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Sample records for accelerated cell aging

  1. Accelerated aging of GaAs concentrator solar cells

    SciTech Connect

    Gregory, P.E.

    1982-04-01

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

  2. Neurodegeneration in accelerated aging.

    PubMed

    Scheibye-Knudsen, Moren

    2016-11-01

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

  3. Accelerated aging and discharge of lithium/thionyl-chloride D cells

    NASA Astrophysics Data System (ADS)

    Cieslak, W. R.

    Lithium/Thionyl-Chloride spiral wound 'D' cells from a variety of suppliers have been evaluated. Abuse testing has been used to verify safety of the cells, and accelerated aging has been used to estimate their performance for long life projects.

  4. 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.

  5. Hypercholesterolemia Induces Oxidant Stress That Accelerates the Ageing of Hematopoietic Stem Cells

    PubMed Central

    Tie, Guodong; Messina, Katharine E.; Yan, Jinglian; Messina, Julia A.; Messina, Louis M.

    2014-01-01

    Background Clinical studies suggest that hypercholesterolemia may cause ageing in hematopoietic stem cells (HSCs) because ageing‐associated alterations were found in peripheral blood cells and their bone marrow residing precursors in patients with advanced atherosclerosis. We hypothesized that hypercholesterolemia induces oxidant stress in hematopoietic stems cells that accelerates their ageing. Methods and Results Here we show that HSCs from ApoE−/− mice, as well as HSCs from C57Bl/6 mice fed a high cholesterol diet (HCD) accumulated oxLDL and had greater ROS levels. In accordance, the expression pattern of the genes involved in ROS metabolism changed significantly in HSCs from ApoE−/− mice. Hypercholesterolemia caused a significant reduction in phenotypically defined long‐term HSC compartment, telomere length, and repopulation capacity of KTLS cells, indicating accelerated ageing in these cells. Gene array analysis suggested abnormal cell cycle status, and the key cell cycle regulators including p19ARF, p27Kip1 and p21Waf1 were upregulated in KTLS cells from hypercholesterolemic mice. These effects were p38‐dependent and reversed in vivo by treatment of hypercholesterolemic mice with antioxidant N‐acetylcysteine. The oxidant stress also caused aberrant expression of Notch1 that caused loss of quiescence and proliferation leading to the expansion of KTLS compartment in hypercholesterolemic mice. Conclusion Taken together, we provide evidence that hypercholesterolemia can cause oxidant stress that accelerates the ageing and impairs the reconstitution capacity of HSCs. PMID:24470519

  6. Menopause accelerates biological aging

    PubMed Central

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

    2016-01-01

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

  7. 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.

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

    DTIC Science & Technology

    2014-07-01

    Induced Pluripotent Stem Cell Lines from Patients with Parkinson’s Disease PRINCIPAL INVESTIGATOR: Dr. Birgitt Schuele CONTRACTING...contained in this report are those of the author( s ) and should not be construed as an official Department of the Army position, policy or decision...Aging in Induced Pluripotent Stem Cell Lines from Patients with Parkinson’s Disease 5b. GRANT NUMBER W81XWH-12-1-0003 5c. PROGRAM ELEMENT NUMBER

  9. Accelerated delimitation of the infarct zone by capillary-derived nestin-positive cells in aged rats.

    PubMed

    Popa-Wagner, Aurel; Dinca, Ivona; Yalikun, Suofu; Walker, Lary; Kroemer, Heyo; Kessler, Christof

    2006-02-01

    brain has the capability to mount a cytoproliferative response to injury, but the timing of the cellular and genetic reaction to cerebral insult is accelerated in aged animals; (ii) the proliferating cells contribute to the formation of the glial scar, but few of the cells appear to become neurons; and (iii) the vasculature plays a hitherto unrecognized role as a source of proliferating cells after stroke. Because capillary-derived cells help to form the glial scar, elucidating the molecular basis of this phenomenon and its acceleration in the aging brain could yield novel approaches to enhancing neurorestoration in the elderly.

  10. 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

  11. Accelerated aging in the tumor microenvironment

    PubMed Central

    Martinez-Outschoorn, Ubaldo E; Pavlides, Stephanos; Whitaker-Menezes, Diana; Pestell, Richard G; Howell, Anthony

    2011-01-01

    Cancer is thought to be a disease associated with aging. Interestingly, normal aging is driven by the production of ROS and mitochondrial oxidative stress, resulting in the cumulative accumulation of DNA damage. Here, we discuss how ROS signaling, NFκB- and HIF1-activation in the tumor micro-environment induces a form of “accelerated aging,” which leads to stromal inflammation and changes in cancer cell metabolism. Thus, we present a unified model where aging (ROS), inflammation (NFκB) and cancer metabolism (HIF1), act as co-conspirators to drive autophagy (“self-eating”) in the tumor stroma. Then, autophagy in the tumor stroma provides high-energy “fuel” and the necessary chemical building blocks, for accelerated tumor growth and metastasis. Stromal ROS production acts as a “mutagenic motor” and allows cancer cells to buffer—at a distance—exactly how much of a mutagenic stimulus they receive, further driving tumor cell selection and evolution. Surviving cancer cells would be selected for the ability to induce ROS more effectively in stromal fibroblasts, so they could extract more nutrients from the stroma via autophagy. If lethal cancer is a disease of “accelerated host aging” in the tumor stroma, then cancer patients may benefit from therapy with powerful antioxidants. Antioxidant therapy should block the resulting DNA damage, and halt autophagy in the tumor stroma, effectively “cutting off the fuel supply” for cancer cells. These findings have important new implications for personalized cancer medicine, as they link aging, inflammation and cancer metabolism with novel strategies for more effective cancer diagnostics and therapeutics. PMID:21654190

  12. Infant's DNA Methylation Age at Birth and Epigenetic Aging Accelerators

    PubMed Central

    Chen, Weidan; Lin, Fangqin

    2016-01-01

    Knowing the biological age of the neonates enables us to evaluate and better understand the health and maturity comprehensively. However, because of dearth of biomarkers, it is difficult to quantify the neonatal biological age. Here we sought to quantify and assess the variability in biological age at birth and to better understand how the aging rates before birth are influenced by exposure in intrauterine period by employing a novel epigenetic biomarker of aging (epigenetic clock). We observed that the methylation age at birth was independent of the infant's sex but was significantly influenced by race. Partial correlation analysis showed a significant negative relationship between maternal socioeconomic status and infants' methylation age (rs = −0.48, Ps = 0.005). A significant association with the risk of fast aging was observed for prenatal exposure to tobacco smoke with OR (95% CI) of 3.17 (1.05–9.56). Both estimated cell abundance measures and lymphocyte subpopulations in cord blood showed that tobacco exposed group exhibit an altered T cell compartment, specifically substantial loss of naive T cells. Present study provides the first evidence that common perinatal exposure (such as maternal smoking and lower socioeconomic status) may be important aging accelerators and substantial loss of naive T cells may play a role in the smoking-related fast aging phenomenon. PMID:28058257

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

    DTIC Science & Technology

    2012-11-01

    differentiation We had established a neuronal differentiation protocol using embryoid body differentiation to obtain neural progenitor cells (NPC) (Mak...derive NPCs. We are now in the process to establish a new protocol without embryoid body differentiation to derive NPCs within 10-14 days (Figure 2

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

    DTIC Science & Technology

    2013-11-01

    centrifugation in a tabletop microcentrifuge. Soluble protein concentrations were measured by a standard Bradford assay . KCl stimulated samples were thawed...y-H2AX, and 53BP1, We will also use a senescent cell staining kit (Sigman Aldrich) to stain from SA-b-galactose. The gene array assay will be...collected and dopamine assayed by HPLC with electrochemical detection (Coularray detector, ESA, Chelmsford, MA) using a reverse phase C18 column (Perkin

  15. Age-related alterations in the expression of glial cell line-derived neurotrophic factor in the senescence-accelerated mouse brain.

    PubMed

    Miyazaki, Hiroyuki; Okuma, Yasunobu; Nomura, Jun; Nagashima, Kazuo; Nomura, Yasuyuki

    2003-05-01

    Senescence-accelerated mouse prone 8 (SAMP8) and prone 10 (SAMP10) are useful murine model of accelerated aging. SAMP8 shows marked impairment of learning and memory, whereas SAMP10 shows brain atrophy and aging-associated depressive behavior. This study examined the expression of glial cell line-derived neurotrophic factor (GDNF) in SAMP8 and SAMP10 brains, relative to that in SAM resistant 1 (SAMR1) controls, which age normally. Hippocampal GDNF mRNA expression decreased in an age-dependent manner (10- vs 2-month-old animals) in the SAMR1, but not in the SAMP8 or SAMP10 strains. Furthermore, GDNF mRNA expression in 2-month-old SAMP8 and SAMP10 strains was less than in SAMR1 specimens of the same age. The number of surviving neurons in the CA1 region decreased with age in SAMP8 and SAMP10, and also decreased relative to the number of neurons in 10-month-old SAMR1 controls. Immunohistochemistry revealed that cells that were positive for GDNF-like activity in 10-month-old SAMP8 and SAMP10 were diffusely distributed, in part, around the pyramidal cell layer in the hippocampus. These findings suggest that low GDNF expression in young SAMP8 and SAMP10 may be involved in hippocampal dysfunctions, such as age-related learning impairment and neuronal death.

  16. 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.

  17. 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

  18. 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.

  19. Microwave-assisted synthesis of N-pyrazole ureas and the p38alpha inhibitor BIRB 796 for study into accelerated cell ageing.

    PubMed

    Bagley, Mark C; Davis, Terence; Dix, Matthew C; Widdowson, Caroline S; Kipling, David

    2006-11-21

    Microwave irradiation of substituted hydrazines and beta-ketoesters gives 5-aminopyrazoles in excellent yield, which can be transformed to the corresponding N-carbonyl derivatives by treatment with an isocyanate or chloroformate. Derivatization of 4-nitronaphth-1-ol using predominantly microwave heating methods and reaction with an N-pyrazole carbamate provides a rapid route to the N-pyrazole urea BIRB 796 in high purity, as a potent and selective inhibitor of p38alpha mitogen-activated protein kinase for the study of accelerated ageing in Werner syndrome cells.

  20. Is biological aging accelerated in drug addiction?

    PubMed

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

    2017-02-01

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

  1. Accelerate Genomic Aging in Congenital Neutropenia

    DTIC Science & Technology

    2015-08-01

    myeloid leukemia (AML) is perhaps the major clinical concern in patients with severe congenital neutropenia (SCN) and Shwachman- Diamond syndrome (SDS... Diamond syndrome (SDS), cyclic neutropenia, or age-matched healthy controls. Aim 2. To determine whether increased G-CSF signaling accelerates the...agents, such as radiation. 2. KEYWORDS Congenital neutropenia Severe congenital neutropenia Shwachman Diamond syndrome Cyclic neutropenia

  2. Compromised cellular responses to DNA damage accelerate chronological aging by incurring cell wall fragility in Saccharomyces cerevisiae.

    PubMed

    Yu, Shanshan; Zhang, Xian-En; Chen, Guanjun; Liu, Weifeng

    2012-04-01

    Elevated levels of reactive oxygen species (ROS) can attack almost all cell components including genomic DNA to induce many types of DNA damage. In this study, we used Saccharomyces cerevisiae with various mutations in a biological network supposed to prevent deleterious effects of endogenous ROS to test the effect of such a network on yeast chronological aging. Our results showed that cells with defects in cellular antioxidation, DNA repair and DNA damage checkpoints displayed a mutation rate higher than that of wild-type strain. Moreover, the chronological life span of most mutants as determined by colony formation was found to be shorter than that of wild-type cells, especially for the mutants defective in DNA replication and DNA damage checkpoints, although the observed cell number was almost the same for wild-type and mutant strains. The mutants were finally found to be more sensitive to SDS and lysing enzyme treatment, and that the degree of sensitivity was correlated with their chronological life span.

  3. Is schizophrenia a syndrome of accelerated aging?

    PubMed

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

    2008-11-01

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

  4. Of sound mind and body: depression, disease, and accelerated aging

    PubMed Central

    M. Wolkowitz, Owen; I. Reus, Victor; H. Mellon, Synthia

    2011-01-01

    Major depressive disorder (MDD) is associated with a high rate of developing serious medical comorbidities such as cardiovascular disease, stroke, dementia, osteoporosis, diabetes, and the metabolic syndrome. These are conditions that typically occur late in life, and it has been suggested that MDD may be associated with “accelerated aging.” We review several moderators and mediators that may accompany MDD and that may give rise to these comorbid medical conditions. We first review the moderating effects of psychological styles of coping, genetic predisposition, and epigenetic modifications (eg, secondary to childhood adversity). We then focus on several interlinked mediators occurring in MDD (or at least in subtypes of MDD) that may contribute to the medical comorbidity burden and to accelerated aging: limbic-hypothalamic-pituitary-adrenal axis alterations, diminution in glucocorticoid receptor function, altered glucose tolerance and insulin sensitivity, excitotoxicity, increases in intracellular calcium, oxidative stress, a proinflammatory milieu, lowered levels of “counter-regulatory” neurosteroids (such as allopregnanolone and dehydroepiandrosterone), diminished neurotrophic activity, and accelerated cell aging, manifest as alterations in telomerase activity and as shortening of telomeres, which can lead to apoptosis and cell death. In this model, MDD is characterized by a surfeit of potentially destructive mediators and an insufficiency of protective or restorative ones. These factors interact in increasing the likelihood of physical disease and of accelerated aging at the cellular level. We conclude with suggestions for novel mechanism-based therapeutics based on these mediators. PMID:21485744

  5. 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.

  6. Insights into accelerated aging of SSL luminaires

    DOE PAGES

    Davis, J. Lynn; Lamvik, Michael; Bittle, James; ...

    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

  7. 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.

  8. 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.

  9. 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.

  10. 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)

  11. Premature and accelerated aging: HIV or HAART?

    PubMed Central

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

    2013-01-01

    Highly active antiretroviral therapy (HAART) has significantly increased life expectancy of the human immunodeficiency virus (HIV)-positive population. Nevertheless, the average lifespan of HIV-patients remains shorter compared to uninfected individuals. Immunosenescence, a current explanation for this difference invokes heavily on viral stimulus despite HAART efficiency in viral suppression. We propose here that the premature and accelerated aging of HIV-patients can also be caused by adverse effects of antiretroviral drugs, specifically those that affect the mitochondria. The nucleoside reverse transcriptase inhibitor (NRTI) antiretroviral drug class for instance, is known to cause depletion of mitochondrial DNA via inhibition of the mitochondrial specific DNA polymerase-γ. Besides NRTIs, other antiretroviral drug classes such as protease inhibitors also cause severe mitochondrial damage by increasing oxidative stress and diminishing mitochondrial function. We also discuss important areas for future research and argue in favor of the use of Caenorhabditis elegans as a novel model system for studying these effects. PMID:23372574

  12. 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.

  13. 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.

  14. Accelerated aging in the tumor microenvironment: connecting aging, inflammation and cancer metabolism with personalized medicine.

    PubMed

    Lisanti, Michael P; Martinez-Outschoorn, Ubaldo E; Pavlides, Stephanos; Whitaker-Menezes, Diana; Pestell, Richard G; Howell, Anthony; Sotgia, Federica

    2011-07-01

    Cancer is thought to be a disease associated with aging. Interestingly, normal aging is driven by the production of ROS and mitochondrial oxidative stress, resulting in the cumulative accumulation of DNA damage. Here, we discuss how ROS signaling, NFκB- and HIF1-activation in the tumor microenvironment induces a form of "accelerated aging," which leads to stromal inflammation and changes in cancer cell metabolism. Thus, we present a unified model where aging (ROS), inflammation (NFκB) and cancer metabolism (HIF1), act as co-conspirators to drive autophagy ("self-eating") in the tumor stroma. Then, autophagy in the tumor stroma provides high-energy "fuel" and the necessary chemical building blocks, for accelerated tumor growth and metastasis. Stromal ROS production acts as a "mutagenic motor" and allows cancer cells to buffer-at a distance-exactly how much of a mutagenic stimulus they receive, further driving tumor cell selection and evolution. Surviving cancer cells would be selected for the ability to induce ROS more effectively in stromal fibroblasts, so they could extract more nutrients from the stroma via autophagy. If lethal cancer is a disease of "accelerated host aging" in the tumor stroma, then cancer patients may benefit from therapy with powerful antioxidants. Antioxidant therapy should block the resulting DNA damage, and halt autophagy in the tumor stroma, effectively "cutting off the fuel supply" for cancer cells. These findings have important new implications for personalized cancer medicine, as they link aging, inflammation and cancer metabolism with novel strategies for more effective cancer diagnostics and therapeutics.

  15. 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.

  16. 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.

  17. Epigenetic Age Acceleration Assessed With Human White-Matter Images.

    PubMed

    Hodgson, Karen; Carless, Melanie A; Kulkarni, Hemant; Curran, Joanne E; Sprooten, Emma; Knowles, Emma E; Mathias, Samuel; Göring, Harald Hh; Yao, Nailin; Olvera, Rene L; Fox, Peter T; Almasy, Laura; Duggirala, Ravi; Blangero, John; Glahn, David C

    2017-04-06

    The accurate estimation of age using methylation data has proved a useful and heritable biomarker, with acceleration in epigenetic age predicting a number of age-related phenotypes. Measures of white matter integrity in the brain are also heritable and highly sensitive to both normal and pathological aging processes across adulthood. We consider the phenotypic and genetic interrelationships between epigenetic age acceleration and white matter integrity in humans. Our goal was to investigate processes that underlie inter-individual variability in age-related changes in the brain. Using blood taken from a Mexican-American extended pedigree sample (n=628; age=23.28-93.11 years), epigenetic age was estimated using the method developed by S. Horvath (2013). For n=376 individuals, DTI scans were also available. The interrelationship between epigenetic age acceleration and global white matter integrity were investigated with variance decomposition methods. To test for neuroanatomical specificity, 16 specific tracts were additionally considered. We observed negative phenotypic correlations between epigenetic age acceleration and global white matter tract integrity (ρpheno=-0.119, p=0.028), with evidence of shared genetic (ρgene=-0.463, p=0.013) but not environmental influences. Negative phenotypic and genetic correlations with age acceleration were also seen for a number of specific white matter tracts, along with additional negative phenotypic correlations between granulocyte abundance and white matter integrity. These findings that increased acceleration in epigenetic age in peripheral blood correlates with reduced white matter integrity in the brain, and shares common genetic influences. provide a window into the neurobiology of aging processes within the brain and a potential biomarker of normal and pathological brain aging.SIGNIFICANCE STATEMENTEpigenetic measures can be used to predict age with a high degree of accuracy and so capture acceleration in biological age

  18. The coming acceleration of global population ageing.

    PubMed

    Lutz, Wolfgang; Sanderson, Warren; Scherbov, Sergei

    2008-02-07

    The future paths of population ageing result from specific combinations of declining fertility and increasing life expectancies in different parts of the world. Here we measure the speed of population ageing by using conventional measures and new ones that take changes in longevity into account for the world as a whole and for 13 major regions. We report on future levels of indicators of ageing and the speed at which they change. We show how these depend on whether changes in life expectancy are taken into account. We also show that the speed of ageing is likely to increase over the coming decades and to decelerate in most regions by mid-century. All our measures indicate a continuous ageing of the world's population throughout the century. The median age of the world's population increases from 26.6 years in 2000 to 37.3 years in 2050 and then to 45.6 years in 2100, when it is not adjusted for longevity increase. When increases in life expectancy are taken into account, the adjusted median age rises from 26.6 in 2000 to 31.1 in 2050 and only to 32.9 in 2100, slightly less than what it was in the China region in 2005. There are large differences in the regional patterns of ageing. In North America, the median age adjusted for life expectancy change falls throughout almost the entire century, whereas the conventional median age increases significantly. Our assessment of trends in ageing is based on new probabilistic population forecasts. The probability that growth in the world's population will end during this century is 88%, somewhat higher than previously assessed. After mid-century, lower rates of population growth are likely to coincide with slower rates of ageing.

  19. Telomere Recombination Accelerates Cellular Aging in Saccharomyces cerevisiae

    PubMed Central

    Chen, Xiao-Fen; Meng, Fei-Long; Zhou, Jin-Qiu

    2009-01-01

    Telomeres are nucleoprotein structures located at the linear ends of eukaryotic chromosomes. Telomere integrity is required for cell proliferation and survival. Although the vast majority of eukaryotic species use telomerase as a primary means for telomere maintenance, a few species can use recombination or retrotransposon-mediated maintenance pathways. Since Saccharomyces cerevisiae can use both telomerase and recombination to replicate telomeres, budding yeast provides a useful system with which to examine the evolutionary advantages of telomerase and recombination in preserving an organism or cell under natural selection. In this study, we examined the life span in telomerase-null, post-senescent type II survivors that have employed homologous recombination to replicate their telomeres. Type II recombination survivors stably maintained chromosomal integrity but exhibited a significantly reduced replicative life span. Normal patterns of cell morphology at the end of a replicative life span and aging-dependent sterility were observed in telomerase-null type II survivors, suggesting the type II survivors aged prematurely in a manner that is phenotypically consistent with that of wild-type senescent cells. The shortened life span of type II survivors was extended by calorie restriction or TOR1 deletion, but not by Fob1p inactivation or Sir2p over-expression. Intriguingly, rDNA recombination was decreased in type II survivors, indicating that the premature aging of type II survivors was not caused by an increase in extra-chromosomal rDNA circle accumulation. Reintroduction of telomerase activity immediately restored the replicative life span of type II survivors despite their heterogeneous telomeres. These results suggest that telomere recombination accelerates cellular aging in telomerase-null type II survivors and that telomerase is likely a superior telomere maintenance pathway in sustaining yeast replicative life span. PMID:19557187

  20. Tissue-specific accelerated aging in nucleotide excision repair deficiency

    PubMed Central

    Niedernhofer, Laura J.

    2008-01-01

    Nucleotide excision repair (NER) is a multi-step DNA repair mechanism that removes helix-distorting modified nucleotides from the genome. NER is divided into two subpathways depending on the location of DNA damage in the genome and how it is first detected. Global genome NER identifies and repairs DNA lesions throughout the genome. This subpathway of NER primarily protects against the accumulation of mutations in the genome. Transcription-coupled (TC) NER rapidly repairs lesions in the transcribed strand of DNA that block transcription by RNA polymerase II. TC-NER prevents cell death in response to stalled transcription. Defects in NER cause three distinct human diseases: xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. Each of these syndromes is characterized by premature onset of pathologies that overlap with those associated with old age in humans. This reveals the contribution of DNA damage to multiple age-related diseases. Tissues affected include the skin, eye, bone marrow, nervous system and endocrine axis. This review emphasizes accelerated aging associated with xeroderma pigmentosum and discusses the cause of these pathologies, either mutation accumulation or cell death as a consequence of failure to repair DNA damage. PMID:18538374

  1. Accelerated food source location in aging Drosophila.

    PubMed

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

    2015-10-01

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

  2. 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

  3. Accelerated stress testing of terrestrial solar cells

    NASA Technical Reports Server (NTRS)

    Lathrop, J. W.; Hawkins, D. C.; Prince, J. L.; Walker, H. A.

    1982-01-01

    The development of an accelerated test schedule for terrestrial solar cells is described. This schedule, based on anticipated failure modes deduced from a consideration of IC failure mechanisms, involves bias-temperature testing, humidity testing (including both 85-85 and pressure cooker stress), and thermal-cycle thermal-shock testing. Results are described for 12 different unencapsulated cell types. Both gradual electrical degradation and sudden catastrophic mechanical change were observed. These effects can be used to discriminate between cell types and technologies relative to their reliability attributes. Consideration is given to identifying laboratory failure modes which might lead to severe degradation in the field through second quadrant operation. Test results indicate that the ability of most cell types to withstand accelerated stress testing depends more on the manufacturer's design, processing, and worksmanship than on the particular metallization system. Preliminary tests comparing accelerated test results on encapsulated and unencapsulated cells are described.

  4. [The accelerated aging of the population in Brazil].

    PubMed

    Cassab, Amanda Kampa

    2013-01-01

    Formerly a young country, Brazil is now undergoing a period of acceleration in the ageing of its population. The Brazilian geriatric heathcare sector must prepare itself to advocate and optimise the care of elderly patients. The training of professionals in gerontology must be a priority and public policies need to evolve.

  5. Bacterial cells enhance laser driven ion acceleration

    PubMed Central

    Dalui, Malay; Kundu, M.; Trivikram, T. Madhu; Rajeev, R.; Ray, Krishanu; Krishnamurthy, M.

    2014-01-01

    Intense laser produced plasmas generate hot electrons which in turn leads to ion acceleration. Ability to generate faster ions or hotter electrons using the same laser parameters is one of the main outstanding paradigms in the intense laser-plasma physics. Here, we present a simple, albeit, unconventional target that succeeds in generating 700 keV carbon ions where conventional targets for the same laser parameters generate at most 40 keV. A few layers of micron sized bacteria coating on a polished surface increases the laser energy coupling and generates a hotter plasma which is more effective for the ion acceleration compared to the conventional polished targets. Particle-in-cell simulations show that micro-particle coated target are much more effective in ion acceleration as seen in the experiment. We envisage that the accelerated, high-energy carbon ions can be used as a source for multiple applications. PMID:25102948

  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.

  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. Progranulin Knockout Accelerates Intervertebral Disc Degeneration in Aging Mice

    PubMed Central

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

    2015-01-01

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

  9. Mechanisms of aging in senescence-accelerated mice

    PubMed Central

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

    2005-01-01

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

  10. 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.

  11. Shelf life determination of an epoxy resin by accelerated aging

    SciTech Connect

    Smith, H.M.

    1983-11-01

    The objectives of the study reported were to first define the rate and mode of degradation of an epoxy resin at two storage conditions, 4.4/sup 0/C and 25/sup 0/C, by means of a thermally accelerated aging experiment. Then, samples which had been aged the equivalent of at least 10 years at each storage condition would be tested for conformance to the material specifications. The study's results demonstrate that the commercial resin could be acquired and stored for the required 10 to 11 years without concern over degradation. The expected changes at the two storage temperatures have been defined. Aged resin samples are shown to yield an acceptable product. Sufficient data exist to predict the changes in viscosity and epoxide equivalent of the resin at any other storage temperature of interest. (LEW)

  12. Accelerated retinal aging in PACAP knock-out mice.

    PubMed

    Kovács-Valasek, Andrea; Szabadfi, Krisztina; Dénes, Viktória; Szalontai, Bálint; Tamás, Andrea; Kiss, Péter; Szabó, Aliz; Setalo, Gyorgy; Reglődi, Dóra; Gábriel, Robert

    2017-02-13

    Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurotrophic and neuroprotective peptide. PACAP and its receptors are widely distributed in the retina. A number of reports provided evidence that PACAP is neuroprotective in retinal degenerations. The current study compared retina cell type-specific differences in young (3-4months) and aged adults (14-16months), of wild-type (WT) mice and knock-out (KO) mice lacking endogenous PACAP production during the course of aging. Histological, immunocytochemical and Western blot examinations were performed. The staining for standard neurochemical markers (tyrosine hydroxylase for dopaminergic cells, calbindin 28 kDa for horizontal cells, protein kinase Cα for rod bipolar cells) of young adult PACAP KO retinas showed no substantial alterations compared to young adult WT retinas, except for the specific PACAP receptor (PAC1-R) staining. We could not detect PAC1-R immunoreactivity in bipolar and horizontal cells in young adult PACAP KO animals. Some other age-related changes were observed only in the PACAP KO mice only. These alterations included horizontal and rod bipolar cell dendritic sprouting into the photoreceptor layer and decreased ganglion cell number. Also, Müller glial cells showed elevated GFAP expression compared to the aging WT retinas. Furthermore, Western blot analyses revealed significant differences between the phosphorylation state of ERK1/2 and JNK in KO mice, indicating alterations in the MAPK signaling pathway. These results support the conclusion that endogenous PACAP contributes to protection against aging of the nervous system.

  13. 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

  14. Accelerated Aging Experiments for Capacitor Health Monitoring and Prognostics

    NASA Technical Reports Server (NTRS)

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

    2012-01-01

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

  15. Accelerated Aging Influences Cardiovascular Disease Risk in Rheumatoid Arthritis

    PubMed Central

    Crowson, Cynthia S.; Therneau, Terry M.; Davis, John M.; Roger, Véronique L.; Matteson, Eric L.; Gabriel, Sherine E.

    2014-01-01

    OBJECTIVE To determine whether the impact of aging on cardiovascular disease (CVD) risk in the general population (as estimated by the Framingham risk score [FRS]) differs in patients with rheumatoid arthritis (RA). METHODS A population-based inception cohort of Olmsted County, Minnesota residents aged ≥30 years who fulfilled 1987 ACR criteria for RA in 1988–2008 was assembled and followed until death, migration, or 7-1-2012. Data on CVD events were collected by medical record review. The 10-year FRS for CVD was calculated. Cox models adjusted for FRS were used to examine the influence of age on CVD risk. RESULTS The study included 563 patients with RA without prior CVD (mean age: 55 years, 72% women; 69% seropositive [i.e., rheumatoid factor and/or anti-citrullinated protein antibody positive]). During a mean follow-up of 8.2 years, 98 patients developed CVD (74 seropositive and 24 seronegative), but FRS predicted only 59.7 events (35.4 seropositive and 24.3 seronegative). The gap between observed and predicted CVD risk increased exponentially across age, and the age effect on CVD risk in seropositive RA was nearly double its effect in the general population with additional log(age) coefficients of 2.91 for women (p=0.002) and 2.06 for men (p=0.027). CONCLUSION Age exerts an exponentially increasing effect on CVD risk in seropositive RA, but no increased effect among seronegative patients. The causes of accelerated aging in patients with seropositive RA deserve further investigation. PMID:23818136

  16. 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.

  17. 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

  18. Cardiorespiratory Fitness and Accelerated Cognitive Decline With Aging

    PubMed Central

    2014-01-01

    Background. Growing evidence suggests that self-reported physical activity accounts for variability in cognitive function among older adults, and aerobic intervention may improve cognitive function in this population. However, much less is known about the longitudinal association between direct measures of cardiorespiratory fitness and cognitive function across the life span. The present study examined the prospective association between symptom-limited maximal oxygen consumption (VO2max) and longitudinal performance on a comprehensive neuropsychological battery. Methods. Up to 1,400 participants aged 19–94 years underwent initial VO2max assessment and completed subsequent tests of memory, attention, perceptuomotor speed, language, and executive function, in addition to cognitive screening measures, on up to six occasions (mean, M = 2; standard deviation, SD = 1) for up to 18 years (M = 7, SD = 3). Mixed-effects regression models were adjusted for demographic, biomedical, and behavioral confounders. Results. Analyses revealed significant longitudinal associations between baseline VO2max and trajectory of performance on multiple measures of verbal and visual memory, as well as on a cognitive screening test (all ps < .05). Individuals with lower VO2max demonstrated accelerated trajectories of cognitive decline over time. Conclusions. Baseline cardiorespiratory fitness is related to longitudinal neuropsychological performance, and memory appears to be a particularly vulnerable domain. Evidence that aerobic fitness is associated with accelerated cognitive decline emphasizes the possible importance of behavioral interventions to optimize cognitive aging over time. PMID:24192540

  19. Instrumentation for accelerated life tests of concentrator solar cells.

    PubMed

    Núñez, N; Vázquez, M; González, J R; Jiménez, F J; Bautista, J

    2011-02-01

    Concentrator photovoltaic is an emergent technology that may be a good economical and efficient alternative for the generation of electricity at a competitive cost. However, the reliability of these new solar cells and systems is still an open issue due to the high-irradiation level they are subjected to as well as the electrical and thermal stresses that they are expected to endure. To evaluate the reliability in a short period of time, accelerated aging tests are essential. Thermal aging tests for concentrator photovoltaic solar cells and systems under illumination are not available because no technical solution to the problem of reaching the working concentration inside a climatic chamber has been available. This work presents an automatic instrumentation system that overcomes the aforementioned limitation. Working conditions have been simulated by forward biasing the solar cells to the current they would handle at the working concentration (in this case, 700 and 1050 times the irradiance at one standard sun). The instrumentation system has been deployed for more than 10 000 h in a thermal aging test for III-V concentrator solar cells, in which the generated power evolution at different temperatures has been monitored. As a result of this test, the acceleration factor has been calculated, thus allowing for the degradation evolution at any temperature in addition to normal working conditions to be obtained.

  20. Instrumentation for accelerated life tests of concentrator solar cells

    NASA Astrophysics Data System (ADS)

    Núñez, N.; Vázquez, M.; González, J. R.; Jiménez, F. J.; Bautista, J.

    2011-02-01

    Concentrator photovoltaic is an emergent technology that may be a good economical and efficient alternative for the generation of electricity at a competitive cost. However, the reliability of these new solar cells and systems is still an open issue due to the high-irradiation level they are subjected to as well as the electrical and thermal stresses that they are expected to endure. To evaluate the reliability in a short period of time, accelerated aging tests are essential. Thermal aging tests for concentrator photovoltaic solar cells and systems under illumination are not available because no technical solution to the problem of reaching the working concentration inside a climatic chamber has been available. This work presents an automatic instrumentation system that overcomes the aforementioned limitation. Working conditions have been simulated by forward biasing the solar cells to the current they would handle at the working concentration (in this case, 700 and 1050 times the irradiance at one standard sun). The instrumentation system has been deployed for more than 10 000 h in a thermal aging test for III-V concentrator solar cells, in which the generated power evolution at different temperatures has been monitored. As a result of this test, the acceleration factor has been calculated, thus allowing for the degradation evolution at any temperature in addition to normal working conditions to be obtained.

  1. 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.

  2. 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.

  3. Stem cells and healthy aging.

    PubMed

    Goodell, Margaret A; Rando, Thomas A

    2015-12-04

    Research into stem cells and aging aims to understand how stem cells maintain tissue health, what mechanisms ultimately lead to decline in stem cell function with age, and how the regenerative capacity of somatic stem cells can be enhanced to promote healthy aging. Here, we explore the effects of aging on stem cells in different tissues. Recent research has focused on the ways that genetic mutations, epigenetic changes, and the extrinsic environmental milieu influence stem cell functionality over time. We describe each of these three factors, the ways in which they interact, and how these interactions decrease stem cell health over time. We are optimistic that a better understanding of these changes will uncover potential strategies to enhance stem cell function and increase tissue resiliency into old age.

  4. 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.

  5. Senescence-accelerated Mice (SAMs) as a Model for Brain Aging and Immunosenescence

    PubMed Central

    Shimada, Atsuyoshi; Hasegawa-Ishii, Sanae

    2011-01-01

    The Senescence-Accelerated Mouse (SAM) represents a group of inbred mouse strains developed as a model for the study of human aging and age-related diseases. Senescence-prone (SAMP) strains exhibit an early onset of age-related decline in the peripheral immunity such as thymic involution, loss of CD4+ T cells, impaired helper T cell function, decreased antibody-forming capacity, dysfunction of antigen-presenting cells, decreased natural killer activity, increased auto-antibodies, and susceptibility to virus infection. Senescence-prone SAMP10 mice undergo age-related changes in the brain such as brain atrophy, shrinkage and loss of cortical neurons, retraction of cortical neuronal dendrites, loss of dendritic spines, loss of synapses, impaired learning and memory, depressive behavior, accumulation of neuronal DNA damage, neuronal ubiquitinated inclusions, reduced hippocampal cholinergic receptors, decreased neurotrophic factors, decreased hippocampal zinc and zinc transporters, increased sphyngomyelinase, and elevated oxidative-nitrative stress. Recent data indicating increased pro-inflammatory cytokines in the brain of SAMP10 mice are directing investigators toward an integration of immune and neural abnormalities to enhance understanding of the principles of brain aging. We highlight how mouse brain cells adopt cytokine-mediated responses and how SAMP10 mice are defective in these responses. SAMP10 model would be useful to study how age-related disturbances in peripheral immunity have an impact on dysregulation of brain tissue homeostasis, resulting in age-related neurodegeneration. PMID:22396891

  6. Accelerated aging in schizophrenia patients: the potential role of oxidative stress.

    PubMed

    Okusaga, Olaoluwa O

    2014-08-01

    Several lines of evidence suggest that schizophrenia, a severe mental illness characterized by delusions, hallucinations and thought disorder is associated with accelerated aging. The free radical (oxidative stress) theory of aging assumes that aging occurs as a result of damage to cell constituents and connective tissues by free radicals arising from oxygen-associated reactions. Schizophrenia has been associated with oxidative stress and chronic inflammation, both of which also appear to reciprocally induce each other in a positive feedback manner. The buildup of damaged macromolecules due to increased oxidative stress and failure of protein repair and maintenance systems is an indicator of aging both at the cellular and organismal level. When compared with age-matched healthy controls, schizophrenia patients have higher levels of markers of oxidative cellular damage such as protein carbonyls, products of lipid peroxidation and DNA hydroxylation. Potential confounders such as antipsychotic medication, smoking, socio-economic status and unhealthy lifestyle make it impossible to solely attribute the earlier onset of aging-related changes or oxidative stress to having a diagnosis of schizophrenia. Regardless of whether oxidative stress can be attributed solely to a diagnosis of schizophrenia or whether it is due to other factors associated with schizophrenia, the available evidence is in support of increased oxidative stress-induced cellular damage of macromolecules which may play a role in the phenomenon of accelerated aging presumed to be associated with schizophrenia.

  7. Accelerated Aging in Schizophrenia Patients: The Potential Role of Oxidative Stress

    PubMed Central

    Okusaga, Olaoluwa O

    2014-01-01

    Several lines of evidence suggest that schizophrenia, a severe mental illness characterized by delusions, hallucinations and thought disorder is associated with accelerated aging. The free radical (oxidative stress) theory of aging assumes that aging occurs as a result of damage to cell constituents and connective tissues by free radicals arising from oxygen-associated reactions. Schizophrenia has been associated with oxidative stress and chronic inflammation, both of which also appear to reciprocally induce each other in a positive feedback manner. The buildup of damaged macromolecules due to increased oxidative stress and failure of protein repair and maintenance systems is an indicator of aging both at the cellular and organismal level. When compared with age-matched healthy controls, schizophrenia patients have higher levels of markers of oxidative cellular damage such as protein carbonyls, products of lipid peroxidation and DNA hydroxylation. Potential confounders such as antipsychotic medication, smoking, socio-economic status and unhealthy lifestyle make it impossible to solely attribute the earlier onset of aging-related changes or oxidative stress to having a diagnosis of schizophrenia. Regardless of whether oxidative stress can be attributed solely to a diagnosis of schizophrenia or whether it is due to other factors associated with schizophrenia, the available evidence is in support of increased oxidative stress-induced cellular damage of macromolecules which may play a role in the phenomenon of accelerated aging presumed to be associated with schizophrenia. PMID:25110609

  8. Cycle life estimation of lithium secondary battery by extrapolation method and accelerated aging test

    NASA Astrophysics Data System (ADS)

    Takei, K.; Kumai, K.; Kobayashi, Y.; Miyashiro, H.; Terada, N.; Iwahori, T.; Tanaka, T.

    The testing methods to estimate the life cycles of lithium ion batteries for a short period, have been developed using a commercialized cell with LiCoO 2/hard carbon cell system. The degradation reactions with increasing cycles were suggested to occur predominantly above 4 V from the results of operating voltage range divided tests. In the case of the extrapolation method using limited cycle data, the straight line approximation was useful as the cycle performance has the linearity, but the error is at most 40% in using the initial short cycle data. In the case of the accelerated aging tests using the following stress factors, the charge and/or discharge rate, large accelerated coefficients were obtained in the high charge rate and the high temperature thermal stress.

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

    PubMed

    Bashkireva, A S

    2012-01-01

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

  10. Programmed cell death in aging.

    PubMed

    Tower, John

    2015-09-01

    Programmed cell death (PCD) pathways, including apoptosis and regulated necrosis, are required for normal cell turnover and tissue homeostasis. Mis-regulation of PCD is increasingly implicated in aging and aging-related disease. During aging the cell turnover rate declines for several highly-mitotic tissues. Aging-associated disruptions in systemic and inter-cell signaling combined with cell-autonomous damage and mitochondrial malfunction result in increased PCD in some cell types, and decreased PCD in other cell types. Increased PCD during aging is implicated in immune system decline, skeletal muscle wasting (sarcopenia), loss of cells in the heart, and neurodegenerative disease. In contrast, cancer cells and senescent cells are resistant to PCD, enabling them to increase in abundance during aging. PCD pathways limit life span in fungi, but whether PCD pathways normally limit adult metazoan life span is not yet clear. PCD is regulated by a balance of negative and positive factors, including the mitochondria, which are particularly subject to aging-associated malfunction.

  11. 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

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

    PubMed

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

    2010-10-01

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

  13. Ageing induced vascular smooth muscle cell senescence in atherosclerosis.

    PubMed

    Uryga, Anna K; Bennett, Martin R

    2016-04-15

    Atherosclerosis is a disease of ageing in that its incidence and prevalence increase with age. However, atherosclerosis is also associated with biological ageing, manifest by a number of typical hallmarks of ageing in the atherosclerotic plaque. Thus, accelerated biological ageing may be superimposed on the effects of chronological ageing in atherosclerosis. Tissue ageing is seen in all cells that comprise the plaque, but particularly in vascular smooth muscle cells (VSMCs). Hallmarks of ageing include evidence of cell senescence, DNA damage (including telomere attrition), mitochondrial dysfunction, a pro-inflammatory secretory phenotype, defects in proteostasis, epigenetic changes, deregulated nutrient sensing, and exhaustion of progenitor cells. In this model, initial damage to DNA (genomic, telomeric, mitochondrial and epigenetic changes) results in a number of cellular responses (cellular senescence, deregulated nutrient sensing and defects in proteostasis). Ultimately, ongoing damage and attempts at repair by continued proliferation overwhelm reparative capacity, causing loss of specialised cell functions, cell death and inflammation. This review summarises the evidence for accelerated biological ageing in atherosclerosis, the functional consequences of cell ageing on cells comprising the plaque, and the causal role that VSMC senescence plays in atherogenesis.

  14. The cell biology of aging

    PubMed Central

    DiLoreto, Race; Murphy, Coleen T.

    2015-01-01

    One of the original hypotheses of organismal longevity posits that aging is the natural result of entropy on the cells, tissues, and organs of the animal—a slow, inexorable slide into nonfunctionality caused by stochastic degradation of its parts. We now have evidence that aging is instead at least in part genetically regulated. Many mutations have been discovered to extend lifespan in organisms of all complexities, from yeast to mammals. The study of metazoan model organisms, such as Caenorhabditis elegans, has been instrumental in understanding the role of genetics in the cell biology of aging. Longevity mutants across the spectrum of model organisms demonstrate that rates of aging are regulated through genetic control of cellular processes. The regulation and subsequent breakdown of cellular processes represent a programmatic decision by the cell to either continue or abandon maintenance procedures with age. Our understanding of cell biological processes involved in regulating aging have been particularly informed by longevity mutants and treatments, such as reduced insulin/IGF-1 signaling and dietary restriction, which are critical in determining the distinction between causes of and responses to aging and have revealed a set of downstream targets that participate in a range of cell biological activities. Here we briefly review some of these important cellular processes. PMID:26668170

  15. Stem cell mitochondria during aging.

    PubMed

    Min-Wen, Jason Chua; Jun-Hao, Elwin Tan; Shyh-Chang, Ng

    2016-04-01

    Mitochondria are the central hubs of cellular metabolism, equipped with their own mitochondrial DNA (mtDNA) blueprints to direct part of the programming of mitochondrial oxidative metabolism and thus reactive oxygen species (ROS) levels. In stem cells, many stem cell factors governing the intricate balance between self-renewal and differentiation have been found to directly regulate mitochondrial processes to control stem cell behaviors during tissue regeneration and aging. Moreover, numerous nutrient-sensitive signaling pathways controlling organismal longevity in an evolutionarily conserved fashion also influence stem cell-mediated tissue homeostasis during aging via regulation of stem cell mitochondria. At the genomic level, it has been demonstrated that heritable mtDNA mutations and variants affect mammalian stem cell homeostasis and influence the risk for human degenerative diseases during aging. Because such a multitude of stem cell factors and signaling pathways ultimately converge on the mitochondria as the primary mechanism to modulate cellular and organismal longevity, it would be most efficacious to develop technologies to therapeutically target and direct mitochondrial repair in stem cells, as a unified strategy to combat aging-related degenerative diseases in the future.

