    2010-01-01

    Endothelium-dependent vasodilatation is reduced with advancing age in humans, as evidenced by blunted vasodilator responsiveness to acetylcholine (ACh). Circulating adenosine triphosphate (ATP) has been implicated in the control of skeletal muscle vascular tone during mismatches in oxygen delivery and demand (e.g. exercise) via binding to purinergic receptors (P2Y) on the endothelium evoking subsequent vasodilatation, and ageing is typically associated with reductions in muscle blood flow under such conditions. Therefore, we tested the hypothesis that ATP-mediated vasodilatation is impaired with age in healthy humans. We measured forearm blood flow (venous occlusion plethysmography) and calculated vascular conductance (FVC) responses to local intra-arterial infusions of ACh, ATP, and sodium nitroprusside (SNP) before and during ascorbic acid (AA) infusion in 13 young and 13 older adults. The peak increase in FVC to ACh was significantly impaired in older compared with young adults (262 ± 71%vs. 618 ± 97%; P < 0.05), and this difference was abolished during AA infusion (510 ± 82%vs. 556 ± 71%; not significant, NS). In contrast, peak FVC responses were not different between older and young adults to either ATP (675 ± 105%vs. 734 ± 126%) or SNP (1116 ± 111%vs. 1138 ± 148%) and AA infusion did not alter these responses in either age group (both NS). In another group of six young and six older adults, we determined whether vasodilator responses to adenosine and ATP were influenced by P1-receptor blockade via aminophylline. The peak FVC responses to adenosine were not different in young (350 ± 65%) versus older adults (360 ± 80%), and aminophylline blunted these responses by ∼50% in both groups. The peak FVC responses to ATP were again not different in young and older adults, and aminophylline did not impact the vasodilatation in either group. Thus, in contrast to the observed impairments in ACh responses, the vasodilatory response to exogenous ATP is not

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

    NASA Technical Reports Server (NTRS)

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

    2012-01-01

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

  7. Mice deficient in Rbm38, a target of the p53 family, are susceptible to accelerated aging and spontaneous tumors

    PubMed Central

    Zhang, Jin; Xu, Enshun; Ren, Cong; Yan, Wensheng; Zhang, Min; Chen, Mingyi; Cardiff, Robert D.; Imai, Denise M.; Wisner, Erik; Chen, Xinbin

    2014-01-01

    RNA-binding motif protein 38 (Rbm38), also called RNPC1 [RNA-binding region (RNP1, RRM) containing 1], is a target of the p53 family and modulates p53 expression via mRNA translation. To investigate the biological function of Rbm38 in vivo, we generated an Rbm38-null mouse model. We showed that mice deficient in Rbm38 exhibit signs of accelerated aging and are prone to hematopoietic defects and spontaneous tumors. To determine the biological significance of the p53-Rbm38 loop, we showed that Rbm38 deficiency enhances accumulation of p53 induced by ionizing radiation (IR) and sensitizes mice to IR-induced lethality in a p53-dependent manner. Most importantly, Rbm38 deficiency markedly decreases the tumor penetrance in mice heterozygous for p53 via enhanced p53 expression. Interestingly, we found that Rbm38 deficiency shortens the life span of, and promotes lymphomagenesis in, mice deficient in p53. These results provide genetic evidence that Rbm38 is necessary for normal hematopoiesis and for suppressing accelerated aging and tumorigenesis. Thus, the p53-Rbm38 axis might be explored for extending longevity and for tumor suppression. PMID:25512531

  8. Multi-Directional Sprinting and Acceleration Phase in Basketball and Handball Players Aged 14 and 15 Years.

    PubMed

    Popowczak, Marek; Rokita, Andrzej; Struzik, Artur; Cichy, Ireneusz; Dudkowski, Andrzej; Chmura, Paweł

    2016-10-01

    An important role in handball and basketball is played by ability to accelerate and ability to repeat multiple sprints. The aim of the study was to assess level of ability in multi-directional sprinting and running time over the first 5 m of the 30 m sprint in 93 basketball and handball players (46 boys and 47 girls) aged 14 to 15 years. The attempts were also made to find the relationships between the time of a 5-m run to evaluate initial acceleration phase and multi-directional sprinting evaluated using Five-Time Shuttle Run To Gates Test Statistical analysis revealed no important differences in times of 5-m runs and times of multi-directional sprinting between groups with different ages, genders, and sports specialties. Furthermore, no significant correlations were found based on Spearman's rank correlation coefficient between times of 5-m run and multi-directional sprinting in the most of subgroups studied. PMID:27565172

  9. In silico analysis of gene expression profiles in the olfactory mucosae of aging senescence-accelerated mice.

    PubMed

    Getchell, Thomas V; Peng, Xuejun; Green, C Paul; Stromberg, Arnold J; Chen, Kuey-Chu; Mattson, Mark P; Getchell, Marilyn L

    2004-08-01

    We utilized high-density Affymetrix oligonucleotide arrays to investigate gene expression in the olfactory mucosae of near age-matched aging senescence-accelerated mice (SAM). The senescence-prone (SAMP) strain has a significantly shorter lifespan than does the senescence-resistant (SAMR) strain. To analyze our data, we applied biostatistical methods that included a correlation analysis to evaluate sources of methodologic and biological variability; a two-sided t-test to identify a subpopulation of Present genes with a biologically relevant P-value <0.05; and a false discovery rate (FDR) analysis adjusted to a stringent 5% level that yielded 127 genes with a P-value of <0.001 that were differentially regulated in near age-matched SAMPs (SAMP-Os; 13.75 months) compared to SAMRs (SAMR-Os, 12.5 months). Volcano plots related the variability in the mean hybridization signals as determined by the two-sided t-test to fold changes in gene expression. The genes were categorized into the six functional groups used previously in gene profiling experiments to identify candidate genes that may be relevant for senescence at the genomic and cellular levels in the aging mouse brain (Lee et al. [2000] Nat Genet 25:294-297) and in the olfactory mucosa (Getchell et al. [2003] Ageing Res Rev 2:211-243), which serves several functions that include chemosensory detection, immune barrier function, xenobiotic metabolism, and neurogenesis. Because SAMR-Os and SAMP-Os have substantially different median lifespans, we related the rate constant alpha in the Gompertz equation on aging to intrinsic as opposed to environmental mechanisms of senescence based on our analysis of genes modulated during aging in the olfactory mucosa. PMID:15248299

  10. Accelerated aging studies of UHMWPE. I. Effect of resin, processing, and radiation environment on resistance to mechanical degradation.

    PubMed

    Edidin, A A; Herr, M P; Villarraga, M L; Muth, J; Yau, S S; Kurtz, S M

    2002-08-01

    The resin and processing route have been identified as potential variables influencing the mechanical behavior, and hence the clinical performance, of ultra-high molecular weight polyethylene (UHMWPE) orthopedic components. Researchers have reported that components fabricated from 1900 resin may oxidize to a lesser extent than components fabricated from GUR resin during shelf aging after gamma sterilization in air. Conflicting reports on the oxidation resistance for 1900 raise the question of whether resin or manufacturing method, or an interaction between resin and manufacturing method, influences the mechanical behavior of UHMWPE. We conducted a series of accelerated aging studies (no aging, aging in oxygen or in nitrogen) to systematically examine the influence of resin (GUR or 1900), manufacturing method (bulk compression molding or extrusion), and sterilization method (none, in air, or in nitrogen) on the mechanical behavior of UHMWPE. The small punch testing technique was used to evaluate the mechanical behavior of the materials, and Fourier transform infrared spectroscopy was used to characterize the oxidation in selected samples. Our study showed that the sterilization environment, aging condition, and specimen location (surface or subsurface) significantly affected the mechanical behavior of UHMWPE. Each of the three polyethylenes evaluated seem to degrade according to a similar pathway after artificial aging in oxygen and gamma irradiation in air. The initial ability of the materials to exhibit post-yield strain hardening was significantly compromised by degradation. In general, there were only minor differences in the aging behavior of molded and extruded GUR 1050, whereas the molded 1900 material seemed to degrade slightly faster than either of the 1050 materials.

  11. Accelerating aging of zirconia femoral head implants: change of surface structure and mechanical properties.

    PubMed

    Chowdhury, S; Vohra, Yogesh K; Lemons, Jack E; Ueno, Masaru; Ikeda, Junji

    2007-05-01

    Recently, alternations of zirconia ceramic femoral heads of total hip prostheses during in vivo conditions have caused concern in the medical disciplines regarding phase transformation of zirconia prosthetic components. In this paper, we have investigated the mechanical and structural properties of different laboratory aged zirconia femoral heads and correlated changes in mechanical properties with the phase compositions of the sample. From laser microscope observation, cross-sectional Scanning electron microscopy imaging, and X-ray diffraction analysis on the surface of the zirconia femoral heads, we found monoclinic to tetragonal phase transformation in zirconia prostheses over time during the aging process in the laboratory. Mechanical properties, mainly hardness (H) and Young's modulus (E) values, were measured by nanoindentation technique on the surface of these implants. The results showed that both H and E values decreased with increased monoclinic phase in zirconia, thus confirming a phase transformation over time during aging.

  12. Influence of artificially accelerated ageing on the adhesive joint of plasma treated polymer materials

    NASA Astrophysics Data System (ADS)

    Lehocký, M.; Lapčik, L.; Dlabaja, R.; Rachünek, L.; Stoch, J.

    2004-03-01

    An influence of simulated ageing on the adhesive joint of plasma treated polyethylene (PE) and polypropylene (PP) was tested. Plasma surface treatment was performed in the rf-plasma reactor operating at 13,56 MHz. The simulated ageing of prepared specimens for following tensile testing was carried out under conditions given by Volkswagen standard P-VW 1200. Temperature of ageing was regularly oscillating between -40°C and 80°C (relative humidity 80%) for required time. The mechanical tensile properties of adhesive joint were measured according to the standard ISO 527. Surface analysis of treated polymer substrates was characterized by XPS measurement. The observation of surface structure and morphology was obtained using SEM. We used convenient cyanoacrylate adhesive Loctite E 406 for PE and PP joints. Tested adhesive joints were prepared in compliance with the standard ISO 4587.

  13. Spatial distribution of the human enamel fracture toughness with aging.

    PubMed

    Zheng, Qinghua; Xu, Haiping; Song, Fan; Zhang, Lan; Zhou, Xuedong; Shao, Yingfeng; Huang, Dingming

    2013-10-01

    A better understanding of the fracture toughness (KIC) of human enamel and the changes induced by aging is important for the clinical treatment of teeth cracks and fractures. We conducted microindentation tests and chemical content measurements on molar teeth from "young" (18 ≤ age ≤ 25) and "old" (55 ≤ age) patients. The KIC and the mineral contents (calcium and phosphorus) in the outer, the middle, and the inner enamel layers within the cuspal and the intercuspal regions of the crown were measured through the Vickers toughness test and Energy Dispersive X-Ray Spectroscopy (EDS), respectively. The elastic modulus used for the KIC calculation was measured through atomic force microscope (AFM)-based nanoindentation tests. In the outer enamel layer, two direction-specific values of the KIC were calculated separately (direction I, crack running parallel to the occlusal surface; direction II, perpendicular to direction I). The mean KIC of the outer enamel layer was lower than that of the internal layers (p<0.05). No other region-related differences in the mechanical properties were found in both groups. In the outer enamel layer, old enamel has a lower KIC, II and higher mineral contents than young enamel (p<0.05). The enamel surface becomes more prone to cracks with aging partly due to the reduction in the interprismatic organic matrix observed with the maturation of enamel.

  14. Age-dependent motor unit remodelling in human limb muscles.

    PubMed

    Piasecki, Mathew; Ireland, Alex; Jones, David A; McPhee, Jamie S

    2016-06-01

    Voluntary control of skeletal muscle enables humans to interact with and manipulate the environment. Lower muscle mass, weakness and poor coordination are common complaints in older age and reduce physical capabilities. Attention has focused on ways of maintaining muscle size and strength by exercise, diet or hormone replacement. Without appropriate neural innervation, however, muscle cannot function. Emerging evidence points to a neural basis of muscle loss. Motor unit number estimates indicate that by age around 71 years, healthy older people have around 40 % fewer motor units. The surviving low- and moderate-threshold motor units recruited for moderate intensity contractions are enlarged by around 50 % and show increased fibre density, presumably due to collateral reinnervation of denervated fibres. Motor unit potentials show increased complexity and the stability of neuromuscular junction transmissions is decreased. The available evidence is limited by a lack of longitudinal studies, relatively small sample sizes, a tendency to examine the small peripheral muscles and relatively few investigations into the consequences of motor unit remodelling for muscle size and control of movements in older age. Loss of motor neurons and remodelling of surviving motor units constitutes the major change in ageing muscles and probably contributes to muscle loss and functional impairments. The deterioration and remodelling of motor units likely imposes constraints on the way in which the central nervous system controls movements. PMID:26667009

  15. Physical properties of three maxillofacial materials as a function of accelerated aging.

    PubMed

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

    1994-04-01

    This study compares the tensile strength, elongation, Shore-A hardness, and tear resistance of three silicone maxillofacial materials before and after aging to provide comparative data for evaluation of new or experimental elastomers. The materials evaluated were MDX-4-4210, Factor II (A-2186), and Cosmesil. Tests were conducted 24 hours after specimen preparation and were repeated after aging for 900 hours in a Weather-Ometer device. Five samples were made for each material under all test conditions. After testing, mean values were calculated for all materials under all test conditions and were compared by two-way analysis of variance and Tukey intervals at p < or = 0.05.

  16. Age-dependent capacity to accelerate protein synthesis dictates the extent of compensatory growth in skeletal muscle following undernutrition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In both humans and animals, impaired growth during early life compromises adult lean body mass and muscle strength despite skeletal muscle’s large regenerative capacity. To identify the significance of developmental age on skeletal muscle’s capacity for catch-up growth following an episode of under ...

  17. Raman spectroscopy of human skin: looking for a quantitative algorithm to reliably estimate human age

    NASA Astrophysics Data System (ADS)

    Pezzotti, Giuseppe; Boffelli, Marco; Miyamori, Daisuke; Uemura, Takeshi; Marunaka, Yoshinori; Zhu, Wenliang; Ikegaya, Hiroshi

    2015-06-01

    The possibility of examining soft tissues by Raman spectroscopy is challenged in an attempt to probe human age for the changes in biochemical composition of skin that accompany aging. We present a proof-of-concept report for explicating the biophysical links between vibrational characteristics and the specific compositional and chemical changes associated with aging. The actual existence of such links is then phenomenologically proved. In an attempt to foster the basics for a quantitative use of Raman spectroscopy in assessing aging from human skin samples, a precise spectral deconvolution is performed as a function of donors' ages on five cadaveric samples, which emphasizes the physical significance and the morphological modifications of the Raman bands. The outputs suggest the presence of spectral markers for age identification from skin samples. Some of them appeared as authentic "biological clocks" for the apparent exactness with which they are related to age. Our spectroscopic approach yields clear compositional information of protein folding and crystallization of lipid structures, which can lead to a precise identification of age from infants to adults. Once statistically validated, these parameters might be used to link vibrational aspects at the molecular scale for practical forensic purposes.

  18. Raman spectroscopy of human skin: looking for a quantitative algorithm to reliably estimate human age.

    PubMed

    Pezzotti, Giuseppe; Boffelli, Marco; Miyamori, Daisuke; Uemura, Takeshi; Marunaka, Yoshinori; Zhu, Wenliang; Ikegaya, Hiroshi

    2015-06-01

    The possibility of examining soft tissues by Raman spectroscopy is challenged in an attempt to probe human age for the changes in biochemical composition of skin that accompany aging. We present a proof-of-concept report for explicating the biophysical links between vibrational characteristics and the specific compositional and chemical changes associated with aging. The actual existence of such links is then phenomenologically proved. In an attempt to foster the basics for a quantitative use of Raman spectroscopy in assessing aging from human skin samples, a precise spectral deconvolution is performed as a function of donors' ages on five cadaveric samples, which emphasizes the physical significance and the morphological modifications of the Raman bands. The outputs suggest the presence of spectral markers for age identification from skin samples. Some of them appeared as authentic "biological clocks" for the apparent exactness with which they are related to age. Our spectroscopic approach yields clear compositional information of protein folding and crystallization of lipid structures, which can lead to a precise identification of age from infants to adults. Once statistically validated, these parameters might be used to link vibrational aspects at the molecular scale for practical forensic purposes.

  19. Human mesenchymal stem cell-engineered hepatic cell sheets accelerate liver regeneration in mice

    PubMed Central

    Itaba, Noriko; Matsumi, Yoshiaki; Okinaka, Kaori; Ashla, An Afida; Kono, Yohei; Osaki, Mitsuhiko; Morimoto, Minoru; Sugiyama, Naoyuki; Ohashi, Kazuo; Okano, Teruo; Shiota, Goshi

    2015-01-01

    Mesenchymal stem cells (MSCs) are an attractive cell source for cell therapy. Based on our hypothesis that suppression of Wnt/β-catenin signal enhances hepatic differentiation of human MSCs, we developed human mesenchymal stem cell-engineered hepatic cell sheets by a small molecule compound. Screening of 10 small molecule compounds was performed by WST assay, TCF reporter assay, and albumin mRNA expression. Consequently, hexachlorophene suppressed TCF reporter activity in time- and concentration-dependent manner. Hexachlorophene rapidly induced hepatic differentiation of human MSCs judging from expression of liver-specific genes and proteins, PAS staining, and urea production. The effect of orthotopic transplantation of human mesenchymal stem cell-engineered hepatic cell sheets against acute liver injury was examined in one-layered to three-layered cell sheets system. Transplantation of human mesenchymal stem cell-engineered hepatic cell sheets enhanced liver regeneration and suppressed liver injury. The survival rates of the mice were significantly improved. High expression of complement C3 and its downstream signals including C5a, NF-κB, and IL-6/STAT-3 pathway was observed in hepatic cell sheets-grafted tissues. Expression of phosphorylated EGFR and thioredoxin is enhanced, resulting in reduction of oxidative stress. These findings suggest that orthotopic transplantation of hepatic cell sheets manufactured from MSCs accelerates liver regeneration through complement C3, EGFR and thioredoxin. PMID:26553591

  20. Exposure to radiation accelerates normal brain aging and produces deficits in spatial learning and memory

    NASA Astrophysics Data System (ADS)

    Shukitt-Hale, B.; Casadesus, G.; Carey, A.; Rabin, B. M.; Joseph, J. A.

    Previous studies have shown that radiation exposure, particularly to particles of high energy and charge (HZE particles), produces deficits in spatial learning and memory. These adverse behavioral effects are similar to those seen in aged animals. It is possible that these shared effects may be produced by the same mechanism; oxidative stress damage to the central nervous system caused by an increased release of reactive oxygen species is likely responsible for the deficits seen in aging and following irradiation. Both aged and irradiated rats display cognitive impairment in tests of spatial learning and memory such as the Morris water maze and the radial arm maze. These rats have decrements in the ability to build spatial representations of the environment and they utilize non-spatial strategies to solve tasks. Furthermore, they show a lack of spatial preference, due to a decline in the ability to process or retain place (position of a goal with reference to a "map" provided by the configuration of numerous cues in the environment) information. These declines in spatial memory occur in measures dependent on both reference and working memory, and in the flexibility to reset mental images. These results show that irradiation with high-energy particles produces age-like decrements in cognitive behavior that may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere. Supported by NASA Grants NAG9-1190 and NAG9-1529

  1. Replicative senescence: the human fibroblast comes of age.

    PubMed

    Goldstein, S

    1990-09-01

    Human diploid fibroblasts undergo replicative senescence predominantly because of arrest at the G1/S boundary of the cell cycle. Senescent arrest resembles a process of terminal differentiation that appears to involve repression of proliferation-promoting genes with reciprocal new expression of antiproliferative genes, although post-transcriptional factors may also be involved. Identification of participating genes and clarification of their mechanisms of action will help to elucidate the universal cellular decline of biological aging and an important obverse manifestation, the rare escape of cells from senescence leading to immortalization and oncogenesis.

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

    SciTech Connect

    Phadke, Manali; Krynetskaia, Natalia; Mishra, Anurag; Krynetskiy, Evgeny

    2011-07-29

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

  3. Human stem cells as targets for the aging and diseases of aging processes.

    PubMed

    Trosko, James E

    2003-03-01

    While many theories have been proposed for the aging process, and many debates on the matter of aging and the diseases of aging being either the result of the same or independent processes, most have not considered humans as a hierarchical system made up of cybernetically interacting levels of organization. To understand the aging process and the diseases of aging, one must view the human as the result of the total genomic DNA in the single fertilized egg that proliferates, differentiates and develops into an individual of about 100 trillion cells, organized by different cell types (pluri-potent stem cells, progenitor stem cells, terminally differentiated cells) into multiple tissue, organ and organ systems which interact with each other via endogenous factors and with exogenous factors. Our hypothesis is that both aging and diseases of aging are dependent of the normal functioning of the pluri-potent stem cell pool. Specifically, the concept involves the cybernetic feedback between the 'quantity' of the stem cell pool in each tissue niche with the 'quality' of the stem cells in the pool. The process of gap junctional inter-cellular communication (GJIC), which has been implicated in the evolution from the single cell organism to the multi-cellular organisms, requiring growth control, differentiation, apoptosis, adaptive response capability of differentiated cells and senescence, is speculated to be a shared mechanism in stem cell biology and in many chronic disease processes (teratogenesis; carcinogenesis, atherogenesis, diabetigenesis, etc.). Specifically, stem cells are assumed to be 'immortal' until induced to express their connexin genes and have functional GJIC, at which time they can differentiate and become 'mortal'. As long as the stem cells are communicating with their differentiated daughters via some extra-cellular soluble negative growth factor, the homeostatic control of their growth and differentiation is maintained for the organism. However, if the

  4. Sympathetic activity during passive heat stress in healthy aged humans

    PubMed Central

    Gagnon, Daniel; Schlader, Zachary J; Crandall, Craig G

    2015-01-01

    Abstract Cardiovascular adjustments during heat stress are generally attenuated in healthy aged humans, which could be due to lower increases in sympathetic activity compared to the young. We compared muscle sympathetic nerve activity (MSNA) between 11 young (Y: 28 ± 4 years) and 10 aged (A: 70 ± 5 years) subjects prior to and during passive heating. Furthermore, MSNA responses were compared when a cold pressor test (CPT) and lower body negative pressure (LBNP) were superimposed upon heating. Baseline MSNA burst frequency (Y: 15 ± 4 vs. A: 31 ± 3 bursts min−1, P ≤ 0.01) and burst incidence (Y: 26 ± 8 vs. A: 50 ± 7 bursts (100 cardiac cycles (CC))−1, P ≤ 0.01) were greater in the aged. Heat stress increased core temperature to a similar extent in both groups (Y: +1.2 ± 0.1 vs. A: +1.2 ± 0.0°C, P = 0.99). Absolute levels of MSNA remained greater in the aged during heat stress (burst frequency: Y: 47 ± 6 vs. A: 63 ± 11 bursts min−1, P ≤ 0.01; burst incidence: Y: 48 ± 8 vs. A: 67 ± 9 bursts (100 CC)−1, P ≤ 0.01); however, the increase in both variables was similar between groups (both P ≥ 0.1). The CPT and LBNP further increased MSNA burst frequency and burst incidence, although the magnitude of increase was similar between groups (both P ≥ 0.07). These results suggest that increases in sympathetic activity during heat stress are not attenuated in healthy aged humans. Key points Cardiovascular adjustments to heat stress are attenuated in healthy aged individuals, which could contribute to their greater prevalence of heat-related illnesses and deaths during heat waves. The attenuated cardiovascular adjustments in the aged could be due to lower increases in sympathetic nerve activity during heat stress. We examined muscle sympathetic nerve activity (MSNA) and plasma catecholamine concentrations in healthy young and aged individuals during whole-body passive heat stress. The main finding

  5. Age-related trends in gene expression in the chemosensory-nasal mucosae of senescence-accelerated mice.

    PubMed

    Getchell, Thomas V; Peng, Xuejun; Stromberg, Arnold J; Chen, Kuey-Chu; Paul Green, C; Subhedar, Nishikant K; Shah, Dharmen S; Mattson, Mark P; Getchell, Marilyn L

    2003-04-01

    We have utilized high-density GeneChip oligonucleotide arrays to investigate the use of the senescence-accelerated mouse (SAM) as a biogerontological resource to identify patterns of gene expression in the chemosensory-nasal mucosa. Gene profiling in chronologically young and old mice of the senescence-resistant (SAMR) and senescence-prone (SAMP) strains revealed 133 known genes that were modulated by a three-fold or greater change either in one strain or the other or in both strains during aging. We also identified known genes in our study which based on their encoded proteins were identified as aging-related genes in the aging neocortex and cerebellum of mice as reported by Lee et al. (2000) [Nat. Genet. 25 (2000) 294]. Changes in gene profiles for chemosensory-related genes including olfactory and vomeronasal receptors, sensory transduction-associated proteins, and odor and pheromone transport molecules in the young SAMR and SAMP were compared with age-matched C57BL/6J mice. An analysis of known gene expression profiles suggests that changes in the expression of immune factor genes and genes associated with cell cycle progression and cell death were particularly prominent in the old SAM strains. A preliminary cellular validation study supported the dysregulation of cell cycle-related genes in the old SAM strains. The results of our initial study indicated that the use of the SAM models of aging could provide substantive information leading to a more fundamental understanding of the aging process in the chemosensory-nasal mucosa at the genomic, molecular, and cellular levels. PMID:12605961

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

    PubMed

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

    2016-01-22

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

  7. Towards Prognostics of Power MOSFETs: Accelerated Aging and Precursors of Failure

    NASA Technical Reports Server (NTRS)

    Celaya, Jose R.; Saxena, Abhinav; Wysocki, Philip; Saha, Sankalita; Goebel, Kai

    2010-01-01

    This paper presents research results dealing with power MOSFETs (metal oxide semiconductor field effect transistor) within the prognostics and health management of electronics. Experimental results are presented for the identification of the on-resistance as a precursor to failure of devices with die-attach degradation as a failure mechanism. Devices are aged under power cycling in order to trigger die-attach damage. In situ measurements of key electrical and thermal parameters are collected throughout the aging process and further used for analysis and computation of the on-resistance parameter. Experimental results show that the devices experience die-attach damage and that the on-resistance captures the degradation process in such a way that it could be used for the development of prognostics algorithms (data-driven or physics-based).

  8. Inflammatory insult during pregnancy accelerates age-related behavioral and neurobiochemical changes in CD-1 mice.

    PubMed

    Li, Xue-Yan; Wang, Fang; Chen, Gui-Hai; Li, Xue-Wei; Yang, Qi-Gang; Cao, Lei; Yan, Wen-Wen

    2016-06-01

    Data shows that inflammation during pregnancy significantly exerts a long-term influence on offspring, such as increasing the risk of adult cognition decline in animals. However, it is unclear whether gestational inflammation affects the neurobehavioral and neurobiochemical outcomes in the mother-self during aging. In this study, pregnant CD-1 mice intraperitoneally received lipopolysaccharide (LPS) in two doses (25 and 50 g/kg, respectively) or normal saline daily during gestational days 15-17. At the age of 15 months, a battery of behavioral tasks was employed to evaluate their species-typical behaviors, sensorimotor ability, anxiety levels, and spatial learning and memory abilities. An immunohistochemical method was utilized preliminarily to detect neurobiochemical indicators consisting of amyloid-β, phosphorylated tau, presynaptic proteins synaptotagmin-1 and syntaxin-1, glial fibrillary acidic protein (GFAP), and histone-4 acetylation on the K8 site (H4K8ac). The behavioral results showed that LPS exposure during pregnancy exacerbated a decline in 15-month-old CD-1 mice's abilities to nest, their sensorimotor and spatial learning and memory capabilities, and increased their anxiety levels. The neurobiochemical results indicated that gestational LPS exposure also intensified age-related hippocampal changes, including increased amyloid-β42, phosphorylated tau, synaptotagmin-1 and GFAP, and decreased syntaxin-1 and H4K8ac. Our results suggested that the inflammatory insult during pregnancy could be an important risk factor for the development of Alzheimer's disease, and the H4K8 acetylation might play an important role in the underlying mechanism. This study offers a perspective for improving strategies that support healthy development and successful aging.

  9. Energy excess is the main cause of accelerated aging of mammals

    PubMed Central

    Biliński, Tomasz; Paszkiewicz, Tadeusz; Zadrag-Tecza, Renata

    2015-01-01

    The analysis of cases of unusually high longevity of naked mole rats and an alternative explanation of the phenomenon of calorie restriction effects in monkeys allowed for postulating that any factor preventing an excess of energy consumed, leads to increased lifespan, both in evolutionary and an individual lifetime scale. It is postulated that in mammals the most destructive processes resulting in shortening of life are not restricted to the phenomena explained by the hyperfunction theory of Mikhail Blagosklonny. Hyperfunction, understood as unnecessary or even adverse syntheses of cell components, can be to some extent prevented by lowered intake of nutrients when body growth ceases. We postulate also the contribution of glyco/lipotoxicity to aging, resulting from the excess of energy. Besides two other factors seem to participate in aging. One of them is lack of telomerase activity in some somatic cells. The second factor concerns epigenetic phenomena. Excessive activity of epigenetic maintenance system probably turns off some crucial organismal functions. Another epigenetic factor playing important role could be the micro RNA system deciding on expression of numerous age-related diseases. However, low extrinsic mortality from predation is a conditio sine qua non of the expression of all longevity phenotypes in animals. Among all long-lived animals, naked mole rats are unique in the elimination of neoplasia, which is accompanied by delayed functional symptoms of senescence. The question whether simultaneous disappearance of neoplasia and delayed senescence is accidental or not remains open. PMID:26079722

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

    SciTech Connect

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

    1997-02-01

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

  11. Gut Bifidobacteria Populations in Human Health and Aging

    PubMed Central

    Arboleya, Silvia; Watkins, Claire; Stanton, Catherine; Ross, R. Paul

    2016-01-01

    The intestinal microbiota has increasingly been shown to have a vital role in various aspects of human health. Indeed, several studies have linked alterations in the gut microbiota with the development of different diseases. Among the vast gut bacterial community, Bifidobacterium is a genus which dominates the intestine of healthy breast-fed infants whereas in adulthood the levels are lower but relatively stable. The presence of different species of bifidobacteria changes with age, from childhood to old age. Bifidobacterium longum, B. breve, and B. bifidum are generally dominant in infants, whereas B. catenulatum, B. adolescentis and, as well as B. longum are more prevalent in adults. Increasingly, evidence is accumulating which shows beneficial effects of supplementation with bifidobacteria for the improvement of human health conditions ranging from protection against infection to different extra- and intra-intestinal positive effects. Moreover, bifidobacteria have been associated with the production of a number of potentially health promoting metabolites including short chain fatty acids, conjugated linoleic acid and bacteriocins. The aim of this mini-review is to describe the bifidobacteria compositional changes associated with different stages in life, highlighting their beneficial role, as well as their presence or absence in many disease states.

  12. Gut Bifidobacteria Populations in Human Health and Aging

    PubMed Central

    Arboleya, Silvia; Watkins, Claire; Stanton, Catherine; Ross, R. Paul

    2016-01-01

    The intestinal microbiota has increasingly been shown to have a vital role in various aspects of human health. Indeed, several studies have linked alterations in the gut microbiota with the development of different diseases. Among the vast gut bacterial community, Bifidobacterium is a genus which dominates the intestine of healthy breast-fed infants whereas in adulthood the levels are lower but relatively stable. The presence of different species of bifidobacteria changes with age, from childhood to old age. Bifidobacterium longum, B. breve, and B. bifidum are generally dominant in infants, whereas B. catenulatum, B. adolescentis and, as well as B. longum are more prevalent in adults. Increasingly, evidence is accumulating which shows beneficial effects of supplementation with bifidobacteria for the improvement of human health conditions ranging from protection against infection to different extra- and intra-intestinal positive effects. Moreover, bifidobacteria have been associated with the production of a number of potentially health promoting metabolites including short chain fatty acids, conjugated linoleic acid and bacteriocins. The aim of this mini-review is to describe the bifidobacteria compositional changes associated with different stages in life, highlighting their beneficial role, as well as their presence or absence in many disease states. PMID:27594848

  13. Gut Bifidobacteria Populations in Human Health and Aging.

    PubMed

    Arboleya, Silvia; Watkins, Claire; Stanton, Catherine; Ross, R Paul

    2016-01-01

    The intestinal microbiota has increasingly been shown to have a vital role in various aspects of human health. Indeed, several studies have linked alterations in the gut microbiota with the development of different diseases. Among the vast gut bacterial community, Bifidobacterium is a genus which dominates the intestine of healthy breast-fed infants whereas in adulthood the levels are lower but relatively stable. The presence of different species of bifidobacteria changes with age, from childhood to old age. Bifidobacterium longum, B. breve, and B. bifidum are generally dominant in infants, whereas B. catenulatum, B. adolescentis and, as well as B. longum are more prevalent in adults. Increasingly, evidence is accumulating which shows beneficial effects of supplementation with bifidobacteria for the improvement of human health conditions ranging from protection against infection to different extra- and intra-intestinal positive effects. Moreover, bifidobacteria have been associated with the production of a number of potentially health promoting metabolites including short chain fatty acids, conjugated linoleic acid and bacteriocins. The aim of this mini-review is to describe the bifidobacteria compositional changes associated with different stages in life, highlighting their beneficial role, as well as their presence or absence in many disease states. PMID:27594848

  14. Aging of microstructural compartments in human compact bone

    NASA Technical Reports Server (NTRS)

    Akkus, Ozan; Polyakova-Akkus, Anna; Adar, Fran; Schaffler, Mitchell B.