  16. Stem cells, mitochondria and aging.

    PubMed

    Ahlqvist, Kati J; Suomalainen, Anu; Hämäläinen, Riikka H

    2015-11-01

    Decline in metabolism and regenerative potential of tissues are common characteristics of aging. Regeneration is maintained by somatic stem cells (SSCs), which require tightly controlled energy metabolism and genomic integrity for their homeostasis. Recent data indicate that mitochondrial dysfunction may compromise this homeostasis, and thereby contribute to tissue degeneration and aging. Progeroid Mutator mouse, accumulating random mtDNA point mutations in their SSCs, showed disturbed SSC homeostasis, emphasizing the importance of mtDNA integrity for stem cells. The mechanism involved changes in cellular redox-environment, including subtle increase in reactive oxygen species (H₂O₂and superoxide anion), which did not cause oxidative damage, but disrupted SSC function. Mitochondrial metabolism appears therefore to be an important regulator of SSC fate determination, and defects in it in SSCs may underlie premature aging. Here we review the current knowledge of mitochondrial contribution to SSC dysfunction and aging. This article is part of a Special Issue entitled: Mitochondrial Dysfunction in Aging.

  17. BBU design of linear induction accelerator cells for radiography application

    SciTech Connect

    Shang, C.C.; Chen, Y.J.; Gaporaso, G.J.; Houck, T.L.; Molau, N.E.; Focklen, J.; Gregory, S.

    1997-05-06

    There is an ongoing effort to develop accelerating modules for high-current electron accelerators for advanced radiography application. Accelerating modules with low beam-cavity coupling impedances along with gap designs with acceptable field stresses comprise a set of fundamental design criteria. We examine improved cell designs which have been developed for accelerator application in several radiographic operating regimes. We evaluate interaction impedances, analyze the effects of beam structure coupling on beam dynamics (beam break-up instability and corkscrew motion). We also provide estimates of coupling through interesting new high-gradient insulators and evaluate their potential future application in induction cells.

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

    PubMed

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

    2016-02-01

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

  19. Mitochondrial role in cell aging

    NASA Technical Reports Server (NTRS)

    Miquel, J.; Fleming, J.; Economos, A. C.; Johnson, J. E., Jr.

    1980-01-01

    The experimental studies on the mitochondria of insect and mammalian cells are examined with a view to an analysis of intrinsic mitochondrial senescence, and its relation to the age-related changes in other cell organelles. The fine structural and biochemical data support the concept that the mitochondria of fixed postmitotic cells may be the site of intrinsic aging because of the attack by free radicals and lipid peroxides originating in the organelles as a by-product of oxygen reduction during respiration. Although the cells have numerous mechanisms for counteracting lipid peroxidation injury, there is a slippage in the antioxidant protection. Intrinsic mitochondrial aging could thus be considered as a specific manifestation of oxygen toxicity. It is proposed that free radical injury renders an increasing number of the mitochondria unable to divide, probably because of damage to the lipids of the inner membrane and to mitochondrial DNA.

  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

    2010-06-10

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

    PubMed

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

    2014-09-01

    Aging is associated with reduced function, degenerative changes, and increased neuroinflammation of the central nervous system (CNS). Increasing evidence suggests that changes in microglia cells contribute to the age-related deterioration of the CNS. The most prominent age-related change of microglia is enhanced sensitivity to inflammatory stimuli, referred to as priming. It is unclear if priming is due to intrinsic microglia ageing or induced by the ageing neural environment. We have studied this in Ercc1 mutant mice, a DNA repair-deficient mouse model that displays features of accelerated aging in multiple tissues including the CNS. In Ercc1 mutant mice, microglia showed hallmark features of priming such as an exaggerated response to peripheral lipopolysaccharide exposure in terms of cytokine expression and phagocytosis. Specific targeting of the Ercc1 deletion to forebrain neurons resulted in a progressive priming response in microglia exemplified by phenotypic alterations. Summarizing, these data show that neuronal genotoxic stress is sufficient to switch microglia from a resting to a primed state.

  2. Acceleration of Age-Associated Methylation Patterns in HIV-1-Infected Adults

    PubMed Central

    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 x10-200 and 0.47, p<1x10-200. 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=1.27x 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 similar to

  3. Klotho, stem cells, and aging

    PubMed Central

    Bian, Ao; Neyra, Javier A; Zhan, Ming; Hu, Ming Chang

    2015-01-01

    Aging is an inevitable and progressive biological process involving dysfunction and eventually destruction of every tissue and organ. This process is driven by a tightly regulated and complex interplay between genetic and acquired factors. Klotho is an antiaging gene encoding a single-pass transmembrane protein, klotho, which serves as an aging suppressor through a wide variety of mechanisms, such as antioxidation, antisenescence, antiautophagy, and modulation of many signaling pathways, including insulin-like growth factor and Wnt. Klotho deficiency activates Wnt expression and activity contributing to senescence and depletion of stem cells, which consequently triggers tissue atrophy and fibrosis. In contrast, the klotho protein was shown to suppress Wnt-signaling transduction, and inhibit cell senescence and preserve stem cells. A better understanding of the potential effects of klotho on stem cells could offer novel insights into the cellular and molecular mechanisms of klotho deficiency-related aging and disease. The klotho protein may be a promising therapeutic agent for aging and aging-related disorders. PMID:26346243

  4. Klotho, stem cells, and aging.

    PubMed

    Bian, Ao; Neyra, Javier A; Zhan, Ming; Hu, Ming Chang

    2015-01-01

    Aging is an inevitable and progressive biological process involving dysfunction and eventually destruction of every tissue and organ. This process is driven by a tightly regulated and complex interplay between genetic and acquired factors. Klotho is an antiaging gene encoding a single-pass transmembrane protein, klotho, which serves as an aging suppressor through a wide variety of mechanisms, such as antioxidation, antisenescence, antiautophagy, and modulation of many signaling pathways, including insulin-like growth factor and Wnt. Klotho deficiency activates Wnt expression and activity contributing to senescence and depletion of stem cells, which consequently triggers tissue atrophy and fibrosis. In contrast, the klotho protein was shown to suppress Wnt-signaling transduction, and inhibit cell senescence and preserve stem cells. A better understanding of the potential effects of klotho on stem cells could offer novel insights into the cellular and molecular mechanisms of klotho deficiency-related aging and disease. The klotho protein may be a promising therapeutic agent for aging and aging-related disorders.

  5. Aging of solidified/stabilized electrolytic manganese solid waste with accelerated carbonation and aging inhibition.

    PubMed

    Du, Bing; Zhou, Changbo; Dan, Zhigang; Zhao, Zhiyuan; Peng, Xianjia; Liu, Jianguo; Duan, Ning

    2016-12-01

    High concentrations of soluble Mn in electrolytic manganese solid waste (EMSW) in soil cause the severe contamination in China. Calcium oxide and magnesium oxide-dominated stabilizers are suitable for the solidification/stabilization (s/s) of EMSW. However, the long-term performance of s/s using those two types of stabilizer is problematic. The aim of this study was to develop an accelerated aging method to simulate the long-term natural carbonation of solidified/stabilized EMSW. The joint use of accelerated carbonation, leaching test, mineralogical analysis, and microstructural observation was applied to assess the long-term performance of the s/s EMSW system. On an accelerated carbonation test for solidified/stabilized EMSW, an increase in Mn leaching from 13.6 to 408 mg/kg and a 1.5-2.3 decrease in pH was achieved by using CaO-dominated stabilizers, while an increase in manganese (Mn) from 30 to 266 mg/kg and a decrease in pH of 0.17-0.68 was seen using MgO-dominated stabilizers. CaO+Na3PO4 and CaO+CaCO3 were exceptions in that the leaching value of soluble Mn was lower after carbonation. Mineralogical analysis showed that rhodochrosite in the carbonated s/s system was generated not only from the reduction of hausmannite but also from the reversible reaction between Mn(OH)2 and MnCO3. Carbonation destroyed the tight particle structure resulting in a porous and loose structure. As for s/s EMSW treated by MgO-dominated stabilizers, carbonation affected the agglomerating structure and mineralogical composition by increasing magnesium (Mg) migration, thereby forming hydromagnesite that had weak binding ability and a nested porous shape. Therefore, carbonation by itself does not cause deterioration to s/s products of the soluble Mn but does have significant effects on the microstructure and mineralogical composition. It is recommended to add Na3PO4 or CaCO3 into a single CaO stabilized EMSW system to prevent aging of the system, allow formation of Mn phosphate

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

    PubMed Central

    Gurkar, Aditi U.; Niedernhofer, Laura J.

    2015-01-01

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

  7. GPU-Accelerated Molecular Modeling Coming Of Age

    PubMed Central

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

    2010-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

  9. Leydig cell aging and hypogonadism.

    PubMed

    Beattie, M C; Adekola, L; Papadopoulos, V; Chen, H; Zirkin, B R

    2015-08-01

    Leydig cell testosterone (T) production is reduced with age, resulting in reduced serum T levels (hypogonadism). A number of cellular changes have been identified in the steroidogenic pathway of aged Leydig cells that are associated with reduced T formation, including reductions in luteinizing hormone (LH)-stimulated cAMP production, the cholesterol transport proteins steroidogenic acute regulatory (STAR) protein and translocator protein (TSPO), and downstream steroidogenic enzymes of the mitochondria and smooth endoplasmic reticulum. Many of the changes in steroid formation that characterize aged Leydig cells can be elicited by the experimental alteration of the redox environment of young cells, suggesting that changes in the intracellular redox balance may cause reduced T production. Hypogonadism is estimated to affect about 5 million American men, including both aged and young. This condition has been linked to mood changes, worsening cognition, fatigue, depression, decreased lean body mass, reduced bone mineral density, increased visceral fat, metabolic syndrome, decreased libido, and sexual dysfunction. Exogenous T administration is now used widely to elevate serum T levels in hypogonadal men and thus to treat symptoms of hypogonadism. However, recent evidence suggests that men who take exogenous T may face increased risk of stroke, heart attack, and prostate tumorigenesis. Moreover, it is well established that administered T can have suppressive effects on LH, resulting in lower Leydig cell T production, reduced intratesticular T concentration, and reduced spermatogenesis. This makes exogenous T administration inappropriate for men who wish to father children. There are promising new approaches to increase serum T by directly stimulating Leydig cell T production rather than by exogenous T therapy, thus potentially avoiding some of its negative consequences.

  10. Neuroligin-2 accelerates GABAergic synapse maturation in cerebellar granule cells

    PubMed Central

    Fu, Zhanyan; Vicini, Stefano

    2009-01-01

    Neuroligins (NLGs) are postsynaptic cell adhesion molecules that are thought to function in synaptogenesis. To investigate the role of NLGs on synaptic transmission once the synapse is formed, we transfected neuroligin-2(NLG2) in cultured mouse cerebellar granule cells (CGCs), and recorded GABAA (γ-aminobutyric acid) receptor mediated miniature postsynaptic currents (mISPCs). NLG2 transfected cells had mIPSCs with faster decay than matching GFP expressing controls at young culture ages (days in vitro, DIV 7-8). Down-regulation of NLG2 by the isoform specific shRNA-NLG2 resulted in an opposite effect. We and others have shown that the switch of α subunits of GABAA Rs from α2/3 to α1 underlies developmental speeding of the IPSC decay in various CNS regions, including the cerebellum. To assess whether the reduced decay time of mIPSCs by NLG2 is due to the recruitment of more α1 containing GABAARs at the synapses, we examined the prolongation of current decay by the zolpidem, which has been shown to preferentially enhance the activity of α1 subunit containing GABA channel. The application of zolpidem resulted in a significantly greater prolongation kinetics of synaptic currents in NLG2 over-expressing cells than control cells, suggesting that NLG2 over-expression accelerates synapse maturation by promoting incorporation of the α1 subunit-containing GABAARs at postsynaptic sites in immature cells. In addition, the effect of NLG2 on the speeding of decay time course of synaptic currents was abolished when we used CGC cultures from α1-/- mice. Lastly, to exclude the possibility that the fast decay of mIPSCs induced by NLG2 could be also due to the impacts of NLG2 on the GABA transient in synaptic cleft, we measured the sensitivity of mIPSCs to the fast-off competitive antagonists TPMPA. We found that TPMPA similarly inhibits mIPSCs in control and NLG2 over-expressing CGCs both at young age (DIV8) and old age (DIV14) of cultures. However, we confirm our previous

  11. 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

  12. Accelerated Aging in Glaucoma: Immunohistochemical Assessment of Advanced Glycation End Products in the Human Retina and Optic Nerve Head

    PubMed Central

    Tezel, Gülgün; Luo, Cheng; Yang, Xiangjun

    2008-01-01

    PURPOSE This study aimed to determine the association between advanced glycation end products (AGEs) and glaucoma based on the known synergism between oxidative stress with AGEs and the evidence of oxidative stress during glaucomatous neurodegeneration. METHODS The extent and cellular localization of immunolabeling for AGEs and their receptor, RAGE, were determined in histologic sections of the retina and optic nerve head obtained from 38 donor eyes with glaucoma and 30 eyes from age-matched donors without glaucoma. RESULTS The extent of AGE and RAGE immunolabeling was greater in older than in younger donor eyes. However, compared with age-matched controls, an enhanced accumulation of AGEs and an up-regulation of RAGE were detectable in the glaucomatous retina and optic nerve head. Although some retinal ganglion cells (RGCs) and glia exhibited intracellular immunolabeling for AGEs, increased AGE immunolabeling in glaucomatous eyes was predominantly extracellular and included laminar cribriform plates in the optic nerve head. Some RAGE immunolabeling was detectable on RGCs; however, increased RAGE immunolabeling in glaucomatous eyes was predominant on glial cells, primarily Müller cells. CONCLUSIONS Given that the generation of AGEs is an age-dependent event, increased AGE accumulation in glaucomatous tissues supports that an accelerated aging process accompanies neurodegeneration in glaucomatous eyes. One of the potential consequences of AGE accumulation in glaucomatous eyes appears to be its contribution to increased rigidity of the lamina cribrosa. The presence of RAGE on RGCs and glia also makes them susceptible to AGE-mediated events through receptor-mediated signaling, which may promote cell death or dysfunction during glaucomatous neurodegeneration. PMID:17325164

  13. 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

  14. 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.

  15. 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.

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

    NASA Astrophysics Data System (ADS)

    Pavlendová, Gabriela; Podoba, Rudolf; Baník, Ivan

    2014-11-01

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

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

    PubMed Central

    Miller, Mark W.; Sadeh, Naomi

    2014-01-01

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

  18. Accelerating forward genetics for cell wall deconstruction

    PubMed Central

    Vidaurre, Danielle; Bonetta, Dario

    2012-01-01

    The elucidation of the genes involved in cell wall synthesis and assembly remains one of the biggest challenges of cell wall biology. Although traditional genetic approaches, using simple yet elegant screens, have identified components of the cell wall, many unknowns remain. Exhausting the genetic toolbox by performing sensitized screens, adopting chemical genetics or combining these with improved cell wall imaging, hold the promise of new gene discovery and function. With the recent introduction of next-generation sequencing technologies, it is now possible to quickly and efficiently map and clone genes of interest in record time. The combination of a classical genetics approach and cutting edge technology will propel cell wall biology in plants forward into the future. PMID:22685448

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

    PubMed

    Mahomed, Aziza; Pormehr, Negin Bagheri

    2016-11-25

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

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

    PubMed Central

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

    2016-01-01

    Anxiety disorders (AnxDs) are highly prevalent throughout the lifespan, with detrimental effects on daily-life functioning, somatic health, and quality of life. An emerging perspective suggested that AnxDs may be associated with accelerated aging. In this paper, we explored the association between AnxDs and hallmarks of accelerated aging, with a specific focus on neuroprogression. We reviewed animal and human findings that suggest an overlap between processes of impaired neurogenesis, neurodegeneration, structural, functional, molecular, and cellular modifications in AnxDs, and aging. Although this research is at an early stage, our review suggests a link between anxiety and accelerated aging across multiple processes involved in neuroprogression. Brain structural and functional changes that accompany normal aging were more pronounced in subjects with AnxDs than in coevals without AnxDs, including reduced grey matter density, white matter alterations, impaired functional connectivity of large-scale brain networks, and poorer cognitive performance. Similarly, molecular correlates of brain aging, including telomere shortening, Aβ accumulation, and immune-inflammatory and oxidative/nitrosative stress, were overrepresented in anxious subjects. No conclusions about causality or directionality between anxiety and accelerated aging can be drawn. Potential mechanisms of this association, limitations of the current research, and implications for treatments and future studies are discussed. PMID:26881136

  1. Hollow fiber culture accelerates differentiation of Caco-2 cells.

    PubMed

    Deng, Xudong; Zhang, Guoliang; Shen, Chong; Yin, Jian; Meng, Qin

    2013-08-01

    Caco-2 cells usually require 21 days of culture for developing sufficient differentiation in traditional two-dimensional Transwell culture, deviating far away from the quick differentiation of enterocytes in vivo. The recently proposed three-dimensional cultures of Caco-2 cells, though imitating the villi/crypt-like microstructure of intestinal epithelium, showed no effect on accelerating the differentiation of Caco-2 cells. In this study, a novel culture of Caco-2 cells on hollow fiber bioreactor was applied to morphologically mimic the human small intestine lumen for accelerating the expression of intestine functions. The porous hollow fibers of polyethersulfone (PES), a suitable membrane material for Caco-2 cell culture, successfully promoted cells to form confluent monolayer on the inner surface. The differentiated functions of Caco-2 cells, represented by alkaline phosphatase, γ-glutamyltransferase, and P-glycoprotein activity, were greatly higher in a 10-day hollow fiber culture than in a 21-day Transwell culture. Moreover, the Caco-2 cells on PES hollow fibers expressed higher F-actin and zonula occludens-1 protein than those on Transwell culture, indicative of an increased mechanical stress in Caco-2 cells on PES hollow fibers. The accelerated differentiation of Caco-2 cells on PES hollow fibers was unassociated with membrane chemical composition and surface roughness, but could be stimulated by hollow fiber configuration, since PES flat membranes with either rough or smooth surface failed to enhance the differentiation of Caco-2. Therefore, the accelerated expression of Caco-2 cell function on hollow fiber culture might show great values in simulation of the tissue microenvironment in vivo and guide the construction of intestinal tissue engineering apparatus.

  2. 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.

  3. Accelerated Tumor Cell Death by Angiogenic Modifiers

    DTIC Science & Technology

    2004-08-01

    neuroendocrine factors. They can guide cancer cell perineural invasion and dissemination through the release of soluble and solid matrix factors (see review (32...Ooshima, A. Targeted disruption of TGF-betal/Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral

  4. TESTING METGLAS FOR USE IN DARHT ACCELERATOR CELLS

    SciTech Connect

    E.A. ROSE; D.A. DALMAS; J.N. DOWNING; R.D. TEMPLE

    2001-06-01

    The Dual Axis Radiographic Hydrotest Facility [DARHT] at Los Alamos will use two induction linacs to produce high-energy electron beams. The electron beams will be used to generate x-rays from bremsstrahlung targets. The x-rays will be used to produce radiographs. The first accelerator is operational now, producing a 60-nanosecond electron beam. The second accelerator is under construction. It will produce a 2-microsecond electron beam. The 78 induction cells of the second axis accelerator require a total Metglas capacity of approximately 40 volt seconds of flux. Four Metglas cores are used in each of the 5-foot diameter accelerator cells. Each Metglas core weighs approximately 3000 pounds. This paper presents the measurement techniques and results of the Metglas tests. Routine automated analysis and archival of the pulse data provided hysteresis curves, energy loss curves and total flux swing in the operating regime. Results of the tests were used to help the manufacturer improve quality control and increase the average flux swing of the cores. Results of the tests were used to match Metglas cores and to assemble accelerator cells with equal volt-second ratings.

  5. Mechanisms of accelerated degradation in the front cells of PEMFC stacks and some mitigation strategies

    NASA Astrophysics Data System (ADS)

    Li, Pengcheng; Pei, Pucheng; He, Yongling; Yuan, Xing; Chao, Pengxiang; Wang, Xizhong

    2013-11-01

    The accelerated degradation in the front cells of a polymer electrolyte membrane fuel cell(PEMFC) stack seriously reduces the reliability and durability of the whole stack. Most researches only focus on the size and configuration of the gas intake manifold, which may lead to the maldistribution of flow and pressure. In order to find out the mechanisms of the accelerated degradation in the front cells, an extensive program of experimental and simulation work is initiated and the results are reported. It is found that after long-term lifetime tests the accelerated degradation in the front cells occurs in all three fuel cell stacks with different flow-fields under the U-type feed configuration. Compared with the rear cells of the stack, the voltage of the front cells is much lower at the same current densities and the membrane electrode assembly(MEA) has smaller active area, more catalyst particle agglomeration and higher ohmic impedance. For further investigation, a series of three dimensional isothermal numerical models are built to investigate the degradation mechanisms based on the experimental data. The simulation results reveal that the dry working condition of the membrane and the effect of high-speed gas scouring the MEA are the main causes of the accelerated degradation in the front cells of a PEM fuel cell stack under the U-type feed configuration. Several mitigation strategies that would mitigate these phenomena are presented: removing cells that have failed and replacing them with those of the same aging condition as the average of the stack; choosing a Z-type feed pattern instead of a U-type one; putting several air flow-field plates without MEA in the front of the stack; or exchanging the gas inlet and outlet alternately at a certain interval. This paper specifies the causes of the accelerated degradation in the front cells and provides the mitigation strategies.

  6. Mesenchymal stem cells, aging and regenerative medicine

    PubMed Central

    Raggi, Chiara; Berardi, Anna C.

    2012-01-01

    Summary Tissue maintenance and regeneration is dependent on stem cells and increasing evidence has shown to decline with age. Stem cell based-aging is thought to influence therapeutic efficacy. Mesenchymal stromal cells (MSCs) are involved in tissue regeneration. Here, we discuss the effects of age-related changes on MSC properties considering their possible use in research or regenerative medicine. PMID:23738303

  7. Accelerated Tumor Cell Death by Angiogenic Modifiers

    DTIC Science & Technology

    2003-08-01

    form an active autocrine loop. fibrosis . Luminal epithelial cells of PIA lesions have elev- A recent study indicated the increase of both IL-6 and...its receptor dothelin-3 (ET-3), and endothelin-4 (ET-4) (Cun- ( CXCR4 ), may play a role as prostate cancer bone meta- ningham et al., 1997). All...members of the endothelin stasis homing signals. The level of CXCR4 increased family contain two essential disulfide bridges and six with the malignancy of

  8. 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

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

    PubMed

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

    2013-01-01

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

  10. 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

    2016-06-01

    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.

  11. Astrocytes show reduced support of motor neurons with aging that is accelerated in a rodent model of ALS.

    PubMed

    Das, Melanie M; Svendsen, Clive N

    2015-02-01

    Astrocytes play a crucial role in supporting motor neurons in health and disease. However, there have been few attempts to understand how aging may influence this effect. Here, we report that rat astrocytes show an age-dependent senescence phenotype and a significant reduction in their ability to support motor neurons. In a rodent model of familial amyotrophic lateral sclerosis (ALS) overexpressing mutant superoxide dismutase 1 (SOD1), the rate of astrocytes acquiring a senescent phenotype is accelerated and they subsequently provide less support to motor neurons. This can be partially reversed by glial cell line-derived neurotrophic factor (GDNF). Replacing aging astrocytes with young ones producing GDNF may therefore have a significant survival promoting affect on aging motor neurons and those lost through diseases such as ALS.

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

    PubMed

    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.

  14. 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.

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

    DTIC Science & Technology

    2010-10-01

    Annual Conference of the Prognostics and Health Management Society, 2010 Towards Prognostics of Power MOSFETs : Accelerated Aging and Precursors of...research results dealing with power MOSFETs (metal oxide semiconductor field effect tran- sistor) within the prognostics and health management of...electronics. Gate controlled power transistors like power MOSFETs (metal oxide semiconductor field effect tran- sistor) are power semiconductor

  16. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  18. Effect of aging on stem cells

    PubMed Central

    Ahmed, Abu Shufian Ishtiaq; Sheng, Matilda HC; Wasnik, Samiksha; Baylink, David J; Lau, Kin-Hing William

    2017-01-01

    Pluripotent stem cells have the remarkable self-renewal ability and are capable of differentiating into multiple diverse cells. There is increasing evidence that the aging process can have adverse effects on stem cells. As stem cells age, their renewal ability deteriorates and their ability to differentiate into the various cell types is altered. Accordingly, it is suggested aging-induced deterioration of stem cell functions may play a key role in the pathophysiology of the various aging-associated disorders. Understanding the role of the aging process in deterioration of stem cell function is crucial, not only in understanding the pathophysiology of aging-associated disorders, but also in future development of novel effective stem cell-based therapies to treat aging-associated diseases. This review article first focuses on the basis of the various aging disease-related stem cell dysfunction. It then addresses the several concepts on the potential mechanism that causes aging-related stem cell dysfunction. It also briefly discusses the current potential therapies under development for aging-associated stem cell defects. PMID:28261550

  19. Rationale for practical medical device accelerated aging programs in AAMI TIR 17

    NASA Astrophysics Data System (ADS)

    Lambert, Byron J.; Tang, Fuh-Wei

    2000-03-01

    A Technical Information Report, TIR 17, entitled, "Radiation Sterilization Material Qualification" has been published by the Association for the Advancement of Medical Instrumentation (AAMI) to provide guidance in order to increase the quality and reduce the cost and amount of time required for performing medical device material qualifications. It contains four sections that cover the fundamentals of material selection, processing, testing and accelerated aging programs. The last of these sections, entitled "Accelerating Aging Programs," provides step-by-step guidance for simple, empirical accelerated programs of use to the medical device industry. The methods are based on van't Hoff's observation that the rate of chemical reactions increases by a factor of two for every 10°C increase in temperature, the Q10=2 rule. With critical patient safety concerns in the medical device industry, it is appropriate for both device manufacturers and regulators to ask if simple, empirical methods such as those outlined in TIR 17 are reasonable and responsible. One reason for confidence in the methods is their success when used in aging environments that are much more severe than those commonly used in the medical device industry. Another reason for confidence in the methods is found from the observation that the working equations of the method can be derived from theory. This paper provides an overview of the thermal accelerated aging theory that forms the basis for the working equations of the accelerated aging programs of TIR 17. Assumptions used are examined and found reasonable; the theoretical foundation is established. While this foundation provides added confidence for the application of the methods of TIR 17 to the medical device industry, it is emphasized that application of the methods within appropriate boundaries is critical. Theoretical boundaries are explained and demonstrated by means of Arrhenius plots, and practical boundaries discussed.

  20. Polysulfide promotes neuroblastoma cell differentiation by accelerating calcium influx.

    PubMed

    Koike, Shin; Shibuya, Norihiro; Kimura, Hideo; Ishii, Kazuyuki; Ogasawara, Yuki

    2015-04-10

    Polysulfides are a typical type of bound sulfur, which is physiologically stable form of sulfur species, derived from the hydrogen sulfide (H2S) that is generated endogenously in cells. We previously reported that bound sulfur protects neuronal cells from oxidative injury. In the present study, we demonstrated that polysulfides inhibited cell growth and promoted neurite outgrowth in mouse neuroblastoma Neuro2A (N2A) cells. However, Na2S showed no effect on neurite outgrowth in N2A cells. Furthermore, 2-APB and SKF96365, which are typical transient receptor potential (TRP) channel inhibitors, suppressed the neurite outgrowth induced by Na2S4. These new findings suggest that bound sulfur could induce neurite outgrowth and cell differentiation of N2A cells by accelerating calcium influx.

  1. Possible acceleration of aging by adjuvant chemotherapy: a cause of early onset frailty?

    PubMed

    Maccormick, Ronald Eric

    2006-01-01

    Cancer chemotherapy has three main applications. It is curative for a small number of malignancies including childhood leukemia, Hodgkin's and non-Hodgkin's lymphoma, and germ cell malignancies. It has a palliative role for most metastatic epithelial malignancies. Finally, it has an adjuvant role in several types of resected epithelial malignancies particularly breast cancer. First successfully employed in the mid 1970s, adjuvant chemotherapy is associated with up to a 30% relative improvement in long-term overall survival in high risk breast cancer but demonstrates significantly less absolute improvement. Now that adjuvant chemotherapy is being used in lower risk disease, both the relative and absolute improvement in overall survival is even less impressive. With a growing number of long-term survivors, we are only now able to define the delayed implications of adjuvant chemotherapy. These long-term side effects include acceleration of neurocognitive decline, musculoskeletal complications such as early onset osteoporosis, premature skin and ocular changes and the most common long-term complaint; mild to profound fatigue. This complex of problems is suggestive of early onset frailty. This paper explores various potential mechanisms of aging including accumulation of free-radical damage, accumulation of DNA damage, telomere shortening with accompanying decline in telomerase activity and finally a decline in neuroendocrine/immune function. The impact of chemotherapy, particularly those agents used in the adjuvant setting, in relationship to these aging mechanisms is explored. There is good evidence that chemotherapy can effect all these aging mechanisms leading to early onset frailty. The implications of this hypothesis are quite profound. Whereas short-term toxicity of chemotherapy can usually be considered acceptable even for a small improvement in survival, long-term toxicity such as early onset frailty can have an impact on quality of life that could last for

  2. Manganese-mediated acceleration of age-related hearing loss in mice

    PubMed Central

    Ohgami, Nobutaka; Yajima, Ichiro; Iida, Machiko; Li, Xiang; Oshino, Reina; Kumasaka, Mayuko Y.; Kato, Masashi

    2016-01-01

    Despite the fact that manganese (Mn) is known to be a neurotoxic element relevant to age-related disorders, the risk of oral exposure to Mn for age-related hearing loss remains unclear. In this study, we orally exposed wild-type young adult mice to Mn (Mn-exposed WT-mice) at 1.65 and 16.50 mg/L for 4 weeks. Mn-exposed WT-mice showed acceleration of age-related hearing loss. Mn-exposed WT-mice had neurodegeneration of spiral ganglion neurons (SGNs) with increased number of lipofuscin granules. Mn-exposed WT-mice also had increased hypoxia-inducible factor-1 alpha (Hif-1α) protein with less hydroxylation at proline 564 and decreased c-Ret protein in SGNs. Mn-mediated acceleration of age-related hearing loss involving neurodegeneration of SGNs was rescued in RET-transgenic mice carrying constitutively activated RET. Thus, oral exposure to Mn accelerates age-related hearing loss in mice with Ret-mediated neurodegeneration of SGNs. PMID:27824154

  3. 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

    2016-02-04

    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.

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

    NASA Astrophysics Data System (ADS)

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

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

  5. 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.

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

    PubMed

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

    2016-07-01

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

  7. 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.

  8. Glutamate Cysteine Ligase Modifier Subunit (Gclm) Null Mice Have Increased Ovarian Oxidative Stress and Accelerated Age-Related Ovarian Failure

    PubMed Central

    Lim, Jinhwan; Nakamura, Brooke N.; Mohar, Isaac; Kavanagh, Terrance J.

    2015-01-01

    Glutathione (GSH) is the one of the most abundant intracellular antioxidants. Mice lacking the modifier subunit of glutamate cysteine ligase (Gclm), the rate-limiting enzyme in GSH synthesis, have decreased GSH. Our prior work showed that GSH plays antiapoptotic roles in ovarian follicles. We hypothesized that Gclm−/− mice have accelerated ovarian aging due to ovarian oxidative stress. We found significantly decreased ovarian GSH concentrations and oxidized GSH/oxidized glutathione redox potential in Gclm−/− vs Gclm+/+ ovaries. Prepubertal Gclm−/− and Gclm+/+ mice had similar numbers of ovarian follicles, and as expected, the total number of ovarian follicles declined with age in both genotypes. However, the rate of decline in follicles was significantly more rapid in Gclm−/− mice, and this was driven by accelerated declines in primordial follicles, which constitute the ovarian reserve. We found significantly increased 4-hydroxynonenal immunostaining (oxidative lipid damage marker) and significantly increased nitrotyrosine immunostaining (oxidative protein damage marker) in prepubertal and adult Gclm−/− ovaries compared with controls. The percentage of small ovarian follicles with increased granulosa cell proliferation was significantly higher in prepubertal and 2-month-old Gclm−/− vs Gclm+/+ ovaries, indicating accelerated recruitment of primordial follicles into the growing pool. The percentages of growing follicles with apoptotic granulosa cells were increased in young adult ovaries. Our results demonstrate increased ovarian oxidative stress and oxidative damage in young Gclm−/− mice, associated with an accelerated decline in ovarian follicles that appears to be mediated by increased recruitment of follicles into the growing pool, followed by apoptosis at later stages of follicular development. PMID:26083875

  9. Chronic stress impairs learning and hippocampal cell proliferation in senescence-accelerated prone mice.

    PubMed

    Yan, Weihong; Zhang, Ting; Jia, Weiping; Sun, Xiaojiang; Liu, Xueyuan

    2011-02-25

    Chronic stress can induce cognitive impairment. It is unclear whether a higher susceptibility to chronic stress is associated with the progression of pathological brain aging. Senescence-accelerated prone mouse 8 (SAMP8) is a naturally occurring animal model of accelerated brain aging. Senescence-accelerated resistant mouse 1 (SAMR1) is usually used as the normal control. In this study, we examined the effects of chronic restraint stress (CRS) on learning in the Y-maze, hippocampal cell proliferation, and the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus of 4-month-old SAMP8 and SAMR1. The results showed that exposure to CRS impaired learning and hippocampal cell proliferation in SAMP8 and SAMR1 but to a much greater extent in SAMP8. Furthermore, CRS significantly decreased the expression of BDNF protein and mRNA in the hippocampus of SAMP8 and SAMR1. These data indicated that SAMP8 is more sensitive to the deleterious effects of CRS on learning than SAMR1. A greater decrease in hippocampal cell proliferation caused by chronic stress may be part of the underlying mechanism for the more severe learning deficit observed in SAMP8. In addition, our findings suggested a role of BDNF in the stress-induced impairment of learning and hippocampal cell proliferation in both strains.

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

    PubMed Central

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

    2015-01-01

    This review provides balanced analysis of the advances in systemic regulation of young and old tissue stem cells and suggests strategies for accelerating development of therapies to broadly combat age-related tissue degenerative pathologies. Many highlighted recent reports on systemic tissue rejuvenation combine parabiosis with a “silver bullet” putatively responsible for the positive effects. Attempts to unify these papers reflect the excitement about this experimental approach and add value in reproducing previous work. At the same time, defined molecular approaches, which are “beyond parabiosis” for the rejuvenation of multiple old organs represent progress toward attenuating or even reversing human tissue aging. PMID:26540176

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

    PubMed

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

    2015-10-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Norman, Amanda; Hulse, Gary Kenneth

    2017-01-01

    Background Amphetamine abuse is becoming more widespread internationally. The possibility that its many cardiovascular complications are associated with a prematurely aged cardiovascular system, and indeed biological organism systemically, has not been addressed. Methods Radial arterial pulse tonometry was performed using the SphygmoCor system (Sydney). 55 amphetamine exposed patients were compared with 107 tobacco smokers, 483 non-smokers and 68 methadone patients (total=713 patients) from 2006 to 2011. A cardiovascular-biological age (VA) was determined. Results The age of the patient groups was 30.03±0.51–40.45±1.15 years. This was controlled for with linear regression. The sex ratio was the same in all groups. 94% of amphetamine exposed patients had used amphetamine in the previous week. When the (log) VA was regressed against the chronological age (CA) and a substance-type group in both cross-sectional and longitudinal models, models quadratic in CA were superior to linear models (both p<0.02). When log VA/CA was regressed in a mixed effects model against time, body mass index, CA and drug type, the cubic model was superior to the linear model (p=0.001). Interactions between CA, (CA)2 and (CA)3 on the one hand and exposure type were significant from p=0.0120. The effects of amphetamine exposure persisted after adjustment for all known cardiovascular risk factors (p<0.0001). Conclusions These results show that subacute exposure to amphetamines is associated with an advancement of cardiovascular-organismal age both over age and over time, and is robust to adjustment. That this is associated with power functions of age implies a feed-forward positively reinforcing exacerbation of the underlying ageing process. PMID:28243315

  14. Chronic stress induces ageing-associated degeneration in rat Leydig cells

    PubMed Central

    Wang, Fei-Fei; Wang, Qian; Chen, Yong; Lin, Qiang; Gao, Hui-Bao; Zhang, Ping

    2012-01-01

    Several studies have suggested that stress and ageing exert inhibitory effects on rat Leydig cells. In a pattern similar to the normal process of Leydig cell ageing, stress-mediated increases in glucocorticoid levels inhibit steroidogenic enzyme expression that then results in decreased testosterone secretion. We hypothesized that chronic stress accelerates the degenerative changes associated with ageing in Leydig cells. To test this hypothesis, we established a model of chronic stress to evaluate stress-induced morphological and functional alterations in Brown Norway rat Leydig cells; additionally, intracellular lipofuscin levels, reactive oxygen species (ROS) levels and DNA damage were assessed. The results showed that chronic stress accelerated ageing-related changes: ultrastructural alterations associated with ageing, cellular lipofuscin accumulation, increased ROS levels and more extensive DNA damage were observed. Additionally, testosterone levels were decreased. This study sheds new light on the idea that chronic stress contributes to the degenerative changes associated with ageing in rat Leydig cells in vivo. PMID:22609820

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

    PubMed

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

    2016-05-01

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

  16. Accelerated aging-related transcriptome changes in the female prefrontal cortex.

    PubMed

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

    2012-10-01

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

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

    PubMed

    Ford, Judith H

    2013-12-13

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

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

    PubMed

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

    2014-09-01

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

  19. Spectroscopic characterization of the oligomeric surface structures on polyamide materials formed during accelerated aging.

    PubMed

    Chernev, Boril S; Eder, Gabriele C

    2011-10-01

    Crystalline surface species were observed at the surface of polyamide 12 materials upon accelerated aging. After detection of the depositions with scanning electron microscopy (SEM), the crystalline surface precipitations were analyzed with Fourier transform infrared (FT-IR) and Raman imaging microscopy. These surface species were supposed to be cyclic oligomers (dimer and trimer) of the PA12 monomer laurolactam, which are usually present in polyamide materials and tend to migrate to the surface when the material is subjected to accelerated aging. The evidence for the chemical identity of the crystalline surface structures to be mainly the cyclic dimer and trimer of laurolactam was given by melting-point identification and mass spectroscopic analysis of the methanol eluate of the surface. The Raman and FT-IR spectra of the mixture were extracted from the recorded images.

  20. 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.

  1. Mobilised bone marrow-derived cells accelerate wound healing.

    PubMed

    Wang, Yu; Sun, Yu; Yang, Xiao-Yan; Ji, Shi-Zhao; Han, Shu; Xia, Zhao-Fan

    2013-08-01

    Massive skin defects caused by severe burn and trauma are a clinical challenge to surgeons. Timely and effective wound closure is often hindered by the lack of skin donor site. Bone marrow-derived cells (BMDCs) have been shown to 'differentiate' into multiple tissue cells. In this study we focused on the direct manipulation of endogenous BMDCs, avoiding the immunocompatibility issues and complicated cell isolation, purification, identification and amplification procedures in vitro on wound repair. We found that mobilisation of the BMDCs into the circulation significantly increased the amount of BMDCs at the injury site which in turn accelerated healing of large open wound. We used a chimeric green fluorescent protein (GFP) mouse model to track BMDCs and to investigate their role in full-thickness skin excisional wounds. We have shown that bone marrow mobilisation by granulocyte colony stimulating factor (G-CSF) exerted multiple beneficial effects on skin repair, both by increasing the engraftment of BMDCs into the skin to differentiate into multiple skin cell types and by upregulating essential cytokine mRNAs critical to wound repair. The potential trophic effects of G-CSF on bone marrow stem cells to accelerate wound healing could have a significant clinical impact.

  2. Aging characteristics of Li/SO(sub 2) cells

    NASA Astrophysics Data System (ADS)

    Levy, Samuel C.; Bouchard, Darryl A.

    Delays in the launch of the Galileo probe to Jupiter have resulted in a new trajectory that will increase the fly-out time such that batteries will be greater than seven years old at the time of descent into the Jovian atmosphere. The longest real time data for flight design cells was five years at the time of launch. A program was initiated to establish a methodology and data base so that the performance of these cells may be predicted at the time they are expected to complete the mission. Cells from five lots and five storage temperatures, ranging from one year to seven years in age, were studied. Chemical analysis was performed on one cell from each lot/storage group. The remaining cells in each group were discharged at the mission load and temperature. Additional cells were placed on high temperature accelerated storage, and then discharged.

  3. Experimental design and analysis for accelerated degradation tests with Li-ion cells.

    SciTech Connect

    Doughty, Daniel Harvey; Thomas, Edward Victor; Jungst, Rudolph George; Roth, Emanuel Peter

    2003-08-01

    This document describes a general protocol (involving both experimental and data analytic aspects) that is designed to be a roadmap for rapidly obtaining a useful assessment of the average lifetime (at some specified use conditions) that might be expected from cells of a particular design. The proposed experimental protocol involves a series of accelerated degradation experiments. Through the acquisition of degradation data over time specified by the experimental protocol, an unambiguous assessment of the effects of accelerating factors (e.g., temperature and state of charge) on various measures of the health of a cell (e.g., power fade and capacity fade) will result. In order to assess cell lifetime, it is necessary to develop a model that accurately predicts degradation over a range of the experimental factors. In general, it is difficult to specify an appropriate model form without some preliminary analysis of the data. Nevertheless, assuming that the aging phenomenon relates to a chemical reaction with simple first-order rate kinetics, a data analysis protocol is also provided to construct a useful model that relates performance degradation to the levels of the accelerating factors. This model can then be used to make an accurate assessment of the average cell lifetime. The proposed experimental and data analysis protocols are illustrated with a case study involving the effects of accelerated aging on the power output from Gen-2 cells. For this case study, inadequacies of the simple first-order kinetics model were observed. However, a more complex model allowing for the effects of two concurrent mechanisms provided an accurate representation of the experimental data.

  4. 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.

  5. 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.

  6. Metal-accelerated oxidation in plant cell death

    SciTech Connect

    Czuba, M. )

    1993-05-01

    Cadmium and mercury toxicity is further enhanced by external oxidizing conditions O[sub 3] or inherent plant processes. Lepidium sativum L, Lycopersicon esculentum Mill., or Phaseolus vulgaris L, were grown inpeat-lite to maturity under continuous cadmium exposure followed by one oxidant (O[sub 3]-6 hr. 30 pphm) exposure, with or without foliar calcium pretreatments. In comparison, Daucus carota, L and other species grown in a 71-V suspension, with or without 2,4-D were exposed continuously to low levels of methylmercury during exponential growth and analyzed in aggregates of distinct populations. Proteins were extracted and analyzed. Mechanisms of toxicity and eventual cell death are Ca-mediated and involve chloroplast, stomatal-water relations and changes in oxidant-anti-oxidant components in cells. Whether the metal-accelerated oxidative damage proceeds to cell death, depends on the species and its differential biotransformation system and cell association component.

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

    PubMed Central

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

    2010-01-01

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

  8. Cell Senescence: Aging and Cancer

    ScienceCinema

    Campisi, Judith

    2016-07-12

    Scientists have identified a molecular cause behind the ravages of old age and in doing so have also shown how a natural process for fighting cancer in younger persons can actually promote cancer in older individuals.

  9. Dynamic Scaling of Lipofuscin Deposition in Aging Cells

    NASA Astrophysics Data System (ADS)

    Family, Fereydoon; Mazzitello, K. I.; Arizmendi, C. M.; Grossniklaus, H. E.

    2011-07-01

    Lipofuscin is a membrane-bound cellular waste that can be neither degraded nor ejected from the cell but can only be diluted through cell division and subsequent growth. The fate of postmitotic (non-dividing) cells such as neurons, cardiac myocytes, skeletal muscle fibers, and retinal pigment epithelial cells (RPE) is to accumulate lipofuscin, which as an "aging pigment" has been considered a reliable biomarker for the age of cells. Environmental stress can accelerate the accumulation of lipofuscin. For example, accumulation in brain cells appears to be an important issue connected with heavy consumption of alcohol. Lipofuscin is made of free-radical-damaged protein and fat, whose abnormal accumulation is related to a range of disorders including Type IV mucolipidosis (ML4), Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease, Parkinson disease, and age-related macular degeneration (AMD) which is the leading cause of blindness beyond the age of 50 years. The study of lipofuscin formation and growth is important, because of their association with cellular aging. We introduce a model of non-equilibrium cluster growth and aggregation that we have developed for studying the formation and growth of lipofuscin. As an example of lipofuscin deposit in a given kind of postmitotic cell, we study the kinetics of lipofuscin growth in a RPE cell. Our results agree with a linear growth of the number of lipofuscin granules with age. We apply the dynamic scaling approach to our model and find excellent data collapse for the cluster size distribution. An unusual feature of our model is that while small particles are removed from the cell the larger ones become fixed and grow by aggregation.

  10. Improved Accelerated Stress Tests Based on Fuel Cell Vehicle Data

    SciTech Connect

    Patterson, Timothy; Motupally, Sathya

    2012-06-01

    UTC will led a top-tier team of industry and national laboratory participants to update and improve DOE’s Accelerated Stress Tests (AST’s) for hydrogen fuel cells. This in-depth investigation will focused on critical fuel cell components (e.g. membrane electrode assemblies - MEA) whose durability represented barriers for widespread commercialization of hydrogen fuel cell technology. UTC had access to MEA materials that had accrued significant load time under real-world conditions in PureMotion® 120 power plant used in transit buses. These materials are referred to as end-of-life (EOL) components in the rest of this document. Advanced characterization techniques were used to evaluate degradation mode progress using these critical cell components extracted from both bus power plants and corresponding materials tested using the DOE AST’s. These techniques were applied to samples at beginning-of-life (BOL) to serve as a baseline. These comparisons advised the progress of the various failure modes that these critical components were subjected to, such as membrane degradation, catalyst support corrosion, platinum group metal dissolution, and others. Gaps in the existing ASTs predicted the degradation observed in the field in terms of these modes were outlined. Using the gaps, new AST’s were recommended and tested to better reflect the degradation modes seen in field operation. Also, BOL components were degraded in a test vehicle at UTC designed to accelerate the bus field operation.

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

    NASA Astrophysics Data System (ADS)

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

    2017-02-01

    Service lifetime of ethylene propylene diene monomer (EPDM) rubber at room temperature (25 °C) was estimated based on accelerated aging tests. The study followed sealing stress loss on compressed cylinder samples by compression stress relaxation methods. The results showed that the cylinder samples of EPDM can quickly reach the physical relaxation equilibrium by using the over-compression method. The non-Arrhenius behavior occurred at the lowest aging temperature. A significant linear relationship was observed between compression set values and normalized stress decay results, and the relationship was not related to the ambient temperature of aging. It was estimated that the sealing stress loss in view of practical application would occur after around 86.8 years at 25 °C. The estimations at 25 °C based on the non-Arrhenius behavior were in agreement with compression set data from storage aging tests in natural environment.

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

    PubMed Central

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

    2010-01-01

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

  13. 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.

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

    PubMed

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

    2009-10-01

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

  15. 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.

  16. 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.

  17. 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.

  18. Boron Accelerates Cultured Osteoblastic Cell Activity through Calcium Flux.

    PubMed

    Capati, Mark Luigi Fabian; Nakazono, Ayako; Igawa, Kazunari; Ookubo, Kensuke; Yamamoto, Yuya; Yanagiguchi, Kajirou; Kubo, Shisei; Yamada, Shizuka; Hayashi, Yoshihiko

    2016-12-01

    A low concentration of boron (B) accelerates the proliferation and differentiation of mammalian osteoblasts. The aim of this study was to investigate the effects of 0.1 mM of B on the membrane function of osteoblastic cells in vitro. Genes involved in cell activity were investigated using gene expression microarray analyses. The Ca(2+) influx and efflux were evaluated to demonstrate the activation of L-type Ca(2+) channel for the Ca(2+) influx, and that of Na(+)/K(+)-ATPase for the Ca(2+) efflux. A real-time PCR analysis revealed that the messenger RNA (mRNA) expression of four mineralization-related genes was clearly increased after 3 days of culture with a B-supplemented culture medium. Using microarray analyses, five genes involved in cell proliferation and differentiation were upregulated compared to the control group. Regarding the Ca(2+) influx, in the nifedipine-pretreated group, the relative fluorescence intensity for 1 min after adding B solution did not increase compared with that for 1 min before addition. In the control group, the relative fluorescence intensity was significantly increased compared with the experimental group (P < 0.05). Regarding the Ca(2+) efflux, in the experimental group cultured in 0.1 mM of B-supplemented medium, the relative fluorescence intensity for 10 min after ouabain treatment revealed a significantly lower slope value compared with the control group (P < 0.01). This is the first study to demonstrate the acceleration of Ca(2+) flux by B supplementation in osteoblastic cells. Cell membrane stability is related to the mechanism by which a very low concentration of B promotes the proliferation and differentiation of mammalian osteoblastic cells in vitro.

  19. Mutagenic effect of accelerated heavy ions on bacterial cells

    NASA Astrophysics Data System (ADS)

    Boreyko, A. V.; Krasavin, E. A.

    2011-11-01

    The heavy ion accelerators of the Joint Institute for Nuclear Research were used to study the regularities and mechanisms of formation of different types of mutations in prokaryote cells. The induction of direct (lac-, ton B-, col B) mutations for Esherichia coli cells and reverse his- → His+ mutations of Salmonella typhimurium, Bacillus subtilis cells under the action of radiation in a wide range of linear energy transfer (LET) was studied. The regularities of formation of gene and structural (tonB trp-) mutations for Esherichia coli bacteria under the action of accelerated heavy ions were studied. It was demonstrated that the rate of gene mutations as a function of the dose under the action of Γ rays and accelerated heavy ions is described by linear-quadratic functions. For structural mutations, linear "dose-effect" dependences are typical. The quadratic character of mutagenesis dose curves is determined by the "interaction" of two independent "hitting" events in the course of SOS repair of genetic structures. The conclusion made was that gene mutations under the action of accelerated heavy ions are induced by δ electron regions of charged particle tracks. The methods of SOS chromotest, SOS lux test, and λ prophage induction were used to study the regularities of SOS response of cells under the action of radiations in a wide LET range. The following proposition was substantiated: the molecular basis for formation of gene mutations are cluster single-strand DNA breaks, and that for structural mutations, double-strand DNA breaks. It was found out that the LET dependence of the relative biological efficiency of accelerated ions is described by curves with a local maximum. It was demonstrated that the biological efficiency of ionizing radiations with different physical characteristics on cells with different genotype, estimated by the lethal action, induction of gene and deletion mutations, precision excision of transposons, is determined by the specific

  20. Adult Stem Cells and Diseases of Aging

    PubMed Central

    Boyette, Lisa B.; Tuan, Rocky S.

    2014-01-01

    Preservation of adult stem cells pools is critical for maintaining tissue homeostasis into old age. Exhaustion of adult stem cell pools as a result of deranged metabolic signaling, premature senescence as a response to oncogenic insults to the somatic genome, and other causes contribute to tissue degeneration with age. Both progeria, an extreme example of early-onset aging, and heritable longevity have provided avenues to study regulation of the aging program and its impact on adult stem cell compartments. In this review, we discuss recent findings concerning the effects of aging on stem cells, contributions of stem cells to age-related pathologies, examples of signaling pathways at work in these processes, and lessons about cellular aging gleaned from the development and refinement of cellular reprogramming technologies. We highlight emerging therapeutic approaches to manipulation of key signaling pathways corrupting or exhausting adult stem cells, as well as other approaches targeted at maintaining robust stem cell pools to extend not only lifespan but healthspan. PMID:24757526

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

    PubMed

    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.

  2. Heme oxygenase-1 accelerates erastin-induced ferroptotic cell death.

    PubMed

    Kwon, Min-Young; Park, Eunhee; Lee, Seon-Jin; Chung, Su Wol

    2015-09-15

    The oncogenic RAS-selective lethal small molecule Erastin triggers a unique iron-dependent form of nonapoptotic cell death termed ferroptosis. Ferroptosis is dependent upon the production of intracellular iron-dependent reactive oxygen species (ROS), but not other metals. However, key regulators remain unknown. The heme oxygenase (HO) is a major intracellular source of iron. In this study, the role of heme oxygenase in Erastin-triggered ferroptotic cancer cell death has been investigated. Zinc protoporphyrin IX (ZnPP), a HO-1 inhibitor, prevented Erastin-triggered ferroptotic cancer cell death. Furthermore, Erastin induced the protein and mRNA levels of HO-1 in HT-1080 fibrosarcoma cells. HO-1+/+ and HO-1-/- fibroblast, HO-1 overexpression, and chycloheximide-treated experiments revealed that the expression of HO-1 has a decisive effects in Erastin-triggered cell death. Hemin and CO-releasing molecules (CORM) promote Erastin-induced ferroptotic cell death, not by biliverdin and bilirubin. In addition, hemin and CORM accelerate the HO-1 expression in the presence of Erastin and increase membranous lipid peroxidation. Thus, HO-1 is an essential enzyme for iron-dependent lipid peroxidation during ferroptotic cell death.

  3. Loss of Vhl in cartilage accelerated the progression of age-associated and surgically induced murine osteoarthritis

    PubMed Central

    Weng, Tujun; Xie, Yangli; Yi, Lingxian; Huang, Junlan; Luo, Fengtao; Du, Xiaolan; Chen, Liang; Liu, Chongyang; Chen, Di; Chen, Lin

    2014-01-01

    Objective To investigate the role of Vhl in maintaining the integrity of articular cartilage and in the development of experimental osteoarthritis (OA). Method Histology of articular cartilage and subchondral bone in both Vhl cKO and WT mice were analyzed by histopathology and micro-CT. Articular cartilage destruction and proteoglycan loss were scored in aged (12-month-old) mice as well as in mice with surgically induced OA. Apoptosis of cartilage in age-related and surgically induced OA was detected with TUNNEL assay. Expressions of VHL, Fas, LC-3, HIF-1α, HIF-2α, p-mTOR and MMP-13 in the knee joints were analyzed by immunostaining. Results No gross differences in cartilage were observed between Vhl cKO and WT mice at age 4 months. However, Vhl cKO mice displayed accelerated age-associated spontaneous OA and surgically induced OA. Cartilage destruction and proteoglycan loss were observed in the absence of Vhl. In addition, inactivation of Vhl resulted in up-regulation of HIF-2α and increased chondrocyte apoptosis and decreased expression of autophagy during OA development. Immunohistochemical staining also showed that Vhl deficiency led to increased expression of Fas, p-mTOR and MMP-13, and those genes were associated with cell apoptosis, autophagy and cartilage matrix breakdown, respectively. Conclusion Loss of Vhl in adult articular cartilage is associated with earlier dysregulation of cartilage homeostasis, characterized by an increased chondrocyte apoptosis, compromised chondrocyte autophagy, and an accelerated age-related and surgery-induced OA development. These results highlight the novel role of Vhl in maintaining joint homeostasis and OA development. PMID:24999110

  4. 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.

  5. Accelerate Climate Models with the IBM Cell Processor

    NASA Astrophysics Data System (ADS)

    Zhou, S.; Duffy, D.; Clune, T.; Williams, S.; Suarez, M.; Halem, M.

    2008-12-01

    Ever increasing model resolutions and physical processes in climate models demand continual computing power increases. The IBM Cell processor's order-of- magnitude peak performance increase over conventional processors makes it very attractive for fulfilling this requirement. However, the Cell's characteristics: 256KB local memory per SPE and the new low-level communication mechanism, make it very challenging to port an application. We selected the solar radiation component of the NASA GEOS-5 climate model, which: (1) is representative of column physics components (~50% total computation time), (2) has a high computational load relative to data traffic to/from main memory, and (3) performs independent calculations across multiple columns. We converted the baseline code (single-precision, Fortran code) to C and ported it to an IBM BladeCenter QS20, manually SIMDizing 4 independent columns, and found that a Cell with 8 SPEs can process more than 3000 columns per second. Compared with the baseline results, the Cell is ~6.76x, ~8.91x, ~9.85x faster than a core on Intel's Xeon Woodcrest, Dempsey, and Itanium2 respectively. Our analysis shows that the Cell could also speed up the dynamics component (~25% total computation time). We believe this dramatic performance improvement makes the Cell processor very competitive, at least as an accelerator. We will report our experience in porting both the C and Fortran codes and will discuss our work in porting other climate model components.

  6. New Aging Index Using Signal Features of Both Photoplethysmograms and Acceleration Plethysmograms

    PubMed Central

    2017-01-01

    Objectives Acceleration plethysmograms (APGs) are obtained by taking the second derivative of photoplethysmograms (PPGs) and are noninvasive circulatory signals related to risk factors for atherosclerosis with age. There has been growing interest in the development of mobile devices to collect and analyze PPG single features for ambulatory health monitoring. The present study aimed to extract a new feature from the morphologies of APG and PPG signals to classify the dominant indices related to the pulsatile volume of blood in tissue according to age. Methods Ten APG and 14 PPG indices were simultaneously extracted. All indices were compared via Pearson correlation coefficients (r) and a regression analysis. We introduced a combined index extracted from both the PPG and APG indices defined as the inflection point area plus the d_peak (IPAD). The participants included 93 healthy adults aged 36–86 years with a mean ± standard deviation age of 57.43 ± 11.99 years. Results The d_peak and age index for the APG indices were significantly correlated with age (r = −0.408, p < 0.0001 and r = 0.296, p = 0.0039, respectively). Only the A1 time for PPG indices was moderately correlated with age (r = −0.247, p = 0.017). The stiffness index, including individual height information, was not related to age (r = −0.031, p = 0.7713). However, the combined IPAD index was significantly more correlated with age (r = 0.56, p < 0.001) than the other indices. Conclusions The proposed index outperformed the other 24 indices for evaluating vascular aging. We suggest that the IPAD is a significant factor related to the clinical information embedded in the PPG waveform. PMID:28261531

  7. Excessive daytime sleepiness and fatigue may indicate accelerated brain aging in cognitively normal late middle-aged and older adults.

    PubMed

    Carvalho, Diego Z; St Louis, Erik K; Boeve, Bradley F; Mielke, Michelle M; Przybelski, Scott A; Knopman, David S; Machulda, Mary M; Roberts, Rosebud O; Geda, Yonas E; Petersen, Ronald C; Jack, Clifford R; Vemuri, Prashanthi

    2017-04-01

    Excessive daytime sleepiness (EDS) and fatigue increases with age. The aim of this study was to investigate the association between EDS and fatigue with cortical thickness and hippocampal volume in cognitively normal, late middle-aged and older adults. We performed a cross-sectional observational study of 1374 cognitively-normal subjects aged 50 years and older who had a structural MRI. Regional cortical thickness and hippocampal volume were measured. Multiple linear regression models were fit to explore associations between EDS and fatigue and structural MRI measures in different brain regions, adjusting for multiple covariates. EDS was defined as Epworth Sleepiness Scale ≥10. Fatigue severity was assessed with the Beck Depression Inventory-2. 208 participants had EDS, 27 had significant fatigue, and 11 had both. Participants with EDS or fatigue had significantly lower cognitive scores, more disturbed sleep, and medical comorbidities. The presence of EDS was associated with both global and regional atrophy, whereas fatigue was more associated with frontal and temporal changes. Cortical thinning predicted by EDS and fatigue was maximal in the temporal region with average reduction of 34.2 μm (95% CI, -54.1, -14.3; P = 0.001) and 90.2 μm (95% CI, -142.1, -38.2; P = 0.001), respectively. Fatigue was also associated with hippocampal volume reduction of -374.2 mm(3) (95% CI, -670.8, -77.7; P = 0.013). Temporal cortical thinning predicted by presence of EDS and fatigue was equivalent to more than 3.5 and 9 additional years of aging, respectively. EDS and fatigue were associated with cortical thickness reduction primarily in regions with increased age-susceptibility, which may indicate accelerated brain aging.

  8. Measuring the Aging Process in Stem Cells

    PubMed Central

    Liu, Yi; Van Zant, Gary; Liang, Ying

    2015-01-01

    Summary Stem cells persist in replenishing functional mature cells throughout life by self-renewal and multilineage differentiation. Hematopoietic stem cells (HSCs) are among the best-characterized and understood stem cells, and they are responsible for the life-long production of all lineages of blood cells. HSCs are a heterogeneous population containing lymphoid-biased, myeloid-biased and balanced subsets. HSCs undergo age-associated phenotypic and functional changes, and the composition of the HSC pool alters with aging. HSCs and their lineage-biased subfractions can be identified and analyzed by flow cytometry based on cell surface makers. Fluorescence-activated cell sorting (FACS) enables the isolation and purification of HSCs that greatly facilitates the mechanistic study of HSCs and their aging process at both cellular and molecular levels. The mouse model has been extensively used in HSC aging study. Bone marrow cells are isolated from young and old mice and stained with fluorescence-conjugated antibodies specific for differentiated and stem cells. HSCs are selected based on the negative expression of lineage markers and positive selection for several sets of stem cell markers. Lineage-biased HSCs can be further distinguished by the level of SLAM/CD150 expression and the extent of Hoechst efflux. PMID:25388383

  9. Degradation mechanisms and accelerated testing in PEM fuel cells

    SciTech Connect

    Borup, Rodney L; Mukundan, Rangachary

    2010-01-01

    The durability of PEM fuel cells is a major barrier to the commercialization of these systems for stationary and transportation power applications. Although there has been recent progress in improving durability, further improvements are needed to meet the commercialization targets. Past improvements have largely been made possible because of the fundamental understanding of the underlying degradation mechanisms. By investigating component and cell degradation modes; defining the fundamental degradation mechanisms of components and component interactions new materials can be designed to improve durability. Various factors have been shown to affect the useful life of PEM fuel cells. Other issues arise from component optimization. Operational conditions (such as impurities in either the fuel and oxidant stream), cell environment, temperature (including subfreezing exposure), pressure, current, voltage, etc.; or transient versus continuous operation, including start-up and shutdown procedures, represent other factors that can affect cell performance and durability. The need for Accelerated Stress Tests (ASTs) can be quickly understood given the target lives for fuel cell systems: 5000 hours ({approx} 7 months) for automotive, and 40,000 hrs ({approx} 4.6 years) for stationary systems. Thus testing methods that enable more rapid screening of individual components to determine their durability characteristics, such as off-line environmental testing, are needed for evaluating new component durability in a reasonable turn-around time. This allows proposed improvements in a component to be evaluated rapidly and independently, subsequently allowing rapid advancement in PEM fuel cell durability. These tests are also crucial to developers in order to make sure that they do not sacrifice durability while making improvements in costs (e.g. lower platinum group metal [PGM] loading) and performance (e.g. thinner membrane or a GDL with better water management properties). To

  10. Ageing and cell-mediated immunity.

    PubMed

    Fixa, B; Komárková, O; Chmelar, V

    1975-01-01

    The lymphocyte transformation test with phytohemagglutinin as mitogen estimated according to the incorporation of 2-(14)C-thymidine in DNA was used as an indicator of cell-mediated reactivity in 53 healthy subjects. Three age groups were examined: up to 20 years (21 subjects), 21-40 years (10 subjects) and over 70 years (22 subjects). The responsiveness of lymphocytes decreased significantly with age. In the highest age group 12 pathologically low values were found.

  11. Delayed animal aging through the recovery of stem cell senescence by platelet rich plasma.

    PubMed

    Liu, Hen-Yu; Huang, Chiung-Fang; Lin, Tzu-Chieh; Tsai, Ching-Yu; Tina Chen, Szu-Yu; Liu, Alice; Chen, Wei-Hong; Wei, Hong-Jian; Wang, Ming-Fu; Williams, David F; Deng, Win-Ping

    2014-12-01

    Aging is related to loss of functional stem cell accompanying loss of tissue and organ regeneration potentials. Previously, we demonstrated that the life span of ovariectomy-senescence accelerated mice (OVX-SAMP8) was significantly prolonged and similar to that of the congenic senescence-resistant strain of mice after platelet rich plasma (PRP)/embryonic fibroblast transplantation. The aim of this study is to investigate the potential of PRP for recovering cellular potential from senescence and then delaying animal aging. We first examined whether stem cells would be senescent in aged mice compared to young mice. Primary adipose derived stem cells (ADSCs) and bone marrow derived stem cells (BMSCs) were harvested from young and aged mice, and found that cell senescence was strongly correlated to animal aging. Subsequently, we demonstrated that PRP could recover cell potential from senescence, such as promote cell growth (cell proliferation and colony formation), increase osteogenesis, decrease adipogenesis, restore cell senescence related markers and resist the oxidative stress in stem cells from aged mice. The results also showed that PRP treatment in aged mice could delay mice aging as indicated by survival, body weight and aging phenotypes (behavior and gross morphology) in term of recovering the cellular potential of their stem cells compared to the results on aged control mice. In conclusion these findings showed that PRP has potential to delay aging through the recovery of stem cell senescence and could be used as an alternative medicine for tissue regeneration and future rejuvenation.

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

    NASA Astrophysics Data System (ADS)

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

    2016-11-01

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

  13. 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.

  14. Epigenetic regulation of hematopoietic stem cell aging

    SciTech Connect

    Beerman, Isabel

    2014-12-10

    Aging is invariably associated with alterations of the hematopoietic stem cell (HSC) compartment, including loss of functional capacity, altered clonal composition, and changes in lineage contribution. Although accumulation of DNA damage occurs during HSC aging, it is unlikely such consistent aging phenotypes could be solely attributed to changes in DNA integrity. Another mechanism by which heritable traits could contribute to the changes in the functional potential of aged HSCs is through alterations in the epigenetic landscape of adult stem cells. Indeed, recent studies on hematopoietic stem cells have suggested that altered epigenetic profiles are associated with HSC aging and play a key role in modulating the functional potential of HSCs at different stages during ontogeny. Even small changes of the epigenetic landscape can lead to robustly altered expression patterns, either directly by loss of regulatory control or through indirect, additive effects, ultimately leading to transcriptional changes of the stem cells. Potential drivers of such changes in the epigenetic landscape of aged HSCs include proliferative history, DNA damage, and deregulation of key epigenetic enzymes and complexes. This review will focus largely on the two most characterized epigenetic marks – DNA methylation and histone modifications – but will also discuss the potential role of non-coding RNAs in regulating HSC function during aging.

  15. Accelerated failure time models provide a useful statistical framework for aging research.

    PubMed

    Swindell, William R

    2009-03-01

    Survivorship experiments play a central role in aging research and are performed to evaluate whether interventions alter the rate of aging and increase lifespan. The accelerated failure time (AFT) model is seldom used to analyze survivorship data, but offers a potentially useful statistical approach that is based upon the survival curve rather than the hazard function. In this study, AFT models were used to analyze data from 16 survivorship experiments that evaluated the effects of one or more genetic manipulations on mouse lifespan. Most genetic manipulations were found to have a multiplicative effect on survivorship that is independent of age and well-characterized by the AFT model "deceleration factor". AFT model deceleration factors also provided a more intuitive measure of treatment effect than the hazard ratio, and were robust to departures from modeling assumptions. Age-dependent treatment effects, when present, were investigated using quantile regression modeling. These results provide an informative and quantitative summary of survivorship data associated with currently known long-lived mouse models. In addition, from the standpoint of aging research, these statistical approaches have appealing properties and provide valuable tools for the analysis of survivorship data.

  16. Diabetes exacerbates amyloid and neurovascular pathology in aging-accelerated mice.

    PubMed

    Currais, Antonio; Prior, Marguerite; Lo, David; Jolivalt, Corinne; Schubert, David; Maher, Pamela

    2012-12-01

    Mounting evidence supports a link between diabetes, cognitive dysfunction, and aging. However, the physiological mechanisms by which diabetes impacts brain function and cognition are not fully understood. To determine how diabetes contributes to cognitive dysfunction and age-associated pathology, we used streptozotocin to induce type 1 diabetes (T1D) in senescence-accelerated prone 8 (SAMP8) and senescence-resistant 1 (SAMR1) mice. Contextual fear conditioning demonstrated that T1D resulted in the development of cognitive deficits in SAMR1 mice similar to those seen in age-matched, nondiabetic SAMP8 mice. No further cognitive deficits were observed when the SAMP8 mice were made diabetic. T1D dramatically increased Aβ and glial fibrillary acidic protein immunoreactivity in the hippocampus of SAMP8 mice and to a lesser extent in age-matched SAMR1 mice. Further analysis revealed aggregated Aβ within astrocyte processes surrounding vessels. Western blot analyses from T1D SAMP8 mice showed elevated amyloid precursor protein processing and protein glycation along with increased inflammation. T1D elevated tau phosphorylation in the SAMR1 mice but did not further increase it in the SAMP8 mice where it was already significantly higher. These data suggest that aberrant glucose metabolism potentiates the aging phenotype in old mice and contributes to early stage central nervous system pathology in younger animals.

  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. 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

  19. Transient mitochondrial DNA double strand breaks in mice cause accelerated aging phenotypes in a ROS-dependent but p53/p21-independent manner.

    PubMed

    Pinto, Milena; Pickrell, Alicia M; Wang, Xiao; Bacman, Sandra R; Yu, Aixin; Hida, Aline; Dillon, Lloye M; Morton, Paul D; Malek, Thomas R; Williams, Siôn L; Moraes, Carlos T

    2017-02-01

    We observed that the transient induction of mtDNA double strand breaks (DSBs) in cultured cells led to activation of cell cycle arrest proteins (p21/p53 pathway) and decreased cell growth, mediated through reactive oxygen species (ROS). To investigate this process in vivo we developed a mouse model where we could transiently induce mtDNA DSBs ubiquitously. This transient mtDNA damage in mice caused an accelerated aging phenotype, preferentially affecting proliferating tissues. One of the earliest phenotypes was accelerated thymus shrinkage by apoptosis and differentiation into adipose tissue, mimicking age-related thymic involution. This phenotype was accompanied by increased ROS and activation of cell cycle arrest proteins. Treatment with antioxidants improved the phenotype but the knocking out of p21 or p53 did not. Our results demonstrate that transient mtDNA DSBs can accelerate aging of certain tissues by increasing ROS. Surprisingly, this mtDNA DSB-associated senescence phenotype does not require p21/p53, even if this pathway is activated in the process.

  20. Accelerated infarct development, cytogenesis and apoptosis following transient cerebral ischemia in aged rats.

    PubMed

    Popa-Wagner, Aurel; Badan, Irina; Walker, Lary; Groppa, Sergiu; Patrana, Nicoleta; Kessler, Christof

    2007-03-01

    Old age is associated with a deficient recovery from stroke, but the cellular mechanisms underlying such phenomena are poorly understood. To address this issue, focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery in 3- and 20-month-old male Sprague-Dawley rats. Aged rats showed a delayed and suboptimal functional recovery in the post-stroke period. Using BrdU-labeling, quantitative immunohistochemistry and 3-D reconstruction of confocal images, we found that aged rats are predisposed to rapidly develop an infarct within the first few days after ischemia. The emergence of the necrotic zone is associated with a high rate of cellular degeneration, premature accumulation of proliferating BrdU-positive cells that appear to emanate from capillaries in the infarcted area, and a large number of apoptotic cells. With double labeling techniques, we were able to identify, for the first time, over 60% of BrdU-positive cells either as reactive microglia (45%), oligodendrocyte progenitors (17%), astrocytes (23%), CD8+ lymphocytes (4%), or apoptotic cells (<1%). Paradoxically, despite a robust reactive phenotype of microglia and astrocytes in aged rats, at 1-week post-stroke, the number of proliferating microglia and astrocytes was lower in aged rats than in young rats. Our data indicate that aging is associated with rapid infarct development and a poor prognosis for full recovery from stroke that is correlated with premature cellular proliferation and increased cellular degeneration and apoptosis in the infarcted area.

  1. Diet restriction delays accelerated aging and genomic stress in DNA repair deficient mice

    PubMed Central

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

    2016-01-01

    DNA repair-deficient Ercc1Δ/− mice show numerous accelerated aging features limiting lifespan to 4–6 month1–4. Simultaneously they exhibit a ‘survival response’, which suppresses growth and enhances maintenance, resembling the anti-aging response induced by dietary restriction (DR)1,5. Here we report that subjecting these progeroid, dwarf mutants to 30% DR tripled median and maximal remaining lifespan, and drastically retarded numerous aspects of accelerated aging, e.g. DR animals retained 50% more neurons and maintained full motoric function, even far beyond the lifespan of ad libitum (AL) animals. Repair-deficient, progeroid Xpg−/− mice, a Cockayne syndrome model6, responded similarly, extending this observation to other repair mutants. The DR response in Ercc1Δ/− mice closely resembled DR in wild type animals. Interestingly, AL Ercc1Δ/− liver showed preferential extinction of expression of long genes, a phenomenon we also observe in several normal aging tissues. This is consistent with accumulation of stochastic, transcription-blocking lesions, affecting long genes more than short ones. DR largely prevented declining transcriptional output and reduced γH2AX DNA damage foci, indicating that DR preserves genome function by alleviating DNA damage. Our findings establish Ercc1Δ/− mice as powerful model for interventions sustaining health, reveal untapped potential for reducing endogenous damage, provide new venues for understanding the molecular mechanism of DR, and suggest a counterintuitive DR-like therapy for human progeroid genome instability syndromes and possibly neurodegeneration in general. PMID:27556946

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

    PubMed

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

    2016-09-15

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

  3. 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.

  4. 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.

  5. Lysosomal cell death mechanisms in aging.

    PubMed

    Gómez-Sintes, Raquel; Ledesma, María Dolores; Boya, Patricia

    2016-12-01

    Lysosomes are degradative organelles essential for cell homeostasis that regulate a variety of processes, from calcium signaling and nutrient responses to autophagic degradation of intracellular components. Lysosomal cell death is mediated by the lethal effects of cathepsins, which are released into the cytoplasm following lysosomal damage. This process of lysosomal membrane permeabilization and cathepsin release is observed in several physiopathological conditions and plays a role in tissue remodeling, the immune response to intracellular pathogens and neurodegenerative diseases. Many evidences indicate that aging strongly influences lysosomal activity by altering the physical and chemical properties of these organelles, rendering them more sensitive to stress. In this review we focus on how aging alters lysosomal function and increases cell sensitivity to lysosomal membrane permeabilization and lysosomal cell death, both in physiological conditions and age-related pathologies.

  6. 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.

  7. Caveolin-1 and accelerated host aging in the breast tumor microenvironment: chemoprevention with rapamycin, an mTOR inhibitor and anti-aging drug.

    PubMed

    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

    2012-07-01

    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).

  8. 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.

  9. Accelerating particle-in-cell simulations using multilevel Monte Carlo

    NASA Astrophysics Data System (ADS)

    Ricketson, Lee

    2015-11-01

    Particle-in-cell (PIC) simulations have been an important tool in understanding plasmas since the dawn of the digital computer. Much more recently, the multilevel Monte Carlo (MLMC) method has accelerated particle-based simulations of a variety of systems described by stochastic differential equations (SDEs), from financial portfolios to porous media flow. The fundamental idea of MLMC is to perform correlated particle simulations using a hierarchy of different time steps, and to use these correlations for variance reduction on the fine-step result. This framework is directly applicable to the Langevin formulation of Coulomb collisions, as demonstrated in previous work, but in order to apply to PIC simulations of realistic scenarios, MLMC must be generalized to incorporate self-consistent evolution of the electromagnetic fields. We present such a generalization, with rigorous results concerning its accuracy and efficiency. We present examples of the method in the collisionless, electrostatic context, and discuss applications and extensions for the future.

  10. Cerium migration during PEM fuel cell accelerated stress testing

    SciTech Connect

    Baker, Andrew M.; Mukundan, Rangachary; Borup, Rodney L.; Spernjak, Dusan; Judge, Elizabeth J.; Advani, Suresh G.; Prasad, Ajay K.

    2016-01-01

    Cerium is a radical scavenger which improves polymer electrolyte membrane (PEM) fuel cell durability. During operation, however, cerium rapidly migrates in the PEM and into the catalyst layers (CLs). In this work, membrane electrode assemblies (MEAs) were subjected to accelerated stress tests (ASTs) under different humidity conditions. Cerium migration was characterized in the MEAs after ASTs using X-ray fluorescence. During fully humidified operation, water flux from cell inlet to outlet generated in-plane cerium gradients. Conversely, cerium profiles were flat during low humidity operation, where in-plane water flux was negligible, however, migration from the PEM into the CLs was enhanced. Humidity cycling resulted in both in-plane cerium gradients due to water flux during the hydration component of the cycle, and significant migration into the CLs. Fluoride and cerium emissions into effluent cell waters were measured during ASTs and correlated, which signifies that ionomer degradation products serve as possible counter-ions for cerium emissions. Fluoride emission rates were also correlated to final PEM cerium contents, which indicates that PEM degradation and cerium migration are coupled. Lastly, it is proposed that cerium migrates from the PEM due to humidification conditions and degradation, and is subsequently stabilized in the CLs by carbon catalyst supports.

  11. Cerium migration during PEM fuel cell accelerated stress testing

    DOE PAGES

    Baker, Andrew M.; Mukundan, Rangachary; Borup, Rodney L.; ...

    2016-01-01

    Cerium is a radical scavenger which improves polymer electrolyte membrane (PEM) fuel cell durability. During operation, however, cerium rapidly migrates in the PEM and into the catalyst layers (CLs). In this work, membrane electrode assemblies (MEAs) were subjected to accelerated stress tests (ASTs) under different humidity conditions. Cerium migration was characterized in the MEAs after ASTs using X-ray fluorescence. During fully humidified operation, water flux from cell inlet to outlet generated in-plane cerium gradients. Conversely, cerium profiles were flat during low humidity operation, where in-plane water flux was negligible, however, migration from the PEM into the CLs was enhanced. Humiditymore » cycling resulted in both in-plane cerium gradients due to water flux during the hydration component of the cycle, and significant migration into the CLs. Fluoride and cerium emissions into effluent cell waters were measured during ASTs and correlated, which signifies that ionomer degradation products serve as possible counter-ions for cerium emissions. Fluoride emission rates were also correlated to final PEM cerium contents, which indicates that PEM degradation and cerium migration are coupled. Lastly, it is proposed that cerium migrates from the PEM due to humidification conditions and degradation, and is subsequently stabilized in the CLs by carbon catalyst supports.« less

  12. 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

  13. A long-standing hyperglycaemic condition impairs skin barrier by accelerating skin ageing process.

    PubMed

    Park, Hwa-Young; Kim, Jae-Hong; Jung, Minyoung; Chung, Choon Hee; Hasham, Rosnani; Park, Chang Seo; Choi, Eung Ho

    2011-12-01

    Uncontrolled chronic hyperglycaemia including type 2 diabetes mellitus (DM) induces many skin problems related to chronic impaired skin barrier state. However, little is known about the skin barrier state of chronic hyperglycaemia patients, the dysfunction of which may be a major cause of their skin problems. In this study, we investigated whether a long-standing hyperglycaemic condition including type 2 DM impairs skin barrier homoeostasis in proportion to the duration and its pathomechanism. We utilized the Otsuka Long-Evans Tokushima Fatty (OLETF) rats as an animal model of long-standing hyperglycaemia and Long-Evans Tokushima Otsuka rats as a control strain. We confirmed that a long-standing hyperglycaemia delayed skin barrier homoeostasis, which correlated with haemoglobin A1c levels. OLETF rats as a long-standing hyperglycaemia model exhibited decreased epidermal lipid synthesis and antimicrobial peptide expression with increasing age. Decreased epidermal lipid synthesis accounted for decreased lamellar body production. In addition, OLETF rats had significantly higher serum levels of advanced glycation end products (AGEs) and elevated levels of the receptor for AGE in the epidermis. A long-standing hyperglycaemic condition impairs skin barrier function including permeability and antimicrobial barriers by accelerating skin ageing process in proportion to the duration of hyperglycaemia, which could be a major pathophysiology underlying cutaneous complications of DM.

  14. Aging, metabolism and stem cells: Spotlight on muscle stem cells.

    PubMed

    García-Prat, Laura; Muñoz-Cánoves, Pura

    2017-04-15

    All tissues and organs undergo a progressive regenerative decline as they age. This decline has been mainly attributed to loss of stem cell number and/or function, and both stem cell-intrinsic changes and alterations in local niches and/or systemic environment over time are known to contribute to the stem cell aging phenotype. Advancing in the molecular understanding of the deterioration of stem cell cells with aging is key for targeting the specific causes of tissue regenerative dysfunction at advanced stages of life. Here, we revise exciting recent findings on why stem cells age and the consequences on tissue regeneration, with a special focus on regeneration of skeletal muscle. We also highlight newly identified common molecular pathways affecting diverse types of aging stem cells, such as altered proteostasis, metabolism, or senescence entry, and discuss the questions raised by these findings. Finally, we comment on emerging stem cell rejuvenation strategies, principally emanating from studies on muscle stem cells, which will surely burst tissue regeneration research for future benefit of the increasing human aging population.

  15. Increased Th9 cells and IL-9 levels accelerate disease progression in experimental atherosclerosis

    PubMed Central

    Li, Qing; Ming, Tingting; Wang, Yuanmin; Ding, Shaowei; Hu, Chaojie; Zhang, Cuiping; Cao, Qi; Wang, Yiping

    2017-01-01

    Atherosclerosis (AS) is the number one killer in developed countries, and currently considered a chronic inflammatory disease. The central role of T cells in the pathogenesis of atherosclerosis is well documented. However, little is known about the newly described T cell subset-Th9 cells and their role in AS pathogenesis. Here, the amounts of Th9 cells as well as their key transcription factors and relevant cytokines during atherosclerosis were assessed in ApoE-/- mice and age-matched C57BL/6J mice. Significantly increased Th9 cell number, Th9 related cytokine (IL-9), and key transcription factor (PU.1) were found in ApoE-/- mice compared with age-matched C57BL/6J mice. Additionally, treatment with rIL-9 accelerated atherosclerotic development, which was attenuated by anti-IL-9 antibodies. These data suggested that both Th9 cells and related IL-9 play key roles in the pathogenesis of atherosclerosis, and antibodies against these antigens offer a novel therapeutic approach in AS treatment. PMID:28386359

  16. Laser-induced wakefield acceleration by using density-tapered gas-cell

    NASA Astrophysics Data System (ADS)

    Kim, Minseok; Nam, Inhyuk; Lee, Seungwoo; Suk, Hyyong

    2015-11-01

    The plasma sources with upward density gradient can be used to increase a dephasing length and an accelerating field in laser wakefield acceleration (LWFA) mechanism. As a result, the electron energy accelerated is expected to be increased and we developed a density-tapered gas-cell on this account. Using a 20 TW Ti:Sapphire laser constructed at GIST, we performed the acceleration experiments with the gas-cell and gas-jet with density-gradient. In this presentation, the results of acceleration experiments will be presented in detail.

  17. T CELL REPLICATIVE SENESCENCE IN HUMAN AGING

    PubMed Central

    Chou, Jennifer P.; Effros, Rita B.

    2013-01-01

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

  18. 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

  19. Accelerated discovery of materials for solar fuel cells at JCAP

    NASA Astrophysics Data System (ADS)

    Mitrovic, Slobodan; Cornell, Earl; Gregoire, John; Haber, Joel; Kan, Kevin; Lin, Sean; Liu, Xiaonao; Marcin, Martin; Soedarmadji, Edward; Suram, Santosh; Xiang, Chengxiang; Jin, Jian

    2013-03-01

    High-Throughput Experimentation group at the Joint Center for Artificial Photosynthesis has a formidable mission: provide accelerated discovery of new photon absorbers and heterogeneous (photo)catalysts for solar fuel cells at the rate far beyond anything attempted in material science to date. The HTE pipeline includes material synthesis, screening and characterization. Within the first year of operations, our fabrication capabilities have risen to 100,000 samples per day using combinatorial inkjet-printing. Such high rate of sample production is setting daunting requirements on screening methods. We are developing and testing methods for fast bandgap measurements, using colorimetry and uv-vis spectroscopy. Material thickness and roughness is determined by confocal chromatic spectroscopy. Catalytic activity is screen through a massively parallel bubble screen and a fast scanning droplet (photo)electrochemical cell. Concurrently, we are developing protocols for high-throughput determination of phase and structure (XRD), surface composition and chemistry (XPS), surface area measurement, etc. on the characterization side of the pipeline. This work was performed at Joint Center for Artificial Photosynthesis, a DOE Energy Innovation Hub, supported through the Office of Science of the U.S. Department of Energy under Award No. DE-SC0004993

  20. Wear resistance of highly cross-linked and remelted polyethylenes after ion implantation and accelerated ageing.

    PubMed

    Medel, F J; Puértolas, J A

    2008-08-01

    Ion implantation may provide medical polyethylenes with excellent mechanical and tribological properties, helping to lower the risk of long-term osteolysis. Highly crosslinked and remelted polyethylenes, materials currently used as soft components in artificial joints, were implanted with N+ and He+ ions at different ion fluences. The mechanical and tribological properties under distilled water lubrication at body temperature were assessed after ion implantation by means of microhardness and pin-on-disc tests respectively. Thus, the influences of the ionic species and implantation dose on surface hardness, friction coefficient, and wear factor were fully characterized. Furthermore, the tribological behaviour was evaluated after an accelerated ageing protocol (120 degrees C for 36h). Ion implantation increased the surface hardness, as well as friction coefficients, and decreased the wear factors especially at the highest doses. Also, even though all artificially aged materials showed a worse wear behaviour, polyethylenes implanted with either N+ or He+ at the highest doses maintained a relatively good wear factor in comparison with the aged non-implanted material. The origins of these modifications are discussed according to the effects of ion implantation on the microstructure of the polymer.

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

    NASA Astrophysics Data System (ADS)

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

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

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

    PubMed

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

    2012-05-01

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

  3. Mutation Induction in Mammalian Cells by Accelerated Heavy Ions

    NASA Astrophysics Data System (ADS)

    Rosendahl, I. M.; Baumstark-Khan, C.; Rink, H.

    The deleterious effects of accelerated heavy ions on living cells are of increasing importance for long duration human space flight activities. An important aspect of this field is attributed to the type and quality of biological damage induced by these densely ionizing particles. To address this aspect, cell inactivation and mutation induction at the hprt locus (coding for hypoxanthine-guanine-phosphoribosyl-transferase) was investigated in cultured V79 Chinese Hamster Cells irradiated with accelerated heavy ions (8-O, 20-Ca, 79-Au, and 92-U) and X-rays. Specific energies of the ions ranged from 1.9 to 69.7 MeV/u and corresponding LET values were between 62 band 15,580 keV/μ m. 30 spontaneous and 196 heavy-ion induced 6-thioguanine resistant hprt mutant colonies were characterized by Southern technique using the restriction enzymes EcoRI, PstI and BglII and a full length hprt cDNA probe isolated from the plasmid pHpt12 (kindly provided by Dr. J. Thacker). While inactivation cross sections (σ i) rise over the whole LET range, mutation induction cross sections (σ m) increase up to approximately 300 keV/μ m (O-ions) but decline with heavier ions and more extreme LET values. A similar behaviour is seen with mutation frequency dependent on particle fluence. After irradiation with accelerated uranium ions (8.8 MeV/u, 15,580 keV/μ m) a significant decrease of mutation frequency was found with higher particle fluences (3× 106 particles cm-2). Nearly no mutants were recovered with 8× 106 particles cm-2. All restriction patterns of the spontaneous hprt mutants were indistinguishable from the wild type pattern. These mutants probably contain small deletions or point mutations in the hprt locus. In contrast, the overall spectrum of heavy ion induced mutations revealed a majority (67%) of partial or complete deletions of the hprt gene. With constant particle fluence (3× 106 particles cm-2) the quality of heavy ion induced mutations in the hprt locus depends on physical

  4. 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.

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

    For the past several decades, research in understanding the molecular basis of human aging has progressed significantly with the analysis of premature aging syndromes. Progerin, an altered form of lamin A, has been identified as the cause of premature aging in Hutchinson-Gilford Progeria Syndrome (HGPS), and may be a contributing causative factor in normal aging. However, the question of whether HGPS actually recapitulates the normal aging process at the cellular and organismal level, or simply mimics the aging phenotype is widely debated. In the present study we analyzed publicly available microarray datasets for fibroblasts undergoing cellular aging in culture, as well as fibroblasts derived from young, middle-age, and old-age individuals, and patients with HGPS. Using GeroScope pathway analysis and drug discovery platform we analyzed the activation states of 65 major cellular signaling pathways. Our analysis reveals that signaling pathway activation states in cells derived from chronologically young patients with HGPS strongly resemble cells taken from normal middle-aged and old individuals. This clearly indicates that HGPS may truly represent accelerated aging, rather than being just a simulacrum. Our data also points to potential pathways that could be targeted to develop drugs and drug combinations for both HGPS and normal aging. PMID:25587796

  7. 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.