    2003-01-01

    Composition of microstructural compartments in compact bone of aging male subjects was assessed using Raman microscopy. Secondary mineralization of unremodeled fragments persisted for two decades. Replacement of these tissue fragments with secondary osteons kept mean composition constant over age, but at a fully mineralized limit. Slowing of remodeling may increase fracture susceptibility through an increase in proportion of highly mineralized tissue. In this study, the aging process in the microstructural compartments of human femoral cortical bone was investigated and related to changes in the overall tissue composition within the age range of 17-73 years. Raman microprobe analysis was used to assess the mineral content, mineral crystallinity, and carbonate substitution in fragments of primary lamellar bone that survived remodeling for decades. Tissue composition of the secondary osteonal population was investigated to determine the composition of turned over tissue volume. Finally, Raman spectral analysis of homogenized tissue was performed to evaluate the effects of unremodeled and newly formed tissue on the overall tissue composition. The chemical composition of the primary lamellar bone exhibited two chronological stages. Organic matrix became more mineralized and the crystallinity of the mineral improved during the first stage, which lasted for two decades. The mineral content and the mineral crystallinity did not vary during the second stage. The results for the primary lamellar bone demonstrated that physiological mineralization, as evidenced by crystal growth and maturation, is a continuous process that may persist as long as two decades, and the growth and maturation process stops after the organic matrix becomes "fully mineralized." The average mineral content and the average mineral crystallinity of the homogenized tissue did not change with age. It was also observed that the mineral content of the homogenized tissue was consistently greater than the

  15. Trypsin and thrombin accelerate aggregation of human endocrine pancreas precursor cells.

    PubMed

    Wei, Chiju; Geras-Raaka, Elizabeth; Marcus-Samuels, Bernice; Oron, Yoram; Gershengorn, Marvin C

    2006-02-01

    Human islet-derived precursor cells (hIPCs) and human pancreatic ductal carcinoma (PANC-1) cells can be induced to form aggregates that subsequently differentiate into hormone-expressing islet-like cell aggregates (ICAs). We show that challenge of hIPCs or PANC-1 cells with thrombin or trypsin resulted in stimulation of signaling via the inositol-tris-phosphate second messenger pathway leading to rapid, transient increases in cytosolic calcium ion concentration in the majority of the cells. Because we found that hIPCs, PANC-1 cells, human fetal pancreas, and human adult islets express two protease-activated receptors (PARs), PAR-1 and PAR-2, we tested whether the effects of thrombin and trypsin were mediated, at least in part, by these receptors. Peptide agonists that are relatively specific for PAR-1 (SFLLRN-amide) or PAR-2 (SLIGRL-amide) stimulated increases in inositol phosphates and cytosolic calcium ion concentration, and increased the phosphorylation of Rho, a small G-protein associated with cytoskeletal changes affecting cellular morphology and migration. Most importantly, we show that these agonists increased the rate of hIPC aggregation leading to the formation of more viable, smaller ICAs. Our data show that thrombin and trypsin accelerate aggregation, an early stage of hIPC differentiation in vitro, and imply that pancreatic trypsin and thrombin may be involved in islet development in vivo. PMID:16021635

  16. Maladaptive bias for extrahippocampal navigation strategies in aging humans.

    PubMed

    Wiener, Jan M; de Condappa, Olivier; Harris, Mathew A; Wolbers, Thomas

    2013-04-01

    Efficient spatial navigation requires not only accurate spatial knowledge but also the selection of appropriate strategies. Using a novel paradigm that allowed us to distinguish between beacon, associative cue, and place strategies, we investigated the effects of cognitive aging on the selection and adoption of navigation strategies in humans. Participants were required to rejoin a previously learned route encountered from an unfamiliar direction. Successful performance required the use of an allocentric place strategy, which was increasingly observed in young participants over six experimental sessions. In contrast, older participants, who were able to recall the route when approaching intersections from the same direction as during encoding, failed to use the correct place strategy when approaching intersections from novel directions. Instead, they continuously used a beacon strategy and showed no evidence of changing their behavior across the six sessions. Given that this bias was already apparent in the first experimental session, the inability to adopt the correct place strategy is not related to an inability to switch from a firmly established response strategy to an allocentric place strategy. Rather, and in line with previous research, age-related deficits in allocentric processing result in shifts in preferred navigation strategies and an overall bias for response strategies. The specific preference for a beacon strategy is discussed in the context of a possible dissociation between beacon-based and associative-cue-based response learning in the striatum, with the latter being more sensitive to age-related changes.

  17. Rejuvenation of senescent cells-the road to postponing human aging and age-related disease?

    PubMed

    Sikora, Ewa

    2013-07-01

    Cellular senescence is the state of permanent inhibition of cell proliferation. Replicative senescence occurs due to the end replication problem and shortening telomeres with each cell division leading to DNA damage response (DDR). The number of short telomeres increases with age and age-related pathologies. Stress induced senescence, although not accompanied by attrition of telomeres, is also attributed to the DDR induced by irreparable DNA lesions in telomeric DNA. Senescent cells characterized by the presence of γH2AX, the common marker of double DNA strand breaks, and other senescence markers including activity of SA-β-gal, accumulate in tissues of aged animals and humans as well as at sites of pathology. It is believed that cellular senescence evolved as a cancer barrier since non-proliferating senescent cells cannot be transformed to neoplastic cells. On the other hand senescent cells favor cancer development, just like other age-related pathologies, by creating a low grade inflammatory state due to senescence associated secretory phenotype (SASP). Reversal/inhibition of cellular senescence could prolong healthy life span, thus many attempts have been undertaken to influence cellular senescence. The two main approaches are genetic and pharmacological/nutritional modifications of cell fate. The first one concerns cell reprogramming by induced pluripotent stem cells (iPSCs), which in vitro is effective even in cells undergoing senescence, or derived from very old or progeroid patients. The second approach concerns modification of senescence signaling pathways just like TOR-induced by pharmacological or with natural agents. However, knowing that aging is unavoidable we cannot expect its elimination, but prolonging healthy life span is a goal worth serious consideration. PMID:23064316

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

    PubMed

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

    2012-11-01

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

  19. Deterioration of the Medial Olivocochlear Efferent System Accelerates Age-Related Hearing Loss in Pax2-Isl1 Transgenic Mice.

    PubMed

    Chumak, Tetyana; Bohuslavova, Romana; Macova, Iva; Dodd, Nicole; Buckiova, Daniela; Fritzsch, Bernd; Syka, Josef; Pavlinkova, Gabriela

    2016-05-01

    The development, maturation, and maintenance of the inner ear are governed by temporal and spatial expression cascades of transcription factors that form a gene regulatory network. ISLET1 (ISL1) may be one of the major players in this cascade, and in order to study its role in the regulation of inner ear development, we produced a transgenic mouse overexpressing Isl1 under the Pax2 promoter. Pax2-regulated ISL1 overexpression increases the embryonic ISL1(+) domain and induces accelerated nerve fiber extension and branching in E12.5 embryos. Despite these gains in early development, the overexpression of ISL1 impairs the maintenance and function of hair cells of the organ of Corti. Mutant mice exhibit hyperactivity, circling behavior, and progressive age-related decline in hearing functions, which is reflected in reduced otoacoustic emissions (DPOAEs) followed by elevated hearing thresholds. The reduction of the amplitude of DPOAEs in transgenic mice was first detected at 1 month of age. By 6-9 months of age, DPOAEs completely disappeared, suggesting a functional inefficiency of outer hair cells (OHCs). The timing of DPOAE reduction coincides with the onset of the deterioration of cochlear efferent terminals. In contrast to these effects on efferents, we only found a moderate loss of OHCs and spiral ganglion neurons. For the first time, our results show that the genetic alteration of the medial olivocochlear (MOC) efferent system induces an early onset of age-related hearing loss. Thus, the neurodegeneration of the MOC system could be a contributing factor to the pathology of age-related hearing loss.

  20. Mevastatin accelerates loss of synaptic proteins and neurite degeneration in aging cortical neurons in a heme-independent manner.

    PubMed

    Kannan, Madhuvanthi; Steinert, Joern R; Forsythe, Ian D; Smith, Andrew G; Chernova, Tatyana

    2010-09-01

    The therapeutic use of statins in reducing cholesterol requires careful assessment of potential neuroprotective and/or neurotoxic mechanisms. Chronic treatment with mevastatin (MV) exerts effects on cortical neuron morphology, protein expression and synaptic function in primary culture. MV impaired expression of synaptic proteins, reduced N-methyl-d-aspartate receptor (NMDAR) currents and accelerated neurodegeneration associated with aging. The down-regulating effect of MV on neuronal protein expression was additive with aging-associated decline in culture. Induction of Heme oxygenase-1 (HMOX1) by MV was superimposed on age-related up-regulation. Comparison of MV-treated and heme-deficient neurons showed that inhibition of heme synthesis (by succinyl acetone) had similar damaging effect on neurite integrity and MNDAR expression and function but not on expression of the receptor for neuropeptide Y1 (NPY1R). Replacement of heme in heme-deficient cultures restored protein expression but had no effect in those cultures co-treated with MV. Despite the dramatic induction of HMOX1, intracellular heme remained sufficient in MV-treated cultures, consistent with a heme-independent mechanism of MV-induced neurotoxicity and this was confirmed by analysing neurons with lentiviral over-expression of HMOX1. We conclude that MV exerts a neurotoxic effect in cultured neurons in a heme-independent manner.

  1. Accelerated age-related olfactory decline among type 1 Usher patients

    PubMed Central

    Ribeiro, João Carlos; Oliveiros, Bárbara; Pereira, Paulo; António, Natália; Hummel, Thomas; Paiva, António; Silva, Eduardo D.

    2016-01-01

    Usher Syndrome (USH) is a rare disease with hearing loss, retinitis pigmentosa and, sometimes, vestibular dysfunction. A phenotype heterogeneity is reported. Recent evidence indicates that USH is likely to belong to an emerging class of sensory ciliopathies. Olfaction has recently been implicated in ciliopathies, but the scarce literature about olfaction in USH show conflicting results. We aim to evaluate olfactory impairment as a possible clinical manifestation of USH. Prospective clinical study that included 65 patients with USH and 65 normal age-gender-smoking-habits pair matched subjects. A cross culturally validated version of the Sniffin’ Sticks olfaction test was used. Young patients with USH have significantly better olfactory scores than healthy controls. We observe that USH type 1 have a faster ageing olfactory decrease than what happens in healthy subjects, leading to significantly lower olfactory scores in older USH1 patients. Moreover, USH type 1 patients showed significantly higher olfactory scores than USH type 2, what can help distinguishing them. Olfaction represents an attractive tool for USH type classification and pre diagnostic screening due to the low cost and non-invasive nature of the testing. Olfactory dysfunction should be considered among the spectrum of clinical manifestations of Usher syndrome. PMID:27329700

  2. The Age-Related Orientational Changes of Human Semicircular Canals

    PubMed Central

    Lyu, Hui-Ying; Chen, Ke-Guang; Yin, Dong-Ming; Hong, Juan; Yang, Lin; Zhang, Tian-Yu; Dai, Pei-Dong

    2016-01-01

    Objectives Some changes are found in the labyrinth anatomy during postnatal development. Although the spatial orientation of semicircular canals was thought to be stable after birth, we investigated the age-related orientational changes of human semicircular canals during development. Methods We retrospectively studied the computed tomography (CT) images of both ears of 76 subjects ranged from 1 to 70 years old. They were divided into 4 groups: group A (1–6 years), group B (7–12 years), group C (13–18 years), and group D (>18 years). The anatomical landmarks of the inner ear structures were determined from CT images. Their coordinates were imported into MATLAB software for calculating the semicircular canals orientation, angles between semicircular canal planes and the jugular bulb (JB) position. Differences between age groups were analyzed using multivariate statistics. Relationships between variables were analyzed using Pearson analysis. Results The angle between the anterior semicircular canal plane and the coronal plane, and the angle between the horizontal semicircular canal plane and the coronal plane were smaller in group D than those in group A (P<0.05). The JB position, especially the anteroposterior position of right JB, correlated to the semicircular canals orientation (P<0.05). However, no statistically significant differences in the angles between ipsilateral canal planes among different age groups were found. Conclusion The semicircular canals had tendencies to tilt anteriorly simultaneously as a whole with age. The JB position correlated to the spatial arrangement of semicircular canals, especially the right JB. Our calculation method helps detect developmental and pathological changes in vestibular anatomy. PMID:27090280

  3. Aging and fracture of human cortical bone and tooth dentin

    NASA Astrophysics Data System (ADS)

    Koester, Kurt J.; Ager, Joel W.; Ritchie, Robert O.

    2008-06-01

    Mineralized tissues, such as bone and tooth dentin, serve as structural materials in the human body and, as such, have evolved to resist fracture. In assessing their quantitative fracture resistance or toughness, it is important to distinguish between intrinsic toughening mechanisms, which function ahead of the crack tip, such as plasticity in metals, and extrinsic mechanisms, which function primarily behind the tip, such as crack bridging in ceramics. Bone and dentin derive their resistance to fracture principally from extrinsic toughening mechanisms, which have their origins in the hierarchical microstructure of these mineralized tissues. Experimentally, quantification of these toughening mechanisms requires a crack-growth resistance approach, which can be achieved by measuring the crack-driving force (e.g., the stress intensity) as a function of crack extension (“R-curve approach”). Here this methodology is used to study the effect of aging on the fracture properties of human cortical bone and human dentin in order to discern the microstructural origins of toughness in these materials.

  4. Aging and Fracture of Human Cortical Bone and Tooth Dentin

    SciTech Connect

    Ager, Joel; Koester, Kurt J.; Ager III, Joel W.; Ritchie, Robert O.

    2008-05-07

    Mineralized tissues, such as bone and tooth dentin, serve as structural materials in the human body and, as such, have evolved to resist fracture. In assessing their quantitative fracture resistance or toughness, it is important to distinguish between intrinsic toughening mechanisms which function ahead of the crack tip, such as plasticity in metals, and extrinsic mechanisms which function primarily behind the tip, such as crack bridging in ceramics. Bone and dentin derive their resistance to fracture principally from extrinsic toughening mechanisms which have their origins in the hierarchical microstructure of these mineralized tissues. Experimentally, quantification of these toughening mechanisms requires a crack-growth resistance approach, which can be achieved by measuring the crack-driving force, e.g., the stress intensity, as a function of crack extension ("R-curve approach"). Here this methodology is used to study of the effect of aging on the fracture properties of human cortical bone and human dentin in order to discern the microstructural origins of toughness in these materials.

  5. Metabolomics of human brain aging and age-related neurodegenerative diseases.

    PubMed

    Jové, Mariona; Portero-Otín, Manuel; Naudí, Alba; Ferrer, Isidre; Pamplona, Reinald

    2014-07-01

    Neurons in the mature human central nervous system (CNS) perform a wide range of motor, sensory, regulatory, behavioral, and cognitive functions. Such diverse functional output requires a great diversity of CNS neuronal and non-neuronal populations. Metabolomics encompasses the study of the complete set of metabolites/low-molecular-weight intermediates (metabolome), which are context-dependent and vary according to the physiology, developmental state, or pathologic state of the cell, tissue, organ, or organism. Therefore, the use of metabolomics can help to unravel the diversity-and to disclose the specificity-of metabolic traits and their alterations in the brain and in fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of aging and neurodegenerative diseases. Here, we review the current applications of metabolomics in studies of CNS aging and certain age-related neurodegenerative diseases such as Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Neurometabolomics will increase knowledge of the physiologic and pathologic functions of neural cells and will place the concept of selective neuronal vulnerability in a metabolic context.

  6. Accelerator mass spectrometry of strontium-90 for homeland security, environmental monitoring and human health

    NASA Astrophysics Data System (ADS)

    Tumey, Scott J.; Brown, Thomas A.; Hamilton, Terry E.; Hillegonds, Darren J.

    2008-05-01

    Strontium-90 is one of the most hazardous materials managed by agencies charged with protecting the public from radiation. Traditional radiometric methods have been limited by low sample throughput and slow turnaround times. Mass spectrometry offers the advantage of shorter analysis times and the ability to measure samples immediately after processing, however conventional mass spectrometric techniques are susceptible to molecular isobaric interferences that limit their overall sensitivity. In contrast, accelerator mass spectrometry is insensitive to molecular interferences and we have therefore begun developing a method for determination of 90Sr by accelerator mass spectrometry. Despite a pervasive interference from 90Zr, our initial development has yielded an instrumental background of ∼108 atoms (75 mBq) per sample. Further refinement of our system (e.g. redesign of our detector, use of alternative target materials) is expected to push the background below 106 atoms, close to the theoretical limit for AMS. Once we have refined our system and developed suitable sample preparation protocols, we will utilize our capability in applications to homeland security, environmental monitoring and human health.