  8. Accelerated Bone Mass Senescence After Hematopoietic Stem Cell Transplantation

    PubMed Central

    Serio, B; Pezzullo, L; Fontana, R; Annunziata, S; Rosamilio, R; Sessa, M; Giudice, V; Ferrara, I; Rocco, M; De Rosa, G; Ricci, P; Tauchmanovà, L; Montuori, N; Selleri, C.

    2013-01-01

    Osteoporosis and avascular necrosis (AVN) are long-lasting and debilitating complications of hematopoietic stem cell transplantation (HSCT). We describe the magnitude of bone loss, AVN and impairment in osteogenic cell compartment following autologous (auto) and allogeneic (allo) HSCT, through the retrospective bone damage revaluation of 100 (50 auto- and 50 allo-HSCT) long-term survivors up to 15 years after transplant. Current treatment options for the management of these complications are also outlined. We found that auto- and allo-HSCT recipients show accelerated bone mineral loss and micro-architectural deterioration during the first years after transplant. Bone mass density (BMD) at the lumbar spine, but not at the femur neck, may improve in some patients after HSCT, suggesting more prolonged bone damage in cortical bone. Phalangeal BMD values remained low for even more years, suggesting persistent bone micro-architectural alterations after transplant. The incidence of AVN was higher in allo-HSCT recipients compared to auto-HSCT recipients. Steroid treatment length, but not its cumulative dose was associated with a higher incidence of bone loss. Allo-HSCT recipients affected by chronic graft versus host disease seem to be at greater risk of continuous bone loss and AVN development. Reduced BMD and higher incidence of AVN was partly related to a reduced regenerating capacity of the normal marrow osteogenic cell compartment. Our results suggest that all patients after auto-HSCT and allo-HSCT should be evaluated for their bone status and treated with anti-resorptive therapy as soon as abnormalities are detected. PMID:23905076

  9. Cardiac stem cell aging and heart failure.

    PubMed

    Cesselli, Daniela; Aleksova, Aneta; Mazzega, Elisa; Caragnano, Angela; Beltrami, Antonio Paolo

    2017-01-19

    A side effect of the medical improvements of the last centuries is the progressive aging of the world population, which is estimated to reach the impressive number of 2 billion people with more than 65 years by 2050. As a consequence, age-related diseases, such as heart failure, will affect more and more patients in the next years. To understand the biological bases of these diseases will be a crucial task in order to find better treatments, and possibly slow age-related morbidity and mortality. Cardiac stem cells have been at the center of a heated debate and their potential involvement in cardiac homeostasis has been questioned. In this review, we summarize evidence obtained by independent groups, on different animal models and humans, that strongly support the important role played by immature, cardiac resident cells in the cardioprotection against heart failure.

  10. Stem Cells, Redox Signaling, and Stem Cell Aging

    PubMed Central

    Liang, Raymond

    2014-01-01

    Abstract Significance: Functional stem cell decline has been postulated to result in loss of maintenance of tissue homeostasis leading to organismal decline and diseases of aging. Recent Advances: Recent findings implicate redox metabolism in the control of stem cell pool and stem cell aging. Although reactive oxygen species (ROS) are better known for their damaging properties to DNA, proteins and lipids, recent findings suggest that ROS may also be an integral physiological mediator of cellular signaling in primary cells. Critical Issues: Here we review recent published work on major signaling pathways and transcription factors that are regulated by ROS and mediate ROS regulation of stem cell fate. We will specifically focus on how alterations in this regulation may be implicated in disease and particularly in diseases of stem cell aging. In general, based on the work described here we propose a model in which ROS function as stem cell rheostat. Future Directions: Future work in elucidating how ROS control stem cell cycling, apoptotic machinery, and lineage determination should shed light on mechanisms whereby ROS may control stem cell aging. Antioxid. Redox Signal. 20, 1902–1916. PMID:24383555

  11. 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.

  12. 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.

  13. Splicing-directed therapy in a new mouse model of human accelerated aging.

    PubMed

    Osorio, Fernando G; Navarro, Claire L; Cadiñanos, Juan; López-Mejía, Isabel C; Quirós, Pedro M; Bartoli, Catherine; Rivera, José; Tazi, Jamal; Guzmán, Gabriela; Varela, Ignacio; Depetris, Danielle; de Carlos, Félix; Cobo, Juan; Andrés, Vicente; De Sandre-Giovannoli, Annachiara; Freije, José M P; Lévy, Nicolas; López-Otín, Carlos

    2011-10-26

    Hutchinson-Gilford progeria syndrome (HGPS) is caused by a point mutation in the LMNA gene that activates a cryptic donor splice site and yields a truncated form of prelamin A called progerin. Small amounts of progerin are also produced during normal aging. Studies with mouse models of HGPS have allowed the recent development of the first therapeutic approaches for this disease. However, none of these earlier works have addressed the aberrant and pathogenic LMNA splicing observed in HGPS patients because of the lack of an appropriate mouse model. Here, we report a genetically modified mouse strain that carries the HGPS mutation. These mice accumulate progerin, present histological and transcriptional alterations characteristic of progeroid models, and phenocopy the main clinical manifestations of human HGPS, including shortened life span and bone and cardiovascular aberrations. Using this animal model, we have developed an antisense morpholino-based therapy that prevents the pathogenic Lmna splicing, markedly reducing the accumulation of progerin and its associated nuclear defects. Treatment of mutant mice with these morpholinos led to a marked amelioration of their progeroid phenotype and substantially extended their life span, supporting the effectiveness of antisense oligonucleotide-based therapies for treating human diseases of accelerated aging.

  14. Stability of ethyl glucuronide in hair reference materials after accelerated aging.

    PubMed

    Ammann, D; Becker, R; Nehls, I

    2015-12-01

    Two different hair reference materials, one produced from authentic hair displaying an ethyl glucuronide (EtG) content of about 25 pg/mg and one obtained by fortification of blank hair to an EtG level of 85 pg/mg were submitted to accelerated aging between 4 °C and 60 °C for periods between one and 24 months. Subsequently, the EtG content was determined in the aged samples and untreated reference samples stored at -22 °C under repeatability conditions following the so-called isochronous approach. The EtG content remained stable even at 40 °C for 24 months and at 60 °C over six months. This is in contrast to many organic analytes contained in trace concentrations in diverse matrices. A slight but significant increase of the recovered EtG in case of authentic hair samples having been exposed for 24 months between 4 °C and 60 °C may be due to a temperature-driven process that allows increased recoveries of the physiologically embedded EtG.

  15. Obesity and aging: determinants of endothelial cell dysfunction and atherosclerosis.

    PubMed

    Barton, Matthias

    2010-10-01

    Endothelial cells are both the source and target of factors contributing to atherosclerosis. After the discovery of the endothelium-derived relaxing factor (EDRF) by Robert F. Furchgott in 1980 it soon became clear that endothelial cells also release vasoactive factors distinct from nitric oxide (NO) namely, endothelium-derived contracting factors (EDCF) as well as hyperpolarizing factors (EDHF). Vasoactive factors derived from endothelial cells include NO/EDRF, reactive oxygen species, endothelins and angiotensins which have either EDRF or EDCF functions, cyclooxygenase-derived EDCFs and EDRFs, and EDHFs. Endothelial factors are formed by enzymes such as NO synthase, cyclooxygenase, converting enyzmes, NADPH oxidases, and epoxigenases, among others, and participate in the regulation of vascular homeostasis under physiological conditions; however, their abnormal regulation due to endothelial cell dysfunction contributes to disease processes such as atherosclerosis, arterial hypertension, and renal disease. Because of recent changes in world demographics and the declining health status of the world's population, both aging and obesity as independent risk factors for atherosclerosis-related diseases such as coronary artery disease and stroke, will continue to increase in the years to come. Obesity and associated conditions such as arterial hypertension and diabetes are now also some of the primary health concerns among children and adolescents. The similarities of pathomechanisms activated in obesity and aging suggest that obesity--at least in the vasculature--can be considered to have effects consistent with accelerated, "premature" aging. Pathomechanisms as well as the clinical issues of obesity- and aging-associated vascular changes important for atherosclerosis development and prevention are discussed.

  16. The anti-aging effects of LW-AFC via correcting immune dysfunctions in senescence accelerated mouse resistant 1 (SAMR1) strain

    PubMed Central

    Wang, Jianhui; Cheng, Xiaorui; Zhang, Xiaorui; Cheng, Junping; Xu, Yiran; Zeng, Ju; Zhou, Wenxia; Zhang, Yongxiang

    2016-01-01

    Although there were considerable advances in the anti-aging medical field, it is short of therapeutic drug for anti-aging. Mounting evidence indicates that the immunosenescence is the key physiopathological mechanism of aging. This study showed the treatment of LW-AFC, an herbal medicine, decreased the grading score of senescence, increased weight, prolonged average life span and ameliorated spatial memory impairment in 12- and 24-month-old senescence accelerated mouse resistant 1 (SAMR1) strain. And these anti-aging effects of LW-AFC were more excellent than melatonin. The administration of LW-AFC enhanced ConA- and LPS-induced splenocyte proliferation in aged SAMR1 mice. The treatment of LW-AFC not only reversed the decreased the proportions of helper T cells, suppressor T cells and B cells, the increased regulatory T cells in the peripheral blood of old SAMR1 mice, but also could modulate the abnormal secretion of IL-1β, IL-2, IL-6, IL-17, IL-23, GM-CSF, IFN-γ, TNF-α, TNF-β, RANTES, eotaxin, MCP-1, IL-4, IL-5, IL-10 and G-CSF. These data indicated that LW-AFC reversed the immunosenescence status by restoring immunodeficiency and decreasing chronic inflammation and suggested LW-AFC may be an effective anti-aging agent. PMID:27105505

  17. The anti-aging effects of LW-AFC via correcting immune dysfunctions in senescence accelerated mouse resistant 1 (SAMR1) strain.

    PubMed

    Wang, Jianhui; Cheng, Xiaorui; Zhang, Xiaorui; Cheng, Junping; Xu, Yiran; Zeng, Ju; Zhou, Wenxia; Zhang, Yongxiang

    2016-05-10

    Although there were considerable advances in the anti-aging medical field, it is short of therapeutic drug for anti-aging. Mounting evidence indicates that the immunosenescence is the key physiopathological mechanism of aging. This study showed the treatment of LW-AFC, an herbal medicine, decreased the grading score of senescence, increased weight, prolonged average life span and ameliorated spatial memory impairment in 12- and 24-month-old senescence accelerated mouse resistant 1 (SAMR1) strain. And these anti-aging effects of LW-AFC were more excellent than melatonin. The administration of LW-AFC enhanced ConA- and LPS-induced splenocyte proliferation in aged SAMR1 mice. The treatment of LW-AFC not only reversed the decreased the proportions of helper T cells, suppressor T cells and B cells, the increased regulatory T cells in the peripheral blood of old SAMR1 mice, but also could modulate the abnormal secretion of IL-1β, IL-2, IL-6, IL-17, IL-23, GM-CSF, IFN-γ, TNF-α, TNF-β, RANTES, eotaxin, MCP-1, IL-4, IL-5, IL-10 and G-CSF. These data indicated that LW-AFC reversed the immunosenescence status by restoring immunodeficiency and decreasing chronic inflammation and suggested LW-AFC may be an effective anti-aging agent.

  18. Cannabis exposure as an interactive cardiovascular risk factor and accelerant of organismal ageing: a longitudinal study

    PubMed Central

    Reece, Albert Stuart; Hulse, Gary Kenneth

    2016-01-01

    Objectives Many reports exist of the cardiovascular toxicity of smoked cannabis but none of arterial stiffness measures or vascular age (VA). In view of its diverse toxicology, the possibility that cannabis-exposed patients may be ageing more quickly requires investigation. Design Cross-sectional and longitudinal, observational. Prospective. Setting Single primary care addiction clinic in Brisbane, Australia. Participants 11 cannabis-only smokers, 504 tobacco-only smokers, 114 tobacco and cannabis smokers and 534 non-smokers. Exclusions: known cardiovascular disease or therapy or acute exposure to alcohol, amphetamine, heroin or methadone. Intervention Radial arterial pulse wave tonometry (AtCor, SphygmoCor, Sydney) performed opportunistically and sequentially on patients between 2006 and 2011. Main outcome measure Algorithmically calculated VA. Secondary outcomes: other central haemodynamic variables. Results Differences between group chronological ages (CA, 30.47±0.48 to 40.36±2.44, mean±SEM) were controlled with linear regression. Between-group sex differences were controlled by single-sex analysis. Mean cannabis exposure among patients was 37.67±7.16 g-years. In regression models controlling for CA, Body Mass Index (BMI), time and inhalant group, the effect of cannabis use on VA was significant in males (p=0.0156) and females (p=0.0084). The effect size in males was 11.84%. A dose–response relationship was demonstrated with lifetime exposure (p<0.002) additional to that of tobacco and opioids. In both sexes, the effect of cannabis was robust to adjustment and was unrelated to its acute effects. Significant power interactions between cannabis exposure and the square and cube of CA were demonstrated (from p<0.002). Conclusions Cannabis is an interactive cardiovascular risk factor (additional to tobacco and opioids), shows a prominent dose–response effect and is robust to adjustment. Cannabis use is associated with an acceleration of the cardiovascular

  19. Accelerated calendar and pulse life analysis of lithium-ion cells

    NASA Astrophysics Data System (ADS)

    Jungst, Rudolph G.; Nagasubramanian, Ganesan; Case, Herbert L.; Liaw, Bor Yann; Urbina, Angel; Paez, Thomas L.; Doughty, Daniel H.

    Sandia National Laboratories has been studying calendar and pulse discharge life of prototype high-power lithium-ion cells as part of the Advanced Technology Development (ATD) Program. One of the goals of ATD is to establish validated accelerated life test protocols for lithium-ion cells in the hybrid electric vehicle application. In order to accomplish this, aging experiments have been conducted on 18650-size cells containing a chemistry representative of these high-power designs. Loss of power and capacity are accompanied by increasing interfacial impedance at the cathode. These relationships are consistent within a given state-of-charge (SOC) over the range of storage temperatures and times. Inductive models have been used to construct detailed descriptions of the relationships between power fade and aging time and to relate power fade, capacity loss and impedance rise. These models can interpolate among the different experimental conditions and can also describe the error surface when fitting life prediction models to the data.

  20. Aging and defective lymphoid cell activation.

    PubMed

    Coffman, F D; Cohen, S

    1989-01-01

    Activation of lymphocytes for proliferation is a crucial process in the immune response. Age-related deficiencies in this cellular response strongly correlate with deficiencies in the immune system response, with concomitant increase in disease severity and mortality. Defects associated with the transmission of the initial activation signal and with IL-2 production contribute to the depressed response, but defects in the IL-2 response mechanism also play important roles. A major factor in this area is the inability of the nuclei of these cells to respond to the intracellular factor ADR, which plays a crucial role in the initiation of DNA replication. These cells produce normal levels of ADR; thus, either the nuclei cannot bind ADR in a productive manner or the defect lies beyond the point of ADR binding, perhaps in one of the other proteins of the initiation complex. An interesting contrast to the age-related failure of nuclei to respond to ADR is the failure of neoplastic nuclei to respond to the ADR inhibitor. This inhibitor, found in the cytoplasm of quiescent cells, suppresses both the activation of quiescent nuclei by ADR and the ongoing DNA synthesis in isolated nuclei from activated cells. Nuclei from spontaneous proliferating cell lines were not affected by this inhibitor, which may be an important factor in the uncontrolled growth seen in neoplastic cells. The investigation of ADR has given hints that perhaps two of the fundamental questions in biology, namely why some cells don't proliferate and why some others won't stop proliferating, may be two sides of the same coin.

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

    PubMed

    Os'mak, E D; Asanov, É O

    2014-01-01

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

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

    PubMed

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

    2017-01-09

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

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

    PubMed

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

    2015-05-30

    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.

  4. 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

  5. Effect of Accelerated Artificial Aging on Translucency of Methacrylate and Silorane-Based Composite Resins

    PubMed Central

    Shirinzad, Mehdi; Rezaei-Soufi, Loghman; Mirtorabi, Maryam Sadat; Vahdatinia, Farshid

    2016-01-01

    Objectives: Composite restorations must have tooth-like optical properties namely color and translucency and maintain them for a long time. This study aimed to compare the effect of accelerated artificial aging (AAA) on the translucency of three methacrylate-based composites (Filtek Z250, Filtek Z250XT and Filtek Z350XT) and one silorane-based composite resin (Filtek P90). Materials and Methods: For this in vitro study, 56 composite discs were fabricated (n=14 for each group). Using scanning spectrophotometer, CIE L*a*b* parameters and translucency of each specimen were measured at 24 hours and after AAA for 384 hours. Data were analyzed using one-way ANOVA, Tukey's test and paired t-test at P=0.05 level of significance. Results: The mean (±standard deviation) translucency parameter for Filtek Z250, Filtek Z250XT, Filtek Z350XT and Filtek P90 was 5.67±0.64, 4.59±0.77, 7.87±0.82 and 4.21±0.71 before AAA and 4.25±0.615, 3.53±0.73, 5.94±0.57 and 4.12±0.54 after AAA, respectively. After aging, the translucency of methacrylate-based composites decreased significantly (P<0.05). However, the translucency of Filtek P90 did not change significantly (P>0.05). Conclusions: The AAA significantly decreased the translucency of methacrylate-based composites (Filtek Z250, Filtek Z250XT and Filtek Z350XT) but no change occurred in the translucency of Filtek P90 silorane-based composite. PMID:27928237

  6. 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

  7. 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.

  8. 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.

  9. Effect of Accelerated Aging on Color Change of Direct and Indirect Fiber-Reinforced Composite Restorations

    PubMed Central

    Tabatabaei, Masoumeh Hasani; Farahat, Farnaz; Ahmadi, Elham; Hassani, Zahra

    2016-01-01

    Objectives: The aim of this study was to assess the effect of artificial accelerated aging (AAA) on color change of direct and indirect fiber-reinforced composite (FRC) restorations. Materials and Methods: Direct (Z250) and indirect (Gradia) composite resins were reinforced with glass (GF) and polyethylene fibers (PF) based on the manufacturers’ instructions. Forty samples were fabricated and divided into eight groups (n=5). Four groups served as experimental groups and the remaining four served as controls. Color change (ΔE) and color parameters (ΔL*, Δa*, Δb*) were read at baseline and after AAA based on the CIELAB system. Three-way ANOVA and Tukey’s test were used for statistical analysis. Results: Significant differences were found in ΔE, ΔL*, Δa* and Δb* among the groups after AAA (P<0.05). Most of the studied samples demonstrated an increase in lightness and a red-yellow shift after AAA. Conclusions: The obtained ΔE values were unacceptable after AAA (ΔE≥ 3.3). All indirect samples showed a green-blue shift with a reduction in lightness except for Gradia/PF+ NuliteF. PMID:28392813

  10. TP508 accelerates fracture repair by promoting cell growth over cell death

    SciTech Connect

    Li Xinmin; Wang Hali; Touma, Edward; Qi Yuchen; Rousseau, Emma; Quigg, Richard J.; Ryaby, James T.

    2007-12-07

    TP508 is a synthetic 23-amino acid peptide representing a receptor-binding domain of human thrombin. We have previously shown that a single injection of TP508 accelerates fracture healing in a rat femoral fracture model. To understand how TP508 acts at the protein level during fracture healing, we compared the translational profiles between saline-control and fractured femur at six time points after TP508 treatment using the second generation of BD Clontech{sup TM} Antibody Microarray. Here, we demonstrate that TP508 accelerates fracture healing by modulating expression levels of proteins primarily involved in the functional categories of cell cycle, cellular growth and proliferation, and cell death. The majority of those proteins are physically interrelated and functionally overlapped. The action of those proteins is highlighted by a central theme of promoting cell growth via balance of cell survival over cell death signals. This appears to occur through the stimulation of several bone healing pathways including cell cycle-G1/S checkpoint regulation, apoptosis, JAK/STAT, NF-{kappa}B, PDGF, PI3K/AKT, PTEN, and ERK/MAPK.

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

    PubMed Central

    Magano, Sara; Marrana, Francisco; Andrade, José P.

    2015-01-01

    Abstract The model of accelerated senescence with the prolonged administration of d-galactose is used in anti-aging studies because it mimics several aging-associated alterations such as increase of oxidative stress and decline of cognition. However, there is no standardized protocol for this aging model, and recently some reports have questioned its effectiveness. To clarify this issue, we used a model of high-dose d-galactose on 1-month-old male Wistar rats and studied the hippocampus, one of the most affected brain regions. In one group (n = 10), d-galactose was daily administered intraperitoneally (300 mg/kg) during 8 weeks whereas age-matched controls (n = 10) were injected intraperitoneally with saline. A third group (n = 10) was treated with the same dose of d-galactose and with oral epigallocatechin-3-gallate (EGCG) (2 grams/L), a green tea catechin with anti-oxidant and neuroprotective properties. After treatments, animals were submitted to open-field, elevated plus-maze and Morris water maze tests, and neurogenesis in the dentate gyrus subgranular layer was quantified. There were no significant alterations when the three groups were compared in the number of doublecortin- and Ki-67–immunoreactive cells, and also on anxiety levels, spatial learning, and memory. Therefore, d-galactose was not effective in the induction of accelerated aging, and EGCG administered to d-galactose–treated animals did not improve behavior and had no effects on neurogenesis. We conclude that daily 300 mg/kg of d-galactose administered intraperitoneally may not be a suitable model for inducing age-related neurobehavioral alterations in young male Wistar rats. More studies are necessary to obtain a reliable and reproducible model of accelerated senescence in rodents using d-galactose. PMID:25936362

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    2011-01-01

    Aging is unavoidable and natural phenomenon of life. Modern gerontologists are realizing the fact that aging is a disease, which Ayurveda had accepted as natural disease since long. Rate of aging is determined by one's biological, social, lifestyle, and psychological conditions and adversity of which leads to accelerated form of aging (Akalaja jara or premature aging). The aim of this study is to identify potential factors that may accelerate aging in the context of dietry factors, lifestyle and mental makeup. The 120 diagnosed subjects of premature-ageing of 30-60 years were randomly selected in the survey study. Premature ageing was common among females (75.83%), in 30-40 age group (70%), 86.67% were married, had secondary level of education (36.66%), house-views (61.67%), belongs top middle class (58.33%) and engaged in occupations that dominating physical labour (88.33%). The maximum patients are constipated (60%), had mandagni (80%), vata-kapha prakriti (48.33%), rajasika prakriti (58.33%), madhyama vyayama shakti (73.33%), and madhyama jarana shakti (85.83%). Collectively, 43.33% patients were above normal BMI. The more patients had anushna (38.33%) and vishamasana dietary pattern (25.83%), consumed Lavana (88.33%) and Amla rasa (78.33%) in excess on regular basis. Some patients had addicted to tobacco (11.67%) and beetle chewing (5.83%). The maximum patients had no any exercise (79.17%) and specific hobby (79.17%) in their leisure times. Analyzing Hamilton Anxiety and Depression Rating Scales revealed that 39.80%, 37.86%, 33.98%, 24.27% and 18.44% patients had insomnia, depression, tension, GIT symptoms and anxious mood respectively. These data suggest that certain social, dietary and lifestyle factors contribute towards accelerated ageing among young individuals. PMID:22529643

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

    PubMed

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

    2011-07-01

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

  15. Memory B cell subpopulations in the aged.

    PubMed

    Colonna-Romano, Giuseppina; Aquino, Alessandra; Bulati, Matteo; Di Lorenzo, Gabriele; Listì, Florinda; Vitello, Salvatore; Lio, Domenico; Candore, Giuseppina; Clesi, Gioacchino; Caruso, Calogero

    2006-01-01

    The literature on immunosenescence has focused mainly on T cell impairment. With the aim of gaining insight into B cell immunosenescence, the authors investigated the serum IgD levels in 24 young and 21 old people and analyzed their relationship with the number of CD19+CD27+ memory cells. Serum IgD were quantified by the use of radial immunodiffusion and the lymphocyte population CD19+CD27+ was identified by a FACScan flow cytometer. Serum IgD levels were significantly lower (p < 0.0001) in old subjects, and the percentage of CD19+CD27+ lymphocytes were significantly increased (p = 0.01) in old subjects. Finally, a significant negative correlation was found (p = 0.01) between serum concentrations of IgD and CD19+CD27+. The present results show that the levels of IgD are negatively age-related to the amount of B memory cells. This suggests that the B repertoire available to respond to new antigenic challenges is decreased in the elderly. In fact, many memory IgD- B cells fill immunologic space, and the number of naïve IgD+ B cells is dramatically decreased. Therefore, these preliminary results suggest that a decrease of naïve IgD+CD27- B cells and a concomitant increase of memory IgD-CD27+ B cells could represent hallmarks of B immunosenescence, might provide biomarkers related to the lifespan of humans, and could be useful for the evaluation of antiaging treatments.

  16. Aging and insulin signaling differentially control normal and tumorous germline stem cells.

    PubMed

    Kao, Shih-Han; Tseng, Chen-Yuan; Wan, Chih-Ling; Su, Yu-Han; Hsieh, Chang-Che; Pi, Haiwei; Hsu, Hwei-Jan

    2015-02-01

    Aging influences stem cells, but the processes involved remain unclear. Insulin signaling, which controls cellular nutrient sensing and organismal aging, regulates the G2 phase of Drosophila female germ line stem cell (GSC) division cycle in response to diet; furthermore, this signaling pathway is attenuated with age. The role of insulin signaling in GSCs as organisms age, however, is also unclear. Here, we report that aging results in the accumulation of tumorous GSCs, accompanied by a decline in GSC number and proliferation rate. Intriguingly, GSC loss with age is hastened by either accelerating (through eliminating expression of Myt1, a cell cycle inhibitory regulator) or delaying (through mutation of insulin receptor (dinR) GSC division, implying that disrupted cell cycle progression and insulin signaling contribute to age-dependent GSC loss. As flies age, DNA damage accumulates in GSCs, and the S phase of the GSC cell cycle is prolonged. In addition, GSC tumors (which escape the normal stem cell regulatory microenvironment, known as the niche) still respond to aging in a similar manner to normal GSCs, suggesting that niche signals are not required for GSCs to sense or respond to aging. Finally, we show that GSCs from mated and unmated females behave similarly, indicating that female GSC-male communication does not affect GSCs with age. Our results indicate the differential effects of aging and diet mediated by insulin signaling on the stem cell division cycle, highlight the complexity of the regulation of stem cell aging, and describe a link between ovarian cancer and aging.

  17. Aging and insulin signaling differentially control normal and tumorous germline stem cells

    PubMed Central

    Kao, Shih-Han; Tseng, Chen-Yuan; Wan, Chih-Ling; Su, Yu-Han; Hsieh, Chang-Che; Pi, Haiwei; Hsu, Hwei-Jan

    2015-01-01

    Aging influences stem cells, but the processes involved remain unclear. Insulin signaling, which controls cellular nutrient sensing and organismal aging, regulates the G2 phase of Drosophila female germ line stem cell (GSC) division cycle in response to diet; furthermore, this signaling pathway is attenuated with age. The role of insulin signaling in GSCs as organisms age, however, is also unclear. Here, we report that aging results in the accumulation of tumorous GSCs, accompanied by a decline in GSC number and proliferation rate. Intriguingly, GSC loss with age is hastened by either accelerating (through eliminating expression of Myt1, a cell cycle inhibitory regulator) or delaying (through mutation of insulin receptor (dinR) GSC division, implying that disrupted cell cycle progression and insulin signaling contribute to age-dependent GSC loss. As flies age, DNA damage accumulates in GSCs, and the S phase of the GSC cell cycle is prolonged. In addition, GSC tumors (which escape the normal stem cell regulatory microenvironment, known as the niche) still respond to aging in a similar manner to normal GSCs, suggesting that niche signals are not required for GSCs to sense or respond to aging. Finally, we show that GSCs from mated and unmated females behave similarly, indicating that female GSC–male communication does not affect GSCs with age. Our results indicate the differential effects of aging and diet mediated by insulin signaling on the stem cell division cycle, highlight the complexity of the regulation of stem cell aging, and describe a link between ovarian cancer and aging. PMID:25470527

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

    PubMed

    Jaroonwitchawan, Thiranut; Muangchan, Pattamon; Noisa, Parinya

    2016-12-02

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

  19. 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.

  20. Antioxidants, free radicals, storage proteins, puroindolines, and proteolytic activities in bread wheat (Triticum aestivum) seeds during accelerated aging.

    PubMed

    Calucci, Lucia; Capocchi, Antonella; Galleschi, Luciano; Ghiringhelli, Silvia; Pinzino, Calogero; Saviozzi, Franco; Zandomeneghi, Maurizio

    2004-06-30

    Seeds of bread wheat were incubated at 40 degrees C and 100% relative humidity for 0, 3, 4, 6, and 10 days. The effects of accelerated aging on seed germinability and some biochemical properties of flour (carotenoid, free radical, and protein contents and proteolytic activity) and gluten (free radical content and flexibility) were investigated. Seed germinability decreased during aging, resulting in seed death after 10 days. A progressive decrease of carotenoid content, in particular, lutein, was observed, prolonging the incubation, whereas the free radical content increased in both flour and gluten. A degradation of soluble and storage proteins was found, associated with a marked increase of proteolytic activity and a loss of viscoelastic properties of gluten. On the contrary, puroindolines were quite resistant to the treatment. The results are discussed in comparison with those previously obtained during accelerated aging of durum wheat seeds.

  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. 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.

  3. 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.

  4. 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

  5. Accelerated test program for sealed nickel-cadmium spacecraft batteries/cells

    NASA Technical Reports Server (NTRS)

    Goodman, L. A.

    1976-01-01

    The feasibility was examined of inducing an accelerated test on sealed Nickel-Cadmium batteries or cells as a tool for spacecraft projects and battery users to determine: (1) the prediction of life capability; (2) a method of evaluating the effect of design and component changes in cells; and (3) a means of reducing time and cost of cell testing.

  6. 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.

  7. [Morphological changes of neurons and neuroglial cells in the brain of senescence-accelerated prone 1 (SAMP1) mice].

    PubMed

    Khudoerkov, R M; Sal'kov, V N; Sal'nikova, O V; Sobolev, V B

    2014-01-01

    Computerized morphometry was used to examine the sizes of neuronal bodies and the compactness of arrangement of neurons and neuroglial cells in layers III and V of the sensorimotor cortex in senescence-accelerated prone 1 (SAMP1) mice (an experimental group) and senescence-accelerated-resistant strain 1 (SAMR1) ones (a control group). In the SAMP1 mice as compared to the SAMR1 ones, the neuronal body sizes were significantly unchanged; the compactness of their arrangement decreased by 17 and 20% in layers III and V, respectively; that of neuroglial cells significantly increased by 14% in layer III only. In the SAMP1 mice versus the SAMR1 ones, the glial index rose by 36% in layer III and by 24% in layer V. During simulation of physiological aging, the sizes of neuronal bodies were shown to be virtually unchanged in the cerebral cortex; the compactness of their arrangement (cell counts) moderately reduced and that of neuroglial cells increased, which caused a rise in the glioneuronal index that was indicative of the enhanced supporting function of neuroglial cells during the physiological aging of brain structures.

  8. Cell cycle of primitive hematopoietic progenitors decelerated in senescent mice is reactively accelerated after 2-Gy whole-body irradiation.

    PubMed

    Hirabayashi, Yoko; Tsuboi, Isao; Kuramoto, Kazunao; Kusunoki, Yoichiro; Inoue, Tohru

    2016-03-01

    Aging is considered to be a functional retardation of continuous xenobiotic responses over a lifetime after the developmental period; thus, the effects of ionizing radiation over a lifetime may be somewhat accounted for by a modifier of aging effects. This study was conducted to evaluate the possible/synergic effects of radiation during aging by determining cell-cycle parameters of hematopoietic stem cells/hematopoietic progenitor cells (HSCs/HPCs), such as the percent of cells in cycling, the generation doubling time, and the cumulative cycling-cell fraction, by bromodeoxyuridine-ultraviolet assay, which enables the determination of their cycling capacity in vivo. Colony-forming progenitor cells, such as colony-forming unit (CFU)-granulocyte/macrophage (GM), CFU in the spleen on day 9 (CFU-S9), and CFU-S on day 13 (CFU-S13) for mature, less mature, and immature HPCs, respectively, were evaluated in young and old mice (6 weeks and 21 months of age, respectively) with or without 2-Gy whole-body irradiation and a 4-week recovery period. Then, cell-cycle parameters were evaluated and compared. As a result, the generation doubling time of all types of HPC was prolonged by the irradiation in both young and old mouse groups, except that of CFU-S13 in old mice, which showed acceleration of the cell cycle following the irradiation. In addition, only CFU-S13 in irradiated old mice showed a significant increase in the cumulative cycling-cell-fraction ratio. Significant changes due to the effects of aging and irradiation on HPCs were observed only in the immature HPCs, i.e., the cell cycle of immature HPCs was suppressed by aging without irradiation and was, in contrast, accelerated as the cells recovered from radiation-induced damage. This suggests that the mechanisms of peripheral blood recovery after 2-Gy whole-body irradiation are markedly different between young and old mice, although 21-month-old mice showed almost the same level of recovery as the young mice.

  9. 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

  10. 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.

  11. 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

    2015-04-24

    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. Accelerated aging of thermally activated batteries which utilize the Li/Si//LiCl-KCl/FeS2 system

    NASA Astrophysics Data System (ADS)

    Searcy, J. Q.; Neiswander, P. A.

    The thermally activated Li(Si)/LiCl-KCl/FeS2 batteries considered are intended for applications which require high reliability and a shelf life of 25 years. In order to determine the feasibility of achieving these requirements, an accelerated aging study was undertaken. The major objective of this work was to identify deleterious chemical reactions that could affect performance and reliability during the 25 year shelf life. The approach used was to accelerate the aging of batteries by storage at elevated temperature, and then to examine and analyze materials from some batteries, while discharging others. The results of the study indicate that the reaction of Li(Si) with water outgassed from the various battery parts is deleterious to shelf life. No other deleterious effects were observed.

  13. 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.

  14. Effect of age on epithelial cell migration in small intestine of chickens.

    PubMed

    Moon, H W; Skartvedt, S M

    1975-02-01

    Villous length, crypt depth, epithelial cell migration rate, and replacement time were studied by autoradiography of histologic sections of small intestine from normal chickens exposed to tritiated thymidine (3-H-TdR). The results indicated that villi and crypts elongate, and epithelial cell migration accelerates between 1 day and 6 months of age. Epithelial replacement time seemed to increase with age of the chickens. Replacement was nearly complete in the 1-day-old group of chickens 5 days after thymidine exposure. In contrast, at this same time, replacement was only approximately 75 and 50% complete in the 3-week-old and 6-month-old groups of chickens, respectively.

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

    PubMed Central

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

    2010-01-01

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

  16. Aging affects initiation and continuation of T cell proliferation.

    PubMed

    Jiang, Jiu; Gross, Diara; Elbaum, Philip; Murasko, Donna M

    2007-04-01

    Aging is associated with a decline in immune responses, particularly within the T cell compartment. While the expansion of specific T cells in response to virus infections is consistently decreased in aged mice, the differences in T cell activation between young and aged mice as demonstrated in each round of proliferation remain poorly defined. In the present study, we utilized the T cell mitogen, ConA, to explore if fewer T cells of aged mice initiate proliferation upon mitogen stimulation or if similar numbers of T cells of aged mice begin proliferation but undergo fewer rounds of division. We also examined whether these age-associated changes in proliferation are reflected by differences in T cell activation by comparing activation markers (CD25, CD69, CD44, and CD62L) on T cells of young and aged mice at each round of proliferation. Not only was the kinetics of the expression of these markers greatly different between young and aged mice on the entire CD8 T cell population, but also at each round of proliferation. Our results demonstrate that a larger percentage of CD8 T cells of aged mice do not proliferate at all upon stimulation. Of the CD8 T cells of aged mice that do proliferate, a larger percentage start later and stop sooner. These results suggest that multiple levels of alteration may need to be considered when trying to maximize the immune response of aged individuals.

  17. 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.

  18. Increased superoxide in vivo accelerates age-associated muscle atrophy through mitochondrial dysfunction and neuromuscular junction degeneration

    PubMed Central

    Jang, Youngmok C.; Lustgarten, Michael S.; Liu, Yuhong; Muller, Florian L.; Bhattacharya, Arunabh; Liang, Hanyu; Salmon, Adam B.; Brooks, Susan V.; Larkin, Lisa; Hayworth, Christopher R.; Richardson, Arlan; Van Remmen, Holly

    2010-01-01

    Oxidative stress has been implicated in the etiology of age-related muscle loss (sarcopenia). However, the underlying mechanisms by which oxidative stress contributes to sarcopenia have not been thoroughly investigated. To directly examine the role of chronic oxidative stress in vivo, we used a mouse model that lacks the antioxidant enzyme CuZnSOD (Sod1). Sod1−/− mice are characterized by high levels of oxidative damage and an acceleration of sarcopenia. In the present study, we demonstrate that muscle atrophy in Sod1−/− mice is accompanied by a progressive decline in mitochondrial bioenergetic function and an elevation of mitochondrial generation of reactive oxygen species. In addition, Sod1−/− muscle exhibits a more rapid induction of mitochondrial-mediated apoptosis and loss of myonuclei. Furthermore, aged Sod1−/− mice show a striking increase in muscle mitochondrial content near the neuromuscular junctions (NMJs). Despite the increase in content, the function of mitochondria is significantly impaired, with increased denervated NMJs and fragmentation of acetylcholine receptors. As a consequence, contractile force in aged Sod1−/− muscles is greatly diminished. Collectively, we show that Sod1−/− mice display characteristics of normal aging muscle in an accelerated manner and propose that the superoxide-induced NMJ degeneration and mitochondrial dysfunction are potential mechanisms of sarcopenia.—Jang, Y. C., Lustgarten, M. S., Liu, Y., Muller, F. L., Bhattacharya, A., Liang, H., Salmon, A. B., Brooks, S. V., Larkin, L., Hayworth, C. R., Richardson, A., and Van Remmen, H. Increased superoxide in vivo accelerates age-associated muscle atrophy through mitochondrial dysfunction and neuromuscular junction degeneration. PMID:20040516

  19. Targeting dendritic cells to accelerate T-cell activation overcomes a bottleneck in tuberculosis vaccine efficacy

    PubMed Central

    Griffiths, Kristin L.; Ahmed, Mushtaq; Das, Shibali; Gopal, Radha; Horne, William; Connell, Terry D.; Moynihan, Kelly D.; Kolls, Jay K.; Irvine, Darrell J.; Artyomov, Maxim N.; Rangel-Moreno, Javier; Khader, Shabaana A.

    2016-01-01

    The development of a tuberculosis (TB) vaccine that induces sterilizing immunity to Mycobacterium tuberculosis infection has been elusive. Absence of sterilizing immunity induced by TB vaccines may be due to delayed activation of mucosal dendritic cells (DCs), and subsequent delay in antigen presentation and activation of vaccine-induced CD4+ T-cell responses. Here we show that pulmonary delivery of activated M. tuberculosis antigen-primed DCs into vaccinated mice, at the time of M. tuberculosis exposure, can overcome the delay in accumulation of vaccine-induced CD4+ T-cell responses. In addition, activating endogenous host CD103+ DCs and the CD40–CD40L pathway can similarly induce rapid accumulation of vaccine-induced lung CD4+ T-cell responses and limit early M. tuberculosis growth. Thus, our study provides proof of concept that targeting mucosal DCs can accelerate vaccine-induced T-cell responses on M. tuberculosis infection, and provide insights to overcome bottlenecks in TB vaccine efficacy. PMID:28004802

  20. 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.

  1. Mechanisms Underlying T Cell Immunosenescence: Aging and Cytomegalovirus Infection

    PubMed Central

    Tu, Wenjuan; Rao, Sudha

    2016-01-01

    The ability of the human immune system to protect against infectious disease declines with age and efficacy of vaccination reduces significantly in the elderly. Aging of the immune system, also termed as immunosenescence, involves many changes in human T cell immunity that is characterized by a loss in naïve T cell population and an increase in highly differentiated CD28- memory T cell subset. There is extensive data showing that latent persistent human cytomegalovirus (HCMV) infection is also associated with age-related immune dysfunction in the T cells, which might enhance immunosenescence. Understanding the molecular mechanisms underlying age-related and HCMV-related immunosenescence is critical for the development of effective age-targeted vaccines and immunotherapies. In this review, we will address the role of both aging and HCMV infection that contribute to the T cell senescence and discuss the potential molecular mechanisms in aged T cells. PMID:28082969

  2. The role of aging upon β cell turnover

    PubMed Central

    Kushner, Jake A.

    2013-01-01

    Preservation and regeneration of β cell endocrine function is a long-sought goal in diabetes research. Defective insulin secretion from β cells underlies both type 1 and type 2 diabetes, thus fueling considerable interest in molecules capable of rebuilding β cell secretion capacity. Though early work in rodents suggested that regeneration might be possible, recent studies have revealed that aging powerfully restricts cell cycle entry of β cells, which may limit regeneration capacity. Consequently, aging has emerged as an enigmatic challenge that might limit β cell regeneration therapies. This Review summarizes recent data regarding the role of aging in β cell regeneration and proposes models explaining these phenomena. PMID:23454762

  3. 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.

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

    DOE PAGES

    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

  5. Degradation Mechanisms and Accelerated Testing in PEM Fuel Cells

    SciTech Connect

    Borup, Rodney L.

    2011-01-01

    The durability of PEM fuel cells is a major barrier to the commercialization of these systems for stationary and transportation power applications. Although there has been recent progress in improving durability, further improvements are needed to meet the commercialization targets. Past improvements have largely been made possible because of the fundamental understanding of the underlying degradation mechanisms. By investigating component and cell degradation modes; defining the fundamental degradation mechanisms of components and component interactions new materials can be designed to improve durability. Various factors have been shown to affect the useful life of PEM fuel cells. Other issues arise from component optimization. Operational conditions (such as impurities in either the fuel or oxidant stream), cell environment, temperature (including subfreezing exposure), pressure, current, voltage, etc.; or transient versus continuous operation, including start-up and shutdown procedures, represent other factors that can affect cell performance and durability.

  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. Successful ageing: from cell to self.

    PubMed Central

    Lupien, S J; Wan, N

    2004-01-01

    Many people see ageing as a time of cognitive and physical decline. For the past three decades, most scientists and the general public have accepted this negative age-stereotype as the norm, but fortunately this view is now challenged. New findings show that well-being and a positive view of ageing are major protective factors against the effects of age on the organism. These results challenge the scientific studies that place emphasis on the negative side of ageing. This ageism view has been observed in each sphere of science, from genetics to social sciences. Perspectives from each domain are described, and new integrative views of successful ageing are summarized. PMID:15347532

  8. Successful ageing: from cell to self.

    PubMed

    Lupien, S J; Wan, N

    2004-09-29

    Many people see ageing as a time of cognitive and physical decline. For the past three decades, most scientists and the general public have accepted this negative age-stereotype as the norm, but fortunately this view is now challenged. New findings show that well-being and a positive view of ageing are major protective factors against the effects of age on the organism. These results challenge the scientific studies that place emphasis on the negative side of ageing. This ageism view has been observed in each sphere of science, from genetics to social sciences. Perspectives from each domain are described, and new integrative views of successful ageing are summarized.

  9. 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.