  7. Recombinant Human Epidermal Growth Factor Accelerates Recovery of Mouse Small Intestinal Mucosa After Radiation Damage

    SciTech Connect

    Lee, Kang Kyoo; Jo, Hyang Jeong; Hong, Joon Pio; Lee, Sang-wook Sohn, Jung Sook; Moon, Soo Young; Yang, Sei Hoon; Shim, Hyeok; Lee, Sang Ho; Ryu, Seung-Hee; Moon, Sun Rock

    2008-07-15

    Purpose: To determine whether systemically administered recombinant human epidermal growth factor (rhEGF) accelerates the recovery of mouse small intestinal mucosa after irradiation. Methods and Materials: A mouse mucosal damage model was established by administering radiation to male BALB/c mice with a single dose of 15 Gy applied to the abdomen. After irradiation, rhEGF was administered subcutaneously at various doses (0.04, 0.2, 1.0, and 5.0 mg/kg/day) eight times at 2- to 3-day intervals. The evaluation methods included histologic changes of small intestinal mucosa, change in body weight, frequency of diarrhea, and survival rate. Results: The recovery of small intestinal mucosa after irradiation was significantly improved in the mice treated with a high dose of rhEGF. In the mice that underwent irradiation without rhEGF treatment, intestinal mucosal ulceration, mucosal layer damage, and severe inflammation occurred. The regeneration of villi was noticeable in mice treated with more than 0.2 mg/kg rhEGF, and the villi recovered fully in mice given more than 1 mg/kg rhEGF. The frequency of diarrhea persisting for more than 3 days was significantly greater in the radiation control group than in the rhEGF-treated groups. Conclusions: Systemic administration of rhEGF accelerates recovery from mucosal damage induced by irradiation. We suggest that rhEGF treatment shows promise for the reduction of small intestinal damage after irradiation.

  8. Accelerator mass spectrometry of Strontium-90 for homeland security, environmental monitoring, and human health

    SciTech Connect

    Tumey, S J; Brown, T A; Hamilton, T F; Hillegonds, D J

    2008-03-03

    Strontium-90 is one of the most hazardous materials managed by agencies charged with protecting the public from radiation. Traditional radiometric methods have been limited by low sample throughput and slow turnaround times. Mass spectrometry offers the advantage of shorter analysis times and the ability to measure samples immediately after processing, however conventional mass spectrometric techniques are susceptible to molecular isobaric interferences that limit their overall sensitivity. In contrast, accelerator mass spectrometry is insensitive to molecular interferences and we have therefore begun developing a method for determination of {sup 90}Sr by accelerator mass spectrometry. Despite a pervasive interference from {sup 90}Zr, our initial development has yielded an instrumental background of {approx} 10{sup 8} atoms (75 mBq) per sample. Further refinement of our system (e.g., redesign of our detector, use of alternative target materials) is expected to push the background below 10{sup 6} atoms, close to the theoretical limit for AMS. Once we have refined our system and developed suitable sample preparation protocols, we will utilize our capability in applications to homeland security, environmental monitoring, and human health.

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

    PubMed

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

    2006-02-22

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

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

    PubMed

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

    2015-01-01

    Diethyl carbonate and dimethyl carbonate are prototype examples of eco-friendly solvents used in lithium-ion batteries. Nevertheless, their degradation products affect both the battery performance and its safety. Therefore, it is of paramount importance to understand the reaction mechanisms involved in the ageing processes. Among those, redox processes are likely to play a critical role. Here we show that radiolysis is an ideal tool to generate the electrolytes degradation products. The major gases detected after irradiation (H2, CH4, C2H6, CO and CO2) are identified and quantified. Moreover, the chemical compounds formed in the liquid phase are characterized by different mass spectrometry techniques. Reaction mechanisms are then proposed. The detected products are consistent with those of the cycling of Li-based cells. This demonstrates that radiolysis is a versatile and very helpful tool to better understand the phenomena occurring in lithium-ion batteries. PMID:25907411

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

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

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

    PubMed Central

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

    2015-01-01

    Diethyl carbonate and dimethyl carbonate are prototype examples of eco-friendly solvents used in lithium-ion batteries. Nevertheless, their degradation products affect both the battery performance and its safety. Therefore, it is of paramount importance to understand the reaction mechanisms involved in the ageing processes. Among those, redox processes are likely to play a critical role. Here we show that radiolysis is an ideal tool to generate the electrolytes degradation products. The major gases detected after irradiation (H2, CH4, C2H6, CO and CO2) are identified and quantified. Moreover, the chemical compounds formed in the liquid phase are characterized by different mass spectrometry techniques. Reaction mechanisms are then proposed. The detected products are consistent with those of the cycling of Li-based cells. This demonstrates that radiolysis is a versatile and very helpful tool to better understand the phenomena occurring in lithium-ion batteries. PMID:25907411

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

    SciTech Connect

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

    1983-07-01

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

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

    NASA Technical Reports Server (NTRS)

    Benson, A. J.; Barnes, G. R.

    1973-01-01

    Human subjects were exposed to a linear acceleration vector that rotated in the transverse plane of the skull without angular counterrotation. Lateral eye movements showed a sinusoidal change in slow phase velocity and an asymmetry or bias in the same direction as vector rotation. A model is developed that attributes the oculomotor response to otolithic mechanisms. It is suggested that the bias component is the manifestation of torsion of the statoconial plaque relative to the base of the utricular macula and that the sinusoidal component represents the translational oscillation of the statoconia. The model subsumes a hypothetical neural mechanism which allows x- and y-axis accelerations to be resolved. Derivation of equations of motion for the statoconial plaque in torsion and translation, which take into account forces acting in shear and normal to the macula, yield estimates of bias and sinusoidal components that are in qualitative agreement with the diverse experimental findings.

  15. Valuable human capital: the aging health care worker.

    PubMed

    Collins, Sandra K; Collins, Kevin S

    2006-01-01

    With the workforce growing older and the supply of younger workers diminishing, it is critical for health care managers to understand the factors necessary to capitalize on their vintage employees. Retaining this segment of the workforce has a multitude of benefits including the preservation of valuable intellectual capital, which is necessary to ensure that health care organizations maintain their competitive advantage in the consumer-driven market. Retaining the aging employee is possible if health care managers learn the motivators and training differences associated with this category of the workforce. These employees should be considered a valuable resource of human capital because without their extensive expertise, intense loyalty and work ethic, and superior customer service skills, health care organizations could suffer severe economic repercussions in the near future. PMID:16905991

  16. Concord grape juice supplementation and neurocognitive function in human aging.

    PubMed

    Krikorian, Robert; Boespflug, Erin L; Fleck, David E; Stein, Amanda L; Wightman, Jolynne D; Shidler, Marcelle D; Sadat-Hossieny, Sara

    2012-06-13

    Polyphenol compounds found in berry fruits, in particular flavonoids, have been associated with health benefits including improvement in cognition and neuronal function with aging. Concord grape juice contains polyphenols, including anthocyanins and flavanols, and previous research has shown improvement in a number of human health conditions with grape juice supplementation. In the current study, older adult subjects with mild cognitive impairment consumed Concord grape juice or placebo for 16 weeks and were administered assessments of memory function and brain activation pre- and postintervention. Participants who consumed grape juice showed reduced semantic interference on memory tasks. Relatively greater activation in anterior and posterior regions of the right hemisphere was also observed with functional magnetic resonance imaging in the grape juice treated subjects. These findings provide further evidence that Concord grape juice can enhance neurocognitive function in older adults with mild memory decline. PMID:22468945

  17. Human eye movements during various forms of linear acceleration and weightlessness. [electronystagmographic recordings of human and fish responses to gravitoinertial conditions

    NASA Technical Reports Server (NTRS)

    Vonbaumgarten, R. J.; Thumler, R.; Shillinger, G. L., Jr.; Baldrighi, G.

    1973-01-01

    Eye movements of human subjects were recorded electronystagmographically in complete darkness during rectilinear horizontal accelerations as achieved in cars on the ground and also during aircraft parabolic flight. The results were compared to the movements of blinded goldfish subjected to similar changes of gravitoinertial forces. The results indicate that there is a human correlation with the gravity reference response of fish. During horizontal forward accelerations on the ground the human eyes turn downward and during horizontal backward acceleration the eyes turn upward. The human eye response to g-loads below 1 g and to weightlessness is the reverse of the tilt of the fish. While fish dive down during low g, or loop forward during weightlessness, the eyes of subjects sitting upright in an aircraft which flies at 0 g move upward.

  18. Lung fibroblasts accelerate wound closure in human alveolar epithelial cells through hepatocyte growth factor/c-Met signaling

    PubMed Central

    Correll, Kelly; Schiel, John A.; Finigan, Jay H.; Prekeris, Rytis; Mason, Robert J.

    2014-01-01

    There are 190,600 cases of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) each year in the United States, and the incidence and mortality of ALI/ARDS increase dramatically with age. Patients with ALI/ARDS have alveolar epithelial injury, which may be worsened by high-pressure mechanical ventilation. Alveolar type II (ATII) cells are the progenitor cells for the alveolar epithelium and are required to reestablish the alveolar epithelium during the recovery process from ALI/ARDS. Lung fibroblasts (FBs) migrate and proliferate early after lung injury and likely are an important source of growth factors for epithelial repair. However, how lung FBs affect epithelial wound healing in the human adult lung has not been investigated in detail. Hepatocyte growth factor (HGF) is known to be released mainly from FBs and to stimulate both migration and proliferation of primary rat ATII cells. HGF is also increased in lung tissue, bronchoalveolar lavage fluid, and serum in patients with ALI/ARDS. Therefore, we hypothesized that HGF secreted by FBs would enhance wound closure in alveolar epithelial cells (AECs). Wound closure was measured using a scratch wound-healing assay in primary human AEC monolayers and in a coculture system with FBs. We found that wound closure was accelerated by FBs mainly through HGF/c-Met signaling. HGF also restored impaired wound healing in AECs from the elderly subjects and after exposure to cyclic stretch. We conclude that HGF is the critical factor released from FBs to close wounds in human AEC monolayers and suggest that HGF is a potential strategy for hastening alveolar repair in patients with ALI/ARDS. PMID:24748602

  19. Analysis of Aged Human Serum Albumin Affinity for Doxazosin.

    PubMed

    Chudzik, Mariola; Równicka-Zubik, Joanna; Pożycka, Jadwiga; Pawelczak, Bartosz; Sulkowska, Anna

    2016-01-01

    Structural changes of human serum albumin (HSA) caused by old age and coexisting diseases result in differences in the binding of doxazosin (DOX). DOX is a postsynaptic α1- adrenoreceptor antagonist used for treatment of hypertension and benign prostatic hyperplasia. In elderly people suffering from various renal or hepatic diseases the significant portion of N-form of human serum albumin (normal) is converted to A-form (aged). The differences in binding of doxazosin to N- and Aform of albumin are an important factor, which may determines therapeutic dosage and toxicity of the test drug. To indicate these differences, the technique of fluorescence spectroscopy was used. The association constant (Ka) obtained from fluorescence quenching demonstrated that doxazosin has higher affinity for AHSA than for HSA. In order to describe the cooperativity in binding process, the values of the Hill's coefficient has been analysed. For DOX-HSA system (λex 295 nm) Hill's coefficient is close to 1 and it indicates that there is a single class of binding sites. For DOX-HSA (λex 275 nm) and DOX-AHSA (λex 275 nm and λex 295 nm) systems we observed positive cooperativity (nH>1). A greater red shift of fluorescence emission maximum of AHSA than HSA in the presence of DOX was observed. This suggests that the binding of DOX to AHSA was accompanied by a stronger increase in polarity around the fluorophores in comparison to HSA. The binding interaction between DOX and HSA has been also studied by molecular docking simulation.

  20. Color and opacity of composites protected with surface sealants and submitted to artificial accelerated aging

    PubMed Central

    Aguilar, Fabiano Gamero; Roberti Garcia, Lucas da Fonseca; Cruvinel, Diogo Rodrigues; Sousa, Ana Beatriz Silva; de Carvalho Panzeri Pires-de-Souza, Fernanda

    2012-01-01

    Objectives: To evaluate the color similarity, stability and opacity of composites (TPH, Charisma, and Concept, shade A2) protected with surface sealants (Fortify Plus and Biscover) and cyanoacrylate (Super Bonder). Methods: Forty specimens of each composite were made and separated into 4 groups (n=10) according to the surface protection: GI - without sealant; GII - cyanoacrylate; GIII - Fortify Plus; GIV - Biscover. Color and opacity readings were taken before and after Artificial Acelerated Aging (AAA) and the values obtained for color stability were submitted to statistical analysis by 2-way ANOVA and Bonferroni’s test (P<.05). The values acquired for color similarity were submitted to 1-way ANOVA and Tukey’s test (P<.05). The specimen sufaces were compared before and after AAA using Scanning Electronic Microscopy (SEM). Results: Studied composites did not present the same values for the coordinates L*, a* and b * before AAA, indicating that there was no color similarity among them. All composites presented color alteration after AAA with clinically unacceptable values. Protected groups presented lower opacity variation after AAA, in comparison with the control goup. SEM evaluation demonstrated that AAA increased the surface irregularities in all of the studied groups. Conclusion: Surface sealants were not effective in maintaining composite color, but were able to maintain opacity. PMID:22229004

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-10-01

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

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

    PubMed

    Godfrey, R W; Weis, A J

    2016-03-01

    This study was designed to evaluate the impact of weaning age on lamb and ewe productivity in an accelerated lambing system. St. Croix White (STX) and Dorper × St. Croix White (DRPX) lambs were assigned at birth based on breed, gender, and litter size to be weaned at 63 (Early-1; 106 lambs and 68 ewes) or 90 d of age (Late-1; 99 lambs and 60 ewes) in Exp.1 or at 63 (Early-2; 77 lambs and 57 ewes) or 120 d of age (Late-2; 75 lambs and 56 ewes) in Exp. 2. After weaning, lambs were weighed weekly and fed a concentrate ration (2% BW·lamb·d) while grazing guinea grass pastures. In Exp. 1, weaning weight was greater ( < 0.0001) for Late-1 lambs than for Early-1 lambs (14.6 ± 0.3 vs. 11.0 ± 0.3 kg, respectively) and greater ( < 0.008) for DRPX lambs than for STX lambs (13.9 ± 0.4 vs. 11.5 ± 0.4 kg, respectively). Litter weaning weight was greater ( < 0.004) for Late-1 ewes than for Early-1 ewes (20.9 ± 0.8 vs. 17.4 ± 0.8 kg, respectively). Ewe efficiency ([ewe BW at weaning/litter weaning weight] × 100) was greater ( < 0.004) for Late-1 ewes than for Early-1 ewes (50.7 ± 1.9 vs. 42.3 ± 1.8%, respectively). Lamb weight gain between 63 and 90 d of age was lower ( < 0.03) for Early-1 lambs than for Late-1 lambs (2.7 ± 0.2 vs. 3.6 ± 0.3 kg, respectively). In Exp. 2, weaning weight was greater ( < 0.0001) for Late-2 lambs than for Early-2 lambs (18.7 ± 0.4 vs. 11.8 ± 0.4 kg, respectively) and greater ( < 0.008) for DRPX lambs than for STX lambs (16.9 ± 0.5 vs. 13.3 ± 0.5 kg, respectively). Litter weaning weight was greater ( < 0.0001) in Late-2 ewes than in Early-2 ewes (27.2 ± 1.0 vs. 17.5 ± 0.9 kg, respectively). Ewe efficiency was greater ( < 0.0001) for Late-2 ewes than for Early-2 ewes (68.1 ± 2.2 vs. 41.9 ± 2.0%, respectively). Lamb weight gain between 63 and 120 d of age was not different ( > 0.06) between Early-2 and Late-2 lambs (5.1 ± 0.2 vs. 5.6 ± 0.3 kg, respectively). In Exp. 1 and 2, ewe BW at breeding and lambing and weaning and lambing

  4. Cigarette Smoking Accelerated Brain Aging and Induced Pre-Alzheimer-Like Neuropathology in Rats

    PubMed Central

    Ho, Yuen-Shan; Yang, Xifei; Yeung, Sze-Chun; Chiu, Kin; Lau, Chi-Fai; Tsang, Andrea Wing-Ting; Mak, Judith Choi-Wo; Chang, Raymond Chuen-Chung

    2012-01-01

    Cigarette smoking has been proposed as a major risk factor for aging-related pathological changes and Alzheimer's disease (AD). To date, little is known for how smoking can predispose our brains to dementia or cognitive impairment. This study aimed to investigate the cigarette smoke-induced pathological changes in brains. Male Sprague-Dawley (SD) rats were exposed to either sham air or 4% cigarette smoke 1 hour per day for 8 weeks in a ventilated smoking chamber to mimic the situation of chronic passive smoking. We found that the levels of oxidative stress were significantly increased in the hippocampus of the smoking group. Smoking also affected the synapse through reducing the expression of pre-synaptic proteins including synaptophysin and synapsin-1, while there were no changes in the expression of postsynaptic protein PSD95. Decreased levels of acetylated-tubulin and increased levels of phosphorylated-tau at 231, 205 and 404 epitopes were also observed in the hippocampus of the smoking rats. These results suggested that axonal transport machinery might be impaired, and the stability of cytoskeleton might be affected by smoking. Moreover, smoking affected amyloid precursor protein (APP) processing by increasing the production of sAPPβ and accumulation of β–amyloid peptide in the CA3 and dentate gyrus region. In summary, our data suggested that chronic cigarette smoking could induce synaptic changes and other neuropathological alterations. These changes might serve as evidence of early phases of neurodegeneration and may explain why smoking can predispose brains to AD and dementia. PMID:22606286