  10. Targeting Epithelial Cell Migration to Accelerate Wound Healing

    DTIC Science & Technology

    2012-02-01

    consisting of the proteins Rsu1, Integrin Linked Kinase (ILK), PINCH, and Parvin. The correct association of these proteins in a functional complex...impacting integrin function and actin polymerization. 15. SUBJECT TERMS Wound healing, cell migration, protein kinase C, protein kinase A 16. SECURITY...epithelial cell migration in wound healing. In addition, the correct association of these proteins in a functional complex depends on their phosphorylation

  11. Accelerating immune reconstitution after hematopoietic stem cell transplantation

    PubMed Central

    Tzannou, Ifigeneia; Leen, Ann M

    2014-01-01

    Viral infections remain a significant cause of morbidity and mortality after hematopoietic stem cell transplantation. Pharmacologic agents are effective against some pathogens, but they are costly and can be associated with significant toxicities. Thus, many groups have investigated adoptive T-cell transfer as a means of hastening immune reconstitution and preventing and treating viral infections. This review discusses the immunotherapeutic strategies that have been explored. PMID:25505959

  12. Targeting Epithelial Cell Migration to Accelerate Wound Healing

    DTIC Science & Technology

    2010-12-01

    the protein kinase C (PKC) family and the process can be enhanced or inhibited by modulating the levels of the RIPP complex proteins as well by...HACAT cells indicates that PKC may modulate migration on two-dimensional surface. 15. SUBJECT TERMS Wound healing, cell migration, protein kinase C ...ABSTRACT U c . THIS PAGE U UU 11 19b. TELEPHONE NUMBER (include area code) Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18

  13. Investigation of accelerated stress factors and failure/degradation mechanisms in terrestrial solar cells

    NASA Technical Reports Server (NTRS)

    Lathrop, J. W.

    1983-01-01

    Results of an ongoing research program into the reliability of terrestrial solar cells are presented. Laboratory accelerated testing procedures are used to identify failure/degradation modes which are then related to basic physical, chemical, and metallurgical phenomena. In the most recent tests, ten different types of production cells, both with and without encapsulation, from eight different manufacturers were subjected to a variety of accelerated tests. Results indicated the presence of a number of hitherto undetected failure mechanisms, including Schottky barrier formation at back contacts and loss of adhesion of grid metallization. The mechanism of Schottky barrier formation is explained by hydrogen, formed by the dissociation of water molecules at the contact surface, diffusing to the metal semiconductor interface. This same mechanism accounts for the surprising increase in sensitivity to accelerated stress conditions that was observed in some cells when encapsulated.

  14. Cell-Nonautonomous Mechanisms Underlying Cellular and Organismal Aging.

    PubMed

    Medkour, Younes; Svistkova, Veronika; Titorenko, Vladimir I

    2016-01-01

    Cell-autonomous mechanisms underlying cellular and organismal aging in evolutionarily distant eukaryotes have been established; these mechanisms regulate longevity-defining processes within a single eukaryotic cell. Recent findings have provided valuable insight into cell-nonautonomous mechanisms modulating cellular and organismal aging in eukaryotes across phyla; these mechanisms involve a transmission of various longevity factors between different cells, tissues, and organisms. Herein, we review such cell-nonautonomous mechanisms of aging in eukaryotes. We discuss the following: (1) how low molecular weight transmissible longevity factors modulate aging and define longevity of cells in yeast populations cultured in liquid media or on solid surfaces, (2) how communications between proteostasis stress networks operating in neurons and nonneuronal somatic tissues define longevity of the nematode Caenorhabditis elegans by modulating the rates of aging in different tissues, and (3) how different bacterial species colonizing the gut lumen of C. elegans define nematode longevity by modulating the rate of organismal aging.

  15. Acceleration of epithelial cell syndecan-1 shedding by anthrax hemolytic virulence factors

    PubMed Central

    Popova, Taissia G; Millis, Bryan; Bradburne, Chris; Nazarenko, Svetlana; Bailey, Charles; Chandhoke, Vikas; Popov, Serguei G

    2006-01-01

    Background It has been recently reported that major pathogens Staphylococcus aureus and Pseudomonas aeruginosa accelerate a normal process of cell surface syndecan-1 (Synd1) ectodomain shedding as a mechanism of host damage due to the production of shedding-inducing virulence factors. We tested if acceleration of Synd1 shedding takes place in vitro upon treatment of epithelial cells with B. anthracis hemolysins, as well as in vivo during anthrax infection in mice. Results The isolated anthrax hemolytic proteins AnlB (sphingomyelinase) and AnlO (cholesterol-binding pore-forming factor), as well as ClnA (B. cereus homolog of B. anthracis phosphatidyl choline-preferring phospholipase C) cause accelerated shedding of Synd1 and E-cadherin from epithelial cells and compromise epithelial barrier integrity within a few hours. In comparison with hemolysins in a similar range of concentrations, anthrax lethal toxin (LT) also accelerates shedding albeit at slower rate. Individual components of LT, lethal factor and protective antigen are inactive with regard to shedding. Inhibition experiments favor a hypothesis that activities of tested bacterial shedding inducers converge on the stimulation of cytoplasmic tyrosine kinases of the Syk family, ultimately leading to activation of cellular sheddase. Both LT and AnlO modulate ERK1/2 and p38 MAPK signaling pathways, while JNK pathway seems to be irrelevant to accelerated shedding. Accelerated shedding of Synd1 also takes place in DBA/2 mice challenged with Bacillus anthracis (Sterne) spores. Elevated levels of shed ectodomain are readily detectable in circulation after 24 h. Conclusion The concerted acceleration of shedding by several virulence factors could represent a new pathogenic mechanism contributing to disruption of epithelial or endothelial integrity, hemorrhage, edema and abnormal cell signaling during anthrax infection. PMID:16464252

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

    PubMed

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

    2013-06-01

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

  17. Acceleration of Multidimensional Discrete Ordinates Methods Via Adjacent-Cell Preconditioners

    SciTech Connect

    Azmy, Y.Y.

    2000-10-15

    The adjacent-cell preconditioner (AP) formalism originally derived in slab geometry is extended to multidimensional Cartesian geometry for generic fixed-weight, weighted diamond difference neutron transport methods. This is accomplished for the thick-cell regime (KAP) and thin-cell regime (NAP). A spectral analysis of the resulting acceleration schemes demonstrates their excellent spectral properties for model problem configurations, characterized by a uniform mesh of infinite extent and homogeneous material composition, each in its own cell-size regime. Thus, the spectral radius of KAP vanishes as the computational cell size approaches infinity, but it exceeds unity for very thin cells, thereby implying instability. In contrast, NAP is stable and robust for all cell sizes, but its spectral radius vanishes more slowly as the cell size increases. For this reason, and to avoid potential complication in the case of cells that are thin in one dimension and thick in another, NAP is adopted in the remainder of this work. The most important feature of AP for practical implementation in production level codes is that it is cell centered, reducing the size of the algebraic system comprising the acceleration stage compared to face-centered schemes. Boundary conditions for finite extent problems and a mixing formula across material and cell-size discontinuity are derived and used to implement NAP in a test code, AHOT, and a production code, TORT. Numerical testing for algebraically linear iterative schemes for the cases embodied in Burre's Suite of Test Problems demonstrates the high efficiency of the new method in reducing the number of iterations required to achieve convergence, especially for optically thick cells where acceleration is most needed. Also, for algebraically nonlinear (adaptive) methods, AP generally performs better than the partial current rebalance method in TORT and the diffusion synthetic acceleration method in TWODANT. Finally, application of the AP

  18. Aging study of Li(Si)/FeS/sub 2/ thermally activated batteries. [Results of accelerated aging at 130/sup 0/C

    SciTech Connect

    Searcy, J. Q.; Neiswander, P. A.

    1980-05-01

    A technique for accelerating the aging process of thermally activated batteries that use iron disulfide was developed. In this approach, storage at 130/sup 0/C for one week was assumed equivalent to a shelf life of five years. Some of the batteries stored at 130/sup 0/C were discharged to test for functionality changes, and others were disassembled and carefully analyzed for evidence of deleterious reactions. Some functionality anomalies were observed. The only deleterious reaction observed was that of Li(Si) reacting with water vapor. 3 figures, 6 tables.

  19. An accelerated stress testing program for determining the reliability sensitivity of silicon solar cells to encapsulation and metallization systems

    NASA Technical Reports Server (NTRS)

    Lathrop, J. W.; Davis, C. W.; Royal, E.

    1982-01-01

    The use of accelerated testing methods in a program to determine the reliability attributes of terrestrial silicon solar cells is discussed. Different failure modes are to be expected when cells with and without encapsulation are subjected to accelerated testing and separate test schedules for each are described. Unencapsulated test cells having slight variations in metallization are used to illustrate how accelerated testing can highlight different diffusion related failure mechanisms. The usefulness of accelerated testing when applied to encapsulated cells is illustrated by results showing that moisture related degradation may be many times worse with some forms of encapsulation than with no encapsulation at all.

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

    PubMed Central

    Puppulin, Leonardo; Zhu, Wenliang; Sugano, Nobuhiko

    2014-01-01

    Three types of commercially available ultra-high molecular weight polyethylene (UHMWPE) acetabular cups currently used in total hip arthroplasty have been studied by means of Raman micro-spectroscopy to unfold the microstructural modification induced by the oxidative degradation after accelerated aging with and without lipid absorption. The three investigated materials were produced by three different manufacturing procedures, as follows: irradiation followed by remelting, one-step irradiation followed by annealing, 3-step irradiation and annealing. Clear microstructural differences were observed in terms of phase contents (i.e. amorphous, crystalline and intermediate phase fraction). The three-step annealed material showed the highest crystallinity fraction in the bulk, while the remelted polyethylene is clearly characterized by the lowest content of crystalline phase and the highest content of amorphous phase. After accelerated aging either with or without lipids, the amount of amorphous phase decreased in all the samples as a consequence of the oxidation-induced recrystallization. The most remarkable variations of phase contents were detected in the remelted and in the single-step annealed materials. The presence of lipids triggered oxidative degradation especially in the remelted polyethylene. Such experimental evidence might be explained by the highest amount of amorphous phase in which lipids can be absorbed prior to accelerated aging. The results of these spectroscopic characterizations help to rationalize the complex effect of different irradiation and post-irradiation treatments on the UHMWPE microstructure and gives useful information on how significantly any single step of the manufacturing procedures might affect the oxidative degradation of the polymer. PMID:25179830

  1. Outcomes of Postoperative Simultaneous Modulated Accelerated Radiotherapy for Head-and-Neck Squamous Cell Carcinoma

    SciTech Connect

    Moon, Sung Ho; Jung, Yuh-Seog; Ryu, Jun Sun; Choi, Sung Weon; Park, Joo Yong; Yun, Tak; Lee, Sang Hyun; Cho, Kwan Ho

    2011-09-01

    Purpose: To evaluate the treatment efficacy and toxicity of postoperative simultaneous modulated accelerated radiotherapy (SMART) for patients with head-and-neck squamous cell carcinoma (HNSCC). Methods and Materials: Between February 2003 and September 2008, 51 patients with histologically confirmed HNSCC received postoperative intensity-modulated radiotherapy (N = 33) or helical tomotherapy (N = 18) using SMART after curative surgical resection. The sites included were the oral cavity (OC), oropharynx (OP), larynx, and hypopharynx in 23, 20, 5, and 3 patients, respectively. Results: The median follow-up duration of all patients and surviving patients were 32 (range, 5-78 months) and 39 months (range, 9-77 months), respectively. The 3-year overall survival, cause-specific survival, disease-free survival, locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) in all patients were 71%, 77%, 75%, 85%, and 82%, respectively. Although no significant difference in 3-year LRRFS were found between OC (82%) and OP (82%) carcinomas, the 3-year DMFS was worse in cases of OC (66%) carcinoma compared with OP carcinoma (95%; p = 0.0414). Acute Grade 3 dermatitis, mucositis, and esophagitis occurred in 10%, 10%, and 2% of patients, respectively. At the last follow-up, Grade 3 xerostomia was documented in 10% of the patients. Young age ({<=}40 years) (p < 0.001) and OC carcinoma primary (p = 0.0142) were poor risk factors on univariate analysis for DMFS. Conclusion: Postoperative SMART was observed to be effective and safe in patients with HNSCC.

  2. Aging of perennial cells and organ parts according to the programmed aging paradigm.

    PubMed

    Libertini, Giacinto; Ferrara, Nicola

    2016-04-01

    If aging is a physiological phenomenon-as maintained by the programmed aging paradigm-it must be caused by specific genetically determined and regulated mechanisms, which must be confirmed by evidence. Within the programmed aging paradigm, a complete proposal starts from the observation that cells, tissues, and organs show continuous turnover: As telomere shortening determines both limits to cell replication and a progressive impairment of cellular functions, a progressive decline in age-related fitness decline (i.e., aging) is a clear consequence. Against this hypothesis, a critic might argue that there are cells (most types of neurons) and organ parts (crystalline core and tooth enamel) that have no turnover and are subject to wear or manifest alterations similar to those of cells with turnover. In this review, it is shown how cell types without turnover appear to be strictly dependent on cells subjected to turnover. The loss or weakening of the functions fulfilled by these cells with turnover, due to telomere shortening and turnover slowing, compromises the vitality of the served cells without turnover. This determines well-known clinical manifestations, which in their early forms are described as distinct diseases (e.g., Alzheimer's disease, Parkinson's disease, age-related macular degeneration, etc.). Moreover, for the two organ parts (crystalline core and tooth enamel) without viable cells or any cell turnover, it is discussed how this is entirely compatible with the programmed aging paradigm.

  3. 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

  4. ADAM12 produced by tumor cells rather than stromal cells accelerates breast tumor progression.

    PubMed

    Fröhlich, Camilla; Nehammer, Camilla; Albrechtsen, Reidar; Kronqvist, Pauliina; Kveiborg, Marie; Sehara-Fujisawa, Atsuko; Mercurio, Arthur M; Wewer, Ulla M

    2011-11-01

    Expression of ADAM12 is low in most normal tissues but is markedly increased in numerous human cancers, including breast carcinomas. We have previously shown that overexpression of ADAM12 accelerates tumor progression in a mouse model of breast cancer (PyMT). In this study, we found that ADAM12 deficiency reduces breast tumor progression in the PyMT model. However, the catalytic activity of ADAM12 seems to be dispensable for its tumor-promoting effect. Interestingly, we show that ADAM12 endogenously expressed in tumor-associated stroma in the PyMT model does not influence tumor progression, but that ADAM12 expression by tumor cells is necessary for tumor progression in these mice. This finding is consistent with our observation that in human breast carcinoma, ADAM12 is almost exclusively located in tumor cells and, only rarely, seen in the tumor-associated stroma. We hypothesized, however, that the tumor-associated stroma may stimulate ADAM12 expression in tumor cells, on the basis of the fact that TGF-β1 stimulates ADAM12 expression and is a well-known growth factor released from tumor-associated stroma. TGF-β1 stimulation of ADAM12-negative Lewis lung tumor cells induced ADAM12 synthesis, and growth of these cells in vivo induced more than 200-fold increase in ADAM12 expression. Our observation that ADAM12 expression is significantly higher in the terminal duct lobular units (TDLU) adjacent to human breast carcinoma compared with TDLUs found in normal breast tissue supports our hypothesis that tumor-associated stroma triggers ADAM12 expression.

  5. Investigation of reliability attributes and accelerated stress factors on terrestrial solar cells

    NASA Technical Reports Server (NTRS)

    Lathrop, J. W.

    1982-01-01

    The accelerated stress test results obtained on all terrestrial solar cells since the inception of the program are summarized. Tested cells were grouped according to the method used to form the conductive metallization layer: solder dipped, vacuum deposited, screen printed, and copper plated. Although metallization systems within each group were quite similar, they differed in numerous details according to the procedures employed by each manufacturer. Test results were summarized for all cells according to both electrical degradation and catastrophic mechanical changes. These results indicated a variability within each metallization category which was dependent on the manufacturer. Only one manufacturer was represented in the copper plated category and, although these showed no signs of detrimental copper diffusion during high temperature testing, their metallization was removed easily during high humidity pressure cooker testing. Preliminary testing of encapsulated cells showed no major differences between encapsulated and unencapsulated cells when subjected to accelerated testing.

  6. Centrosome and microtubule instability in aging Drosophila cells

    NASA Technical Reports Server (NTRS)

    Schatten, H.; Chakrabarti, A.; Hedrick, J.

    1999-01-01

    Several cytoskeletal changes are associated with aging which includes alterations in muscle structure leading to muscular atrophy, and weakening of the microtubule network which affects cellular secretion and maintenance of cell shape. Weakening of the microtubule network during meiosis in aging oocytes can result in aneuploidy or trisomic zygotes with increasing maternal age. Imbalances of cytoskeletal organization can lead to disease such as Alzheimer's, muscular disorders, and cancer. Because many cytoskeletal diseases are related to age we investigated the effects of aging on microtubule organization in cell cultures of the Drosophila cell model system (Schneider S-1 and Kc23 cell lines). This cell model is increasingly being used as an alternative system to mammalian cell cultures. Drosophila cells are amenable to genetic manipulations and can be used to identify and manipulate genes which are involved in the aging processes. Immunofluorescence, scanning, and transmission electron microscopy were employed for the analysis of microtubule organizing centers (centrosomes) and microtubules at various times after subculturing cells in fresh medium. Our results reveal that centrosomes and the microtubule network becomes significantly affected in aging cells after 5 days of subculture. At 5-14 days of subculture, 1% abnormal out of 3% mitoses were noted which were clearly distinguishable from freshly subcultured control cells in which 3% of cells undergo normal mitosis with bipolar configurations. Microtubules are also affected in the midbody during cell division. The midbody in aging cells becomes up to 10 times longer when compared with midbodies in freshly subcultured cells. During interphase, microtubules are often disrupted and disorganized, which may indicate improper function related to transport of cell organelles along microtubules. These results are likely to help explain some cytoskeletal disorders and diseases related to aging.

  7. The downregulation of thioredoxin accelerated Neuro2a cell apoptosis induced by advanced glycation end product via activating several pathways.

    PubMed

    Ren, Xiang; Ma, Haiying; Qiu, Yuanyuan; Liu, Bo; Qi, Hui; Li, Zeyu; Kong, Hui; Kong, Li

    2015-08-01

    Thioredoxin (Trx), a 12 kDa protein, has different functions in different cellular environments, playing important anti-oxidative and anti-apoptotic roles and regulating the expression of transcription factors. Advanced glycation end products (AGEs) are a heterogeneous group of irreversible adducts from glucose-protein condensation reactions and are considered crucial to the development of diabetic nephropathy, retinopathy, neurodegeneration and atherosclerosis. The aim of this study was to use a Trx inhibitor to investigate the effects and mechanism of Trx down-regulation on AGE-induced Neuro2a cell apoptosis. Neuro2a cells were cultured in vitro and treated with different conditions. The apoptosis and proliferation of Neuro2a cells were detected using flow cytometry, DNA-Ladder and CCK8 assays. Rho 123 was used to detect the mitochondrial membrane potential. ROS generation and caspase3 activity were detected using a DCFH-DA probe and micro-plate reader. Western blotting and real-time PCR were used to detect the expression of proteins and genes. We found that the down-regulation of thioredoxin could accelerate AGE-induced apoptosis in Neuro2a cells. A possible underlying mechanism is that the down-regulation of thioredoxin stimulated the up-regulation of ASK1, p-JNK, PTEN, and Txnip, as well as the down-regulation of p-AKT, ultimately increasing ROS levels and caspase3 activity.

  8. Accelerated stress testing of thin film solar cells: Development of test methods and preliminary results

    NASA Technical Reports Server (NTRS)

    Lathrop, J. W.

    1985-01-01

    If thin film cells are to be considered a viable option for terrestrial power generation their reliability attributes will need to be explored and confidence in their stability obtained through accelerated testing. Development of a thin film accelerated test program will be more difficult than was the case for crystalline cells because of the monolithic construction nature of the cells. Specially constructed test samples will need to be fabricated, requiring committment to the concept of accelerated testing by the manufacturers. A new test schedule appropriate to thin film cells will need to be developed which will be different from that used in connection with crystalline cells. Preliminary work has been started to seek thin film schedule variations to two of the simplest tests: unbiased temperature and unbiased temperature humidity. Still to be examined are tests which involve the passage of current during temperature and/or humidity stress, either by biasing in the forward (or reverse) directions or by the application of light during stress. Investigation of these current (voltage) accelerated tests will involve development of methods of reliably contacting the thin conductive films during stress.

  9. Investigation of reliability attributes and accelerated stress factors of terrestrial solar cells. Second annual report

    SciTech Connect

    Lathrop, J.W.; Prince, J.L.

    1980-04-01

    The work covered in this report represents the second year's effort of a continuing program to determine the reliability attributes of terrestrial solar cells. Three main tasks were undertaken during the reporting period: (1) a study of the electrical behavior of cells in the second (reverse) quadrant, (2) the accelerated stress testing of three new state of the art cells and (3) the continued bias-temperature testing of four Block II type silicon cells at 78/sup 0/C and 135/sup 0/C. Electrical characteristics measured in the second quadrant were determined to be a function of the cell's thermal behavior with breakdown depending on the initiation of localized heating. This implied that high breakdown cells may be more fault tolerant when forced to operate in the second quadrant - a result contrary to conventional thinking. The accelerated stress tests used in the first (power) quadrant were bias-temperature, bias-temperature-humidity, temperature-humidity, thermal shock, and thermal cycle. The new type cells measured included an EFG cell, a polycrystalline cell, and a Czochralski cell. Electrical parameters measured included I/sub SC/, V/sub OC/, P/sub M/, and I/sub M/. Incorporated in the report are the distributions of prestress electrical data for all cell types. Significant differences in the response to the various stress tests were observed between cell types. A microprocessed controlled, short interval solar cell tester was designed and construction initiated on a prototype for use in the program.

  10. Age-associated changes in the ecological niche: implications for mesenchymal stem cell aging.

    PubMed

    Asumda, Faizal Z

    2013-05-14

    Adult stem cells are critical for organ-specific regeneration and self-renewal with advancing age. The prospect of being able to reverse tissue-specific post-injury sequelae by harvesting, culturing and transplanting a patient's own stem and progenitor cells is exciting. Mesenchymal stem cells have emerged as a reliable stem cell source for this treatment modality and are currently being tested in numerous ongoing clinical trials. Unfortunately, the fervor over mesenchymal stem cells is mitigated by several lines of evidence suggesting that their efficacy is limited by natural aging. This article discusses the mechanisms and manifestations of age-associated deficiencies in mesenchymal stem cell efficacy. A consideration of recent experimental findings suggests that the ecological niche might be responsible for mesenchymal stem cell aging.

  11. Age-associated changes in the ecological niche: implications for mesenchymal stem cell aging

    PubMed Central

    2013-01-01

    Adult stem cells are critical for organ-specific regeneration and self-renewal with advancing age. The prospect of being able to reverse tissue-specific post-injury sequelae by harvesting, culturing and transplanting a patient’s own stem and progenitor cells is exciting. Mesenchymal stem cells have emerged as a reliable stem cell source for this treatment modality and are currently being tested in numerous ongoing clinical trials. Unfortunately, the fervor over mesenchymal stem cells is mitigated by several lines of evidence suggesting that their efficacy is limited by natural aging. This article discusses the mechanisms and manifestations of age-associated deficiencies in mesenchymal stem cell efficacy. A consideration of recent experimental findings suggests that the ecological niche might be responsible for mesenchymal stem cell aging. PMID:23673056

  12. A cord blood monocyte–derived cell therapy product accelerates brain remyelination

    PubMed Central

    Buntz, Susan; Scotland, Paula; Xu, Li; Noeldner, Pamela; Patel, Sachit; Wollish, Amy; Gunaratne, Aruni; Gentry, Tracy; Matsushima, Glenn K.; Kurtzberg, Joanne; Balber, Andrew E.

    2016-01-01

    Microglia and monocytes play important roles in regulating brain remyelination. We developed DUOC-01, a cell therapy product intended for treatment of demyelinating diseases, from banked human umbilical cord blood (CB) mononuclear cells. Immunodepletion and selection studies demonstrated that DUOC-01 cells are derived from CB CD14+ monocytes. We compared the ability of freshly isolated CB CD14+ monocytes and DUOC-01 cells to accelerate remyelination of the brains of NOD/SCID/IL2Rγnull mice following cuprizone feeding–mediated demyelination. The corpus callosum of mice intracranially injected with DUOC-01 showed enhanced myelination, a higher proportion of fully myelinated axons, decreased gliosis and cellular infiltration, and more proliferating oligodendrocyte lineage cells than those of mice receiving excipient. Uncultured CB CD14+ monocytes also accelerated remyelination, but to a significantly lesser extent than DUOC-01 cells. Microarray analysis, quantitative PCR studies, Western blotting, and flow cytometry demonstrated that expression of factors that promote remyelination including PDGF-AA, stem cell factor, IGF1, MMP9, MMP12, and triggering receptor expressed on myeloid cells 2 were upregulated in DUOC-01 compared to CB CD14+ monocytes. Collectively, our results show that DUOC-01 accelerates brain remyelination by multiple mechanisms and could be beneficial in treating demyelinating conditions. PMID:27699230

  13. Perturbation of NK cell peripheral homeostasis accelerates prostate carcinoma metastasis

    PubMed Central

    Liu, Gang; Lu, Shengjun; Wang, Xuanjun; Page, Stephanie T.; Higano, Celestia S.; Plymate, Stephen R.; Greenberg, Norman M.; Sun, Shaoli; Li, Zihai; Wu, Jennifer D.

    2013-01-01

    The activating receptor NK cell group 2 member D (NKG2D) mediates antitumor immunity in experimental animal models. However, whether NKG2D ligands contribute to tumor suppression or progression clinically remains controversial. Here, we have described 2 novel lines of “humanized” bi-transgenic (bi-Tg) mice in which native human NKG2D ligand MHC class I polypeptide-related sequence B (MICB) or the engineered membrane-restricted MICB (MICB.A2) was expressed in the prostate of the transgenic adenocarcinoma of the mouse prostate (TRAMP) model of spontaneous carcinogenesis. Bi-Tg TRAMP/MICB mice exhibited a markedly increased incidence of progressed carcinomas and metastasis, whereas TRAMP/MICB.A2 mice enjoyed long-term tumor-free survival conferred by sustained NKG2D-mediated antitumor immunity. Mechanistically, we found that cancer progression in TRAMP/MICB mice was associated with loss of the peripheral NK cell pool owing to high serum levels of tumor-derived soluble MICB (sMICB). Prostate cancer patients also displayed reduction of peripheral NK cells and high sMIC levels. Our study has not only provided direct evidence in “humanized” mouse models that soluble and membrane-restricted NKG2D ligands pose opposite impacts on cancer progression, but also uncovered a mechanism of sMIC-induced impairment of NK cell antitumor immunity. Our findings suggest that the impact of soluble NKG2D ligands should be considered in NK cell–based cancer immunotherapy and that our unique mouse models should be valuable for therapy optimization. PMID:24018560

  14. Accelerating Acceptance of Fuel Cell Backup Power Systems - Final Report

    SciTech Connect

    Petrecky, James; Ashley, Christopher

    2014-07-21

    Since 2001, Plug Power has installed more than 800 stationary fuel cell systems worldwide. Plug Power’s prime power systems have produced approximately 6.5 million kilowatt hours of electricity and have accumulated more than 2.5 million operating hours. Intermittent, or backup, power products have been deployed with telecommunications carriers and government and utility customers in North and South America, Europe, the United Kingdom, Japan and South Africa. Some of the largest material handling operations in North America are currently using the company’s motive power units in fuel cell-powered forklifts for their warehouses, distribution centers and manufacturing facilities. The low-temperature GenSys fuel cell system provides remote, off-grid and primary power where grid power is unreliable or nonexistent. Built reliable and designed rugged, low- temperature GenSys delivers continuous or backup power through even the most extreme conditions. Coupled with high-efficiency ratings, low-temperature GenSys reduces operating costs making it an economical solution for prime power requirements. Currently, field trials at telecommunication and industrial sites across the globe are proving the advantages of fuel cells—lower maintenance, fuel costs and emissions, as well as longer life—compared with traditional internal combustion engines.

  15. Rejuvenating Strategies for Stem Cell-Based Therapies in Aging.

    PubMed

    Neves, Joana; Sousa-Victor, Pedro; Jasper, Heinrich

    2017-02-02

    Recent advances in our understanding of tissue regeneration and the development of efficient approaches to induce and differentiate pluripotent stem cells for cell replacement therapies promise exciting avenues for treating degenerative age-related diseases. However, clinical studies and insights from model organisms have identified major roadblocks that normal aging processes impose on tissue regeneration. These new insights suggest that specific targeting of environmental niche components, including growth factors, ECM, and immune cells, and intrinsic stem cell properties that are affected by aging will be critical for the development of new strategies to improve stem cell function and optimize tissue repair processes.

  16. 3.9 GHz superconducting accelerating 9-cell cavity vertical test results

    SciTech Connect

    Khabiboulline, Timergali; Cooper, Charles; Dhanaraj, Nandhini; Edwards, Helen; Foley, Mike; Harms, Elvin; Mitchell, Donald; Rowe, Allan; Solyak, Nikolay; Moeller, Wolf-Dietrich; /DESY

    2007-06-01

    The 3rd harmonic 3.9GHz accelerating cavity was proposed to improve the beam performance of the FLASH (TTF/DESY) facility [1]. In the frame of a collaborative agreement, Fermilab will provide DESY with a cryomodule containing a string of four cavities. In addition, a second cryomodule with one cavity will be fabricated for installation in the Fermilab photo-injector, which will be upgraded for the ILC accelerator test facility. The first 9-cell Nb cavities were tested in a vertical setup and they didn't reach the designed accelerating gradient [2]. The main problem was a multipactor in the HOM couplers, which lead to overheating and quenching of the HOM couplers. New HOM couplers with improved design are integrated in the next 9-cell cavities. In this paper we present all results of the vertical tests.

  17. Investigation of reliability attributes and accelerated stress factors on terrestrial solar cells

    NASA Technical Reports Server (NTRS)

    Lathrop, J. W.; Prince, J. L.

    1980-01-01

    Three tasks were undertaken to investigate reliability attributes of terrestrial solar cells: (1) a study of the electrical behavior of cells in the second (reverse) quadrant; (2) the accelerated stress testing of three new state-of-the-art cells; and (3) the continued bias-temperature testing of four block 2 type silicon cells at 78 C and 135 C. Electrical characteristics measured in the second quadrant were determined to be a function of the cell's thermal behavior with breakdown depending on the initiation of localized heating. This implied that high breakdown cells may be more fault tolerant when forced to operate in the second quadrant, a result contrary to conventional thinking. The accelerated stress tests used in the first (power) quadrant were bias-temperature, bias-temperature-humidity, temperature-humidity, thermal shock, and thermal cycle. The new type cells measured included an EFG cell, a polycrystalline cell, and a Czochralski cell. Significant differences in the response to the various tests were observed between cell types. A microprocessed controlled, short interval solar cell tester was designed and construction initiated on a prototype.

  18. Investigation of reliability attributes and accelerated stress factors on terrestrial solar cells. Third annual report

    SciTech Connect

    Lathrop, J.W.; Hartman, R.A.; Saylor, C.R.

    1981-01-01

    The third year of the accelerated reliability testing program concentrated on electrical measurement instrumentation and in modeling cell behavior in the second quadrant. In addition, some preliminary work was done on correlating cell color changes with electrical degradation. Not reported are results of continuing accelerated stress tests on state of the art cells. A number of new cells were added to the program, but not in time for sufficient data to be obtained, while the older cells are undergoing extended test periods and new data are not yet available on them. The all-digital, microprocessor controlled, short interval tester, which was designed and fabricated, has replaced the manual measurement procedure formerly used. This has improved measurement accuracy and repeatability, reduced measurement time, and through coordinated data management procedures, eliminated data errors. A complete description of the tester including schematics and software is given and its operating procedures described. A computer model, based on the thermal and electrical properties of the cells and encapsulating materials, was developed to relate cell temperature to electrical characteristics in the second quadrant. This model adequately predicted the behavior of both encapsulated and unencapsulated cells, although accurate temperature measurements on encapsulated cells were difficult to obtain. In addition, only cells of one type were used for comparison and other cell types may require different parameter values for fitting. Use of the model should permit the prediction of a cell's sensitivity to degradation in the second quadrant. The computer program is listed together with a description of its operation.

  19. Rejuvenating stem cells to restore muscle regeneration in aging

    PubMed Central

    Bengal, Eyal; Perdiguero, Eusebio; Serrano, Antonio L.; Muñoz-Cánoves, Pura

    2017-01-01

    Adult muscle stem cells, originally called satellite cells, are essential for muscle repair and regeneration throughout life. Besides a gradual loss of mass and function, muscle aging is characterized by a decline in the repair capacity, which blunts muscle recovery after injury in elderly individuals. A major effort has been dedicated in recent years to deciphering the causes of satellite cell dysfunction in aging animals, with the ultimate goal of rejuvenating old satellite cells and improving muscle function in elderly people. This review focuses on the recently identified network of cell-intrinsic and -extrinsic factors and processes contributing to the decline of satellite cells in old animals. Some studies suggest that aging-related satellite-cell decay is mostly caused by age-associated extrinsic environmental changes that could be reversed by a “youthful environment”. Others propose a central role for cell-intrinsic mechanisms, some of which are not reversed by environmental changes. We believe that these proposals, far from being antagonistic, are complementary and that both extrinsic and intrinsic factors contribute to muscle stem cell dysfunction during aging-related regenerative decline. The low regenerative potential of old satellite cells may reflect the accumulation of deleterious changes during the life of the cell; some of these changes may be inherent (intrinsic) while others result from the systemic and local environment (extrinsic). The present challenge is to rejuvenate aged satellite cells that have undergone reversible changes to provide a possible approach to improving muscle repair in the elderly. PMID:28163911

  20. Programming cells by multiplex genome engineering and accelerated evolution

    PubMed Central

    Carr, Peter A.; Sun, Zachary Z.; Xu, George; Forest, Craig R.; Church, George M.

    2015-01-01

    The breadth of genomic diversity found among organisms in nature allows populations to adapt to diverse environments1,2. However, genomic diversity is difficult to generate in the laboratory and new phenotypes do not easily arise on practical timescales3. Although in vitro and directed evolution methods4–9 have created genetic variants with usefully altered phenotypes, these methods are limited to laborious and serial manipulation of single genes and are not used for parallel and continuous directed evolution of gene networks or genomes. Here, we describe multiplex automated genome engineering (MAGE) for large-scale programming and evolution of cells. MAGE simultaneously targets many locations on the chromosome for modification in a single cell or across a population of cells, thus producing combinatorial genomic diversity. Because the process is cyclical and scalable, we constructed prototype devices that automate the MAGE technology to facilitate rapid and continuous generation of a diverse set of genetic changes (mismatches, insertions, deletions). We applied MAGE to optimize the 1-deoxy-d-xylulose-5-phosphate (DXP) biosynthesis pathway in Escherichia coli to overproduce the industrially important isoprenoid lycopene. Twenty-four genetic components in the DXP pathway were modified simultaneously using a complex pool of synthetic DNA, creating over 4.3 billion combinatorial genomic variants per day. We isolated variants with more than fivefold increase in lycopene production within 3 days, a significant improvement over existing metabolic engineering techniques. Our multiplex approach embraces engineering in the context of evolution by expediting the design and evolution of organisms with new and improved properties. PMID:19633652

  1. Particle-in-cell simulation of x-ray wakefield acceleration and betatron radiation in nanotubes

    SciTech Connect

    Zhang, Xiaomei; Tajima, Toshiki; Farinella, Deano; Shin, Youngmin; Mourou, Gerard; Wheeler, Jonathan; Taborek, Peter; Chen, Pisin; Dollar, Franklin; Shen, Baifei

    2016-10-18

    Though wakefield acceleration in crystal channels has been previously proposed, x-ray wakefield acceleration has only recently become a realistic possibility since the invention of the single-cycled optical laser compression technique. We investigate the acceleration due to a wakefield induced by a coherent, ultrashort x-ray pulse guided by a nanoscale channel inside a solid material. By two-dimensional particle-in-cell computer simulations, we show that an acceleration gradient of TeV/cm is attainable. This is about 3 orders of magnitude stronger than that of the conventional plasma-based wakefield accelerations, which implies the possibility of an extremely compact scheme to attain ultrahigh energies. In addition to particle acceleration, this scheme can also induce the emission of high energy photons at ~O(10–100) MeV. Here, our simulations confirm such high energy photon emissions, which is in contrast with that induced by the optical laser driven wakefield scheme. In addition to this, the significantly improved emittance of the energetic electrons has been discussed.

  2. Particle-in-cell simulation of x-ray wakefield acceleration and betatron radiation in nanotubes

    DOE PAGES

    Zhang, Xiaomei; Tajima, Toshiki; Farinella, Deano; ...

    2016-10-18

    Though wakefield acceleration in crystal channels has been previously proposed, x-ray wakefield acceleration has only recently become a realistic possibility since the invention of the single-cycled optical laser compression technique. We investigate the acceleration due to a wakefield induced by a coherent, ultrashort x-ray pulse guided by a nanoscale channel inside a solid material. By two-dimensional particle-in-cell computer simulations, we show that an acceleration gradient of TeV/cm is attainable. This is about 3 orders of magnitude stronger than that of the conventional plasma-based wakefield accelerations, which implies the possibility of an extremely compact scheme to attain ultrahigh energies. In additionmore » to particle acceleration, this scheme can also induce the emission of high energy photons at ~O(10–100) MeV. Here, our simulations confirm such high energy photon emissions, which is in contrast with that induced by the optical laser driven wakefield scheme. In addition to this, the significantly improved emittance of the energetic electrons has been discussed.« less

  3. Particle-in-cell simulation of x-ray wakefield acceleration and betatron radiation in nanotubes

    NASA Astrophysics Data System (ADS)

    Zhang, Xiaomei; Tajima, Toshiki; Farinella, Deano; Shin, Youngmin; Mourou, Gerard; Wheeler, Jonathan; Taborek, Peter; Chen, Pisin; Dollar, Franklin; Shen, Baifei

    2016-10-01

    Though wakefield acceleration in crystal channels has been previously proposed, x-ray wakefield acceleration has only recently become a realistic possibility since the invention of the single-cycled optical laser compression technique. We investigate the acceleration due to a wakefield induced by a coherent, ultrashort x-ray pulse guided by a nanoscale channel inside a solid material. By two-dimensional particle-in-cell computer simulations, we show that an acceleration gradient of TeV /cm is attainable. This is about 3 orders of magnitude stronger than that of the conventional plasma-based wakefield accelerations, which implies the possibility of an extremely compact scheme to attain ultrahigh energies. In addition to particle acceleration, this scheme can also induce the emission of high energy photons at ˜O (10 - 100 ) MeV . Our simulations confirm such high energy photon emissions, which is in contrast with that induced by the optical laser driven wakefield scheme. In addition to this, the significantly improved emittance of the energetic electrons has been discussed.

  4. 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.

  5. 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.

  6. Finding Balance: T cell Regulatory Receptor Expression during Aging.

    PubMed

    Cavanagh, Mary M; Qi, Qian; Weyand, Cornelia M; Goronzy, Jörg J

    2011-10-01

    Aging is associated with a variety of changes to immune responsiveness. Reduced protection against infection, reduced responses to vaccination and increased risk of autoimmunity are all hallmarks of advanced age. Here we consider how changes in the expression of regulatory receptors on the T cell surface contribute to altered immunity during aging.

  7. Investigation of reliability attributes and accelerated stress factors on terrestrial solar cells

    NASA Technical Reports Server (NTRS)

    Prince, J. L.; Lathrop, J. W.

    1979-01-01

    The results of accelerated stress testing of four different types of silicon terrestrial solar cells are discussed. The accelerated stress tests used included bias-temperature tests, bias-temperature-humidity tests, thermal cycle and thermal shock tests, and power cycle tests. Characterization of the cells was performed before stress testing and at periodic down-times, using electrical measurement, visual inspection, and metal adherence pull tests. Electrical parameters measured included short-circuit current, open circuit voltage, and output power, voltage, and current at the maximum power point. Incorporated in the report are the distributions of the prestress electrical data for all cell types. Data were also obtained on cell series and shunt resistance.

  8. Stem cells as vehicles for youthful regeneration of aged tissues.

    PubMed

    Rando, Thomas A; Wyss-Coray, Tony

    2014-06-01

    Stem cells hold great promise for regenerative therapies for a wide spectrum of diseases and disorders of aging by virtue of their ability to regenerate tissues and contribute to their homeostasis. Aging is associated with a marked decline in these functionalities of adult stem cells. As such, regeneration of aged tissues is both less efficient and less effective than that of young tissues. Recent studies have revealed the remarkably dynamic responses of stem cells to systemic signals, including the ability of "youthful" factors in the blood of young animals to enhance the functionality of aged stem cells. Thus, there is much hope that even aged stem cells retain a remarkable regenerative potential if provided with the correct cues and environment to engage in tissue repair. The overall focus of the presentations of this session is to address the determinants of changes in stem cell functionality with age, the key characteristics of stem cells in aged tissues, the extent to which those characteristics are capable of being rejuvenated and by what signals, and the potential for stem cell therapeutics for chronic diseases and acute injuries in aged individuals.

  9. 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.

  10. Early-life adversity accelerates cellular ageing and affects adult inflammation: Experimental evidence from the European starling

    PubMed Central

    Nettle, Daniel; Andrews, Clare; Reichert, Sophie; Bedford, Tom; Kolenda, Claire; Parker, Craig; Martin-Ruiz, Carmen; Monaghan, Pat; Bateson, Melissa

    2017-01-01

    Early-life adversity is associated with accelerated cellular ageing during development and increased inflammation during adulthood. However, human studies can only establish correlation, not causation, and existing experimental animal approaches alter multiple components of early-life adversity simultaneously. We developed a novel hand-rearing paradigm in European starling nestlings (Sturnus vulgaris), in which we separately manipulated nutritional shortfall and begging effort for a period of 10 days. The experimental treatments accelerated erythrocyte telomere attrition and increased DNA damage measured in the juvenile period. For telomere attrition, amount of food and begging effort exerted additive effects. Only the combination of low food amount and high begging effort increased DNA damage. We then measured two markers of inflammation, high-sensitivity C-reactive protein and interleukin-6, when the birds were adults. The experimental treatments affected both inflammatory markers, though the patterns were complex and different for each marker. The effect of the experimental treatments on adult interleukin-6 was partially mediated by increased juvenile DNA damage. Our results show that both nutritional input and begging effort in the nestling period affect cellular ageing and adult inflammation in the starling. However, the pattern of effects is different for different biomarkers measured at different time points. PMID:28094324

  11. Chemotherapy and Stem Cell Transplantation Increase p16(INK4a) Expression, a Biomarker of T-cell Aging.

    PubMed

    Wood, William A; Krishnamurthy, Janakiraman; Mitin, Natalia; Torrice, Chad; Parker, Joel S; Snavely, Anna C; Shea, Thomas C; Serody, Jonathan S; Sharpless, Norman E

    2016-09-01

    The expression of markers of cellular senescence increases exponentially in multiple tissues with aging. Age-related physiological changes may contribute to adverse outcomes in cancer survivors. To investigate the impact of high dose chemotherapy and stem cell transplantation on senescence markers in vivo, we collected blood and clinical data from a cohort of 63 patients undergoing hematopoietic cell transplantation. The expression of p16(INK4a), a well-established senescence marker, was determined in T-cells before and 6months after transplant. RNA sequencing was performed on paired samples from 8 patients pre- and post-cancer therapy. In patients undergoing allogeneic transplant, higher pre-transplant p16(INK4a) expression was associated with a greater number of prior cycles of chemotherapy received (p=0.003), prior autologous transplantation (p=0.01) and prior exposure to alkylating agents (p=0.01). Transplantation was associated with a marked increase in p16(INK4a) expression 6months following transplantation. Patients receiving autologous transplant experienced a larger increase in p16(INK4a) expression (3.1-fold increase, p=0.002) than allogeneic transplant recipients (1.9-fold increase, p=0.0004). RNA sequencing of T-cells pre- and post- autologous transplant or cytotoxic chemotherapy demonstrated increased expression of transcripts associated with cellular senescence and physiological aging. Cytotoxic chemotherapy, especially alkylating agents, and stem cell transplantation strongly accelerate expression of a biomarker of molecular aging in T-cells.

  12. Accelerated age-related cognitive decline and neurodegeneration, caused by deficient DNA repair.

    PubMed

    Borgesius, Nils Z; de Waard, Monique C; van der Pluijm, Ingrid; Omrani, Azar; Zondag, Gerben C M; van der Horst, Gijsbertus T J; Melton, David W; Hoeijmakers, Jan H J; Jaarsma, Dick; Elgersma, Ype

    2011-08-31

    Age-related cognitive decline and neurodegenerative diseases are a growing challenge for our societies with their aging populations. Accumulation of DNA damage has been proposed to contribute to these impairments, but direct proof that DNA damage results in impaired neuronal plasticity and memory is lacking. Here we take advantage of Ercc1(Δ/-) mutant mice, which are impaired in DNA nucleotide excision repair, interstrand crosslink repair, and double-strand break repair. We show that these mice exhibit an age-dependent decrease in neuronal plasticity and progressive neuronal pathology, suggestive of neurodegenerative processes. A similar phenotype is observed in mice where the mutation is restricted to excitatory forebrain neurons. Moreover, these neuron-specific mutants develop a learning impairment. Together, these results suggest a causal relationship between unrepaired, accumulating DNA damage, and age-dependent cognitive decline and neurodegeneration. Hence, accumulated DNA damage could therefore be an important factor in the onset and progression of age-related cognitive decline and neurodegenerative diseases.

  13. Loss of hepatic chaperone-mediated autophagy accelerates proteostasis failure in aging

    PubMed Central

    Schneider, Jaime L; Villarroya, Joan; Diaz-Carretero, Antonio; Patel, Bindi; Urbanska, Aleksandra M; Thi, Mia M; Villarroya, Francesc; Santambrogio, Laura; Cuervo, Ana Maria

    2015-01-01

    Chaperone-mediated autophagy (CMA), a cellular process that contributes to protein quality control through targeting of a subset of cytosolic proteins to lysosomes for degradation, undergoes a functional decline with age. We have used a mouse model with liver-specific defective CMA to identify changes in proteostasis attributable to reduced CMA activity in this organ with age. We have found that other proteolytic systems compensate for CMA loss in young mice which helps to preserve proteostasis. However, these compensatory responses are not sufficient for protection against proteotoxicity induced by stress (oxidative stress, lipid challenges) or associated with aging. Livers from old mice with CMA blockage exhibit altered protein homeostasis, enhanced susceptibility to oxidative stress and hepatic dysfunction manifested by a diminished ability to metabolize drugs, and a worsening of the metabolic dysregulation identified in young mice. Our study reveals that while the regulatory function of CMA cannot be compensated for in young organisms, its contribution to protein homeostasis can be handled by other proteolytic systems. However, the decline in the compensatory ability identified with age explains the more severe consequences of CMA impairment in older organisms and the contribution of CMA malfunction to the gradual decline in proteostasis and stress resistance observed during aging. PMID:25620427

  14. Active immunization of broiler breeder cockerels against chicken inhibin accelerates puberty and prevents age-induced testicular involution.

    PubMed

    Satterlee, D G; Castille, S A; Fioretti, W C

    2006-06-01

    Injection of quail and breeder hens with a recombinant protein antigen (MBP-cINA521)--a fusion of the bacterical maltose-binding protein (MBP) and a fragment of the alpha-subunit of chicken inhibin (cINA521)--accelerates puberty and enhances lay. Herein, the effects of this immunogen on reproductive responses in broiler breeder males were assessed. Cockerels were subcutaneously injected with 0 (vehicular controls), 1, 3, or 5 mg of MBP-cINA521 at 13 wk of age and with one-half of these dosages (boosters) at 18 wk. Bird subsamples were weighed, blood sampled, and killed at 24, 28, and 39 wk of age to assess age and vaccination effects on BW, testes weight (TWT), TWT relative to BW (RTWT), TWT > or = 20 g (TWT20; theoretical threshold TWT for maximum fertility), and plasma testosterone. Breeder males are sexually developing, reach peak sexual activity, and show age-related reproductive decline at these ages. Because vaccine gonadal effects at 24 wk appeared to be dramatic, the size of the left testis was also scored to see if size differences could be detected by mere visual inspection. Male fighting increasingly reduced sample sizes beyond 24 wk. Because mortality was unrelated to the treatments and to insure meaningful statistical comparisons, MBP-cINA521 data were pooled. Body weight (P < 0.04), testis score (P < 0.02), TWT (P < 0.03), RTWT (P = 0.06), and plasma testosterone (P = 0.08) were elevated in immunogen-treated males at 24 wk of age, and more (P < 0.05) MBP-cINA521-treated birds than controls achieved a TWT20 at this time. These variables did not differ by treatment at 28 wk. However, by 39 wk, treatment effects reemerged as follows: TWT (P < 0.04), RTWT (P = 0.06), and TWT20 (P < 0.01) were increased in vaccinated males who also showed nearly 3-fold higher levels of plasma testosterone. We conclude that immunoneutralization of inhibin accelerates puberty and retards age-related sexual senescence that typically occurs in broiler breeder males.

  15. Comparison between the properties of "accelerated-aged" bones and archaeological bones.

    NASA Astrophysics Data System (ADS)

    Abdel Maksoud, Gomaa

    This study focuses on the changes in the properties of bones that resulted from 'heatageing' at different temperatures and long term of exposure compared to archaeological samples. It also aims to prepare aged samples similar to archaeological samples for the experimental studies in the conservation of bone artifacts. FTIR, XRD, UV spectrophotometry, dual-energy X-ray absorptiometry, polarizing and SEM microscopes were used as analytical techniques. The results revealed that 'heat ageing' technique used at different temperatures (200oC and 300OC) and times (from 1 hour to 13 hours) affected the properties of change in colour, loss of bone density, destruction of the surface morphology, increasing the crystallinity index which, was similar with the archaeological sample after 8 and 12 hours of exposure. The study concluded that 'heat ageing' at 300°C after 8 hours can give properties close or similar to archaeological samples.

  16. GPU Acceleration of Particle-In-Cell Methods

    NASA Astrophysics Data System (ADS)

    Cowan, Benjamin; Cary, John; Sides, Scott

    2016-10-01

    Graphics processing units (GPUs) have become key components in many supercomputing systems, as they can provide more computations relative to their cost and power consumption than conventional processors. However, to take full advantage of this capability, they require a strict programming model which involves single-instruction multiple-data execution as well as significant constraints on memory accesses. To bring the full power of GPUs to bear on plasma physics problems, we must adapt the computational methods to this new programming model. We have developed a GPU implementation of the particle-in-cell (PIC) method, one of the mainstays of plasma physics simulation. This framework is highly general and enables advanced PIC features such as high order particles and absorbing boundary conditions. The main elements of the PIC loop, including field interpolation and particle deposition, are designed to optimize memory access. We describe the performance of these algorithms and discuss some of the methods used. Work supported by DARPA Contract No. W31P4Q-16-C-0009.

  17. GPU acceleration of particle-in-cell methods

    NASA Astrophysics Data System (ADS)

    Cowan, Benjamin; Cary, John; Meiser, Dominic

    2015-11-01

    Graphics processing units (GPUs) have become key components in many supercomputing systems, as they can provide more computations relative to their cost and power consumption than conventional processors. However, to take full advantage of this capability, they require a strict programming model which involves single-instruction multiple-data execution as well as significant constraints on memory accesses. To bring the full power of GPUs to bear on plasma physics problems, we must adapt the computational methods to this new programming model. We have developed a GPU implementation of the particle-in-cell (PIC) method, one of the mainstays of plasma physics simulation. This framework is highly general and enables advanced PIC features such as high order particles and absorbing boundary conditions. The main elements of the PIC loop, including field interpolation and particle deposition, are designed to optimize memory access. We describe the performance of these algorithms and discuss some of the methods used. Work supported by DARPA contract W31P4Q-15-C-0061 (SBIR).

  18. ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases

    PubMed Central

    Davalli, Pierpaola; Mitic, Tijana; Caporali, Andrea; Lauriola, Angela; D'Arca, Domenico

    2016-01-01

    The aging process worsens the human body functions at multiple levels, thus causing its gradual decrease to resist stress, damage, and disease. Besides changes in gene expression and metabolic control, the aging rate has been associated with the production of high levels of Reactive Oxygen Species (ROS) and/or Reactive Nitrosative Species (RNS). Specific increases of ROS level have been demonstrated as potentially critical for induction and maintenance of cell senescence process. Causal connection between ROS, aging, age-related pathologies, and cell senescence is studied intensely. Senescent cells have been proposed as a target for interventions to delay the aging and its related diseases or to improve the diseases treatment. Therapeutic interventions towards senescent cells might allow restoring the health and curing the diseases that share basal processes, rather than curing each disease in separate and symptomatic way. Here, we review observations on ROS ability of inducing cell senescence through novel mechanisms that underpin aging processes. Particular emphasis is addressed to the novel mechanisms of ROS involvement in epigenetic regulation of cell senescence and aging, with the aim to individuate specific pathways, which might promote healthy lifespan and improve aging. PMID:27247702

  19. [Tripeptides slow down aging process in renal cell culture].

    PubMed

    Khavinson, V Kh; Tarnovskaia, S I; Lin'kova, N S; Poliakova, V O; Durnova, A O; Nichik, T E; Kvetnoĭ, I M; D'iakonov, M M; Iakutseni, P P

    2014-01-01

    The mechanism of geroprotective effect of peptides AED and EDL was studied in ageing renal cell culture. Peptide AED and EDL increase cell proliferation, decreasing expression of marker of aging p16, p21, p53 and increasing expression of SIRT-6 in young and aged renal cell culture. The reduction of SIRT-6 synthesis in cell is one of the causes of cell senescence. On the basis of experimental data models of interaction of peptides with various sites of DNA were constructed. Both peptides form most energetically favorable complexes with d(ATATATATAT)2 sequences in minor groove of DNA. It is shown that interaction of peptides AED and EDL with DNA is the cause of gene expression, encoded marker of ageing in renal cells.

  20. Neuronal expression of pathological tau accelerates oligodendrocyte progenitor cell differentiation

    PubMed Central

    Ossola, Bernardino; Zhao, Chao; Compston, Alastair; Pluchino, Stefano; Franklin, Robin J. M.

    2015-01-01

    Oligodendrocyte progenitor cell (OPC) differentiation is an important therapeutic target to promote remyelination in multiple sclerosis (MS). We previously reported hyperphosphorylated and aggregated microtubule‐associated protein tau in MS lesions, suggesting its involvement in axonal degeneration. However, the influence of pathological tau‐induced axonal damage on the potential for remyelination is unknown. Therefore, we investigated OPC differentiation in human P301S tau (P301S‐htau) transgenic mice, both in vitro and in vivo following focal demyelination. In 2‐month‐old P301S‐htau mice, which show hyperphosphorylated tau in neurons, we found atrophic axons in the spinal cord in the absence of prominent axonal degeneration. These signs of early axonal damage were associated with microgliosis and an upregulation of IL‐1β and TNFα. Following in vivo focal white matter demyelination we found that OPCs differentiated more efficiently in P301S‐htau mice than wild type (Wt) mice. We also found an increased level of myelin basic protein within the lesions, which however did not translate into increased remyelination due to higher susceptibility of P301S‐htau axons to demyelination‐induced degeneration compared to Wt axons. In vitro experiments confirmed higher differentiation capacity of OPCs from P301S‐htau mice compared with Wt mice‐derived OPCs. Because the OPCs from P301S‐htau mice do not ectopically express the transgene, and when isolated from newborn mice behave like Wt mice‐derived OPCs, we infer that their enhanced differentiation capacity must have been acquired through microenvironmental priming. Our data suggest the intriguing concept that damaged axons may signal to OPCs and promote their differentiation in the attempt at rescue by remyelination. GLIA 2016;64:457–471 PMID:26576485

  1. 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

  2. Particle in cell simulation of laser-accelerated proton beams for radiation therapy.

    PubMed

    Fourkal, E; Shahine, B; Ding, M; Li, J S; Tajima, T; Ma, C M

    2002-12-01

    In this article we present the results of particle in cell (PIC) simulations of laser plasma interaction for proton acceleration for radiation therapy treatments. We show that under optimal interaction conditions protons can be accelerated up to relativistic energies of 300 MeV by a petawatt laser field. The proton acceleration is due to the dragging Coulomb force arising from charge separation induced by the ponderomotive pressure (light pressure) of high-intensity laser. The proton energy and phase space distribution functions obtained from the PIC simulations are used in the calculations of dose distributions using the GEANT Monte Carlo simulation code. Because of the broad energy and angular spectra of the protons, a compact particle selection and beam collimation system will be needed to generate small beams of polyenergetic protons for intensity modulated proton therapy.

  3. Omega-3 polyunsaturated fatty acids accelerate airway repair by activating FFA4 in club cells.

    PubMed

    Lee, Kyoung-Pil; Park, Soo-Jin; Kang, Saeromi; Koh, Jung-Min; Sato, Koichi; Chung, Hae Young; Okajima, Fumikazu; Im, Dong-Soon

    2017-03-17

    A GPCR named FFA4 (also known as GPR120) was found to act as a GPCR for omega-3 polyunsaturated fatty acids. Its expression has been reported in lung epithelial club cells. The authors investigated whether supplementation of the omega-3 fatty acids benefits lung health. Omacor® (7.75 mg kg-1), clinically prescribed preparation of omega-3 fatty acids and FFA4-knockout mice were utilized in a naphthalene-induced mouse model of acute airway injury (one injection of 30 mg kg-1, i.p.). Naphthalene injection induced complete destruction of bronchiolar epithelial cells within a day. Appearance of bronchiolar epithelial cells was observed after 21 days in control mice. It was found, however, that supplementation of omacor accelerated the recovery. The appearance of bronchiolar epithelial cells was observed between 7 and 14 days after naphthalene injury in omacor-treated mice. In isolated club cells, omega-3 fatty acids were found to stimulate cell proliferation and migration but to inhibit cell differentiation. Using pharmacological tools and FFA4-knockout mice, FFA4 was found to be responsible for omega-3 fatty acids-induced proliferation in vitro in club cells. Furthermore, accelerated recovery from naphthalene-induced airway injury in omacor-treated mice was not observed in FFA4-knockout mice in vivo. Present findings indicate that omega-3 fatty acids-induced proliferation of bronchiole epithelial cells through FFA4 is responsible for omacor-induced accelerated recovery from airway injury. Therefore, intermittent administration of omacor needs to be tested for acute airway injury, because omega-3 fatty acids stimulate proliferation but inhibits differentiation of club cells.

  4. Investigation of accelerated stress factors and failure/degradation mechanisms in terrestrial solar cells

    NASA Astrophysics Data System (ADS)

    Lathrop, J. W.

    1986-09-01

    This is the final report of a reliability research program to study the response of amorphous silicon colar cells to accelerated temperature testing. The goal of the research was to utilize accelerated testing to identify failure/degradation modes and to relate them to basic physical, chemical, and metallurgical phenomena. Four types of single junction commercial modules were subjected to 140 C testing, both in the dark and under illuminated conditions. The before and after electrical characteristics of individual cells were measured and compared and correlated with physical evidence. A fifth module type could not be tested because of poor adherence of the films to the glass superstrate. A short term effect of stressing was noted which dramatically improved cells with low Voc on one type of construction. All cells eventually showed long term irreversible degradation, but the time to 50% Pm reduction varied by as much as two orders of magnitude depending on construction. No basic difference could be detected between degradation under illuminated or non-illuminated conditions, when cells were either open or short circuited. Comparison with one type of tendem cell and with published results of Japanese cell testing indicated the marked superiority of the tandem cell to all other types. Cells were examined physically by optical, IR, and scanning electron microscopy and by Auger spectroscopy, spectroscopy, secondary ion mass spectroscopy, and energy dispersive x-ray analysis. The long term degradation was felt to be due to localized penetration of aluminum through the amorphous film.

  5. Cells derived from young bone marrow alleviate renal aging.

    PubMed

    Yang, Hai-Chun; Rossini, Michele; Ma, Li-Jun; Zuo, Yiqin; Ma, Ji; Fogo, Agnes B

    2011-11-01

    Bone marrow-derived stem cells may modulate renal injury, but the effects may depend on the age of the stem cells. Here we investigated whether bone marrow from young mice attenuates renal aging in old mice. We radiated female 12-mo-old 129SvJ mice and reconstituted them with bone marrow cells (BMC) from either 8-wk-old (young-to-old) or 12-mo-old (old-to-old) male mice. Transfer of young BMC resulted in markedly decreased deposition of collagen IV in the mesangium and less β-galactosidase staining, an indicator of cell senescence. These changes paralleled reduced expression of plasminogen activator inhibitor-1 (PAI-1), PDGF-B (PDGF-B), the transdifferentiation marker fibroblast-specific protein-1 (FSP-1), and senescence-associated p16 and p21. Tubulointerstitial and glomerular cells derived from the transplanted BMC did not show β-galactosidase activity, but after 6 mo, there were more FSP-1-expressing bone marrow-derived cells in old-to-old mice compared with young-to-old mice. Young-to-old mice also exhibited higher expression of the anti-aging gene Klotho and less phosphorylation of IGF-1 receptor β. Taken together, these data suggest that young bone marrow-derived cells can alleviate renal aging in old mice. Direct parenchymal reconstitution by stem cells, paracrine effects from adjacent cells, and circulating anti-aging molecules may mediate the aging of the kidney.

  6. Real-time and accelerated outdoor endurance testing of solar cells

    NASA Technical Reports Server (NTRS)

    Forestieri, A. F.; Anagnostou, E.

    1977-01-01

    Real-time and accelerated outdoor endurance testing was performed on a variety of samples of interest to the National Photovoltaic Conversion Program. The real-time tests were performed at seven different sites and the accelerated tests were performed at one of those sites in the southwestern United States. The purpose of the tests were to help evaluate the lifetime of photovoltaic systems. Three types of samples were tested; transmission samples of possible cover materials, sub-modules constructed using these materials attached to solar cells, and solar cell modules produced by the manufacturers for the ERDA program. Results indicate that suitable cover materials are glass, FEP-A and PFA. Dirt accumulation and cleanability are important factors in the selection of solar cell module covers and encapsulants.

  7. Cycle ageing analysis of a LiFePO4/graphite cell with dynamic model validations: Towards realistic lifetime predictions

    NASA Astrophysics Data System (ADS)

    Sarasketa-Zabala, E.; Gandiaga, I.; Martinez-Laserna, E.; Rodriguez-Martinez, L. M.; Villarreal, I.

    2015-02-01

    The present investigation work compares cycling ageing behaviour upon constant operation conditions (static tests) with degradation under non-constant schemes (dynamic tests), through a novel methodology for ageing model dynamic validation. A LFP-based Li-ion cell performance loss is analysed using a DOD and C-rate stress factors Ah-throughput-domain characterisation method, and represented using a semi-empirical model. The proposed stepwise validation approach enables assessing the static ageing tests acceleration factor and systematically improving the ageing model. The result is a simple but comprehensive model. The predictions root-mean-square error, under dynamic cycling operation conditions, is just 1.75%.

  8. TGF-β1 accelerates the DNA damage response in epithelial cells via Smad signaling.

    PubMed

    Lee, Jeeyong; Kim, Mi-Ra; Kim, Hyun-Ji; An, You Sun; Yi, Jae Youn

    2016-08-05

    The evidence suggests that transforming growth factor-beta (TGF-β) regulates the DNA-damage response (DDR) upon irradiation, and we previously reported that TGF-β1 induced DNA ligase IV (Lig4) expression and enhanced the nonhomologous end-joining repair pathway in irradiated cells. In the present study, we investigated the effects of TGF-β1 on the irradiation-induced DDRs of A431 and HaCaT cells. Cells were pretreated with or without TGF-β1 and irradiated. At 30 min post-irradiation, DDRs were detected by immunoblotting of phospho-ATM, phospho-Chk2, and the presence of histone foci (γH2AX). The levels of all three factors were similar right after irradiation regardless of TGF-β1 pretreatment. However, they soon thereafter exhibited downregulation in TGF-β1-pretreated cells, indicating the acceleration of the DDR. Treatment with a TGF-β type I receptor inhibitor (SB431542) or transfections with siRNAs against Smad2/3 or DNA ligase IV (Lig4) reversed this acceleration of the DDR. Furthermore, the frequency of irradiation-induced apoptosis was decreased by TGF-β1 pretreatment in vivo, but this effect was abrogated by SB431542. These results collectively suggest that TGF-β1 could enhance cell survival by accelerating the DDR via Smad signaling and Lig4 expression.

  9. 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.

  10. The ASP at 125: Advancing Science Literacy in an Age of Acceleration

    NASA Astrophysics Data System (ADS)

    Manning, Jim

    2014-01-01

    On February 7, 2014, the Astronomical Society of the Pacific will celebrate its 125th birthday and a century and a quarter of advancing astronomy and astronomy/science education during a period of revolutionary change in our understanding of the universe. In keeping with both the retrospective and forward-looking nature of such milestones, the presenter will: 1) share highlights of the Society’s work in supporting the communication of astronomy research through its professional publications, and creating innovative astronomy education and public outreach projects and networks to advance student, teacher and public understanding of astronomy and science; 2) report on current NASA- and NSF-funded efforts and on plans going forward; 3) and solicit input from the assembled community on how the ASP can best serve its various constituencies and the cause of science education, communication and literacy at a time when both the universe and life on Earth are accelerating at unprecedented rates. Birthdays are for celebrating; come celebrate with us as we rededicate ourselves to a mission of advancing science literacy through astronomy.

  11. 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).

  12. A model for the magnetic cores of linear induction accelerator cells

    SciTech Connect

    Melton, J.G.; Rose, E.A.

    1995-08-01

    Linear induction cells are used in the electron beam accelerator for the proposed Dual Axis Radiographic Hydrotest (DARHT) facility that would be built at Los Alamos National Laboratory. Ferrite cores are used in each cell to produce 250 kV, flat to within {plus_minus}1% for 70 ns. In the course of operating a prototype test stand for the full accelerator, circuit models have been developed for the pulsed power system and the induction cells that have been useful in achieving the {plus_minus}1% flatness requirement. The circuit models use the MicroCap IV{trademark} electronic circuit analysis program, which includes a Jiles-Atherton model for magnetic materials. In addition, the coaxial, ferrite-filled geometry of the cell is modelled by a multiple-section lumped-element transmission line. Propagation of a voltage pulse through the ferrite cores, including saturation effects, can be reproduced. The model has been compared to actual waveforms obtained from prototype operations, and good results have been obtained for a wide range of operating conditions. Interest in possible future applications have led the authors to use the model to predict the behavior of accelerator cells driven by multiple voltage pulses without an intervening magnetic reset of the ferrite cores. Results show that multiple pulses can be applied to the accelerator cells without a magnetic reset, but with some degradation of later pulses. The degradation appears as a droop on the flat portion of the second (and subsequent) pulses. The droop can be corrected by shaping the waveform of the incident pulses.

  13. Investigation of accelerated stress factors and failure/degradation mechanisms in terrestrial solar cells

    NASA Technical Reports Server (NTRS)

    Lathrop, J. W.

    1984-01-01

    Research on the reliability of terrestrial solar cells was performed to identify failure/degradation modes affecting solar cells and to relate these to basic physical, chemical, and metallurgical phenomena. Particular concerns addressed were the reliability attributes of individual single crystalline, polycrystalline, and amorphous thin film silicon cells. Results of subjecting different types of crystalline cells to the Clemson accelerated test schedule are given. Preliminary step stress results on one type of thin film amorphous silicon (a:Si) cell indicated that extraneous degradation modes were introduced above 140 C. Also described is development of measurement procedures which are applicable to the reliability testing of a:Si solar cells as well as an approach to achieving the necessary repeatability of fabricating a simulated a:Si reference cell from crystalline silicon photodiodes.

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

    NASA Astrophysics Data System (ADS)

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

    2016-11-01

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

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

    PubMed Central

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

    2016-01-01

    Natural ageing process occurs throughout the life cycle of textile products, which may possess influences on the release behavior of additives such as silver nanoparticles (Ag NPs). In this study, we assessed the releasability of Ag NPs from a Ag NPs functionalized textile in five different exposure scenarios (i.e. tap water (TW), pond water (PW), rain water (RW), artificial sweat (AS), and detergent solution (DS) along with deionized water (DW) as reference), which were very likely to occur throughout the life cycle of the textile. For the pristine textile, although the most remarkable release was found in DW (6–15 μg Ag/g textile), the highest release rate was found in RW (around 7 μg Ag/(g textile·h)). After ageing treatment, the total released Ag could be increased by 75.7~386.0% in DW, AS and DS. Morphological analysis clearly showed that the Ag NPs were isolated from the surface of the textile fibre due to the ageing treatment. This study provides useful information for risk assessment of nano-enhanced textile products. PMID:27869136

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

    PubMed

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

    2016-11-21

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

  17. Microgrooved Polymer Substrates Promote Collective Cell Migration To Accelerate Fracture Healing in an in Vitro Model.

    PubMed

    Zhang, Qing; Dong, Hua; Li, Yuli; Zhu, Ye; Zeng, Lei; Gao, Huichang; Yuan, Bo; Chen, Xiaofeng; Mao, Chuanbin

    2015-10-21

    Surface topography can affect cell adhesion, morphology, polarity, cytoskeleton organization, and osteogenesis. However, little is known about the effect of topography on the fracture healing in repairing nonunion and large bone defects. Microgrooved topography on the surface of bone implants may promote cell migration into the fracture gap to accelerate fracture healing. To prove this hypothesis, we used an in vitro fracture (wound) healing assay on the microgrooved polycaprolactone substrates to study the effect of microgroove widths and depths on the osteoblast-like cell (MG-63) migration and the subsequent healing. We found that the microgrooved substrates promoted MG-63 cells to migrate collectively into the wound gap, which serves as a fracture model, along the grooves and ridges as compared with the flat substrates. Moreover, the groove widths did not show obvious influence on the wound healing whereas the smaller groove depths tended to favor the collective cell migration and thus subsequent healing. The microgrooved substrates accelerated the wound healing by facilitating the collective cell migration into the wound gaps but not by promoting the cell proliferation. Furthermore, microgrooves were also found to promote the migration of human mesenchymal stem cells (hMSCs) to heal the fracture model. Though osteogenic differentiation of hMSCs was not improved on the microgrooved substrate, collagen I and minerals deposited by hMSCs were organized in a way similar to those in the extracellular matrix of natural bone. These findings suggest the necessity in using microgrooved implants in enhancing fracture healing in bone repair.

  18. Molecular aging and rejuvenation of human muscle stem cells

    PubMed Central

    Carlson, Morgan E; Suetta, Charlotte; Conboy, Michael J; Aagaard, Per; Mackey, Abigail; Kjaer, Michael; Conboy, Irina

    2009-01-01

    Very little remains known about the regulation of human organ stem cells (in general, and during the aging process), and most previous data were collected in short-lived rodents. We examined whether stem cell aging in rodents could be extrapolated to genetically and environmentally variable humans. Our findings establish key evolutionarily conserved mechanisms of human stem cell aging. We find that satellite cells are maintained in aged human skeletal muscle, but fail to activate in response to muscle attrition, due to diminished activation of Notch compounded by elevated transforming growth factor beta (TGF-β)/phospho Smad3 (pSmad3). Furthermore, this work reveals that mitogen-activated protein kinase (MAPK)/phosphate extracellular signal-regulated kinase (pERK) signalling declines in human muscle with age, and is important for activating Notch in human muscle stem cells. This molecular understanding, combined with data that human satellite cells remain intrinsically young, introduced novel therapeutic targets. Indeed, activation of MAPK/Notch restored ‘youthful’ myogenic responses to satellite cells from 70-year-old humans, rendering them similar to cells from 20-year-old humans. These findings strongly suggest that aging of human muscle maintenance and repair can be reversed by ‘youthful’ calibration of specific molecular pathways. PMID:20049743

  19. Accelerated cycle life performance for ovonic nickel-metal hydride cells

    NASA Technical Reports Server (NTRS)

    Otzinger, Burton M.

    1991-01-01

    Nickel-Metal Hydride (Ni-MH) rechargeable batteries have emerged as the leading candidate for commercial replacement of nickel-cadmium (Ni-Cd) batteries. An important incentive is that the Ni-MH cell provides approximately twice the capacity of a Ni-Cd cell for a given size. A six-cell battery was committed to an accelerated cycle life test to determine the effect of separation type on performance. Results of the test may also show the Ni-MH battery to be a replacement candidate for the aerospace Ni-Cd battery.

  20. Particle-in-cell Simulation of Electron Acceleration in Solar Coronal Jets

    NASA Astrophysics Data System (ADS)

    Baumann, G.; Nordlund, Å.

    2012-11-01

    We investigate electron acceleration resulting from three-dimensional magnetic reconnection between an emerging, twisted magnetic flux rope and a pre-existing weak, open magnetic field. We first follow the rise of an unstable, twisted flux tube with a resistive MHD simulation where the numerical resolution is enhanced by using fixed mesh refinement. As in previous MHD investigations of similar situations, the rise of the flux tube into the pre-existing inclined coronal magnetic field results in the formation of a solar coronal jet. A snapshot of the MHD model is then used as an initial and boundary condition for a particle-in-cell simulation, using up to half a billion cells and over 20 billion charged particles. Particle acceleration occurs mainly in the reconnection current sheet, with accelerated electrons displaying a power law in the energy probability distribution with an index of around -1.5. The main acceleration mechanism is a systematic electric field, striving to maintaining the electric current in the current sheet against losses caused by electrons not being able to stay in the current sheet for more than a few seconds at a time.

  1. Particle-in-cell simulations of electron acceleration by a simple capacitative antenna in collisionless plasma

    NASA Astrophysics Data System (ADS)

    Dieckmann, M. E.; Rowlands, G.; Eliasson, B.; Shukla, P. K.

    2004-12-01

    We examine the electron acceleration by a localized electrostatic potential oscillating at high frequencies by means of particle-in-cell (PIC) simulations, in which we apply oscillating electric fields to two neighboring simulation cells. We derive an analytic model for the direct electron heating by the externally driven antenna electric field, and we confirm that it approximates well the electron heating obtained in the simulations. In the simulations, transient waves accelerate electrons in a sheath surrounding the antenna. This increases the Larmor radii of the electrons close to the antenna, and more electrons can reach the antenna location to interact with the externally driven fields. The resulting hot electron sheath is dense enough to support strong waves that produce high-energy sounder-accelerated electrons (SAEs) by their nonlinear interaction with the ambient electrons. By increasing the emission amplitudes in our simulations to values that are representative for the ones of the sounder on board the OEDIPUS C (OC) satellites, we obtain electron acceleration into the energy range which is comparable to the 20 keV energies of the SAE observed by the OC mission. The emission also triggers stable electrostatic waves oscillating at frequencies close to the first harmonic of the electron cyclotron frequency. We find this to be an encouraging first step of examining SAE generation with kinetic numerical simulation codes.

  2. 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

  3. Topical Estrogen Accelerates Cutaneous Wound Healing in Aged Humans Associated with an Altered Inflammatory Response

    PubMed Central

    Ashcroft, Gillian S.; Greenwell-Wild, Teresa; Horan, Michael A.; Wahl, Sharon M.; Ferguson, Mark W. J.

    1999-01-01

    The effects of intrinsic aging on the cutaneous wound healing process are profound, and the resulting acute and chronic wound morbidity imposes a substantial burden on health services. We have investigated the effects of topical estrogen on cutaneous wound healing in healthy elderly men and women, and related these effects to the inflammatory response and local elastase levels, an enzyme known to be up-regulated in impaired wound healing states. Eighteen health status-defined females (mean age, 74.4 years) and eighteen males (mean age, 70.7 years) were randomized in a double-blind study to either active estrogen patch or identical placebo patch attached for 24 hours to the upper inner arm, through which two 4-mm punch biopsies were made. The wounds were excised at either day 7 or day 80 post-wounding. Compared to placebo, estrogen treatment increased the extent of wound healing in both males and females with a decrease in wound size at day 7, increased collagen levels at both days 7 and 80, and increased day 7 fibronectin levels. In addition, estrogen enhanced the strength of day 80 wounds. Estrogen treatment was associated with a decrease in wound elastase levels secondary to reduced neutrophil numbers, and decreased fibronectin degradation. In vitro studies using isolated human neutrophils indicate that one mechanism underlying the altered inflammatory response involves both a direct inhibition of neutrophil chemotaxis by estrogen and an altered expression of neutrophil adhesion molecules. These data demonstrate that delays in wound healing in the elderly can be significantly diminished by topical estrogen in both male and female subjects. PMID:10514397

  4. Esophageal cancer-related gene 4 is a secreted inducer of cell senescence expressed by aged CNS precursor cells.

    PubMed

    Kujuro, Yuki; Suzuki, Norihiro; Kondo, Toru

    2010-05-04

    Mammalian aging is thought to be partially caused by the diminished capacity of stem/precursor cells to undergo self-renewing divisions. Although many cell-cycle regulators are involved in this process, it is unknown to what extent cell senescence, first identified as irreversible growth arrest in vitro, contributes to the aging process. Here, using a serum-induced mouse oligodendrocyte precursor cell (mOPC) senescence model, we identified esophageal cancer-related gene 4 (Ecrg4) as a senescence inducer with implications for the senescence-like state of postmitotic cells in the aging brain. Although mOPCs could proliferate indefinitely when cultured using the appropriate medium (OPC medium), they became senescent in the presence of serum and maintained their senescent phenotype even when the serum was subsequently replaced by OPC medium. We show that Ecrg4 was up-regulated in the senescent OPCs, its overexpression in OPCs induced senescence by accelerating the proteasome-dependent degradation of cyclins D1 and D3, and that its knockdown by a specific short hairpin RNA prevented these phenotypes. We also show that senescent OPCs secreted Ecrg4 and that recombinant Ecrg4 induced OPC senescence in culture. Moreover, increased Ecrg4 expression was observed in the OPCs and neural precursor cells in the aged mouse brain; this was accompanied by the expression of senescence-associated beta-galactosidase activity, indicating the cells' entrance into senescence. These results suggest that Ecrg4 is a factor linking neural-cell senescence and aging.

  5. Effects of aging and sensory loss on glial cells in mouse visual and auditory cortices.

    PubMed

    Tremblay, Marie-Ève; Zettel, Martha L; Ison, James R; Allen, Paul D; Majewska, Ania K

    2012-04-01

    Normal aging is often accompanied by a progressive loss of receptor sensitivity in hearing and vision, whose consequences on cellular function in cortical sensory areas have remained largely unknown. By examining the primary auditory (A1) and visual (V1) cortices in two inbred strains of mice undergoing either age-related loss of audition (C57BL/6J) or vision (CBA/CaJ), we were able to describe cellular and subcellular changes that were associated with normal aging (occurring in A1 and V1 of both strains) or specifically with age-related sensory loss (only in A1 of C57BL/6J or V1 of CBA/CaJ), using immunocytochemical electron microscopy and light microscopy. While the changes were subtle in neurons, glial cells and especially microglia were transformed in aged animals. Microglia became more numerous and irregularly distributed, displayed more variable cell body and process morphologies, occupied smaller territories, and accumulated phagocytic inclusions that often displayed ultrastructural features of synaptic elements. Additionally, evidence of myelination defects were observed, and aged oligodendrocytes became more numerous and were more often encountered in contiguous pairs. Most of these effects were profoundly exacerbated by age-related sensory loss. Together, our results suggest that the age-related alteration of glial cells in sensory cortical areas can be accelerated by activity-driven central mechanisms that result from an age-related loss of peripheral sensitivity. In light of our observations, these age-related changes in sensory function should be considered when investigating cellular, cortical, and behavioral functions throughout the lifespan in these commonly used C57BL/6J and CBA/CaJ mouse models.

  6. AMPK deficiency in chondrocytes accelerated the progression of instability-induced and ageing-associated osteoarthritis in adult mice.

    PubMed

    Zhou, Sheng; Lu, Wanli; Chen, Liang; Ge, Qiting; Chen, Dongyang; Xu, Zhihong; Shi, Dongquan; Dai, Jin; Li, Jianxin; Ju, Huangxian; Cao, Yi; Qin, Jinzhong; Chen, Shuai; Teng, Huajian; Jiang, Qing

    2017-02-22

    Osteoarthritis (OA) is a progressive degenerative disease of the joints that is associated with both joint injury and ageing. Here, we investigated the role of the energy sensor AMP-activated protein kinase (AMPK) in maintaining a healthy state of articular cartilage and in OA development. Using cartilage-specific, tamoxifen-inducible AMPKα1 conditional knockout (AMPKα1 cKO), AMPKα2 conditional knockout (AMPKα2 cKO) and AMPKα1α2 conditional double knockout (AMPKα cDKO) mice, we found that compared with wild-type (WT) littermates, mutant mice displayed accelerated severity of surgically induced OA, especially AMPKα cDKO mice. Furthermore, male but not female AMPKα cDKO mice exhibited severely spontaneous ageing-associated OA lesions at 12 months of age. The chondrocytes isolated from AMPKα cDKO mice resulted in an enhanced interleukin-1β (IL-1β)-stimulated catabolic response. In addition, upregulated expression of matrix metalloproteinase-3 (MMP-3), MMP-13 and phospho-nuclear factor-κB (phospho-NF-κB) p65 and increased levels of apoptotic markers were detected in the cartilage of AMPKα cDKO mice compared with their WT littermates in vivo. Thus, our findings suggest that AMPK activity in chondrocytes is important in maintaining joint homeostasis and OA development.

  7. AMPK deficiency in chondrocytes accelerated the progression of instability-induced and ageing-associated osteoarthritis in adult mice

    PubMed Central

    Zhou, Sheng; Lu, Wanli; Chen, Liang; Ge, Qiting; Chen, Dongyang; Xu, Zhihong; Shi, Dongquan; Dai, Jin; Li, Jianxin; Ju, Huangxian; Cao, Yi; Qin, Jinzhong; Chen, Shuai; Teng, Huajian; Jiang, Qing

    2017-01-01

    Osteoarthritis (OA) is a progressive degenerative disease of the joints that is associated with both joint injury and ageing. Here, we investigated the role of the energy sensor AMP-activated protein kinase (AMPK) in maintaining a healthy state of articular cartilage and in OA development. Using cartilage-specific, tamoxifen-inducible AMPKα1 conditional knockout (AMPKα1 cKO), AMPKα2 conditional knockout (AMPKα2 cKO) and AMPKα1α2 conditional double knockout (AMPKα cDKO) mice, we found that compared with wild-type (WT) littermates, mutant mice displayed accelerated severity of surgically induced OA, especially AMPKα cDKO mice. Furthermore, male but not female AMPKα cDKO mice exhibited severely spontaneous ageing-associated OA lesions at 12 months of age. The chondrocytes isolated from AMPKα cDKO mice resulted in an enhanced interleukin-1β (IL-1β)-stimulated catabolic response. In addition, upregulated expression of matrix metalloproteinase-3 (MMP-3), MMP-13 and phospho-nuclear factor-κB (phospho-NF-κB) p65 and increased levels of apoptotic markers were detected in the cartilage of AMPKα cDKO mice compared with their WT littermates in vivo. Thus, our findings suggest that AMPK activity in chondrocytes is important in maintaining joint homeostasis and OA development. PMID:28225087

  8. Rejuvenation of the aged muscle stem cell population restores strength to injured aged muscles

    PubMed Central

    Cosgrove, Benjamin D.; Gilbert, Penney M.; Porpiglia, Ermelinda; Mourkioti, Foteini; Lee, Steven P.; Corbel, Stephane Y.; Llewellyn, Michael E.; Delp, Scott L.; Blau, Helen M.

    2014-01-01

    The aged suffer from progressive muscle weakness and regenerative failure. We demonstrate that muscle regeneration is impaired with aging due in part to a cell-autonomous functional decline in skeletal muscle stem cells (MuSCs). Two-thirds of aged MuSCs are intrinsically defective relative to young MuSCs, with reduced capacity to repair myofibers and repopulate the stem cell reservoir in vivo following transplantation due to a higher incidence of cells that express senescence markers and that have elevated p38α/β MAPK activity. We show that these limitations cannot be overcome by transplantation into the microenvironment of young recipient muscles. In contrast, subjecting the aged MuSC population to transient inhibition of p38α/β in conjunction with culture on soft hydrogel substrates rapidly expands the residual functional aged MuSC population, rejuvenating its potential for regeneration, serial transplantation, and strengthening damaged muscles of aged mice. These findings reveal a synergy between biophysical and biochemical cues that provides a paradigm for a localized autologous muscle stem cell therapy in aged individuals. PMID:24531378

  9. Targeting of prion-infected lymphoid cells to the central nervous system accelerates prion infection

    PubMed Central

    2012-01-01

    Background Prions, composed of a misfolded protein designated PrPSc, are infectious agents causing fatal neurodegenerative diseases. We have shown previously that, following induction of experimental autoimmune encephalomyelitis, prion-infected mice succumb to disease significantly earlier than controls, concomitant with the deposition of PrPSc aggregates in inflamed white matter areas. In the present work, we asked whether prion disease acceleration by experimental autoimmune encephalomyelitis results from infiltration of viable prion-infected immune cells into the central nervous system. Methods C57Bl/6 J mice underwent intraperitoneal inoculation with scrapie brain homogenates and were later induced with experimental autoimmune encephalomyelitis by inoculation of MOG35-55 in complete Freund's adjuvant supplemented with pertussis toxin. Spleen and lymph node cells from the co-induced animals were reactivated and subsequently injected into naïve mice as viable cells or as cell homogenates. Control groups were infected with viable and homogenized scrapie immune cells only with complete Freund's adjuvant. Prion disease incubation times as well as levels and sites of PrPSc deposition were next evaluated. Results We first show that acceleration of prion disease by experimental autoimmune encephalomyelitis requires the presence of high levels of spleen PrPSc. Next, we present evidence that mice infected with activated prion-experimental autoimmune encephalomyelitis viable cells succumb to prion disease considerably faster than do mice infected with equivalent cell extracts or other controls, concomitant with the deposition of PrPSc aggregates in white matter areas in brains and spinal cords. Conclusions Our results indicate that inflammatory targeting of viable prion-infected immune cells to the central nervous system accelerates prion disease propagation. We also show that in the absence of such targeting it is the load of PrPSc in the inoculum that determines the

  10. Telomere attrition in beta and alpha cells with age.

    PubMed

    Tamura, Yoshiaki; Izumiyama-Shimomura, Naotaka; Kimbara, Yoshiyuki; Nakamura, Ken-Ichi; Ishikawa, Naoshi; Aida, Junko; Chiba, Yuko; Matsuda, Yoko; Mori, Seijiro; Arai, Tomio; Fujiwara, Mutsunori; Poon, Steven S S; Ishizaki, Tatsuro; Araki, Atsushi; Takubo, Kaiyo; Ito, Hideki

    2016-06-01

    We have reported telomere attrition in β and α cells of the pancreas in elderly patients with type 2 diabetes, but it has not been explored how the telomere lengths of these islet cells change according to age in normal subjects. To examine the telomere lengths of β and α cells in individuals without diabetes across a wide range of ages, we conducted measurement of the telomere lengths of human pancreatic β and α cells obtained from 104 autopsied subjects without diabetes ranging in age from 0 to 100 years. As an index of telomere lengths, the normalized telomere-centromere ratio (NTCR) was determined for β (NTCRβ) and α (NTCRα) cells by quantitative fluorescence in situ hybridization (Q-FISH). We found NTCRβ and NTCRα showed almost the same levels and both decreased according to age (p < 0.001 for both). NTCRs decreased more rapidly with age and were more widely distributed (p = 0.036 for NTCRβ, p < 0.001 for NTCRα) in subjects under 18 years of age than in subjects over 18 years. There was a positive correlation between NTCRβ and NTCRα only among adult subjects (p < 0.001). In conclusion, the telomeres of β and α cells become shortened with normal aging process.

  11. Aging and the Dendritic Cell System: Implications for Cancer

    PubMed Central

    Shurin, Michael R.; Shurin, Galina V.; Chatta, Gurkamal S.