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

    PubMed Central

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

    2010-01-01

    We have recently reported that a novel muscle-specific inositide phosphatase (MIP/MTMR14) plays a critical role in [Ca2+]i homeostasis through dephosphorylation of sn-1-stearoyl-2-arachidonoyl phosphatidylinositol (3,5) bisphosphate (PI(3,5)P2). Loss of function mutations in MIP have been identified in human centronuclear myopathy. We developed a MIP knockout (MIPKO) animal model and found that MIPKO mice were more susceptible to exercise-induced muscle damage, a trademark of muscle functional changes in older subjects. We used wild-type (Wt) mice and MIPKO mice to elucidate the roles of MIP in muscle function during aging. We found MIP mRNA expression, MIP protein levels, and MIP phosphatase activity significantly decreased in old Wt mice. The mature MIPKO mice displayed phenotypes that closely resembled those seen in old Wt mice: i) decreased walking speed, ii) decreased treadmill activity, iii) decreased contractile force, and iv) decreased power generation, classical features of sarcopenia in rodents and humans. Defective Ca2+ homeostasis is also present in mature MIPKO and old Wt mice, suggesting a putative role of MIP in the decline of muscle function during aging. Our studies offer a new avenue for the investigation of MIP roles in skeletal muscle function and as a potential therapeutic target to treat aging sarcopenia. PMID:20817957

  6. Is atherosclerosis fundamental to human aging? Lessons from ancient mummies.

    PubMed

    Clarke, Emily M; Thompson, Randall C; Allam, Adel H; Wann, L Samuel; Lombardi, Guido P; Sutherland, M Linda; Sutherland, James D; Cox, Samantha L; Soliman, Muhammad Al-Tohamy; Abd el-Maksoud, Gomaa; Badr, Ibrahem; Miyamoto, Michael I; Frohlich, Bruno; Nur el-din, Abdel-Halim; Stewart, Alexandre F R; Narula, Jagat; Zink, Albert R; Finch, Caleb E; Michalik, David E; Thomas, Gregory S

    2014-05-01

    Case reports from Johan Czermak, Marc Ruffer, and others a century or more ago demonstrated ancient Egyptians had atherosclerosis three millennia ago. The Horus study team extended their findings, demonstrating that atherosclerosis was prevalent among 76 ancient Egyptian mummies and among 61 mummies from each of the ancient cultures of Peru, the American Southwest, and the Aleutian Islands. These findings challenge the assumption that atherosclerosis is a modern disease caused by present day risk factors. An extensive autopsy of an ancient Egyptian teenage male weaver named Nakht found that he was infected with four parasites: Schistosoma haematobium, Taenia species, Trichinella spiralis, and Plasmodium falciparum. Modern day patients with chronic inflammatory disease such as rheumatoid arthritis, systemic lupus erythematosus, and human immunodeficiency virus experience premature atherosclerosis. Could the burden of chronic inflammatory disease have been a risk factor for atherosclerosis in these ancient cultures? The prevalence of atherosclerosis in four diverse ancient cultures is consistent with atherosclerosis being fundamental to aging. The impact of risk factors in modern times, and potentially in ancient times, suggests a strong gene-environmental interplay: human genes provide a vulnerability to atherosclerosis, the environment determines when and if atherosclerosis becomes manifest clinically.

  7. Prognostics of Power Mosfets Under Thermal Stress Accelerated Aging Using Data-Driven and Model-Based Methodologies

    NASA Technical Reports Server (NTRS)

    Celaya, Jose; Saxena, Abhinav; Saha, Sankalita; Goebel, Kai F.

    2011-01-01

    An approach for predicting remaining useful life of power MOSFETs (metal oxide field effect transistor) devices has been developed. Power MOSFETs are semiconductor switching devices that are instrumental in electronics equipment such as those used in operation and control of modern aircraft and spacecraft. The MOSFETs examined here were aged under thermal overstress in a controlled experiment and continuous performance degradation data were collected from the accelerated aging experiment. Dieattach degradation was determined to be the primary failure mode. The collected run-to-failure data were analyzed and it was revealed that ON-state resistance increased as die-attach degraded under high thermal stresses. Results from finite element simulation analysis support the observations from the experimental data. Data-driven and model based prognostics algorithms were investigated where ON-state resistance was used as the primary precursor of failure feature. A Gaussian process regression algorithm was explored as an example for a data-driven technique and an extended Kalman filter and a particle filter were used as examples for model-based techniques. Both methods were able to provide valid results. Prognostic performance metrics were employed to evaluate and compare the algorithms.

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

    SciTech Connect

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

    2000-01-31

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

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

    PubMed

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

    2015-05-01

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

  10. Disentangling the genetic determinants of human aging: biological age as an alternative to the use of survival measures.

    PubMed

    Karasik, David; Demissie, Serkalem; Cupples, L Adrienne; Kiel, Douglas P

    2005-05-01

    The choice of a phenotype is critical for the study of a complex genetically regulated process, such as aging. To date, most of the twin and family studies have focused on broad survival measures, primarily age at death or exceptional longevity. However, on the basis of recent studies of twins and families, biological age has also been shown to have a strong genetic component, with heritability estimates ranging from 27% to 57%. The aim of this review is twofold: first, to summarize growing consensus on reliable methods of biological age assessment, and second, to demonstrate validity of this phenotype for research in the genetics of aging in humans.

  11. Supplementation with Lactobacillus plantarum WCFS1 Prevents Decline of Mucus Barrier in Colon of Accelerated Aging Ercc1−/Δ7 Mice

    PubMed Central

    van Beek, Adriaan A.; Sovran, Bruno; Hugenholtz, Floor; Meijer, Ben; Hoogerland, Joanne A.; Mihailova, Violeta; van der Ploeg, Corine; Belzer, Clara; Boekschoten, Mark V.; Hoeijmakers, Jan H. J.; Vermeij, Wilbert P.; de Vos, Paul; Wells, Jerry M.; Leenen, Pieter J. M.; Nicoletti, Claudio; Hendriks, Rudi W.; Savelkoul, Huub F. J.

    2016-01-01

    Although it is clear that probiotics improve intestinal barrier function, little is known about the effects of probiotics on the aging intestine. We investigated effects of 10-week bacterial supplementation of Lactobacillus plantarum WCFS1, Lactobacillus casei BL23, or Bifidobacterium breve DSM20213 on gut barrier and immunity in 16-week-old accelerated aging Ercc1−/Δ7 mice, which have a median lifespan of ~20 weeks, and their wild-type littermates. The colonic barrier in Ercc1−/Δ7 mice was characterized by a thin (< 10 μm) mucus layer. L. plantarum prevented this decline in mucus integrity in Ercc1−/Δ7 mice, whereas B. breve exacerbated it. Bacterial supplementations affected the expression of immune-related genes, including Toll-like receptor 4. Regulatory T cell frequencies were increased in the mesenteric lymph nodes of L. plantarum- and L. casei-treated Ercc1−/Δ7 mice. L. plantarum- and L. casei-treated Ercc1−/Δ7 mice showed increased specific antibody production in a T cell-dependent immune response in vivo. By contrast, the effects of bacterial supplementation on wild-type control mice were negligible. Thus, supplementation with L. plantarum – but not with L. casei and B. breve – prevented the decline in the mucus barrier in Ercc1−/Δ7 mice. Our data indicate that age is an important factor influencing beneficial or detrimental effects of candidate probiotics. These findings also highlight the need for caution in translating beneficial effects of probiotics observed in young animals or humans to the elderly. PMID:27774093

  12. Attenuated noradrenergic sensitivity during local cooling in aged human skin

    PubMed Central

    Thompson, Caitlin S; Holowatz, Lacy A; Kenney, W. Larry

    2005-01-01

    Reflex-mediated cutaneous vasoconstriction (VC) is impaired in older humans; however, it is unclear whether this blunted VC also occurs during local cooling, which mediates VC through different mechanisms. We tested the hypothesis that the sensitization of cutaneous vessels to noradrenaline (NA) during direct skin cooling seen in young skin is blunted in aged skin. In 11 young (18–30 years) and 11 older (62–76 years) men and women, skin blood flow was monitored at two forearm sites with laser Doppler (LD) flowmetry while local skin temperature was cooled and clamped at 24°C. Cutaneous vascular conductance (CVC; LD flux/mean arterial pressure) was expressed as percentage change from baseline (%ΔCVCbase). At one site, five doses of NA (10−10–10−2m) were sequentially infused via intradermal microdialysis during cooling while the other 24°C site served as control (Ringer solution + cooling). At control sites, VC due to cooling alone was similar in young versus older (−54 ± 5 versus −56 ± 3%ΔCVCbase, P= 0.46). In young, NA infusions induced additional dose-dependent VC (10−8, 10−6, 10−4 and 10−2m: −70 ± 2, −72 ± 3, −78 ± 3 and −79 ± 4%ΔCVCbase; P < 0.05 versus control). In older subjects, further VC did not occur until the highest infused dose of NA (10−2m: −70 ± 5%ΔCVCbase; P < 0.05 versus control). When cutaneous arterioles are sensitized to NA by direct cooling, young skin exhibits the capacity to further constrict to NA in a dose-dependent manner. However, older skin does not display enhanced VC capacity until treated with saturating doses of NA, possibly due to age-associated decrements in Ca2+ availability or α2C-adrenoceptor function. PMID:15705648

  13. A transcriptional profile of aging in the human kidney.

    PubMed

    Rodwell, Graham E J; Sonu, Rebecca; Zahn, Jacob M; Lund, James; Wilhelmy, Julie; Wang, Lingli; Xiao, Wenzhong; Mindrinos, Michael; Crane, Emily; Segal, Eran; Myers, Bryan D; Brooks, James D; Davis, Ronald W; Higgins, John; Owen, Art B; Kim, Stuart K

    2004-12-01

    In this study, we found 985 genes that change expression in the cortex and the medulla of the kidney with age. Some of the genes whose transcripts increase in abundance with age are known to be specifically expressed in immune cells, suggesting that immune surveillance or inflammation increases with age. The age-regulated genes show a similar aging profile in the cortex and the medulla, suggesting a common underlying mechanism for aging. Expression profiles of these age-regulated genes mark not only age, but also the relative health and physiology of the kidney in older individuals. Finally, the set of aging-regulated kidney genes suggests specific mechanisms and pathways that may play a role in kidney degeneration with age.

  14. A Transcriptional Profile of Aging in the Human Kidney

    PubMed Central

    2004-01-01

    In this study, we found 985 genes that change expression in the cortex and the medulla of the kidney with age. Some of the genes whose transcripts increase in abundance with age are known to be specifically expressed in immune cells, suggesting that immune surveillance or inflammation increases with age. The age-regulated genes show a similar aging profile in the cortex and the medulla, suggesting a common underlying mechanism for aging. Expression profiles of these age-regulated genes mark not only age, but also the relative health and physiology of the kidney in older individuals. Finally, the set of aging-regulated kidney genes suggests specific mechanisms and pathways that may play a role in kidney degeneration with age. PMID:15562319

  15. Role of Mineralocorticoid Receptors in Arterial Stiffness in Human Aging

    PubMed Central

    Hwang, Moon-Hyon; Yoo, Jeung-Ki; Luttrell, Meredith; Kim, Han-Kyul; Meade, Thomas H.; English, Mark; Nichols, Wilmer W.; Christou, Demetra D.

    2013-01-01

    Arterial stiffness, an independent predictor of cardiovascular disease, is increased in aging, but the underlying mechanisms are not completely understood. Mineralocorticoid receptors (MR) may contribute to oxidative stress and arterial stiffness in healthy older adults. To test the hypothesis that short-term MR blockade may reduce oxidative stress and improve arterial stiffness, we conducted a randomized, double blind, crossover study using the selective MR blocker Eplerenone or placebo in 23 older adults (age, 64±1 years; mean±SE) free from overt cardiovascular and other clinical disease (e.g, diabetes, renal and liver disease). In response to MR blockade, brachial and carotid blood pressure decreased (P≤0.01). However, MR blockade had no effect on oxidative stress (oxidized LDL, 61.2±6.8 vs. 62.4±7.4 U/L, P=0.9; placebo vs. Eplerenone) and arterial stiffness (aortic pulse wave velocity (PWV), 9.17±1.19 vs. 8.92±1.19 m/sec, P=0.5; leg PWV, 13.45±0.45 vs. 12.81±0.47 m/sec, P=0.3; arm PWV, 11.43±0.62 vs. 11.73±0.68 m/sec, P=0.7; carotid artery compliance, 0.150±0.013 vs. 0.149±0.014 mm2/mmHg, P=0.8; distensibility, 23.1±1.8 vs. 23.3±1.7 10−3/kPa, P=0.8; β stiffness index, 3.5±0.3 vs. 3.6±0.3, P=0.6; and augmentation index, 16.0±2.2 vs. 15.6±2.8 %, P=0.8). These results provide the first evidence that MR do not appear to contribute to oxidative stress in human aging and that short-term MR blockade does not result in reduced oxidative stress and improved arterial stiffness. PMID:23707930

  16. Calcium Isolation from Large-Volume Human Urine Samples for 41Ca Analysis by Accelerator Mass Spectrometry

    PubMed Central

    Miller, James J; Hui, Susanta K; Jackson, George S; Clark, Sara P; Einstein, Jane; Weaver, Connie M; Bhattacharyya, Maryka H

    2013-01-01

    Calcium oxalate precipitation is the first step in preparation of biological samples for 41Ca analysis by accelerator mass spectrometry. A simplified protocol for large-volume human urine samples was characterized, with statistically significant increases in ion current and decreases in interference. This large-volume assay minimizes cost and effort and maximizes time after 41Ca administration during which human samples, collected over a lifetime, provide 41Ca:Ca ratios that are significantly above background. PMID:23672965

  17. Models of Metal-poor Stars with Gravitational Settling and Radiative Accelerations. II. The Age of the Oldest Stars

    NASA Astrophysics Data System (ADS)

    VandenBerg, Don A.; Richard, O.; Michaud, G.; Richer, J.

    2002-05-01

    Isochrones for ages between 12 and 18 Gyr have been derived from the evolutionary tracks presented in Paper I (Richard et al.) for masses from 0.5 to 1.0 Msolar and initial chemical abundances corresponding to (1) Y=0.2352, Z=1.69×10-4 ([Fe/H]=-2.31,[α/Fe]=0.3) and (2) Y=0.2370, Z=1.69×10-3 ([Fe/H=-1.31,[α/Fe]=0.3). These are the first models for Population II stars in which both gravitational settling and radiative accelerations have been taken into account. Allowance for these diffusive processes leads to a 10%-12% reduction in age at a given turnoff luminosity. However, in order for the diffusive models to satisfy the constraints from Li and Fe abundance data (see Paper I) and to reproduce the observed morphologies of globular cluster (GC) color-magnitude diagrams (CMDs) in a straightforward way, extra mixing just below the boundary of the convective envelope seems to be necessary. Indeed, when additional turbulent mixing is invoked, the resultant models are able to satisfy all of these constraints, as well as those provided by the CMDs of local subdwarfs, rather well. Moreover, they imply an age near 13.5 Gyr for M92, which is one of the most metal-deficient (and presumably one of the oldest) of the Galaxy's GCs, if the field subgiant HD 140283 is used to derive the cluster distance. Comparisons of field subdwarfs and subgiants with a recently published fiducial for M5 suggests that the cluster has [Fe/H]<~-1.4, in conflict with some estimates based on high-resolution spectroscopy, if the metallicities of the field stars are to be trusted. In addition, an age of ~11.5 Gyr is found for M5, irrespective of whether diffusive or nondiffusive isochrones are employed in the analysis. The implications of our results for the extragalactic distance scale and for the Hubble constant are briefly discussed in the context of the presently favored ΩM~0.35, ΩΛ~0.65 cosmological model.

  18. Age-related changes in deformability of human erythrocytes.

    PubMed

    Sutera, S P; Gardner, R A; Boylan, C W; Carroll, G L; Chang, K C; Marvel, J S; Kilo, C; Gonen, B; Williamson, J R

    1985-02-01

    The present study was designed to further the characterization of age-related changes in the deformability of human erythrocytes. The top (approximately young) and bottom (approximately old) 10% fractions of density-separated red cells from ten normal donors were subjected to graded levels of shear stress in a rheoscope. Measurements were made of steady-state elongation (cells tank treading in a state of dynamic equilibrium) and the time course of shape recovery following abrupt cessation of shear. In parallel with the rheologic experiments, several physical and chemical properties were assayed to determine correlates of mechanical properties. These included mean cell volume, mean corpuscular hemoglobin concentration, type A1 hemoglobin, glucosylation of membrane proteins, and membrane phospholipid and protein concentration. The microrheologic observations revealed that only about 90% of the old cells retained their capacity to tank tread. However, the tank-treading cells elongated less than their younger counterparts at corresponding levels of shear stress, thus demonstrating a reduced level of deformability. Further analysis of the data indicates that increases in membrane viscosity and elastic modulus along with a significant loss in excess surface area contribute to the limitation of the ability of the older cells to change shape.