    2007-01-01

    The immune system shows a decline in responsiveness to antigens both with aging, as well as in the presence of tumors. The malfunction of the immune system with age can be attributed to developmental and functional alterations in several cell populations. Previous studies have shown defects in humoral responses and abnormalities in T cell function in aged individuals, but have not distinguished between abnormalities in antigen presentation and intrinsic T cell or B cell defects in aged individuals. Dendritic cells (DC) play a pivotal role in regulating immune responses by presenting antigens to naïve T lymphocytes, modulating Th1/Th2/Treg balance, producing numerous regulatory cytokines and chemokines, and modifying survival of immune effectors. DC are receiving increased attention due to their involvement in the immunobiology of tolerance and autoimmunity, as well as their potential role as biological adjuvants in tumor vaccines. Recent advances in the molecular and cell biology of different DC populations allow for addressing the issue of DC and aging both in rodents and humans. Since DC play a crucial role in initiating and regulating immune responses, it is reasonable to hypothesize that they are directly involved in altered antitumor immunity in aging. However, the results of studies focusing on DC in the elderly are conflicting. The present review summarizes the available human and experimental animal data on quantitative and qualitative alterations of DC in aging and discusses the potential role of the DC system in the increased incidence of cancer in the elderly. PMID:17446082

  12. Compatability and accelerated aging study for Li(Si)FeS2 thermally activated batteries

    NASA Astrophysics Data System (ADS)

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

    1982-04-01

    Thermally activated batteries using the Li(Si)/FeS2 system are being developed by Sandia National Laboratories. These components ae used in systems which require a storage life of 25 years and high reliability. A previous aging study was completed on this system, but no organic materials other than those in the electrical match and heat paper fuse strips were included. The present study incorporates all of the materials in the system, both organic and inorganic, except for the electric match and heat paper. There are two main parts in this study: (1) a compatibility study in which the four organic materials under investigation are placed in a hermetically sealed stainless steel container with battery components; (2) an aging study of pairs of material and individual materials in which one organic material is placed in a hermetically sealed stainless steel container with battery components. The compatibility study examines effects of some materials upon others (outgassing, etc.) which would cause degradation and/or functional failure.

  13. 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

  14. Relation Between Motility, Accelerated Aging and Gene Expression in Selected Drosophila Strains under Hypergravity Conditions

    NASA Astrophysics Data System (ADS)

    Serrano, Paloma; van Loon, Jack J. W. A.; Medina, F. Javier; Herranz, Raúl

    2013-02-01

    Motility and aging in Drosophila have proven to be highly modified under altered gravity conditions (both in space and ground simulation facilities). In order to find out how closely connected they are, five strains with altered geotactic response or survival rates were selected and exposed to an altered gravity environment of 2 g. By analysing the different motile and behavioural patterns and the median survival rates, we show that altered gravity leads to changes in motility, which will have a negative impact on the flies' survival. Previous results show a differential gene expression between sessile samples and adults and confirm that environmentally-conditioned behavioural patterns constrain flies' gene expression and life span. Therefore, hypergravity is considered an environmental stress factor and strains that do not respond to this new environment experience an increment in motility, which is the major cause for the observed increased mortality also under microgravity conditions. The neutral-geotaxis selected strain (strain M) showed the most severe phenotype, unable to respond to variations in the gravitational field. Alternatively, the opposite phenotype was observed in positive-geotaxis and long-life selected flies (strains B and L, respectively), suggesting that these populations are less sensitive to alterations in the gravitational load. We conclude that the behavioural response has a greater contribution to aging than the modified energy consumption in altered gravity environments.

  15. CD4+CXCR3+ T cells and plasmacytoid dendritic cells drive accelerated atherosclerosis associated with systemic lupus erythematosus.

    PubMed

    Clement, Marc; Charles, Nicolas; Escoubet, Brigitte; Guedj, Kevin; Chauveheid, Marie-Paule; Caligiuri, Giuseppina; Nicoletti, Antonino; Papo, Thomas; Sacre, Karim

    2015-09-01

    Cardiovascular disease due to accelerated atherosclerosis is the leading cause of death in patients with systemic lupus erythematosus (SLE). Noteworthy, accelerated atherosclerosis in SLE patients appears to be independant of classical Framingham risk factors. This suggests that aggravated atherosclerosis in SLE patients may be a result of increased inflammation and altered immune responses. However, the mechanisms that mediate the acceleration of atherosclerosis in SLE remain elusive. Based on experimental data which includes both humans (SLE patients and control subjects) and rodents (ApoE-/- mice), we herein propose a multi-step model in which the immune dysfunction associated with SLE (i.e. high level of IFN-α production by TLR 9-stimulated pDCs) is associated with, first, an increased frequency of circulating pro inflammatory CD4+CXCR3+ T cells; second, an increased production of CXCR3 ligands by endothelial cells; third, an increased recruitment of pro-inflammatory CD4+CXCR3+ T cells into the arterial wall, and fourth, the development of atherosclerosis. In showing how SLE may promote accelerated atherosclerosis, our model also points to hypotheses for potential interventions, such as pDCs-targeted therapy, that might be studied in the future.

  16. Preliminary results of accelerated exposure testing of solar cell system components

    NASA Technical Reports Server (NTRS)

    Anagnostou, E.; Forestieri, A. F.

    1977-01-01

    Plastic samples and solar cell sub modules were exposed to an accelerated outdoor environment in Arizona and an accelerated simulated environment in a cyclic ultraviolet exposure tester which included humidity exposure. These tests were for preliminary screening of materials suitable for use in the manufacture of solar cell modules which are to have a 20-year lifetime. The samples were exposed for various times up to six months, equivalent to a real time exposure of four years. Suitable materials were found to be FEP-A, FEP-C, PFA, acrylic, silicone compounds and adhesives and possibly parylene. The method of packaging the sub modules was also found to be important to their performance.

  17. Particle-in-cell simulations of plasma accelerators and electron-neutral collisions

    SciTech Connect

    Bruhwiler, David L.; Giacone, Rodolfo E.; Cary, John R.; Verboncoeur, John P.; Mardahl, Peter; Esarey, Eric; Leemans, W.P.; Shadwick, B.A.

    2001-10-01

    We present 2-D simulations of both beam-driven and laser-driven plasma wakefield accelerators, using the object-oriented particle-in-cell code XOOPIC, which is time explicit, fully electromagnetic, and capable of running on massively parallel supercomputers. Simulations of laser-driven wakefields with low ({approx}10{sup 16} W/cm{sup 2}) and high ({approx}10{sup 18} W/cm{sup 2}) peak intensity laser pulses are conducted in slab geometry, showing agreement with theory and fluid simulations. Simulations of the E-157 beam wakefield experiment at the Stanford Linear Accelerator Center, in which a 30 GeV electron beam passes through 1 m of preionized lithium plasma, are conducted in cylindrical geometry, obtaining good agreement with previous work. We briefly describe some of the more significant modifications of XOOPIC required by this work, and summarize the issues relevant to modeling relativistic electron-neutral collisions in a particle-in-cell code.

  18. Accelerated tissue aging and increased oxidative stress in broiler chickens fed allopurinol.

    PubMed

    Klandorf, H; Rathore, D S; Iqbal, M; Shi, X; Van Dyke, K

    2001-06-01

    Uric acid has been hypothesized as being one of the more important antioxidants in limiting the accumulation of glycosylated endproducts in birds. Study 1 was designed to quantitatively manipulate the plasma concentrations of uric acid using hemin and allopurinol while study 2 determined their effects on skin pentosidine, the shear force value of Pectoralis major muscle, plasma glucose, body weight and chemiluminescence monitored oxidative stress in broiler chickens. Hemin was hypothesized to raise uric acid concentrations thereby lowering oxidative stress whereas allopurinol was hypothesized to lower uric acid concentrations and raise measures of oxidative stress. In study 1 feeding allopurinol (10 mg/kg body weight) to 8-week-old broiler chicks (n=50) for 10 days decreased plasma uric acid by 57%. However, hemin (10 mg/kg body weight) increased uric acid concentrations 20%. In study 2, 12-week-old broiler chicks (n=90) were randomly assigned to either an ad libitum (AL) diet or a diet restricted (DR) group. Each group was further divided into three treatments (control, allopurinol or hemin fed). Unexpectedly, hemin did not significantly effect uric acid concentrations but increased (P<0.05) measures of chemiluminescence dependent oxidative stress in both the DR and AL birds probably due to the ability of iron to generate oxygen radicals. Allopurinol lowered concentrations of uric acid and increased (P<0.05) the oxidative stress in the AL birds at week 22, reduced (P<0.05) body weight in both the AL and DR fed birds at 16 and 22 weeks of age, and markedly increased (P<0.001) shear force values of the pectoralis major muscle. Skin pentosidine levels increased (P<0.05) in AL birds fed allopurinol or hemin fed birds, but not in the diet restricted birds at 22 weeks. The significance of these studies is that concentrations of plasma uric acid can be related to measures of oxidative stress, which can be linked to tissue aging.

  19. Ageing of Sony 18650HC Cells in LEO LifeTests

    NASA Astrophysics Data System (ADS)

    Dudley, G.; Buckle, R.; Hendel, B.; Mattle, T.; Spurrett, R.

    2008-09-01

    Results of a long-duration LEO life-test of a battery comprised of 72 Sony 18650HC cells are presented. The ongoing test, started in late 1999, has reached 84,000 cycles, equivalent to more than 14 years in LEO orbit at an acceleration factor of 1.7. Most cells have remained balanced in state of charge during the test but a few have dropped up to 150 mV in end of charge voltage and at the same time exhibited higher than average internal resistances. The battery continues to out-perform the predictions of the ABSL 'LIFE' model. A cell model developed at ESTEC is used to try to gain some insight into the cell ageing processes.

  20. Aging promotes acquisition of naive-like CD8+ memory T cell traits and enhanced functionalities.

    PubMed

    Eberlein, Jens; Davenport, Bennett; Nguyen, Tom; Victorino, Francisco; Haist, Kelsey; Jhun, Kevin; Karimpour-Fard, Anis; Hunter, Lawrence; Kedl, Ross; Clambey, Eric T; Homann, Dirk

    2016-10-03

    Protective T cell memory is an acquired trait that is contingent upon the preservation of its constituents and therefore vulnerable to the potentially deleterious effects of organismal aging. Here, however, we have found that long-term T cell memory in a natural murine host-pathogen system can substantially improve over time. Comprehensive molecular, phenotypic, and functional profiling of aging antiviral CD8+ memory T cells (CD8+ TM) revealed a pervasive remodeling process that promotes the gradual acquisition of distinct molecular signatures, of increasingly homogeneous phenotypes, and of diversified functionalities that combine to confer a CD8+ TM-autonomous capacity for enhanced recall responses and immune protection. Notably, the process of CD8+ TM aging is characterized by a progressive harmonization of memory and naive T cell traits, is broadly amenable to experimental acceleration or retardation, and serves as a constitutional component for the "rebound model" of memory T cell maturation. By casting CD8+ TM populations within the temporal framework of their slowly evolving properties, this model establishes a simple ontogenetic perspective on the principal organization of CD8+ T cell memory that may directly inform the development of improved diagnostic, prophylactic, and therapeutic modalities.

  1. Aging promotes acquisition of naive-like CD8+ memory T cell traits and enhanced functionalities

    PubMed Central

    Davenport, Bennett; Nguyen, Tom; Victorino, Francisco; Haist, Kelsey; Jhun, Kevin; Karimpour-Fard, Anis; Hunter, Lawrence; Kedl, Ross; Clambey, Eric T.

    2016-01-01

    Protective T cell memory is an acquired trait that is contingent upon the preservation of its constituents and therefore vulnerable to the potentially deleterious effects of organismal aging. Here, however, we have found that long-term T cell memory in a natural murine host-pathogen system can substantially improve over time. Comprehensive molecular, phenotypic, and functional profiling of aging antiviral CD8+ memory T cells (CD8+ TM) revealed a pervasive remodeling process that promotes the gradual acquisition of distinct molecular signatures, of increasingly homogeneous phenotypes, and of diversified functionalities that combine to confer a CD8+ TM–autonomous capacity for enhanced recall responses and immune protection. Notably, the process of CD8+ TM aging is characterized by a progressive harmonization of memory and naive T cell traits, is broadly amenable to experimental acceleration or retardation, and serves as a constitutional component for the “rebound model” of memory T cell maturation. By casting CD8+ TM populations within the temporal framework of their slowly evolving properties, this model establishes a simple ontogenetic perspective on the principal organization of CD8+ T cell memory that may directly inform the development of improved diagnostic, prophylactic, and therapeutic modalities. PMID:27617858

  2. Telomere Length and CCL11 Levels are Associated With Gray Matter Volume and Episodic Memory Performance in Schizophrenia: Evidence of Pathological Accelerated Aging.

    PubMed

    Czepielewski, Leticia Sanguinetti; Massuda, Raffael; Panizzutti, Bruna; Grun, Lucas Kich; Barbé-Tuana, Florencia María; Teixeira, Antonio Lucio; Barch, Deanna M; Gama, Clarissa S

    2017-02-22

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

  3. GPU accelerated cell-based adaptive mesh refinement on unstructured quadrilateral grid

    NASA Astrophysics Data System (ADS)

    Luo, Xisheng; Wang, Luying; Ran, Wei; Qin, Fenghua

    2016-10-01

    A GPU accelerated inviscid flow solver is developed on an unstructured quadrilateral grid in the present work. For the first time, the cell-based adaptive mesh refinement (AMR) is fully implemented on GPU for the unstructured quadrilateral grid, which greatly reduces the frequency of data exchange between GPU and CPU. Specifically, the AMR is processed with atomic operations to parallelize list operations, and null memory recycling is realized to improve the efficiency of memory utilization. It is found that results obtained by GPUs agree very well with the exact or experimental results in literature. An acceleration ratio of 4 is obtained between the parallel code running on the old GPU GT9800 and the serial code running on E3-1230 V2. With the optimization of configuring a larger L1 cache and adopting Shared Memory based atomic operations on the newer GPU C2050, an acceleration ratio of 20 is achieved. The parallelized cell-based AMR processes have achieved 2x speedup on GT9800 and 18x on Tesla C2050, which demonstrates that parallel running of the cell-based AMR method on GPU is feasible and efficient. Our results also indicate that the new development of GPU architecture benefits the fluid dynamics computing significantly.

  4. Antimutagenicity of WR-1065 in L5178Y cells exposed to accelerated (56)Fe ions

    NASA Technical Reports Server (NTRS)

    Evans, H. H.; Evans, T. E.; Horng, M. F.

    2002-01-01

    The ability of the aminothiol WR-1065 [N-(2-mercaptoethyl)-1,3-diaminopropane] to protect L5178Y (LY) cells against the cytotoxic and mutagenic effects of exposure to accelerated (56)Fe ions (1.08 GeV/nucleon) was determined. It was found that while WR-1065 reduced the mutagenicity in both cell lines when it was present during the irradiation, the addition of WR-1065 after the exposure had no effect on the mutagenicity of the radiation in either cell line. No marked protection against the cytotoxic effects of exposure to (56)Fe ions was provided by WR-1065 when added either during or after irradiation in either cell line. We reported previously that WR-1065 protected the LY-S1 and LY-SR1 cell lines against both the cytotoxicity and mutagenicity of X radiation when present during exposure, but that its protection when administered after exposure was limited to the mutagenic effects in the radiation-hypersensitive cell line, LY-S1. The results indicate that the mechanisms involved differ in the protection against cytotoxic compared to mutagenic effects and in the protection against damage caused by accelerated (56)Fe ions compared to X radiation.

  5. The static magnetic field accelerates the osteogenic differentiation and mineralization of dental pulp cells

    PubMed Central

    Chang, Jui-Chih

    2010-01-01

    Dental pulp cells (DPCs) can differentiate into osteoblasts and are deemed a promising cell source for bone regeneration. Static magnetic field (SMF) stimulates osteoblast differentiation but the effect in DPCs remains unknown. The aim of this study was to investigate the effect of SMF exposure on the osteogenic differentiation and mineralization of rat DPCs in vitro. Cells were continuously exposed to SMF at 290 mT in the presence/absence of osteogenic induction [dexamethasone (Dex)/β-glycerophosphate (β-GP)]. Results showed that SMF alone did not impair the cell cycle and proliferation. On the other hand, obvious condensation in the metachromatic staining of the extracellular matrix with toluidine blue was observed for SMF-exposed cells as well as the Dex/β-GP treated cells. SMF in combination with Dex/β-GP significantly increased the mRNA expression of osteogenic genes, as well as the ALP activity and extracellular calcium concentration at the early stage, followed by obvious calcium deposits later. Besides, SMF exposure increased the activity of extracellular signal-regulated kinase 1/2 (ERK1/2) at 3 h and accelerated the mRNA expression of osteogenic transcription factor, Cbfa1, advancing its activation time from 168 to 72 h under osteogenic induction. In summary, SMF exposure in combination of Dex/β-GP induction could significantly accelerate the osteogenic differentiation and mineralization of DPCs. PMID:20464482

  6. Aging of the inceptive cellular population: the relationship between stem cells and aging.

    PubMed

    Symonds, Catherine E; Galderisi, Umberto; Giordano, Antonio

    2009-04-02

    The average life expectancy worldwide has about doubled and the global population has increased six fold over the past century. With improving health care in the developed world there is a proportional augmentation in the treatment necessary for elderly patients occasioning the call for increased research in the area of aging and age-related diseases. The manifestation of this research has been focalized on the causative cellular processes and molecular mechanisms involved. Here we will discuss the efforts of this research in the area of stem cells, delving into the regulatory mechanisms and how their de-regulation could be attributed to aging and age-related diseases.

  7. Genotoxic stress accelerates age-associated degenerative changes in intervertebral discs

    PubMed Central

    Nasto, Luigi A.; Wang, Dong; Robinson, Andria R.; Clauson, Cheryl L.; Ngo, Kevin; Dong, Qing; Roughley, Peter; Epperly, Michael; Huq, Saiful M.; Pola, Enrico; Sowa, Gwendolyn; Robbins, Paul D.; Kang, James; Niedernhofer, Laura J.; Vo, Nam V.

    2013-01-01

    Intervertebral disc degeneration (IDD) is the leading cause of debilitating spinal disorders such as chronic lower back pain. Aging is the greatest risk factor for IDD. Previously, we demonstrated IDD in a murine model of a progeroid syndrome caused by reduced expression of a key DNA repair enzyme. This led us to hypothesize that DNA damage promotes IDD. To test our hypothesis, we chronically exposed adult wild-type (Wt) and DNA repair-deficient Ercc1−/Δ mice to the cancer therapeutic agent mechlorethamine (MEC) or ionization radiation (IR) to induce DNA damage and measured the impact on disc structure. Proteoglycan, a major structural matrix constituent of the disc, was reduced 3-5x in the discs of MEC- and IR-exposed animals compared to untreated controls. Expression of the protease ADAMTS4 and aggrecan proteolytic fragments were significantly increased. Additionally, new PG synthesis was reduced 2-3x in MEC- and IR-treated discs compared to untreated controls. Both cellular senescence and apoptosis were increased in discs of treated animals. The effects were more severe in the DNA repair-deficient Ercc1−/Δ mice than in Wt littermates. Local irradiation of the vertebra in Wt mice elicited a similar reduction in PG. These data demonstrate that genotoxic stress drives degenerative changes associated with IDD. PMID:23262094

  8. 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

  9. 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

  10. Cigarette smoking accelerated brain aging and induced pre-Alzheimer-like neuropathology in rats.

    PubMed

    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.

  11. Accelerated cell divisions drive the outgrowth of the regenerating spinal cord in axolotls

    PubMed Central

    Rost, Fabian; Albors, Aida Rodrigo; Mazurov, Vladimir; Brusch, Lutz; Deutsch, Andreas

    2016-01-01

    Axolotls are unique in their ability to regenerate the spinal cord. However, the mechanisms that underlie this phenomenon remain poorly understood. Previously, we showed that regenerating stem cells in the axolotl spinal cord revert to a molecular state resembling embryonic neuroepithelial cells and functionally acquire rapid proliferative divisions (Rodrigo Albors et al., 2015). Here, we refine the analysis of cell proliferation in space and time and identify a high-proliferation zone in the regenerating spinal cord that shifts posteriorly over time. By tracking sparsely-labeled cells, we also quantify cell influx into the regenerate. Taking a mathematical modeling approach, we integrate these quantitative datasets of cell proliferation, neural stem cell activation and cell influx, to predict regenerative tissue outgrowth. Our model shows that while cell influx and neural stem cell activation play a minor role, the acceleration of the cell cycle is the major driver of regenerative spinal cord outgrowth in axolotls. DOI: http://dx.doi.org/10.7554/eLife.20357.001 PMID:27885987

  12. 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.

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

    PubMed

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

    2012-11-01

    Despite extensive experimental and animal evidence about the detrimental effects of iron and its overload on bone metabolism, there have been no clinical studies relating iron stores to bone loss, especially in nonpathologic conditions. In the present study, we performed a large longitudinal study to evaluate serum ferritin concentrations in relation to annualized changes in bone mineral density (BMD) in healthy Koreans. A total of 1729 subjects (940 postmenopausal women and 789 middle-aged men) aged 40 years or older who had undergone comprehensive routine health examinations with an average 3 years of follow-up were enrolled. BMD in proximal femur sites (ie, the total femur, femur neck, and trochanter) was measured with dual-energy X-ray absorptiometry using the same equipment at baseline and follow-up. The mean age of women and men in this study was 55.8 ± 6.0 years and 55.5 ± 7.8 years, respectively, and serum ferritin levels were significantly higher in men than in women (p < 0.001). The overall mean annualized rates of bone loss in the total femur, femur neck, and trochanter were -1.14%/year, -1.17%/year, and -1.51%/year, respectively, in women, and -0.27%/year, -0.34%/year, and -0.41%/year, respectively, in men. After adjustment for potential confounders, the rates of bone loss in all proximal femur sites in both genders were significantly accelerated in a dose-response fashion across increasing ferritin quartile categories (p for trend = 0.043 to <0.001). Consistently, compared with subjects in the lowest ferritin quartile category, those in the third and/or highest ferritin quartile category showed significantly faster bone loss in the total femur and femur neck in both genders (p = 0.023 to <0.001). In conclusion, these data provide the first clinical evidence that increased total body iron stores could be an independent risk factor for accelerated bone loss, even in healthy populations.

  14. When stem cells grow old: phenotypes and mechanisms of stem cell aging

    PubMed Central

    Schultz, Michael B.; Sinclair, David A.

    2016-01-01

    All multicellular organisms undergo a decline in tissue and organ function as they age. An attractive theory is that a loss in stem cell number and/or activity over time causes this decline. In accordance with this theory, aging phenotypes have been described for stem cells of multiple tissues, including those of the hematopoietic system, intestine, muscle, brain, skin and germline. Here, we discuss recent advances in our understanding of why adult stem cells age and how this aging impacts diseases and lifespan. With this increased understanding, it is feasible to design and test interventions that delay stem cell aging and improve both health and lifespan. PMID:26732838

  15. 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).

  16. Salidroside accelerates fracture healing through cell-autonomous and non-autonomous effects on osteoblasts.

    PubMed

    Guo, Xiao Qin; Qi, Lin; Yang, Jing; Wang, Yue; Wang, Chuan; Li, Zong Min; Li, Ling; Qu, Ye; Wang, Dan; Han, Ze Min

    2017-02-01

    Salidroside (SAL), a major active component of Rhodiola rosea L., exhibits diverse pharmacological effects. However, the direct roles of SAL in fracture healing remain largely unknown. Here, we demonstrate that SAL significantly promotes proliferation by altering the cell-cycle distribution of osteoblastic cells. SAL also greatly stimulates osteoblast differentiation and mineralization by inducing the expression of Runx2 and Osterix. In addition to its osteoblast-autonomous effects, SAL can activate the HIF-1α pathway coupling of angiogenesis and osteogenesis through cell-non-autonomous effects. Our in vitro results suggest that SAL significantly up-regulates HIF-1α expression at the mRNA and protein levels. Furthermore, the nuclear translocation and transcriptional activity of HIF-1α and the HIF-responsive gene VEGF increase following SAL treatment. Our mechanistic study revealed that the regulation of osteoblastic proliferation and HIF-1α expression partly involves MAPK/ERK and PI3K/Akt signaling. Our in vivo analysis also demonstrated that SAL can promote angiogenesis within the callus and accelerate fracture healing. Thus, SAL promotes skeletal regeneration in cell-autonomous and cell-non-autonomous ways and might be a potential therapy for accelerating fracture healing.

  17. Running reduces stress and enhances cell genesis in aged mice.

    PubMed

    Kannangara, Timal S; Lucero, Melanie J; Gil-Mohapel, Joana; Drapala, Robert J; Simpson, Jessica M; Christie, Brian R; van Praag, Henriette

    2011-12-01

    Cell proliferation and neurogenesis are diminished in the aging mouse dentate gyrus. However, it is not known whether isolated or social living affects cell genesis and stress levels in old animals. To address this question, aged (17-18 months old) female C57Bl/6 mice were single or group housed, under sedentary or running conditions. We demonstrate that both individual and socially housed aged C57Bl/6 mice have comparable basal cell proliferation levels and demonstrate increased running-induced cell genesis. To assess stress levels in young and aged mice, corticosterone (CORT) was measured at the onset of the active/dark cycle and 4h later. In young mice, no differences in CORT levels were observed as a result of physical activity or housing conditions. However, a significant increase in stress in socially housed, aged sedentary animals was observed at the onset of the dark cycle; CORT returned to basal levels 4h later. Together, these results indicate that voluntary exercise reduces stress in group housed aged animals and enhances hippocampal cell proliferation.

  18. Amniotic Epithelial Cells: A New Tool to Combat Aging and Age-Related Diseases?

    PubMed Central

    Di Germanio, Clara; Bernier, Michel; de Cabo, Rafael; Barboni, Barbara

    2016-01-01

    The number of elderly people is growing at an unprecedented rate and this increase of the aging population is expected to have a direct impact on the incidence of age-related diseases and healthcare-associated costs. Thus, it is imperative that new tools are developed to fight and slow age-related diseases. Regenerative medicine is a promising strategy for the maintenance of health and function late in life; however, stem cell-based therapies face several challenges including rejection and tumor transformation. As an alternative, the placenta offers an extraordinary source of fetal stem cells, including the amniotic epithelial cells (AECs), which retain some of the characteristics of embryonic stem cells, but show low immunogenicity, together with immunomodulatory and anti-inflammatory activities. Because of these characteristics, AECs have been widely utilized in regenerative medicine. This perspective highlights different mechanisms triggered by transplanted AECs that could be potentially useful for anti-aging therapies, which include: Graft and differentiation for tissue regeneration in age-related settings, anti-inflammatory behavior to combat “inflammaging,” anti-tumor activity, direct lifespan and healthspan extension properties, and possibly rejuvenation in a manner reminiscent of heterochronic parabiosis. Here, we critically discuss benefits and limitation of AECs-based therapies in age-related diseases. PMID:27921031

  19. Dendrites of rod bipolar cells sprout in normal aging retina.

    PubMed

    Liets, Lauren C; Eliasieh, Kasra; van der List, Deborah A; Chalupa, Leo M

    2006-08-08

    The aging nervous system is known to manifest a variety of degenerative and regressive events. Here we report the unexpected growth of dendrites in the retinas of normal old mice. The dendrites of many rod bipolar cells in aging mice were observed to extend well beyond their normal strata within the outer plexiform layer to innervate the outer nuclear layer where they appeared to form contacts with the spherules of rod photoreceptors. Such dendritic sprouting increased with age and was evident at all retinal eccentricities. These results provide evidence of retinal plasticity associated with normal aging.

  20. Chronic Central Nervous System Expression of HIV-1 Tat Leads to Accelerated Rarefaction of Neocortical Capillaries and Loss of Red Blood Cell Velocity Heterogeneity

    PubMed Central

    Silva, Jharon N.; Polesskaya, Oksana; Wei, Helen S.; Rasheed, Izad-Yar D.; Chamberlain, Jeffrey M.; Nishimura, Christopher; Feng, Changyong; Dewhurst, Stephen

    2014-01-01

    Objectives HIV-1 infection of the central nervous system is associated with impairment of cerebral blood flow and neurocognitive function, and accelerated signs of aging. Since normal aging is associated with rarefaction of the cerebral vasculature, we set out to examine chronic viral effects on the cerebral vasculature. Methods Doxycycline-inducible HIV-1 Tat transgenic (Tat-tg) and wild-type (WT) control mice were used. Animals were treated with doxycycline for 3 weeks or 5–7 months. Cerebral vessel density and capillary segment length were determined from quantitative image analyses of sectioned cortical tissue. In addition, movement of red blood cells in individual capillaries was imaged in vivo using multiphoton microscopy, to determine red blood cell velocity and flux. Results Mean RBCV was not different between Tat-tg mice and age matched WT controls. However, cortical capillaries from Tat-tg mice showed a significant loss of RBCV heterogeneity and increased RBCF that was attributed to a marked decrease in total cortical capillary length (35–40%) compared to WT mice. Conclusions Cerebrovascular rarefaction is accelerated in HIV-1 Tat transgenic mice, and this is associated with alterations in red cell blood velocity. These changes may have relevance to the pathogenesis of HIV-associated neurocognitive disorders in an aging HIV positive population. PMID:24813724

  1. B cells in the aging immune system: time to consider B-1 cells.

    PubMed

    Holodick, Nichol E; Rothstein, Thomas L

    2015-12-01

    The investigation of immune senescence has uncovered many changes in B cell development, maintenance, and function with increasing age. However, most of these studies have focused on conventional B cell subsets in the spleen. The B-1 cell subset is an essential arm of the innate immune system, which in general has been understudied in terms of immune senescence. Here, we review what is currently known about B cells during aging and go on to describe why B-1 cell biology is an important component of the aging immune system in the context of diseases that most affect the aged population.

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

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

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

  3. Cinnamtannin B-1 Promotes Migration of Mesenchymal Stem Cells and Accelerates Wound Healing in Mice

    PubMed Central

    Fujita, Kosuke; Kuge, Katsunori; Ozawa, Noriyasu; Sahara, Shunya; Zaiki, Kaori; Nakaoji, Koichi; Hamada, Kazuhiko; Takenaka, Yukiko; Tanahashi, Takao; Tamai, Katsuto; Kaneda, Yasufumi; Maeda, Akito

    2015-01-01

    Substances that enhance the migration of mesenchymal stem cells to damaged sites have the potential to improve the effectiveness of tissue repair. We previously found that ethanol extracts of Mallotus philippinensis bark promoted migration of mesenchymal stem cells and improved wound healing in a mouse model. We also demonstrated that bark extracts contain cinnamtannin B-1, a flavonoid with in vitro migratory activity against mesenchymal stem cells. However, the in vivo effects of cinnamtannin B-1 on the migration of mesenchymal stem cells and underlying mechanism of this action remain unknown. Therefore, we examined the effects of cinnamtannin B-1 on in vivo migration of mesenchymal stem cells and wound healing in mice. In addition, we characterized cinnamtannin B-1-induced migration of mesenchymal stem cells pharmacologically and structurally. The mobilization of endogenous mesenchymal stem cells into the blood circulation was enhanced in cinnamtannin B-1-treated mice as shown by flow cytometric analysis of peripheral blood cells. Whole animal imaging analysis using luciferase-expressing mesenchymal stem cells as a tracer revealed that cinnamtannin B-1 increased the homing of mesenchymal stem cells to wounds and accelerated healing in a diabetic mouse model. Additionally, the cinnamtannin B-1-induced migration of mesenchymal stem cells was pharmacologically susceptible to inhibitors of phosphatidylinositol 3-kinase, phospholipase C, lipoxygenase, and purines. Furthermore, biflavonoids with similar structural features to cinnamtannin B-1 also augmented the migration of mesenchymal stem cells by similar pharmacological mechanisms. These results demonstrate that cinnamtannin B-1 promoted mesenchymal stem cell migration in vivo and improved wound healing in mice. Furthermore, the results reveal that cinnamtannin B-1-induced migration of mesenchymal stem cells may be mediated by specific signaling pathways, and the flavonoid skeleton may be relevant to its effects on

  4. Cinnamtannin B-1 Promotes Migration of Mesenchymal Stem Cells and Accelerates Wound Healing in Mice.

    PubMed

    Fujita, Kosuke; Kuge, Katsunori; Ozawa, Noriyasu; Sahara, Shunya; Zaiki, Kaori; Nakaoji, Koichi; Hamada, Kazuhiko; Takenaka, Yukiko; Tanahashi, Takao; Tamai, Katsuto; Kaneda, Yasufumi; Maeda, Akito

    2015-01-01

    Substances that enhance the migration of mesenchymal stem cells to damaged sites have the potential to improve the effectiveness of tissue repair. We previously found that ethanol extracts of Mallotus philippinensis bark promoted migration of mesenchymal stem cells and improved wound healing in a mouse model. We also demonstrated that bark extracts contain cinnamtannin B-1, a flavonoid with in vitro migratory activity against mesenchymal stem cells. However, the in vivo effects of cinnamtannin B-1 on the migration of mesenchymal stem cells and underlying mechanism of this action remain unknown. Therefore, we examined the effects of cinnamtannin B-1 on in vivo migration of mesenchymal stem cells and wound healing in mice. In addition, we characterized cinnamtannin B-1-induced migration of mesenchymal stem cells pharmacologically and structurally. The mobilization of endogenous mesenchymal stem cells into the blood circulation was enhanced in cinnamtannin B-1-treated mice as shown by flow cytometric analysis of peripheral blood cells. Whole animal imaging analysis using luciferase-expressing mesenchymal stem cells as a tracer revealed that cinnamtannin B-1 increased the homing of mesenchymal stem cells to wounds and accelerated healing in a diabetic mouse model. Additionally, the cinnamtannin B-1-induced migration of mesenchymal stem cells was pharmacologically susceptible to inhibitors of phosphatidylinositol 3-kinase, phospholipase C, lipoxygenase, and purines. Furthermore, biflavonoids with similar structural features to cinnamtannin B-1 also augmented the migration of mesenchymal stem cells by similar pharmacological mechanisms. These results demonstrate that cinnamtannin B-1 promoted mesenchymal stem cell migration in vivo and improved wound healing in mice. Furthermore, the results reveal that cinnamtannin B-1-induced migration of mesenchymal stem cells may be mediated by specific signaling pathways, and the flavonoid skeleton may be relevant to its effects on

  5. Engineering Area Investigation of Reliability Attributes and Accelerated Stress Factors on Terrestrial Solar Cells

    NASA Technical Reports Server (NTRS)

    Lathrop, J. W.; Prince, J. L.

    1979-01-01

    Results obtained include the definition of a simplified stress test schedule for terrestrial solar cells based on the work performed during the first program year, and the design and fabrication of improved jigs and fixtures for electrical measurement and stress testing. Implementation of these advanced techniques for accelerated stress testing is underway on three solar cell types. In addition, review of the literature on second quadrant phenomena was begun and some preliminary second-quadrant electrical measurements were performed. Results obtained at the first down time for 75 C B-T testing and biased and unbiased T-H pressure cooker testing of type F cells showed little or no degradation in electrical parameters. Significant physical effects (large solder bubbles) were noted for type F cells subjected to the pressure cooker stress test.

  6. Load management strategy for Particle-In-Cell simulations in high energy particle acceleration

    NASA Astrophysics Data System (ADS)

    Beck, A.; Frederiksen, J. T.; Dérouillat, J.

    2016-09-01

    In the wake of the intense effort made for the experimental CILEX project, numerical simulation campaigns have been carried out in order to finalize the design of the facility and to identify optimal laser and plasma parameters. These simulations bring, of course, important insight into the fundamental physics at play. As a by-product, they also characterize the quality of our theoretical and numerical models. In this paper, we compare the results given by different codes and point out algorithmic limitations both in terms of physical accuracy and computational performances. These limitations are illustrated in the context of electron laser wakefield acceleration (LWFA). The main limitation we identify in state-of-the-art Particle-In-Cell (PIC) codes is computational load imbalance. We propose an innovative algorithm to deal with this specific issue as well as milestones towards a modern, accurate high-performance PIC code for high energy particle acceleration.

  7. A 2D Particle in Cell model for ion extraction and focusing in electrostatic accelerators.

    PubMed

    Veltri, P; Cavenago, M; Serianni, G

    2014-02-01

    Negative ions are fundamental to produce intense and high energy neutral beams used to heat the plasma in fusion devices. The processes regulating the ion extraction involve the formation of a sheath on a scale comparable to the Debye length of the plasma. On the other hand, the ion acceleration as a beam is obtained on distances greater than λD. The paper presents a model for both the phases of ion extraction and acceleration of the ions and its implementation in a numerical code. The space charge of particles is deposited following usual Particle in Cell codes technique, while the field is solved with finite element methods. Some hypotheses on the beam plasma transition are described, allowing to model both regions at the same time. The code was tested with the geometry of the NIO1 negative ions source, and the results are compared with existing ray tracing codes and discussed.

  8. Tamoxifen inhibits ER-negative breast cancer cell invasion and metastasis by accelerating Twist1 degradation.

    PubMed

    Ma, Gang; He, Jianjun; Yu, Yang; Xu, Yixiang; Yu, Xiaobin; Martinez, Jarrod; Lonard, David M; Xu, Jianming

    2015-01-01

    Twist1 is a transcription factor driving epithelial-mesenchymal transition, invasion and metastasis of breast cancer cells. Mice with germ-line Twist1 knockout are embryonic lethal, while adult mice with inducible Twist1 knockout have no obvious health problems, suggesting that Twist1 is a viable therapeutic target for the inhibition of invasion and metastasis of breast cancer in adult patients. In this study, we expressed a luciferase protein or a Twist1-luciferase fusion protein in HeLa cells as part of a high throughput system to screen 1280 compounds in the Library of Pharmacologically Active Compounds (LOPAC) from Sigma-Aldrich for their effects on Twist1 protein expression. One of the most interesting compounds identified is tamoxifen, a selective estrogen receptor (ER) modulator used to treat ER-positive breast cancer. Tamoxifen treatment significantly accelerated Twist1 degradation in multiple cell lines including HEK293 human kidney cells, 4T1 and 168FARN mouse mammary tumor cells with either ectopically or endogenously expressed Twist1. Tamoxifen-induced Twist1 degradation could be blocked by the MG132 proteasome inhibitor, suggesting that tamoxifen induces Twist1 degradation through the ubiquitination-proteasome pathway. However, tamoxifen-induced Twist1 degradation was independent of Twist1 mRNA expression, estrogen signaling and MAPK-mediated Twist1 phosphorylation in these cells. Importantly, tamoxifen also significantly inhibited invasive behavior in Matrigel and lung metastasis in SCID-bg mice of ER-negative 4T1 mammary tumor cells, which depend on endogenous Twist1 to invade and metastasize. These results indicate that tamoxifen can significantly accelerate Twist1 degradation to suppress cancer cell invasion and metastasis, suggesting that tamoxifen can be used not only to treat ER-positive breast cancers but also to reduce Twist1-mediated invasion and metastasis in ER-negative breast cancers.

  9. Preventing aging with stem cell rejuvenation: Feasible or infeasible?

    PubMed Central

    Honoki, Kanya

    2017-01-01

    Characterized by dysfunction of tissues, organs, organ systems and the whole organism, aging results from the reduced function of effective stem cell populations. Recent advances in aging research have demonstrated that old tissue stem cells can be rejuvenated for the purpose of maintaining the old-organ function by youthful re-calibration of the environment where stem cells reside. Biochemical cues regulating tissue stem cell function include molecular signaling pathways that interact between stem cells themselves and their niches. Historically, plasma fractions have been shown to contain factors capable of controlling age phenotypes; subsequently, signaling pathways involved in the aging process have been identified. Consequently, modulation of signaling pathways such as Notch/Delta, Wnt, transforming growth factor-β, JAK/STAT, mammalian target of rapamycin and p38 mitogen-activated protein kinase has demonstrated potential to rejuvenate stem cell function leading to organismic rejuvenation. Several synthetic agents and natural sources, such as phytochemicals and flavonoids, have been proposed to rejuvenate old stem cells by targeting these pathways. However, several concerns still remain to achieve effective organismic rejuvenation in clinical settings, such as possible carcinogenic actions; thus, further research is still required. PMID:28154735

  10. Bone fragility and decline in stem cells in prematurely aging DNA repair deficient trichothiodystrophy mice.

    PubMed

    Diderich, Karin E M; Nicolaije, Claudia; Priemel, Matthias; Waarsing, Jan H; Day, Judd S; Brandt, Renata M C; Schilling, Arndt F; Botter, Sander M; Weinans, Harrie; van der Horst, Gijsbertus T J; Hoeijmakers, Jan H J; van Leeuwen, Johannes P T M

    2012-08-01

    Trichothiodystrophy (TTD) is a rare, autosomal recessive nucleotide excision repair (NER) disorder caused by mutations in components of the dual functional NER/basal transcription factor TFIIH. TTD mice, carrying a patient-based point mutation in the Xpd gene, strikingly resemble many features of the human syndrome and exhibit signs of premature aging. To examine to which extent TTD mice resemble the normal process of aging, we thoroughly investigated the bone phenotype. Here, we show that female TTD mice exhibit accelerated bone aging from 39 weeks onwards as well as lack of periosteal apposition leading to reduced bone strength. Before 39 weeks have passed, bones of wild-type and TTD mice are identical excluding a developmental defect. Albeit that bone formation is decreased, osteoblasts in TTD mice retain bone-forming capacity as in vivo PTH treatment leads to increased cortical thickness. In vitro bone marrow cell cultures showed that TTD osteoprogenitors retain the capacity to differentiate into osteoblasts. However, after 13 weeks of age TTD females show decreased bone nodule formation. No increase in bone resorption or the number of osteoclasts was detected. In conclusion, TTD mice show premature bone aging, which is preceded by a decrease in mesenchymal stem cells/osteoprogenitors and a change in systemic factors, identifying DNA damage and repair as key determinants for bone fragility by influencing osteogenesis and bone metabolism.

  11. Manganese superoxide dismutase expression in endothelial progenitor cells accelerates wound healing in diabetic mice

    PubMed Central

    Marrotte, Eric J.; Chen, Dan-Dan; Hakim, Jeffrey S.; Chen, Alex F.

    2010-01-01

    Amputation as a result of impaired wound healing is a serious complication of diabetes. Inadequate angiogenesis contributes to poor wound healing in diabetic patients. Endothelial progenitor cells (EPCs) normally augment angiogenesis and wound repair but are functionally impaired in diabetics. Here we report that decreased expression of manganese superoxide dismutase (MnSOD) in EPCs contributes to impaired would healing in a mouse model of type 2 diabetes. A decreased frequency of circulating EPCs was detected in type 2 diabetic (db/db) mice, and when isolated, these cells exhibited decreased expression and activity of MnSOD. Wound healing and angiogenesis were markedly delayed in diabetic mice compared with normal controls. For cell therapy, topical transplantation of EPCs onto excisional wounds in diabetic mice demonstrated that diabetic EPCs were less effective than normal EPCs at accelerating wound closure. Transplantation of diabetic EPCs after MnSOD gene therapy restored their ability to mediate angiogenesis and wound repair. Conversely, siRNA-mediated knockdown of MnSOD in normal EPCs reduced their activity in diabetic wound healing assays. Increasing the number of transplanted diabetic EPCs also improved the rate of wound closure. Our findings demonstrate that cell therapy using diabetic EPCs after ex vivo MnSOD gene transfer accelerates their ability to heal wounds in a mouse model of type 2 diabetes. PMID:21060152

  12. Selective Accelerated Proliferation of Malignant Breast Cancer Cells on Planar Graphene Oxide Films.

    PubMed

    Kenry; Chaudhuri, Parthiv Kant; Loh, Kian Ping; Lim, Chwee Teck

    2016-03-22

    Graphene nanomaterials have been actively investigated for biomedical and biological applications, including that of cancer. Despite progress made, most of such studies are conducted on dispersed graphene nanosheets in solution. Consequently, the use of planar graphene films, especially in cancer research, has not been fully explored. Here, we investigate the cellular interactions between the graphene material films and breast cancer cell lines, specifically the effects these films have on cellular proliferation, spreading area, and cytotoxicity. We demonstrate that the graphene oxide (GO) film selectively accelerates the proliferation of both metastatic (MDA-MB-231) and nonmetastatic (MCF-7) breast cancer cells, but not that of noncancer breast epithelial cells (MCF-10A). Contrastingly, this accelerated proliferation is not observed with the use of graphene (G) film. Moreover, GO induces negligible cytotoxicity on these cells. We suggest that the observed phenomena originate from the synergistic effect resulted from the high loading capacity and conformational change of cellular attachment proteins on the GO film, and the high amount of oxygenated groups present in the material. We anticipate that our findings can further shed light on the graphene-cancer cellular interactions and provide better understanding for the future design and application of graphene-based nanomaterials in cancer research.