  19. Interrelationship of age and diet in Romania's oldest human burial.

    PubMed

    Bonsall, Clive; Boroneanţ, Adina; Soficaru, Andrei; McSweeney, Kathleen; Higham, Tom; Miriţoiu, Nicolae; Pickard, Catriona; Cook, Gordon

    2012-04-01

    In 1968, excavations in the Climente II cave in the Iron Gates gorge of the River Danube in southwest Romania unearthed the skeleton of an adult male. The burial was assumed to be of Late Pleistocene age because of the presence of Late Upper Palaeolithic (LUP) artefacts in the cave. However, there was no strong supporting stratigraphic evidence, and the body position is reminiscent of Early Neolithic burial practice in the region. Here, we report the results of radiocarbon and stable isotope analyses of the Climente II skeleton, which show that the skeleton dates to the Bølling-Allerød Interstadial ~14,500 cal BP. This is several millennia older than any previously dated human remains from the Iron Gates region and confirms its status as the oldest known burial from Romania. The stable isotope results indicate a diet with an emphasis on aquatic resources, contrary to the commonly held view that the LUP inhabitants of the Iron Gates subsisted mainly by hunting large land mammals.

  20. Human face processing is tuned to sexual age preferences

    PubMed Central

    Ponseti, J.; Granert, O.; van Eimeren, T.; Jansen, O.; Wolff, S.; Beier, K.; Deuschl, G.; Bosinski, H.; Siebner, H.

    2014-01-01

    Human faces can motivate nurturing behaviour or sexual behaviour when adults see a child or an adult face, respectively. This suggests that face processing is tuned to detecting age cues of sexual maturity to stimulate the appropriate reproductive behaviour: either caretaking or mating. In paedophilia, sexual attraction is directed to sexually immature children. Therefore, we hypothesized that brain networks that normally are tuned to mature faces of the preferred gender show an abnormal tuning to sexual immature faces in paedophilia. Here, we use functional magnetic resonance imaging (fMRI) to test directly for the existence of a network which is tuned to face cues of sexual maturity. During fMRI, participants sexually attracted to either adults or children were exposed to various face images. In individuals attracted to adults, adult faces activated several brain regions significantly more than child faces. These brain regions comprised areas known to be implicated in face processing, and sexual processing, including occipital areas, the ventrolateral prefrontal cortex and, subcortically, the putamen and nucleus caudatus. The same regions were activated in paedophiles, but with a reversed preferential response pattern. PMID:24850896

  1. Dynamic mechanical and molecular weight measurements on polymer bonded explosives from thermally accelerated aging tests. I. Fluoropolymer binders

    SciTech Connect

    Hoffman, D.M.; Caley, L.E.

    1981-01-01

    The dynamic mechanical properties and molecular weight distribution of two polymer bonded explosives, LX-10-1 and PBX-9502, maintained at 23, 60, and 74/sup 0/C for 3 years were studied. LX-10-1 is 94.5% 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane explosive bonded together with 5.5% Viton A fluoropolymer. PBX-9502 is 95% triaminotrinitrobenzene explosive bonded with 5% Kel-F-800 fluoropolymer. There are two mechanical relaxations in the LX-10-1 in the military temperature range. The relaxation at -10/sup 0/C is associated with the glass transition temperature of the Viton A binder. A second weak relaxation occurs at about 30/sup 0/C in all LX-10-1 samples tested. This relaxation is probably associated with small amounts of crystallinity in the binder although this has not been demonstrated. There is a slight increase in modulus of the LX-10-1 with accelerated aging temperature. Changes in the dynamic mechanical properties of PBX-9502 are ascribed to crystallization of the chlorotrifluoroethylene component of the Kel-F-800 binder. The molecular weight of the Viton A binder decreased slight with increasing aging temperature. Using the kinetics of random scission the activation energy for polymer degradation in the presence of the explosive was 1.19 kcal/mole. The Arrhenius preexponential term and activation energy predict an expected use-life in excess of 60 years for LX-10-1. The Kel-F-800 in PBX-9502 is also extremely stable.

  2. Endocrine and fluid metabolism in males and females of different ages after bedrest, acceleration and lower body negative pressure

    NASA Technical Reports Server (NTRS)

    Leach, C. S.; Vernikos-Danellis, J.; Krauhs, J. M.; Sandler, H.

    1985-01-01

    Space shuttle flight simulations were conducted to determine the effects of weightlessness, lower body negative pressure (LBNP), and acceleration of fluid and electrolyte excretion and the hormones that control it. Measurements were made on male and female subjects of different ages before and after bedrest. After admission to a controlled environment, groups of 6 to 14 subjects in the age ranges 25 to 35, 35 to 45, 45 to 55 to 65 years were exposed to +3 G sub z for 15 minutes (G1) and to LBNP (LBNP1) on different days. On 3 days during this prebedrest period, no tests were conducted. Six days of bedrest followed, and the G sub z (G2) and LBNP (LBNP2) tests were run again. Hormones, electrolytes, and other parameters were measured in 24-hour urine pools throughout the experiment. During bedrest, cortisol and aldosterone excretion increased. Urine volume decreased, and specific gravity and osmolality increased. Urinary electrolytes were statistically unchanged from levels during the non-stress control period. During G2, cortisol increased significantly over its control and bedrest levels. Urine volume, sodium, and chloride were significantly lower; specific gravity and osmolality were higher during the control period or bedrest. The retention of fluids and electrolytes after +G sub z may at least partially explain decreased urine volume and increased osmolality observed during bedrest in this study. There were some who indicated that space flight would not affect the fluid and electrolyte metabolism of females or older males any more severely than it has affected that of male astronauts.

  3. High-fat diet intake accelerates aging, increases expression of Hsd11b1, and promotes lipid accumulation in liver of SAMP10 mouse.

    PubMed

    Honma, Taro; Shinohara, Nahoko; Ito, Junya; Kijima, Ryo; Sugawara, Soko; Arai, Tatsuya; Tsuduki, Tsuyoshi; Ikeda, Ikuo

    2012-04-01

    An understanding of the mechanisms of aging is important for prevention of age-related diseases. In this study, we examined age-dependent changes in lipid metabolism in the senescence-accelerated mouse (SAM)P10 fed a high-fat diet to investigate the effects of high-fat intake and aging. Tissue weights and biological parameters in plasma and liver were measured at 6 and 12 months old in SAMP10 mice fed a high-fat diet. These mice showed marked increases in liver triacylglycerol and plasma insulin levels with intake of a high-fat diet intake and aging. Lipid accumulation in hepatocytes and morphological aberrations and hypertrophy in pancreatic islets were also promoted by a high-fat diet and aging. To investigate the underlying mechanisms, the activities and mRNA levels for enzymes associated with lipid metabolism in liver were measured. The results indicated that the lipid metabolic system was activated by a high-fat diet and aging. Liver mRNA level for hydroxysteroid 11-beta dehydrogenase 1 (Hsd11b1), which exhibit age-dependent increases and promote insulin secretion, was also markedly increased. These results suggest that a high-fat diet accelerated aging in the liver of SAMP10 mice by increasing liver mRNA level for Hsd11b1, increasing insulin secretion, and promoting lipid accumulation in the liver.

  4. Folate Acts in E. coli to Accelerate C. elegans Aging Independently of Bacterial Biosynthesis

    PubMed Central

    Virk, Bhupinder; Jia, Jie; Maynard, Claire A.; Raimundo, Adelaide; Lefebvre, Jolien; Richards, Shane A.; Chetina, Natalia; Liang, Yen; Helliwell, Noel; Cipinska, Marta; Weinkove, David

    2016-01-01

    Summary Folates are cofactors for biosynthetic enzymes in all eukaryotic and prokaryotic cells. Animals cannot synthesize folate and must acquire it from their diet or microbiota. Previously, we showed that inhibiting E. coli folate synthesis increases C. elegans lifespan. Here, we show that restriction or supplementation of C. elegans folate does not influence lifespan. Thus, folate is required in E. coli to shorten worm lifespan. Bacterial proliferation in the intestine has been proposed as a mechanism for the life-shortening influence of E. coli. However, we found no correlation between C. elegans survival and bacterial growth in a screen of 1,000+ E. coli deletion mutants. Nine mutants increased worm lifespan robustly, suggesting specific gene regulation is required for the life-shortening activity of E. coli. Disrupting the biosynthetic folate cycle did not increase lifespan. Thus, folate acts through a growth-independent route in E. coli to accelerate animal aging. PMID:26876180

  5. Acceleration of aged-landfill stabilization by combining partial nitrification and leachate recirculation: a field-scale study.

    PubMed

    Chung, Jinwook; Kim, Seungjin; Baek, Seungcheon; Lee, Nam-Hoon; Park, Seongjun; Lee, Junghun; Lee, Heechang; Bae, Wookeun

    2015-03-21

    Leachate recirculation for rapid landfill stabilization can result in the accumulation of high-strength ammonium. An on-site sequencing batch reactor (SBR) was therefore, applied to oxidize the ammonium to nitrite, which was then recirculated to the landfill for denitrification to nitrogen gas. At relatively higher ammonium levels, nitrite accumulated well in the SBR; the nitrite was denitrified stably in the landfill, despite an insufficient biodegradable carbon source in the leachate. As the leachate was recirculated, the methane and carbon dioxide contents produced from the landfill fluctuated, implying that the organic acids and hydrogen produced in the acid production phase acted as the carbon source for denitrification in the landfill. Leachate recirculation combined with ex-situ partial nitrification of the leachate may enhance the biodegradation process by: (a) removing the nitrogen that is contained with the leachate, and (b) accelerating landfill stabilization, because the biodegradation efficiency of landfill waste is increased by supplying sufficient moisture and its byproducts are used as the carbon source for denitrification. In addition, partial nitrification using an SBR has advantages for complete denitrification in the landfill, since the available carbon source is in short supply in aged landfills.

  6. Folate Acts in E. coli to Accelerate C. elegans Aging Independently of Bacterial Biosynthesis.

    PubMed

    Virk, Bhupinder; Jia, Jie; Maynard, Claire A; Raimundo, Adelaide; Lefebvre, Jolien; Richards, Shane A; Chetina, Natalia; Liang, Yen; Helliwell, Noel; Cipinska, Marta; Weinkove, David

    2016-02-23

    Folates are cofactors for biosynthetic enzymes in all eukaryotic and prokaryotic cells. Animals cannot synthesize folate and must acquire it from their diet or microbiota. Previously, we showed that inhibiting E. coli folate synthesis increases C. elegans lifespan. Here, we show that restriction or supplementation of C. elegans folate does not influence lifespan. Thus, folate is required in E. coli to shorten worm lifespan. Bacterial proliferation in the intestine has been proposed as a mechanism for the life-shortening influence of E. coli. However, we found no correlation between C. elegans survival and bacterial growth in a screen of 1,000+ E. coli deletion mutants. Nine mutants increased worm lifespan robustly, suggesting specific gene regulation is required for the life-shortening activity of E. coli. Disrupting the biosynthetic folate cycle did not increase lifespan. Thus, folate acts through a growth-independent route in E. coli to accelerate animal aging.

  7. CCN1 contributes to skin connective tissue aging by inducing age-associated secretory phenotype in human skin dermal fibroblasts.

    PubMed

    Quan, Taihao; Qin, Zhaoping; Robichaud, Patrick; Voorhees, John J; Fisher, Gary J

    2011-08-01

    Dermal connective tissue collagen is the major structural protein in skin. Fibroblasts within the dermis are largely responsible for collagen production and turnover. We have previously reported that dermal fibroblasts, in aged human skin in vivo, express elevated levels of CCN1, and that CCN1 negatively regulates collagen homeostasis by suppressing collagen synthesis and increasing collagen degradation (Quan et al. Am J Pathol 169:482-90, 2006, J Invest Dermatol 130:1697-706, 2010). In further investigations of CCN1 actions, we find that CCN1 alters collagen homeostasis by promoting expression of specific secreted proteins, which include matrix metalloproteinases and proinflammatory cytokines. We also find that CCN1-induced secretory proteins are elevated in aged human skin in vivo. We propose that CCN1 induces an "Age-Associated Secretory Phenotype", in dermal fibroblasts, which mediates collagen reduction and fragmentation in aged human skin.

  8. Nutritional interventions protect against age-related deficits in behavior: from animals to humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aged rats show impaired performance on motor and cognitive tasks. Similar changes in behavior occur in humans with age, and the development of methods to retard or reverse these age-related neuronal and behavioral deficits could increase healthy aging and decrease health care costs. In the present s...

  9. Proteome-wide analysis reveals an age-associated cellular phenotype of in situ aged human fibroblasts

    PubMed Central

    Waldera-Lupa, Daniel M.; Kalfalah, Faiza; Florea, Ana-Maria; Sass, Steffen; Kruse, Fabian; Rieder, Vera; Tigges, Julia; Fritsche, Ellen; Krutmann, Jean; Busch, Hauke; Boerries, Melanie; Meyer, Helmut E.; Boege, Fritz; Theis, Fabian

    2014-01-01

    We analyzed an ex vivo model of in situ aged human dermal fibroblasts, obtained from 15 adult healthy donors from three different age groups using an unbiased quantitative proteome-wide approach applying label-free mass spectrometry. Thereby, we identified 2409 proteins, including 43 proteins with an age-associated abundance change. Most of the differentially abundant proteins have not been described in the context of fibroblasts’ aging before, but the deduced biological processes confirmed known hallmarks of aging and led to a consistent picture of eight biological categories involved in fibroblast aging, namely proteostasis, cell cycle and proliferation, development and differentiation, cell death, cell organization and cytoskeleton, response to stress, cell communication and signal transduction, as well as RNA metabolism and translation. The exhaustive analysis of protein and mRNA data revealed that 77% of the age-associated proteins were not linked to expression changes of the corresponding transcripts. This is in line with an associated miRNA study and led us to the conclusion that most of the age-associated alterations detected at the proteome level are likely caused post-transcriptionally rather than by differential gene expression. In summary, our findings led to the characterization of novel proteins potentially associated with fibroblast aging and revealed that primary cultures of in situ aged fibroblasts are characterized by moderate age-related proteomic changes comprising the multifactorial process of aging. PMID:25411231

  10. Human activity accelerating the rapid desertification of the Mu Us Sandy Lands, North China

    NASA Astrophysics Data System (ADS)

    Miao, Yunfa; Jin, Heling; Cui, Jianxin

    2016-03-01

    Over the past several thousand years, arid and semiarid China has experienced a series of asynchronous desertification events in its semiarid sandy and desert regions, but the precise identification of the driving forces of such events has remained elusive. In this paper we identify two rapid desertification events (RDEs) at ~4.6 ± 0.2 ka BP and ~3.3 ± 0.2 ka BP from the JJ Profile, located in the eastern Mu Us Sandy Lands. These RDEs appear to have occurred immediately following periods marked by persistently frequent and intense fires. We argue that such fire patterns, directly linked to an uncontrolled human use of vegetation as fuel, played a key role in accelerating RDEs by ensuring that the land surface was degraded beyond the threshold required for rapid desertification. This would suggest that the future use of a massive and sustained ecological program of vegetation rehabilitation should reduce the risk of destructive fire.

  11. Magnetic Shielding Accelerates the Proliferation of Human Neuroblastoma Cell by Promoting G1-Phase Progression

    PubMed Central

    Liu, Ying; Bartlett, Perry F.; He, Rong-qiao

    2013-01-01

    Organisms have been exposed to the geomagnetic field (GMF) throughout evolutionary history. Exposure to the hypomagnetic field (HMF) by deep magnetic shielding has recently been suggested to have a negative effect on the structure and function of the central nervous system, particularly during early development. Although changes in cell growth and differentiation have been observed in the HMF, the effects of the HMF on cell cycle progression still remain unclear. Here we show that continuous HMF exposure significantly increases the proliferation of human neuroblastoma (SH-SY5Y) cells. The acceleration of proliferation results from a forward shift of the cell cycle in G1-phase. The G2/M-phase progression is not affected in the HMF. Our data is the first to demonstrate that the HMF can stimulate the proliferation of SH-SY5Y cells by promoting cell cycle progression in the G1-phase. This provides a novel way to study the mechanism of cells in response to changes of environmental magnetic field including the GMF. PMID:23355897

  12. Graphics processing unit accelerated one-dimensional blood flow computation in the human arterial tree.

    PubMed

    Itu, Lucian; Sharma, Puneet; Kamen, Ali; Suciu, Constantin; Comaniciu, Dorin

    2013-12-01

    One-dimensional blood flow models have been used extensively for computing pressure and flow waveforms in the human arterial circulation. We propose an improved numerical implementation based on a graphics processing unit (GPU) for the acceleration of the execution time of one-dimensional model. A novel parallel hybrid CPU-GPU algorithm with compact copy operations (PHCGCC) and a parallel GPU only (PGO) algorithm are developed, which are compared against previously introduced PHCG versions, a single-threaded CPU only algorithm and a multi-threaded CPU only algorithm. Different second-order numerical schemes (Lax-Wendroff and Taylor series) are evaluated for the numerical solution of one-dimensional model, and the computational setups include physiologically motivated non-periodic (Windkessel) and periodic boundary conditions (BC) (structured tree) and elastic and viscoelastic wall laws. Both the PHCGCC and the PGO implementations improved the execution time significantly. The speed-up values over the single-threaded CPU only implementation range from 5.26 to 8.10 × , whereas the speed-up values over the multi-threaded CPU only implementation range from 1.84 to 4.02 × . The PHCGCC algorithm performs best for an elastic wall law with non-periodic BC and for viscoelastic wall laws, whereas the PGO algorithm performs best for an elastic wall law with periodic BC.

  13. Human activity accelerating the rapid desertification of the Mu Us Sandy Lands, North China

    PubMed Central

    Miao, Yunfa; Jin, Heling; Cui, Jianxin

    2016-01-01

    Over the past several thousand years, arid and semiarid China has experienced a series of asynchronous desertification events in its semiarid sandy and desert regions, but the precise identification of the driving forces of such events has remained elusive. In this paper we identify two rapid desertification events (RDEs) at ~4.6 ± 0.2 ka BP and ~3.3 ± 0.2 ka BP from the JJ Profile, located in the eastern Mu Us Sandy Lands. These RDEs appear to have occurred immediately following periods marked by persistently frequent and intense fires. We argue that such fire patterns, directly linked to an uncontrolled human use of vegetation as fuel, played a key role in accelerating RDEs by ensuring that the land surface was degraded beyond the threshold required for rapid desertification. This would suggest that the future use of a massive and sustained ecological program of vegetation rehabilitation should reduce the risk of destructive fire. PMID:26961705

  14. Effects of acceleration in the Gz axis on human cardiopulmonary responses to exercise.

    PubMed

    Bonjour, Julien; Bringard, Aurélien; Antonutto, Guglielmo; Capelli, Carlo; Linnarsson, Dag; Pendergast, David R; Ferretti, Guido

    2011-12-01

    The aim of this paper was to develop a model from experimental data allowing a prediction of the cardiopulmonary responses to steady-state submaximal exercise in varying gravitational environments, with acceleration in the G(z) axis (a (g)) ranging from 0 to 3 g. To this aim, we combined data from three different experiments, carried out at Buffalo, at Stockholm and inside the Mir Station. Oxygen consumption, as expected, increased linearly with a (g). In contrast, heart rate increased non-linearly with a (g), whereas stroke volume decreased non-linearly: both were described by quadratic functions. Thus, the relationship between cardiac output and a (g) was described by a fourth power regression equation. Mean arterial pressure increased with a (g) non linearly, a relation that we interpolated again with a quadratic function. Thus, total peripheral resistance varied linearly with a (g). These data led to predict that maximal oxygen consumption would decrease drastically as a (g) is increased. Maximal oxygen consumption would become equal to resting oxygen consumption when a (g) is around 4.5 g, thus indicating the practical impossibility for humans to stay and work on the biggest Planets of the Solar System. PMID:21437604

  15. Human ankle plantar flexor muscle-tendon mechanics and energetics during maximum acceleration sprinting.

    PubMed

    Lai, Adrian; Schache, Anthony G; Brown, Nicholas A T; Pandy, Marcus G

    2016-08-01

    Tendon elastic strain energy is the dominant contributor to muscle-tendon work during steady-state running. Does this behaviour also occur for sprint accelerations? We used experimental data and computational modelling to quantify muscle fascicle work and tendon elastic strain energy for the human ankle plantar flexors (specifically soleus and medial gastrocnemius) for multiple foot contacts of a maximal sprint as well as for running at a steady-state speed. Positive work done by the soleus and medial gastrocnemius muscle fascicles decreased incrementally throughout the maximal sprint and both muscles performed more work for the first foot contact of the maximal sprint (FC1) compared with steady-state running at 5 m s(-1) (SS5). However, the differences in tendon strain energy for both muscles were negligible throughout the maximal sprint and when comparing FC1 to SS5. Consequently, the contribution of muscle fascicle work to stored tendon elastic strain energy was greater for FC1 compared with subsequent foot contacts of the maximal sprint and compared with SS5. We conclude that tendon elastic strain energy in the ankle plantar flexors is just as vital at the start of a maximal sprint as it is at the end, and as it is for running at a constant speed. PMID:27581481

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

    PubMed

    Geiger, Adolf; Walker, Audrey; Nissen, Erwin

    2015-11-13

    Diabetic ulcers represent a substantial societal and healthcare burden worldwide and scarcely respond to current treatment strategies. This study was addressed to evaluate the therapeutic potential of exosomes secreted by human circulating fibrocytes, a population of mesenchymal progenitors involved in normal wound healing via paracrine signaling. The exosomes released from cells sequentially stimulated with platelet-derived growth factor-BB and transforming growth factor-β1, in the presence of fibroblast growth factor 2, did not show potential immunogenicity. These exosomes exhibited in-vitro proangiogenic properties, activated diabetic dermal fibroblasts, induced the migration and proliferation of diabetic keratinocytes, and accelerated wound closure in diabetic mice in vivo. Important components of the exosomal cargo were heat shock protein-90α, total and activated signal transducer and activator of transcription 3, proangiogenic (miR-126, miR-130a, miR-132) and anti-inflammatory (miR124a, miR-125b) microRNAs, and a microRNA regulating collagen deposition (miR-21). This proof-of-concept study demonstrates the feasibility of the use of fibrocytes-derived exosomes for the treatment of diabetic ulcers.

  17. Human activity accelerating the rapid desertification of the Mu Us Sandy Lands, North China.

    PubMed

    Miao, Yunfa; Jin, Heling; Cui, Jianxin

    2016-01-01

    Over the past several thousand years, arid and semiarid China has experienced a series of asynchronous desertification events in its semiarid sandy and desert regions, but the precise identification of the driving forces of such events has remained elusive. In this paper we identify two rapid desertification events (RDEs) at ~4.6 ± 0.2 ka BP and ~3.3 ± 0.2 ka BP from the JJ Profile, located in the eastern Mu Us Sandy Lands. These RDEs appear to have occurred immediately following periods marked by persistently frequent and intense fires. We argue that such fire patterns, directly linked to an uncontrolled human use of vegetation as fuel, played a key role in accelerating RDEs by ensuring that the land surface was degraded beyond the threshold required for rapid desertification. This would suggest that the future use of a massive and sustained ecological program of vegetation rehabilitation should reduce the risk of destructive fire. PMID:26961705

  18. Graphics processing unit accelerated one-dimensional blood flow computation in the human arterial tree.

    PubMed

    Itu, Lucian; Sharma, Puneet; Kamen, Ali; Suciu, Constantin; Comaniciu, Dorin

    2013-12-01

    One-dimensional blood flow models have been used extensively for computing pressure and flow waveforms in the human arterial circulation. We propose an improved numerical implementation based on a graphics processing unit (GPU) for the acceleration of the execution time of one-dimensional model. A novel parallel hybrid CPU-GPU algorithm with compact copy operations (PHCGCC) and a parallel GPU only (PGO) algorithm are developed, which are compared against previously introduced PHCG versions, a single-threaded CPU only algorithm and a multi-threaded CPU only algorithm. Different second-order numerical schemes (Lax-Wendroff and Taylor series) are evaluated for the numerical solution of one-dimensional model, and the computational setups include physiologically motivated non-periodic (Windkessel) and periodic boundary conditions (BC) (structured tree) and elastic and viscoelastic wall laws. Both the PHCGCC and the PGO implementations improved the execution time significantly. The speed-up values over the single-threaded CPU only implementation range from 5.26 to 8.10 × , whereas the speed-up values over the multi-threaded CPU only implementation range from 1.84 to 4.02 × . The PHCGCC algorithm performs best for an elastic wall law with non-periodic BC and for viscoelastic wall laws, whereas the PGO algorithm performs best for an elastic wall law with periodic BC. PMID:24009129

  19. Effects of acceleration in the Gz axis on human cardiopulmonary responses to exercise.

    PubMed

    Bonjour, Julien; Bringard, Aurélien; Antonutto, Guglielmo; Capelli, Carlo; Linnarsson, Dag; Pendergast, David R; Ferretti, Guido

    2011-12-01

    The aim of this paper was to develop a model from experimental data allowing a prediction of the cardiopulmonary responses to steady-state submaximal exercise in varying gravitational environments, with acceleration in the G(z) axis (a (g)) ranging from 0 to 3 g. To this aim, we combined data from three different experiments, carried out at Buffalo, at Stockholm and inside the Mir Station. Oxygen consumption, as expected, increased linearly with a (g). In contrast, heart rate increased non-linearly with a (g), whereas stroke volume decreased non-linearly: both were described by quadratic functions. Thus, the relationship between cardiac output and a (g) was described by a fourth power regression equation. Mean arterial pressure increased with a (g) non linearly, a relation that we interpolated again with a quadratic function. Thus, total peripheral resistance varied linearly with a (g). These data led to predict that maximal oxygen consumption would decrease drastically as a (g) is increased. Maximal oxygen consumption would become equal to resting oxygen consumption when a (g) is around 4.5 g, thus indicating the practical impossibility for humans to stay and work on the biggest Planets of the Solar System.

  20. Magnetic shielding accelerates the proliferation of human neuroblastoma cell by promoting G1-phase progression.

    PubMed

    Mo, Wei-chuan; Zhang, Zi-jian; Liu, Ying; Bartlett, Perry F; He, Rong-qiao

    2013-01-01

    Organisms have been exposed to the geomagnetic field (GMF) throughout evolutionary history. Exposure to the hypomagnetic field (HMF) by deep magnetic shielding has recently been suggested to have a negative effect on the structure and function of the central nervous system, particularly during early development. Although changes in cell growth and differentiation have been observed in the HMF, the effects of the HMF on cell cycle progression still remain unclear. Here we show that continuous HMF exposure significantly increases the proliferation of human neuroblastoma (SH-SY5Y) cells. The acceleration of proliferation results from a forward shift of the cell cycle in G1-phase. The G2/M-phase progression is not affected in the HMF. Our data is the first to demonstrate that the HMF can stimulate the proliferation of SH-SY5Y cells by promoting cell cycle progression in the G1-phase. This provides a novel way to study the mechanism of cells in response to changes of environmental magnetic field including the GMF. PMID:23355897

  1. Biocompatibility of Accelerated Mineral Trioxide Aggregate on Stem Cells Derived from Human Dental Pulp.

    PubMed

    Kulan, Pinar; Karabiyik, Ozge; Kose, Gamze T; Kargul, Betul

    2016-02-01

    The aim of this study was to evaluate the effects of several additives on the setting time and cytotoxicity of accelerated-set mineral trioxide aggregate (MTA) on stem cells of human dental pulp. ProRoot white MTA (WMTA) (Dentsply Tulsa Dental, Johnson City, TN) was mixed with various additives including distilled water, 2.5% disodium hydrogen phosphate (Na2HPO4) (Merck, Darmstadt, Germany), K-Y Jelly (Johnson & Johnson, Markham, ON, Canada), and 5% and 10% calcium chloride (CaCl2) (Merck). The setting times were evaluated using a Vicat apparatus (Alsa Lab, Istanbul, Turkey). Human dental pulp stem cells were isolated and seeded into 48-well plates at 2 × 10(3) cells per well and incubated with MTA samples for 24 hours, 3 days, and 7 days. Cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. MTA mixed with 10% CaCl2 showed the lowest setting time (P < .05). According to the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium results on the 1st, 3rd, and 7th days, a statistically significant difference was found (P < .05) between MTA groups and the control group. MTA mixed with K-Y Jelly in all groups showed the lowest cell viability at all time points (P < .05). The cell viability of MTA mixed with distilled water, 5% CaCl2, 10% CaCl2, and Na2HPO4 increased significantly through time (P < .05). This in vitro study found MTA mixed with 5% and 10% CaCl2 and Na2HPO4 is biocompatible with dental pulp stem cells in terms of cell viability. Further in vitro and in vivo investigations are required to prove the clinical applications of MTA mixed with various additives.

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

    NASA Technical Reports Server (NTRS)

    Kirkpatrick, M.; Brye, R. G.

    1974-01-01

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

  3. Polarized Light for Measuring a Human Skin Feature Indicating Aging

    NASA Astrophysics Data System (ADS)

    Son, Jung-Young; Vashpanov, Yuriy A.; Jung, Dae-Hyun; Lee, Dong-Su; Kwack, Kae-Dal; Kim, Shin-Hwan

    2009-09-01

    The textures of skin on the back of the hand of many men of different ages are analyzed to determine their changes with age. The analysis shows that the textures are segmented by many lines of different lengths and orientations, and the size and number of segments in the skin surface change with age; that is the size increases while the number decreases. As a result, the texture becomes less complex with age. However, the addition of wrinkles from the age of 50 onwards for certain groups of people makes the texture appear somewhat complex.

  4. The transcriptional landscape of age in human peripheral blood.

    PubMed

    Peters, Marjolein J; Joehanes, Roby; Pilling, Luke C; Schurmann, Claudia; Conneely, Karen N; Powell, Joseph; Reinmaa, Eva; Sutphin, George L; Zhernakova, Alexandra; Schramm, Katharina; Wilson, Yana A; Kobes, Sayuko; Tukiainen, Taru; Ramos, Yolande F; Göring, Harald H H; Fornage, Myriam; Liu, Yongmei; Gharib, Sina A; Stranger, Barbara E; De Jager, Philip L; Aviv, Abraham; Levy, Daniel; Murabito, Joanne M; Munson, Peter J; Huan, Tianxiao; Hofman, Albert; Uitterlinden, André G; Rivadeneira, Fernando; van Rooij, Jeroen; Stolk, Lisette; Broer, Linda; Verbiest, Michael M P J; Jhamai, Mila; Arp, Pascal; Metspalu, Andres; Tserel, Liina; Milani, Lili; Samani, Nilesh J; Peterson, Pärt; Kasela, Silva; Codd, Veryan; Peters, Annette; Ward-Caviness, Cavin K; Herder, Christian; Waldenberger, Melanie; Roden, Michael; Singmann, Paula; Zeilinger, Sonja; Illig, Thomas; Homuth, Georg; Grabe, Hans-Jörgen; Völzke, Henry; Steil, Leif; Kocher, Thomas; Murray, Anna; Melzer, David; Yaghootkar, Hanieh; Bandinelli, Stefania; Moses, Eric K; Kent, Jack W; Curran, Joanne E; Johnson, Matthew P; Williams-Blangero, Sarah; Westra, Harm-Jan; McRae, Allan F; Smith, Jennifer A; Kardia, Sharon L R; Hovatta, Iiris; Perola, Markus; Ripatti, Samuli; Salomaa, Veikko; Henders, Anjali K; Martin, Nicholas G; Smith, Alicia K; Mehta, Divya; Binder, Elisabeth B; Nylocks, K Maria; Kennedy, Elizabeth M; Klengel, Torsten; Ding, Jingzhong; Suchy-Dicey, Astrid M; Enquobahrie, Daniel A; Brody, Jennifer; Rotter, Jerome I; Chen, Yii-Der I; Houwing-Duistermaat, Jeanine; Kloppenburg, Margreet; Slagboom, P Eline; Helmer, Quinta; den Hollander, Wouter; Bean, Shannon; Raj, Towfique; Bakhshi, Noman; Wang, Qiao Ping; Oyston, Lisa J; Psaty, Bruce M; Tracy, Russell P; Montgomery, Grant W; Turner, Stephen T; Blangero, John; Meulenbelt, Ingrid; Ressler, Kerry J; Yang, Jian; Franke, Lude; Kettunen, Johannes; Visscher, Peter M; Neely, G Gregory; Korstanje, Ron; Hanson, Robert L; Prokisch, Holger; Ferrucci, Luigi; Esko, Tonu; Teumer, Alexander; van Meurs, Joyce B J; Johnson, Andrew D

    2015-01-01

    Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the 'transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts. PMID:26490707

  5. The transcriptional landscape of age in human peripheral blood

    PubMed Central

    Peters, Marjolein J.; Joehanes, Roby; Pilling, Luke C.; Schurmann, Claudia; Conneely, Karen N.; Powell, Joseph; Reinmaa, Eva; Sutphin, George L.; Zhernakova, Alexandra; Schramm, Katharina; Wilson, Yana A.; Kobes, Sayuko; Tukiainen, Taru; Nalls, Michael A.; Hernandez, Dena G.; Cookson, Mark R.; Gibbs, Raphael J.; Hardy, John; Ramasamy, Adaikalavan; Zonderman, Alan B.; Dillman, Allissa; Traynor, Bryan; Smith, Colin; Longo, Dan L.; Trabzuni, Daniah; Troncoso, Juan; van der Brug, Marcel; Weale, Michael E.; O'Brien, Richard; Johnson, Robert; Walker, Robert; Zielke, Ronald H.; Arepalli, Sampath; Ryten, Mina; Singleton, Andrew B.; Ramos, Yolande F.; Göring, Harald H. H.; Fornage, Myriam; Liu, Yongmei; Gharib, Sina A.; Stranger, Barbara E.; De Jager, Philip L.; Aviv, Abraham; Levy, Daniel; Murabito, Joanne M.; Munson, Peter J.; Huan, Tianxiao; Hofman, Albert; Uitterlinden, André G.; Rivadeneira, Fernando; van Rooij, Jeroen; Stolk, Lisette; Broer, Linda; Verbiest, Michael M. P. J.; Jhamai, Mila; Arp, Pascal; Metspalu, Andres; Tserel, Liina; Milani, Lili; Samani, Nilesh J.; Peterson, Pärt; Kasela, Silva; Codd, Veryan; Peters, Annette; Ward-Caviness, Cavin K.; Herder, Christian; Waldenberger, Melanie; Roden, Michael; Singmann, Paula; Zeilinger, Sonja; Illig, Thomas; Homuth, Georg; Grabe, Hans-Jörgen; Völzke, Henry; Steil, Leif; Kocher, Thomas; Murray, Anna; Melzer, David; Yaghootkar, Hanieh; Bandinelli, Stefania; Moses, Eric K.; Kent, Jack W.; Curran, Joanne E.; Johnson, Matthew P.; Williams-Blangero, Sarah; Westra, Harm-Jan; McRae, Allan F.; Smith, Jennifer A.; Kardia, Sharon L. R.; Hovatta, Iiris; Perola, Markus; Ripatti, Samuli; Salomaa, Veikko; Henders, Anjali K.; Martin, Nicholas G.; Smith, Alicia K.; Mehta, Divya; Binder, Elisabeth B.; Nylocks, K Maria; Kennedy, Elizabeth M.; Klengel, Torsten; Ding, Jingzhong; Suchy-Dicey, Astrid M.; Enquobahrie, Daniel A.; Brody, Jennifer; Rotter, Jerome I.; Chen, Yii-Der I.; Houwing-Duistermaat, Jeanine; Kloppenburg, Margreet; Slagboom, P. Eline; Helmer, Quinta; den Hollander, Wouter; Bean, Shannon; Raj, Towfique; Bakhshi, Noman; Wang, Qiao Ping; Oyston, Lisa J.; Psaty, Bruce M.; Tracy, Russell P.; Montgomery, Grant W.; Turner, Stephen T.; Blangero, John; Meulenbelt, Ingrid; Ressler, Kerry J.; Yang, Jian; Franke, Lude; Kettunen, Johannes; Visscher, Peter M.; Neely, G. Gregory; Korstanje, Ron; Hanson, Robert L.; Prokisch, Holger; Ferrucci, Luigi; Esko, Tonu; Teumer, Alexander; van Meurs, Joyce B. J.; Johnson, Andrew D.

    2015-01-01

    Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the ‘transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts. PMID:26490707

  6. Age-related accumulation of Ig VH gene somatic mutations in peripheral B cells from aged humans

    PubMed Central

    CHONG, Y; IKEMATSU, H; YAMAJI, K; NISHIMURA, M; KASHIWAGI, S; HAYASHI, J

    2003-01-01

    To investigate age-related alterations in human humoral immunity, we analysed Ig heavy chain variable region genes expressed by peripheral B cells from young and aged individuals. Three hundred and twenty-seven cDNA sequences, 163 µ and 164 γ transcripts with VH5 family genes, were analysed for somatic hypermutation and VHDJH recombinational features. Unmutated and mutated µ transcripts were interpreted as being from naive and memory IgM B cells, respectively. In young and aged individuals, the percentages of naive IgM among total µ transcripts were 39% and 42%, respectively. D and JH segment usage in naive IgM from aged individuals was similar to that from young individuals. The mutational frequencies of memory IgM were similar in young and aged individuals. γ transcripts, which are regarded as being from memory IgG B cells, showed a significantly higher mutational frequency (7·6%) in aged than in young individuals (5·8%) (P < 0·01). These findings suggest that VHDJH recombinational diversity was preserved, but that the accumulation of somatic mutations in the IgG VH region was increased in aged humans. The accumulation of somatic mutations in IgG B cells during ageing may imply that an age-related alteration exists in the selection and/or maintenance of peripheral memory B cells. PMID:12823279

  7. Effect of accelerated electron beam on mechanical properties of human cortical bone: influence of different processing methods.

    PubMed

    Kaminski, Artur; Grazka, Ewelina; Jastrzebska, Anna; Marowska, Joanna; Gut, Grzegorz; Wojciechowski, Artur; Uhrynowska-Tyszkiewicz, Izabela

    2012-08-01

    Accelerated electron beam (EB) irradiation has been a sufficient method used for sterilisation of human tissue grafts for many years in a number of tissue banks. Accelerated EB, in contrast to more often used gamma photons, is a form of ionizing radiation that is characterized by lower penetration, however it is more effective in producing ionisation and to reach the same level of sterility, the exposition time of irradiated product is shorter. There are several factors, including dose and temperature of irradiation, processing conditions, as well as source of irradiation that may influence mechanical properties of a bone graft. The purpose of this study was to evaluate the effect e-beam irradiation with doses of 25 or 35 kGy, performed on dry ice or at ambient temperature, on mechanical properties of non-defatted or defatted compact bone grafts. Left and right femurs from six male cadaveric donors, aged from 46 to 54 years, were transversely cut into slices of 10 mm height, parallel to the longitudinal axis of the bone. Compact bone rings were assigned to the eight experimental groups according to the different processing method (defatted or non-defatted), as well as e-beam irradiation dose (25 or 35 kGy) and temperature conditions of irradiation (ambient temperature or dry ice). Axial compression testing was performed with a material testing machine. Results obtained for elastic and plastic regions of stress-strain curves examined by univariate analysis are described. Based on multivariate analysis, including all groups, it was found that temperature of e-beam irradiation and defatting had no consistent significant effect on evaluated mechanical parameters of compact bone rings. In contrast, irradiation with both doses significantly decreased the ultimate strain and its derivative toughness, while not affecting the ultimate stress (bone strength). As no deterioration of mechanical properties was observed in the elastic region, the reduction of the energy

  8. In vitro analysis of different properties of acrylic resins for ocular prosthesis submitted to accelerated aging with or without photopolymerized glaze.

    PubMed

    Santos, Daniela Micheline Dos; Nagay, Bruna Egumi; da Silva, Emily Vivianne Freitas; Bonatto, Liliane da Rocha; Sonego, Mariana Vilela; Moreno, Amália; Rangel, Elidiane Cipriano; da Cruz, Nilson Cristino; Goiato, Marcelo Coelho

    2016-12-01

    The effect of a photopolymerized glaze on different properties of acrylic resin (AR) for ocular prostheses submitted to accelerated aging was investigated. Forty discs were divided into 4 groups: N1 AR without glaze (G1); colorless AR without glaze (G2); N1 AR with glaze (G3); and colorless AR with glaze (G4). All samples were polished with sandpaper (240, 600 and 800-grit). In G1 and G2, a 1200-grit sandpaper was also used. In G3 and G4, samples were coated with MegaSeal glaze. Property analysis of color stability, microhardness, roughness, and surface energy, and assays of atomic force microscopy, scanning electron microscopy, and energy-dispersive spectroscopy were performed before and after the accelerated aging (1008h). Data were submitted to the ANOVA and Tukey Test (p<0.05). Groups with glaze exhibited statistically higher color change and roughness after aging. The surface microhardness significantly decreased in groups with glaze and increased in groups without glaze. The surface energy increased after the aging, independent of the polishing procedure. All groups showed an increase of surface irregularities. Photopolymerized glaze is an inadequate surface treatment for AR for ocular prostheses and it affected the color stability, roughness, and microhardness. The accelerated aging interfered negatively with the properties of resins. PMID:27612795

  9. In vitro analysis of different properties of acrylic resins for ocular prosthesis submitted to accelerated aging with or without photopolymerized glaze.

    PubMed

    Santos, Daniela Micheline Dos; Nagay, Bruna Egumi; da Silva, Emily Vivianne Freitas; Bonatto, Liliane da Rocha; Sonego, Mariana Vilela; Moreno, Amália; Rangel, Elidiane Cipriano; da Cruz, Nilson Cristino; Goiato, Marcelo Coelho

    2016-12-01

    The effect of a photopolymerized glaze on different properties of acrylic resin (AR) for ocular prostheses submitted to accelerated aging was investigated. Forty discs were divided into 4 groups: N1 AR without glaze (G1); colorless AR without glaze (G2); N1 AR with glaze (G3); and colorless AR with glaze (G4). All samples were polished with sandpaper (240, 600 and 800-grit). In G1 and G2, a 1200-grit sandpaper was also used. In G3 and G4, samples were coated with MegaSeal glaze. Property analysis of color stability, microhardness, roughness, and surface energy, and assays of atomic force microscopy, scanning electron microscopy, and energy-dispersive spectroscopy were performed before and after the accelerated aging (1008h). Data were submitted to the ANOVA and Tukey Test (p<0.05). Groups with glaze exhibited statistically higher color change and roughness after aging. The surface microhardness significantly decreased in groups with glaze and increased in groups without glaze. The surface energy increased after the aging, independent of the polishing procedure. All groups showed an increase of surface irregularities. Photopolymerized glaze is an inadequate surface treatment for AR for ocular prostheses and it affected the color stability, roughness, and microhardness. The accelerated aging interfered negatively with the properties of resins.

  10. Differences in gait velocity and trunk acceleration during semicircular turning gait with and without bag in females of very advanced age.

    PubMed

    Shin, Sun-Shil; Yoo, Won-Gyu

    2016-08-01

    [Purpose] Gait velocity and trunk acceleration during semicircular turning gait with and without carrying a hand-held bag were compared in females of very advanced age. [Subjects and Methods] Ten female volunteers of very advanced age who could walk independently were recruited for this study. Gait velocity and trunk acceleration were measured using an accelerometer during semicircular turning gait with and without carrying a hand-held bag. [Results] Gait velocity during semicircular turning gait was greater with the bag than without the bag. [Conclusions] Trunk stability during semicircular turning gait was higher when the subjects carried a bag. Additional arm load could be considered during gait training in females of very advanced age. PMID:27630425

  11. Differences in gait velocity and trunk acceleration during semicircular turning gait with and without bag in females of very advanced age

    PubMed Central

    Shin, Sun-Shil; Yoo, Won-Gyu

    2016-01-01

    [Purpose] Gait velocity and trunk acceleration during semicircular turning gait with and without carrying a hand-held bag were compared in females of very advanced age. [Subjects and Methods] Ten female volunteers of very advanced age who could walk independently were recruited for this study. Gait velocity and trunk acceleration were measured using an accelerometer during semicircular turning gait with and without carrying a hand-held bag. [Results] Gait velocity during semicircular turning gait was greater with the bag than without the bag. [Conclusions] Trunk stability during semicircular turning gait was higher when the subjects carried a bag. Additional arm load could be considered during gait training in females of very advanced age. PMID:27630425

  12. Differences in gait velocity and trunk acceleration during semicircular turning gait with and without bag in females of very advanced age

    PubMed Central

    Shin, Sun-Shil; Yoo, Won-Gyu

    2016-01-01

    [Purpose] Gait velocity and trunk acceleration during semicircular turning gait with and without carrying a hand-held bag were compared in females of very advanced age. [Subjects and Methods] Ten female volunteers of very advanced age who could walk independently were recruited for this study. Gait velocity and trunk acceleration were measured using an accelerometer during semicircular turning gait with and without carrying a hand-held bag. [Results] Gait velocity during semicircular turning gait was greater with the bag than without the bag. [Conclusions] Trunk stability during semicircular turning gait was higher when the subjects carried a bag. Additional arm load could be considered during gait training in females of very advanced age.

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  15. Body acceleration distribution and O2 uptake in humans during running and jumping

    NASA Technical Reports Server (NTRS)

    Bhattacharya, A.; Mccutcheon, E. P.; Shvartz, E.; Greenleaf, J. E.

    1980-01-01

    The distribution of body acceleration and associated oxygen uptake and heart rate responses are investigated in treadmill running and trampoline jumping. Accelerations in the +Gz direction were measured at the lateral ankle, lumbosacral region and forehead of eight young men during level treadmill walking and running at four speeds and trampoline jumping at four heights, together with corresponding oxygen uptake and heart rate. With increasing treadmill speed, peak acceleration at the ankle is found always to exceed that at the back and forehead, and acceleration profiles with higher frequency components than those observed during jumping are observed. Acceleration levels are found to be more uniformly distributed with increasing height in jumping, although comparable oxygen uptake and heat rates are obtained. Results indicate that the magnitude of the biomechanical stimuli is greater in trampoline jumping than in running, which finding could be of use in the design of procedures to avert deconditioning in persons exposed to weightlessness.

  16. Effect of artificial accelerated aging on the optical properties and monomeric conversion of composites used after expiration date.

    PubMed

    Garcia, Lucas da Fonseca Roberti; Mundim, Fabricio Mariano; Pires-de-Souza, Fernanda de Carvalho Panzeri; Puppin Rontani, Regina Maria; Consani, Simonides

    2013-01-01

    This study sought to evaluate how artificial accelerated aging (AAA) affected color stability (ΔE), opacity (ΔOP), and degree of conversion (DOC) for 3 composite materials (Tetric Ceram, Tetric Ceram HB, and Tetric Flow) used both 180 days before and 180 days after their expiration dates. To evaluate the materials' optical properties, 10 specimens of each composite-5 prior to expiration and 5 after the materials' expiration date-were made in a teflon matrix. After polishing, the specimens were submitted to initial color and opacity readings and submitted to AAA for 384 hours; at that point, new readings were taken to determine ΔE and ΔOP. To evaluate monomeric conversion evaluation, 6 specimens from each composite and expiration date-3 prior to AAA and 3 after-were submitted to DOC analysis. Results of the 2-way ANOVA and Bonferroni's tests (P < 0.05) demonstrated that all composites had ΔE values above the clinically acceptable level (ΔE ≥ 3.3). When expiration dates were compared, only Tetric Flow showed a statistically significant difference (P < 0.05). Regardless of the expiration date, ΔOP values for all composites increased after AAA, but not significantly (P > 0.05). The expired Tetric Flow had the highest DOC values (71.42% ± 4.21) before AAA, significantly different than that of the other composites (P > 0.05). It was concluded that both expiration date and AAA affected the properties of the composites tested.

  17. Effect of artificial accelerated aging on the optical properties and monomeric conversion of composites used after expiration date.

    PubMed

    Garcia, Lucas da Fonseca Roberti; Mundim, Fabricio Mariano; Pires-de-Souza, Fernanda de Carvalho Panzeri; Puppin Rontani, Regina Maria; Consani, Simonides

    2013-01-01

    This study sought to evaluate how artificial accelerated aging (AAA) affected color stability (ΔE), opacity (ΔOP), and degree of conversion (DOC) for 3 composite materials (Tetric Ceram, Tetric Ceram HB, and Tetric Flow) used both 180 days before and 180 days after their expiration dates. To evaluate the materials' optical properties, 10 specimens of each composite-5 prior to expiration and 5 after the materials' expiration date-were made in a teflon matrix. After polishing, the specimens were submitted to initial color and opacity readings and submitted to AAA for 384 hours; at that point, new readings were taken to determine ΔE and ΔOP. To evaluate monomeric conversion evaluation, 6 specimens from each composite and expiration date-3 prior to AAA and 3 after-were submitted to DOC analysis. Results of the 2-way ANOVA and Bonferroni's tests (P < 0.05) demonstrated that all composites had ΔE values above the clinically acceptable level (ΔE ≥ 3.3). When expiration dates were compared, only Tetric Flow showed a statistically significant difference (P < 0.05). Regardless of the expiration date, ΔOP values for all composites increased after AAA, but not significantly (P > 0.05). The expired Tetric Flow had the highest DOC values (71.42% ± 4.21) before AAA, significantly different than that of the other composites (P > 0.05). It was concluded that both expiration date and AAA affected the properties of the composites tested. PMID:24192739

  18. Monitoring of pigmented and wooden surfaces in accelerated ageing processes by FT-Raman spectroscopy and multivariate control charts.

    PubMed

    Marengo, Emilio; Robotti, Elisa; Liparota, Maria Cristina; Gennaro, Maria Carla

    2004-07-01

    Two of the most suitable analytical techniques used in the field of cultural heritage are NIR (near-infrared) and Raman spectroscopy. FT-Raman spectroscopy coupled to multivariate control charts is applied here for the development of a new method for monitoring the conservation state of pigmented and wooden surfaces. These materials were exposed to different accelerated ageing processes in order to evaluate the effect of the applied treatments on the goods surfaces. In this work, a new approach based on the principles of statistical process control (SPC) to the monitoring of cultural heritage, has been developed: the conservation state of samples simulating works-of-art has been treated like an industrial process, monitored with multivariate control charts, owing to the complexity of the spectroscopic data collected. The Raman spectra were analysed by principal component analysis (PCA) and the relevant principal components (PCs) were used for constructing multivariate Shewhart and cumulative sum (CUSUM) control charts. These tools were successfully applied for the identification of the presence of relevant modifications occurring on the surfaces. CUSUM charts however proved to be more effective in the identification of the exact beginning of the applied treatment. In the case of wooden boards, where a sufficient number of PCs were available, simultaneous scores monitoring and residuals tracking (SMART) charts were also investigated. The exposure to a basic attack and to high temperatures produced deep changes on the wooden samples, clearly identified by the multivariate Shewhart, CUSUM and SMART charts. A change on the pigment surface was detected after exposure to an acidic solution and to the UV light, while no effect was identified on the painted surface after the exposure to natural atmospheric events. PMID:18969526