  13. Aging

    PubMed Central

    Park, Dong Choon

    2013-01-01

    Aging is initiated based on genetic and environmental factors that operate from the time of birth of organisms. Aging induces physiological phenomena such as reduction of cell counts, deterioration of tissue proteins, tissue atrophy, a decrease of the metabolic rate, reduction of body fluids, and calcium metabolism abnormalities, with final progression onto pathological aging. Despite the efforts from many researchers, the progression and the mechanisms of aging are not clearly understood yet. Therefore, the authors would like to introduce several theories which have gained attentions among the published theories up to date; genetic program theory, wear-and-tear theory, telomere theory, endocrine theory, DNA damage hypothesis, error catastrophe theory, the rate of living theory, mitochondrial theory, and free radical theory. Although there have been many studies that have tried to prevent aging and prolong life, here we introduce a couple of theories which have been proven more or less; food, exercise, and diet restriction. PMID:24653904

  14. The reproductive-cell cycle theory of aging: an update.

    PubMed

    Atwood, Craig S; Bowen, Richard L

    2011-01-01

    The Reproductive-Cell Cycle Theory posits that the hormones that regulate reproduction act in an antagonistic pleiotrophic manner to control aging via cell cycle signaling; promoting growth and development early in life in order to achieve reproduction, but later in life, in a futile attempt to maintain reproduction, become dysregulated and drive senescence. Since reproduction is the most important function of an organism from the perspective of the survival of the species, if reproductive-cell cycle signaling factors determine the rate of growth, determine the rate of development, determine the rate of reproduction, and determine the rate of senescence, then by definition they determine the rate of aging and thus lifespan. The theory is able to explain: 1) the simultaneous regulation of the rate of aging and reproduction as evidenced by the fact that environmental conditions and experimental interventions known to extend longevity are associated with decreased reproductive-cell cycle signaling factors, thereby slowing aging and preserving fertility in a hostile reproductive environment; 2) two phenomena that are closely related to species lifespan-the rate of growth and development and the ultimate size of the animal; 3). the apparent paradox that size is directly proportional to lifespan and inversely proportional to fertility between species but vice versa within a species; 4). how differing rates of reproduction between species is associated with differences in their lifespan; 5). why we develop aging-related diseases; and 6). an evolutionarily credible reason for why and how aging occurs-these hormones act in an antagonistic pleiotrophic manner via cell cycle signaling; promoting growth and development early in life in order to achieve reproduction, but later in life, in a futile attempt to maintain reproduction, become dysregulated and drive senescence (dyosis). In essence, the Reproductive-Cell Cycle Theory can explain aging in all sexually reproductive life

  15. Age-dependent deterioration of nuclear pore complexes causes a loss of nuclear integrity in postmitotic cells.

    PubMed

    D'Angelo, Maximiliano A; Raices, Marcela; Panowski, Siler H; Hetzer, Martin W

    2009-01-23

    In dividing cells, nuclear pore complexes (NPCs) disassemble during mitosis and reassemble into the newly forming nuclei. However, the fate of nuclear pores in postmitotic cells is unknown. Here, we show that NPCs, unlike other nuclear structures, do not turn over in differentiated cells. While a subset of NPC components, like Nup153 and Nup50, are continuously exchanged, scaffold nucleoporins, like the Nup107/160 complex, are extremely long-lived and remain incorporated in the nuclear membrane during the entire cellular life span. Besides the lack of nucleoporin expression and NPC turnover, we discovered an age-related deterioration of NPCs, leading to an increase in nuclear permeability and the leaking of cytoplasmic proteins into the nucleus. Our finding that nuclear "leakiness" is dramatically accelerated during aging and that a subset of nucleoporins is oxidatively damaged in old cells suggests that the accumulation of damage at the NPC might be a crucial aging event.

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

    PubMed Central

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

    2015-01-01

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

  17. Newborn granule cells in the ageing dentate gyrus

    PubMed Central

    Morgenstern, Nicolás A; Lombardi, Gabriela; Schinder, Alejandro F

    2008-01-01

    The dentate gyrus of the hippocampus generates neurons throughout life, but adult neurogenesis exhibits a marked age-dependent decline. Although the decrease in the rate of neurogenesis has been extensively documented in the ageing hippocampus, the specific characteristics of dentate granule cells born in such a continuously changing environment have received little attention. We have used retroviral labelling of neural progenitor cells of the adult mouse dentate gyrus to study morphological properties of neurons born at different ages. Dendritic spine density was measured to estimate glutamatergic afferent connectivity. Fully mature neurons born at the age of 2 months display ∼2.3 spines μm−1 and maintain their overall morphology and spine density in 1-year-old mice. Surprisingly, granule cells born in 10-month-old mice, at which time the rate of neurogenesis has decreased by ∼40-fold, reach a density of dendritic spines similar to that of neurons born in young adulthood. Therefore, in spite of the sharp decline in cell proliferation, differentiation and overall neuronal number, the ageing hippocampus presents a suitable environment for new surviving neurons to reach a high level of complexity, comparable to that of all other dentate granule cells. PMID:18565998

  18. Mitochondrial function and dysfunction in the cell: its relevance to aging and aging-related disease.

    PubMed

    Nicholls, David G

    2002-11-01

    Mitochondria plays a complex multi-factorial role in the cell. In addition to their primary role in ATP generation, the organelles sequester calcium and both generate and detoxify reactive oxygen species. All these functions are intimately inter-linked through the central bioenergetic parameter of the proton electrochemical gradient across the inner mitochondrial membrane. Subtle changes in respiratory chain capacity, substrate supply, glutathione levels, cytoplasmic calcium and membrane potential occur in aging and in conditions predisposing towards neurodegenerative disease. These interactions are incompletely understood and in this review I present an overview of some of the current research in this area, and its possible relevance to aging and aging-related disease.

  19. RCC1-dependent activation of Ran accelerates cell cycle and DNA repair, inhibiting DNA damage–induced cell senescence

    PubMed Central

    Cekan, Pavol; Hasegawa, Keisuke; Pan, Yu; Tubman, Emily; Odde, David; Chen, Jin-Qiu; Herrmann, Michelle A.; Kumar, Sheetal; Kalab, Petr

    2016-01-01

    The coordination of cell cycle progression with the repair of DNA damage supports the genomic integrity of dividing cells. The function of many factors involved in DNA damage response (DDR) and the cell cycle depends on their Ran GTPase–regulated nuclear–cytoplasmic transport (NCT). The loading of Ran with GTP, which is mediated by RCC1, the guanine nucleotide exchange factor for Ran, is critical for NCT activity. However, the role of RCC1 or Ran⋅GTP in promoting cell proliferation or DDR is not clear. We show that RCC1 overexpression in normal cells increased cellular Ran⋅GTP levels and accelerated the cell cycle and DNA damage repair. As a result, normal cells overexpressing RCC1 evaded DNA damage–induced cell cycle arrest and senescence, mimicking colorectal carcinoma cells with high endogenous RCC1 levels. The RCC1-induced inhibition of senescence required Ran and exportin 1 and involved the activation of importin β–dependent nuclear import of 53BP1, a large NCT cargo. Our results indicate that changes in the activity of the Ran⋅GTP–regulated NCT modulate the rate of the cell cycle and the efficiency of DNA repair. Through the essential role of RCC1 in regulation of cellular Ran⋅GTP levels and NCT, RCC1 expression enables the proliferation of cells that sustain DNA damage. PMID:26864624

  20. Effect of gamma radiation and accelerated aging on the mechanical and thermal behavior of HDPE/HA nano-composites for bone tissue regeneration

    PubMed Central

    2013-01-01

    Background The replacement of hard tissues demands biocompatible and sometimes bioactive materials with properties similar to those of bone. Nano-composites made of biocompatible polymers and bioactive inorganic nano particles such as HDPE/HA have attracted attention as permanent bone substitutes due to their excellent mechanical properties and biocompatibility. Method The HDPE/HA nano-composite is prepared using melt blending at different HA loading ratios. For evaluation of the degradation by radiation, gamma rays of 35 kGy, and 70 kGy were used to irradiate the samples at room temperature in vacuum. The effects of accelerated ageing after gamma irradiation on morphological, mechanical and thermal properties of HDPE/HA nano-composites were measured. Results In Vitro test results showed that the HDPE and all HDPE/HA nano-composites do not exhibit any cytotoxicity to WISH cell line. The results also indicated that the tensile properties of HDPE/HA nano-composite increased with increasing the HA content except fracture strain decreased. The dynamic mechanical analysis (DMA) results showed that the storage and loss moduli increased with increasing the HA ratio and the testing frequency. Finally, it is remarked that all properties of HDPE/HA is dependent on the irradiation dose and accelerated aging. Conclusion Based on the experimental results, it is found that the addition of 10%, 20% and 30% HA increases the HDPE stiffness by 23%, 44 and 59% respectively. At the same time, the G’ increased from 2.25E11 MPa for neat HDPE to 4.7E11 MPa when 30% HA was added to the polymer matrix. Also, significant improvements in these properties have been observed due to irradiation. Finally, the overall properties of HDPE and its nano-composite properties significantly decreased due to aging and should be taken into consideration in the design of bone substitutes. It is attributed that the developed HDPE/HA nano-composites could be a good alternative material for bone tissue

  1. β-Cell dedifferentiation, reduced duct cell plasticity, and impaired β-cell mass regeneration in middle-aged rats.

    PubMed

    Téllez, Noèlia; Vilaseca, Marina; Martí, Yasmina; Pla, Arturo; Montanya, Eduard

    2016-09-01

    Limitations in β-cell regeneration potential in middle-aged animals could contribute to the increased risk to develop diabetes associated with aging. We investigated β-cell regeneration of middle-aged Wistar rats in response to two different regenerative stimuli: partial pancreatectomy (Px + V) and gastrin administration (Px + G). Pancreatic remnants were analyzed 3 and 14 days after surgery. β-Cell mass increased in young animals after Px and was further increased after gastrin treatment. In contrast, β-cell mass did not change after Px or after gastrin treatment in middle-aged rats. β-Cell replication and individual β-cell size were similarly increased after Px in young and middle-aged animals, and β-cell apoptosis was not modified. Nuclear immunolocalization of neurog3 or nkx6.1 in regenerative duct cells, markers of duct cell plasticity, was increased in young but not in middle-aged Px rats. The pancreatic progenitor-associated transcription factors neurog3 and sox9 were upregulated in islet β-cells of middle-aged rats and further increased after Px. The percentage of chromogranin A+/hormone islet cells was significantly increased in the pancreases of middle-aged Px rats. In summary, the potential for compensatory β-cell hyperplasia and hypertrophy was retained in middle-aged rats, but β-cell dedifferentiation and impaired duct cell plasticity limited β-cell regeneration.

  2. Natural killer T (NKT) cells accelerate Shiga toxin type 2 (Stx2) pathology in mice

    PubMed Central

    Obata, Fumiko; Subrahmanyam, Priyanka B.; Vozenilek, Aimee E.; Hippler, Lauren M.; Jeffers, Tynae; Tongsuk, Methinee; Tiper, Irina; Saha, Progyaparamita; Jandhyala, Dakshina M.; Kolling, Glynis L.; Latinovic, Olga; Webb, Tonya J.

    2015-01-01

    Shiga toxin-producing Escherichia coli (STEC) is a leading cause of childhood renal disease Hemolytic Uremic Syndrome (HUS). The involvement of renal cytokines and chemokines is suspected to play a critical role in disease progression. In current article, we tested the hypothesis that NKT cells are involved in Stx2-induced pathology in vivo. To address this hypothesis we compared Stx2 toxicity in WT and CD1 knockout (KO) mice. In CD1KO mice, which lack natural killer T (NKT) cells, Stx2-induced pathologies such as weight loss, renal failure, and death were delayed. In WT mice, Stx2-specific selective increase in urinary albumin occurs in later time points, and this was also delayed in NKT cell deficient mice. NKT cell-associated cytokines such as IL-2, IL-4, IFN-γ, and IL-17 were detected in kidney lysates of Stx2-injected WT mice with the peak around 36 h after Stx2 injection. In CD1KO, there was a delay in the kinetics, and increases in these cytokines were observed 60 h post Stx2 injection. These data suggest that NKT cells accelerate Stx2-induced pathology in mouse kidneys. To determine the mechanism by which NKT cells promote Stx2-associated disease, in vitro studies were performed using murine renal cells. We found that murine glomerular endothelial cells and podocytes express functional CD1d molecules and can present exogenous antigen to NKT cells. Moreover, we observed the direct interaction between Stx2 and the receptor Gb3 on the surface of mouse renal cells by 3D STORM-TIRF which provides single molecule imaging. Collectively, these data suggest that Stx2 binds to Gb3 on renal cells and leads to aberrant CD1d-mediated NKT cell activation. Therefore, strategies targeting NKT cells could have a significant impact on Stx2-associated renal pathology in STEC disease. PMID:25904903

  3. Comorbidity-Age Index: A Clinical Measure of Biologic Age Before Allogeneic Hematopoietic Cell Transplantation

    PubMed Central

    Sorror, Mohamed L.; Storb, Rainer F.; Sandmaier, Brenda M.; Maziarz, Richard T.; Pulsipher, Michael A.; Maris, Michael B.; Bhatia, Smita; Ostronoff, Fabiana; Deeg, H. Joachim; Syrjala, Karen L.; Estey, Elihu; Maloney, David G.; Appelbaum, Frederick R.; Martin, Paul J.; Storer, Barry E.

    2014-01-01

    Purpose Age has long been used as a major factor for assessing suitability for allogeneic hematopoietic cell transplantation (HCT). The HCT-comorbidity index (HCT-CI) was developed as a measure of health status to predict mortality risk after HCT. Whether age, comorbidities, or both should guide decision making for HCT is unknown. Patients and Methods Data from 3,033 consecutive recipients of HLA-matched grafts from five institutions contributed to this analysis. Patients were randomly divided into a training set to develop weights for age intervals and a validation set to assess the performance of prognostic models. Results In the training set, patients age 20 to 39 years, 40 to 49 years, 50 to 59 years, and ≥ 60 years had hazard ratios for nonrelapse mortality (NRM) of 1.21 (P = .29), 1.48 (P = .04), 1.75 (P = .004), and 1.84 (P = .005), respectively, compared with those age younger than 20 years. Consequently, age ≥ 40 years was assigned a weight of 1 to be added to the HCT-CI to constitute a composite comorbidity/age index. In the validation set, the composite comorbidity/age score had statistically significantly higher c-statistic estimates for prediction of NRM (0.664 v 0.556; P < .001) and survival (0.682 v 0.560; P < .001) compared with age, respectively. Patients with comorbidity/age scores of 0 to 2 had comparable mortality risks regardless of conditioning regimens. Patients with scores of 3 to 4 and ≥ 5 had statistically significant higher mortality risks after high-dose versus nonmyeloablative regimens. Conclusion Age is a poor prognostic factor. The proposed composite measure allows integration of both comorbidities and age into clinical decision making and comparative-effectiveness research of HCT. PMID:25154831

  4. 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.

  5. Overexpression of prothymosin alpha accelerates proliferation and retards differentiation in HL-60 cells.

    PubMed

    Rodríguez, P; Viñuela, J E; Alvarez-Fernández, L; Buceta, M; Vidal, A; Domínguez, F; Gómez-Márquez, J

    1998-05-01

    Prothymosin alpha (ProTalpha) is an acidic nuclear protein the expression of which is related to the proliferation and differentiation processes in mammalian cells. In the present study we have stably transfected HL-60 cells, a biological system that allows the study of both proliferation and differentiation, with recombinant vectors encoding sense and antisense ProTalpha mRNA. In the HL-60 cell clones overexpressing ProTalpha we observed an acceleration in the growth rate, whereas expression of the antisense orientation showed the opposite effect. Moreover, cell-cycle analysis demonstrated that the G1-phase was shortened in the cells expressing the sense construct. Before studying how ProTalpha affects differentiation, we showed that the down-regulation of ProTalpha gene during differentiation occurs in all mammalian cell lines (HL-60, K562, U937, MEL C88, N2A and PC12) analysed. The biological effect evoked by the induction of the ProTalpha sense vector was the retardation of cell differentiation, although expression of the antisense construct showed no effect on differentiation. In conclusion, our findings provide evidence that ProTalpha is directly implicated in cellular proliferation and that the maintenance of high levels of ProTalpha inside HL-60 cells is incompatible with their ability to differentiate.

  6. Overexpression of prothymosin alpha accelerates proliferation and retards differentiation in HL-60 cells.

    PubMed Central

    Rodríguez, P; Viñuela, J E; Alvarez-Fernández, L; Buceta, M; Vidal, A; Domínguez, F; Gómez-Márquez, J

    1998-01-01

    Prothymosin alpha (ProTalpha) is an acidic nuclear protein the expression of which is related to the proliferation and differentiation processes in mammalian cells. In the present study we have stably transfected HL-60 cells, a biological system that allows the study of both proliferation and differentiation, with recombinant vectors encoding sense and antisense ProTalpha mRNA. In the HL-60 cell clones overexpressing ProTalpha we observed an acceleration in the growth rate, whereas expression of the antisense orientation showed the opposite effect. Moreover, cell-cycle analysis demonstrated that the G1-phase was shortened in the cells expressing the sense construct. Before studying how ProTalpha affects differentiation, we showed that the down-regulation of ProTalpha gene during differentiation occurs in all mammalian cell lines (HL-60, K562, U937, MEL C88, N2A and PC12) analysed. The biological effect evoked by the induction of the ProTalpha sense vector was the retardation of cell differentiation, although expression of the antisense construct showed no effect on differentiation. In conclusion, our findings provide evidence that ProTalpha is directly implicated in cellular proliferation and that the maintenance of high levels of ProTalpha inside HL-60 cells is incompatible with their ability to differentiate. PMID:9560301

  7. Triboelectric Nanogenerator Accelerates Highly Efficient Nonviral Direct Conversion and In Vivo Reprogramming of Fibroblasts to Functional Neuronal Cells.

    PubMed

    Jin, Yoonhee; Seo, Jungmok; Lee, Jung Seung; Shin, Sera; Park, Hyun-Ji; Min, Sungjin; Cheong, Eunji; Lee, Taeyoon; Cho, Seung-Woo

    2016-09-01

    Triboelectric nanogenerators (TENGs) can be an effective cell reprogramming platform for producing functional neuronal cells for therapeutic applications. Triboelectric stimulation accelerates nonviral direct conversion of functional induced neuronal cells from fibroblasts, increases the conversion efficiency, and induces highly matured neuronal phenotypes with improved electrophysiological functionalities. TENG devices may also be used for biomedical in vivo reprogramming.

  8. Translucent tissue defect in potato (Solanum tuberosum L.) tubers is associated with oxidative stress accompanying an accelerated aging phenotype.

    PubMed

    Zommick, Daniel H; Kumar, G N Mohan; Knowles, Lisa O; Knowles, N Richard

    2013-12-01

    Translucent tissue defect (TTD) is an undesirable postharvest disorder of potato tubers characterized by the development of random pockets of semi-transparent tissue containing high concentrations of reducing sugars. Translucent areas turn dark during frying due to the Maillard reaction. The newly released cultivar, Premier Russet, is highly resistant to low temperature sweetening, but susceptible to TTD. Symptoms appeared as early as 170 days after harvest and worsened with time in storage (4-9 °C, 95 % RH). In addition to higher concentrations of glucose, fructose and sucrose, TTD resulted in lower dry matter, higher specific activities of starch phosphorylase and glc-6-phosphate dehydrogenase, higher protease activity, loss of protein, and increased concentrations of free amino acids (esp. asparagine and glutamine). The mechanism of TTD is unknown; however, the disorder has similarities with the irreversible senescent sweetening that occurs in tubers during long-term storage, where much of the decline in quality is a consequence of progressive increases in oxidative stress with advancing age. The respiration rate of non-TTD 'Premier Russet' tubers was inherently higher (ca. 40 %) than that of 'Russet Burbank' tubers (a non-TTD cultivar). Moreover, translucent tissue from 'Premier Russet' tubers had a 1.9-fold higher respiration rate than the average of non-translucent tissue and tissue from non-TTD tubers. Peroxidation of membrane lipids during TTD development resulted in increased levels of malondialdehyde and likely contributed to a measurable increase in membrane permeability. Superoxide dismutase and catalase activities and the ratio of oxidized to total glutathione were substantially higher in translucent tissue. TTD tubers also contained twofold less ascorbate than non-TTD tubers. TTD appears to be a consequence of oxidative stress associated with accelerated aging of 'Premier Russet' tubers.

  9. 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.

  10. 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.

  11. 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.

  12. Delaying histone deacetylase response to injury accelerates conversion into repair Schwann cells and nerve regeneration

    PubMed Central

    Brügger, Valérie; Duman, Mert; Bochud, Maëlle; Münger, Emmanuelle; Heller, Manfred; Ruff, Sophie; Jacob, Claire

    2017-01-01

    The peripheral nervous system (PNS) regenerates after injury. However, regeneration is often compromised in the case of large lesions, and the speed of axon reconnection to their target is critical for successful functional recovery. After injury, mature Schwann cells (SCs) convert into repair cells that foster axonal regrowth, and redifferentiate to rebuild myelin. These processes require the regulation of several transcription factors, but the driving mechanisms remain partially understood. Here we identify an early response to nerve injury controlled by histone deacetylase 2 (HDAC2), which coordinates the action of other chromatin-remodelling enzymes to induce the upregulation of Oct6, a key transcription factor for SC development. Inactivating this mechanism using mouse genetics allows earlier conversion into repair cells and leads to faster axonal regrowth, but impairs remyelination. Consistently, short-term HDAC1/2 inhibitor treatment early after lesion accelerates functional recovery and enhances regeneration, thereby identifying a new therapeutic strategy to improve PNS regeneration after lesion. PMID:28139683

  13. Challenges Encountered during the Processing of the BNL ERL 5 Cell Accelerating Cavity

    SciTech Connect

    A. Burrill; I. Ben-Zvi; R. Calaga; H. Hahn; V. Litvinenko; G. T. McIntyre; P. Kneisel; J. Mammosser; J. P. Preble; C. E. Reece; R. A. Rimmer; J. Saunders

    2007-08-01

    One of the key components for the Energy Recovery Linac being built by the Electron cooling group in the Collider Accelerator Department is the 5 cell accelerating cavity which is designed to accelerate 2 MeV electrons from the gun up to 15-20 MeV, allow them to make one pass through the ring and then decelerate them back down to 2 MeV prior to sending them to the dump. This cavity was designed by BNL and fabricated by AES in Medford, NY. Following fabrication it was sent to Thomas Jefferson Lab in VA for chemical processing, testing and assembly into a string assembly suitable for shipment back to BNL and integration into the ERL. The steps involved in this processing sequence will be reviewed and the deviations from processing of similar SRF cavities will be discussed. The lessons learned from this process are documented to help future projects where the scope is different from that normally encountered.

  14. CHALLENGES ENCOUNTERED DURING THE PROCESSING OF THE BNL ERL 5 CELL ACCELERATING CAVITY

    SciTech Connect

    BURRILL,A.

    2007-06-25

    One of the key components for the Energy Recovery Linac being built by the Electron cooling group in the Collider Accelerator Department is the 5 cell accelerating cavity which is designed to accelerate 2 MeV electrons from the gun up to 15-20 MeV, allow them to make one pass through the ring and then decelerate them back down to 2 MeV prior to sending them to the dump. This cavity was designed by BNL and fabricated by AES in Medford, NY. Following fabrication it was sent to Thomas Jefferson Lab in VA for chemical processing, testing and assembly into a string assembly suitable for shipment back to BNL for integration into the ERL. The steps involved in this processing sequence will be reviewed and the deviations from processing of similar SRF cavities will be discussed. The lessons learned from this process are documented to help future projects where the scope is different from that normally encountered.

  15. Novel methods in the Particle-In-Cell accelerator Code-Framework Warp

    SciTech Connect

    Vay, J-L; Grote, D. P.; Cohen, R. H.; Friedman, A.

    2012-12-26

    The Particle-In-Cell (PIC) Code-Framework Warp is being developed by the Heavy Ion Fusion Science Virtual National Laboratory (HIFS-VNL) to guide the development of accelerators that can deliver beams suitable for high-energy density experiments and implosion of inertial fusion capsules. It is also applied in various areas outside the Heavy Ion Fusion program to the study and design of existing and next-generation high-energy accelerators, including the study of electron cloud effects and laser wakefield acceleration for example. This study presents an overview of Warp's capabilities, summarizing recent original numerical methods that were developed by the HIFS-VNL (including PIC with adaptive mesh refinement, a large-timestep 'drift-Lorentz' mover for arbitrarily magnetized species, a relativistic Lorentz invariant leapfrog particle pusher, simulations in Lorentz-boosted frames, an electromagnetic solver with tunable numerical dispersion and efficient stride-based digital filtering), with special emphasis on the description of the mesh refinement capability. In addition, selected examples of the applications of the methods to the abovementioned fields are given.

  16. Iterative convergence acceleration of neutral particle transport methods via adjacent-cell preconditioners

    SciTech Connect

    Azmy, Y.Y.

    1999-06-10

    The author proposes preconditioning as a viable acceleration scheme for the inner iterations of transport calculations in slab geometry. In particular he develops Adjacent-Cell Preconditioners (AP) that have the same coupling stencil as cell-centered diffusion schemes. For lowest order methods, e.g., Diamond Difference, Step, and 0-order Nodal Integral Method (ONIM), cast in a Weighted Diamond Difference (WDD) form, he derives AP for thick (KAP) and thin (NAP) cells that for model problems are unconditionally stable and efficient. For the First-Order Nodal Integral Method (INIM) he derives a NAP that possesses similarly excellent spectral properties for model problems. The two most attractive features of the new technique are:(1) its cell-centered coupling stencil, which makes it more adequate for extension to multidimensional, higher order situations than the standard edge-centered or point-centered Diffusion Synthetic Acceleration (DSA) methods; and (2) its decreasing spectral radius with increasing cell thickness to the extent that immediate pointwise convergence, i.e., in one iteration, can be achieved for problems with sufficiently thick cells. He implemented these methods, augmented with appropriate boundary conditions and mixing formulas for material heterogeneities, in the test code APID that he uses to successfully verify the analytical spectral properties for homogeneous problems. Furthermore, he conducts numerical tests to demonstrate the robustness of the KAP and NAP in the presence of sharp mesh or material discontinuities. He shows that the AP for WDD is highly resilient to such discontinuities, but for INIM a few cases occur in which the scheme does not converge; however, when it converges, AP greatly reduces the number of iterations required to achieve convergence.

  17. Stem cell transplantation improves aging-related diseases

    PubMed Central

    Ikehara, Susumu; Li, Ming

    2014-01-01

    Aging is a complex process of damage accumulation, and has been viewed as experimentally and medically intractable. The number of patients with age-associated diseases such as type 2 diabetes mellitus (T2DM), osteoporosis, Alzheimer's disease (AD), Parkinson's disease, atherosclerosis, and cancer has increased recently. Aging-related diseases are related to a deficiency of the immune system, which results from an aged thymus and bone marrow cells. Intra bone marrow-bone marrow transplantation (IBM-BMT) is a useful method to treat intractable diseases. This review summarizes findings that IBM-BMT can improve and treat aging-related diseases, including T2DM, osteoporosis and AD, in animal models. PMID:25364723

  18. Langerhans cell histiocytosis in children under 2 years of age.

    PubMed

    Rivera-Luna, R; Alter-Molchadsky, N; Cardenas-Cardos, R; Martínez-Guerra, G

    1996-05-01

    This is a retrospective study of 55 children under the age of 2 years diagnosed with Langerhans cell histiocytosis (LCH). They were classified according to age and organ function and dysfunction following Lahey's criteria. The studied population was divided into four groups by age of diagnosis (0-6, 7-12, 13-18, and 19-24 months). Statistical analysis showed no significant difference in outcome between age groups, although the population under 6 months had a 81.3% fatality rate. The presence of organ dysfunction was a major cause of death in all age groups, being statistically significant in outcome (P > 0.005) compared with patients without organ dysfunction. The presence of thrombocytopenia and/or respiratory dysfunction was also highly associated with a fatal outcome. In the surviving population, no second malignancies have been reported. The late secondary effects of therapy include endocrine, orofacial, and osseous pathologies.

  19. DNA Damage Response in Hematopoietic Stem Cell Ageing.

    PubMed

    Li, Tangliang; Zhou, Zhong-Wei; Ju, Zhenyu; Wang, Zhao-Qi

    2016-06-01

    Maintenance of tissue-specific stem cells is vital for organ homeostasis and organismal longevity. Hematopoietic stem cells (HSCs) are the most primitive cell type in the hematopoietic system. They divide asymmetrically and give rise to daughter cells with HSC identity (self-renewal) and progenitor progenies (differentiation), which further proliferate and differentiate into full hematopoietic lineages. Mammalian ageing process is accompanied with abnormalities in the HSC self-renewal and differentiation. Transcriptional changes and epigenetic modulations have been implicated as the key regulators in HSC ageing process. The DNA damage response (DDR) in the cells involves an orchestrated signaling pathway, consisting of cell cycle regulation, cell death and senescence, transcriptional regulation, as well as chromatin remodeling. Recent studies employing DNA repair-deficient mouse models indicate that DDR could intrinsically and extrinsically regulate HSC maintenance and play important roles in tissue homeostasis of the hematopoietic system. In this review, we summarize the current understanding of how the DDR determines the HSC fates and finally contributes to organismal ageing.

  20. Retinal ON Bipolar Cells Express a New PCP2 Splice Variant That Accelerates the Light Response

    PubMed Central

    Sulaiman, Pyroja; Feddersen, Rod M.; Liu, Jian; Smith, Robert G.; Vardi, Noga

    2008-01-01

    PCP2, a member of the GoLoco domain-containing family, is present exclusively in cerebellar Purkinje cells and retinal ON bipolar cells. Its function in these tissues is unknown. Biochemical and expression system studies suggest that PCP2 is a guanine nucleotide dissociation inhibitor, although a guanine nucleotide exchange factor has also been suggested. Here, we studied the function of PCP2 in ON bipolar cells because their light response depends on Gαo1, which is known to interact with PCP2. We identified a new splice variant of PCP2 (Ret-PCP2) and localized it to rod bipolar and ON cone bipolar cells. Electroretinogram recordings from PCP2-null mice showed a normal a-wave but a slower falling phase of the b-wave (generated by the activity of ON bipolar cells) relative to the wild type. Whole-cell recordings from rod bipolar cells showed, both under Ames medium and after blocking GABAA/C and glycine receptors, that PCP2-null rod bipolar cells were more depolarized than wild-type cells with greater inward current when clamped to −60 mV. Also under both conditions, the rise time of the response to intense light was slower by 28% (Ames) and 44% (inhibitory blockers) in the null cells. Under Ames medium, we also observed >30% longer decay time in the PCP2-null rod bipolar cells. We conclude that PCP2 facilitates cation channels closure in the dark, shortens the rise time of the light response directly, and accelerates the decay time indirectly via the inhibitory network. These data can most easily be explained if PCP2 serves as a guanine nucleotide exchange factor. PMID:18768681

  1. 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.

  2. Anti-aging effects of guanosine in glial cells.

    PubMed

    Souza, Débora Guerini; Bellaver, Bruna; Bobermin, Larissa Daniele; Souza, Diogo Onofre; Quincozes-Santos, André

    2016-12-01

    Guanosine, a guanine-based purine, has been shown to exert beneficial roles in in vitro and in vivo injury models of neural cells. Guanosine is released from astrocytes and modulates important astroglial functions, including glutamatergic metabolism, antioxidant, and anti-inflammatory activities. Astrocytes are crucial for regulating the neurotransmitter system and synaptic information processes, ionic homeostasis, energy metabolism, antioxidant defenses, and the inflammatory response. Aging is a natural process that induces numerous changes in the astrocyte functionality. Thus, the search for molecules able to reduce the glial dysfunction associated with aging may represent an approach for avoiding the onset of age-related neurological diseases. Hence, the aim of this study was to evaluate the anti-aging effects of guanosine, using primary astrocyte cultures from newborn, adult, and aged Wistar rats. Concomitantly, we evaluated the role of heme oxygenase 1 (HO-1) in guanosine-mediated glioprotection. We observed age-dependent changes in glutamate uptake, glutamine synthetase (GS) activity, the glutathione (GSH) system, pro-inflammatory cytokine (tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β)) release, and the transcriptional activity of nuclear factor kB (NFkB), which were prevented by guanosine in an HO-1-dependent manner. Our findings suggest guanosine to be a promising therapeutic agent able to provide glioprotection during the aging process. Thus, this study contributes to the understanding of the cellular and molecular mechanisms of guanosine in the aging process.

  3. Cellular and molecular biology of aging endothelial cells.

    PubMed

    Donato, Anthony J; Morgan, R Garrett; Walker, Ashley E; Lesniewski, Lisa A

    2015-12-01

    Cardiovascular disease (CVD) is the leading cause of death in the United States and aging is a major risk factor for CVD development. One of the major age-related arterial phenotypes thought to be responsible for the development of CVD in older adults is endothelial dysfunction. Endothelial function is modulated by traditional CVD risk factors in young adults, but advancing age is independently associated with the development of vascular endothelial dysfunction. This endothelial dysfunction results from a reduction in nitric oxide bioavailability downstream of endothelial oxidative stress and inflammation that can be further modulated by traditional CVD risk factors in older adults. Greater endothelial oxidative stress with aging is a result of augmented production from the intracellular enzymes NADPH oxidase and uncoupled eNOS, as well as from mitochondrial respiration in the absence of appropriate increases in antioxidant defenses as regulated by relevant transcription factors, such as FOXO. Interestingly, it appears that NFkB, a critical inflammatory transcription factor, is sensitive to this age-related endothelial redox change and its activation induces transcription of pro-inflammatory cytokines that can further suppress endothelial function, thus creating a vicious feed-forward cycle. This review will discuss the two macro-mechanistic processes, oxidative stress and inflammation, that contribute to endothelial dysfunction with advancing age as well as the cellular and molecular events that lead to the vicious cycle of inflammation and oxidative stress in the aged endothelium. Other potential mediators of this pro-inflammatory endothelial phenotype are increases in immune or senescent cells in the vasculature. Of note, genomic instability, telomere dysfunction or DNA damage has been shown to trigger cell senescence via the p53/p21 pathway and result in increased inflammatory signaling in arteries from older adults. This review will discuss the current state

  4. Neuroprotective effect of hydroalcoholic extract of dried fruits of Trapa bispinosa Roxb on lipofuscinogenesis and fluorescence product in brain of D-galactose induced ageing accelerated mice.

    PubMed

    Ambikar, D B; Harle, U N; Khandare, R A; Bore, V V; Vyawahare, N S

    2010-04-01

    Effect of hydroalcoholic extract T. bispinosa (TB) was studied on fluorescence product and biochemical parameter like lipid peroxidation, catalase activity and glutathione peroxidase activity in the brain of female albino mice. Ageing was accelerated by the treatment of 0.5 ml 5% D-galactose for 15 days. This resulted in increased fluorescence product, increase lipid peroxidation and decrease antioxidant enzyme like glutathione peroxides and catalase in cerebral cortex. After cotreatment with hydroalcoholic extract of TB (500 mg/kg, po) there was decrease in fluorescence product in cerebral cortex. Moreover, TB inhibited increase lipid peroxidation and restores glutathione peroxidase and catalase activity in cerebral cortex as compare to ageing accelerated control group. To conclude TB found to be effective antioxidative agent which could to some extent reverse D-galactose induced ageing changes resulted due to oxidative damage.

  5. A reversal of age-dependent proliferative capacity of endothelial progenitor cells from different species origin in in vitro condition

    PubMed Central

    Hassanpour, Mehdi; Cheraghi, Omid; Siavashi, Vahid; Rahbarghazi, Reza; Nouri, Mohammad

    2016-01-01

    Introduction: A large number of cardiovascular disorders and abnormalities, notably accelerated vascular deficiencies could be related to aging changes and increased length of life. During the past decades, the discovery of different stem cells facilitates ongoing attempts for attenuating many disorders, especially in vascular beds. Endothelial progenitor cells (EPCs) are a subtype of stem cells that have potent capacity to differentiate into mature endothelial cells (ECs). However, some documented studies reported an age-related decline in proliferation and function of many stem cells. There is no data on aging effect upon proliferation and morphological feature of EPCs. Methods: To show aging effect on EPCs proliferation and multipotentiality, bone marrow samples were provided from old and young cases in three different species; human, mouse and dog. After 7 days of culture, the cell morphology and clonogenic capacity were evaluated. We also calculated the mean number of colonies both in bone marrow samples from old and young subjects. To confirm the cell phenotype, isolated cells were immune-phenotyped by a panel of antibodies against Tie-2, CD133 and CD309 markers. Results: Our results showed that EPCs exhibited prominent spindle form in all bone marrow samples from young cases while the cell shape became more round by aging. Notably, the number of colonies was reduced in aged samples as compared to parallel young subject samples (P < 0.05). We also detected that the expression of endothelial related markers diminished by aging. Conclusion: The results of this study suggest that the age-related vascular abnormalities could be presumably related to the decline in stemness capacity of EPCs. PMID:27777694

  6. Microfluidic Platform for Studying Chemotaxis of Adhesive Cells Revealed a Gradient-Dependent Migration and Acceleration of Cancer Stem Cells.

    PubMed

    Zou, Heng; Yue, Wanqing; Yu, Wai-Kin; Liu, Dandan; Fong, Chi-Chun; Zhao, Jianlong; Yang, Mengsu

    2015-07-21

    Recent studies reveal that solid tumors consist of heterogeneous cells with distinct phenotypes and functions. However, it is unclear how different subtypes of cancer cells migrate under chemotaxis. Here, we developed a microfluidic device capable of generating multiple stable gradients, culturing cells on-chip, and monitoring single cell migratory behavior. The microfluidic platform was used to study gradient-induced chemotaxis of lung cancer stem cell (LCSC) and differentiated LCSC (dLCSC) in real time. Our results showed the dynamic and differential response of both LCSC and dLCSC to chemotaxis, which was regulated by the β-catenin dependent Wnt signaling pathway. The microfluidic analysis showed that LCSC and dLCSC from the same origin behaved differently in the same external stimuli, suggesting the importance of cancer cell heterogeneity. We also observed for the first time the acceleration of both LCSC and dLCSC during chemotaxis caused by increasing local concentration in different gradients, which could only be realized through the microfluidic approach. The capability to analyze single cell chemotaxis under spatially controlled conditions provides a novel analytical platform for the study of cellular microenvironments and cancer cell metastasis.

  7. Chronic Porphyromonas gingivalis infection accelerates the occurrence of age-related granules in ApoE– / – mice brains

    PubMed Central

    Singhrao, Sim K.; Chukkapalli, Sasanka; Poole, Sophie; Velsko, Irina; Crean, St John; Kesavalu, Lakshmyya

    2017-01-01

    ABSTRACT This study explored the origin of age-related granules in the apolipoprotein E gene knockout (ApoE−/−) B6 background mice brains following chronic gingival infection with Porphyromonas gingivalis for 24 weeks. Intracerebral localization of P. gingivalis was detected by fluorescence in situ hybridization (FISH) and its protease by immunohistochemistry. The age-related granules were observed by periodic acid–Schiff (PAS), silver impregnation, and immunostaining. FISH showed intracerebral dissemination of P. gingivalis cells (p = 0.001). PAS and silver impregnation demonstrated the presence of larger inclusions restricted to the CA1, CA2, and dentate gyrus sectors of the hippocampus. A specific monoclonal antibody to bacterial peptidoglycan detected clusters of granules with variable sizes in mice brains infected with P. gingivalis (p = 0.004), and also highlighted areas of diffuse punctate staining equating to physical tissue damage. Mouse immunoglobulin G was observed in the capillaries of the cerebral parenchyma of all P. gingivalis–infected brains (p = 0.001), and on pyramidal neurons in some severely affected mice, compared with the sham-infected mice. Gingipains was also observed in microvessels of the hippocampus in the infected mice. This study supports the possibility of early appearance of age-related granules in ApoE−/− mice following inflammation-mediated tissue injury, accompanied by loss of cerebral blood-brain barrier integrity. PMID:28326151

  8. Accelerated testing of solid oxide fuel cell stacks for micro combined heat and power application

    NASA Astrophysics Data System (ADS)

    Hagen, Anke; Høgh, Jens Valdemar Thorvald; Barfod, Rasmus

    2015-12-01

    State-of-the-art (SoA) solid oxide fuel cell (SOFC) stacks are tested using profiles relevant for use in micro combined heat and power (CHP) units. Such applications are characterised by dynamic load profiles. In order to shorten the needed testing time and to investigate potential acceleration of degradation, the profiles are executed faster than required for real applications. Operation with fast load cycling, both using hydrogen and methane/steam as fuels, does not accelerate degradation compared to constant operation, which demonstrates the maturity of SoA stacks and enables transferring knowledge from testing at constant conditions to dynamic operation. 7.5 times more cycles than required for 80,000 h lifetime as micro CHP are achieved on one-cell-stack level. The results also suggest that degradation mechanisms that proceed on a longer time-scale, such as creep, might have a more dominating effect for long life-times than regular short time changes of operation. In order to address lifetime testing it is suggested to build a testing program consisting of defined modules that represent different application profiles, such as one module at constant conditions, followed by modules at one set of dynamic conditions etc.

  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. Unphysical kinetic effects in particle-in-cell modeling of laser wakefield accelerators.

    PubMed

    Cormier-Michel, Estelle; Shadwick, B A; Geddes, C G R; Esarey, E; Schroeder, C B; Leemans, W P

    2008-07-01

    Unphysical heating and macroparticle trapping that arise in the numerical modeling of laser wakefield accelerators using particle-in-cell codes are investigated. A dark current free laser wakefield accelerator stage, in which no trapping of background plasma electrons into the plasma wave should occur, and a highly nonlinear cavitated wake with self-trapping, are modeled. Numerical errors can lead to errors in the macroparticle orbits in both phase and momentum. These errors grow as a function of distance behind the drive laser and can be large enough to result in unphysical trapping in the plasma wake. The resulting numerical heating in intense short-pulse laser-plasma interactions grows much faster and to a higher level than the known numerical grid heating of an initially warm plasma in an undriven system. The amount of heating, at least in the region immediately behind the laser pulse, can, in general, be decreased by decreasing the grid size, increasing the number of particles per cell, or using smoother interpolation methods. The effect of numerical heating on macroparticle trapping is less severe in a highly nonlinear cavitated wake, since trapping occurs in the first plasma wave period immediately behind the laser pulse.

  11. Aging: a portrait from gene expression profile in blood cells

    PubMed Central

    Calabria, Elisa; Mazza, Emilia Maria Cristina; Dyar, Kenneth Allen; Pogliaghi, Silvia; Bruseghini, Paolo; Morandi, Carlo; Salvagno, Gian Luca; Gelati, Matteo; Guidi, Gian Cesare; Bicciato, Silvio; Schiaffino, Stefano; Schena, Federico; Capelli, Carlo

    2016-01-01

    The availability of reliable biomarkers of aging is important not only to monitor the effect of interventions and predict the timing of pathologies associated with aging but also to understand the mechanisms and devise appropriate countermeasures. Blood cells provide an easily available tissue and gene expression profiles from whole blood samples appear to mirror disease states and some aspects of the aging process itself. We report here a microarray analysis of whole blood samples from two cohorts of healthy adult and elderly subjects, aged 43±3 and 68±4 years, respectively, to monitor gene expression changes in the initial phase of the senescence process. A number of significant changes were found in the elderly compared to the adult group, including decreased levels of transcripts coding for components of the mitochondrial respiratory chain, which correlate with a parallel decline in the maximum rate of oxygen consumption (VO2max), as monitored in the same subjects. In addition, blood cells show age-related changes in the expression of several markers of immunosenescence, inflammation and oxidative stress. These findings support the notion that the immune system has a major role in tissue homeostasis and repair, which appears to be impaired since early stages of the aging process. PMID:27545843

  12. Impact of Aging on Dendritic Cell Functions in humans

    PubMed Central

    Agrawal, Anshu; Gupta, Sudhir

    2010-01-01

    Aging is a paradox of reduced immunity and chronic inflammation. Dendritic cells are central orchestrators of the immune response with a key role in the generation of immunity and maintenance of tolerance. The functions of DCs are compromised with age. There is no major effect on the numbers and phenotype of DC subsets in aged subjects; nevertheless, their capacity to phagocytose antigens and migrate is impaired with age. There is aberrant cytokine secretion by various DC subsets with CDCs secreting increased basal level of pro-inflammatory cytokines but the response on stimulation to foreign antigens is decreased. In contrast, the response to self antigens is increased suggesting erosion of peripheral self tolerance. PDC subset also secretes reduced IFN-alpha in response to viruses. The capacity of DCs to prime T cell responses is also affected. Aging thus has a profound affect on DC functions. Present review summarizes the effect of advancing age on DC functions in humans in the context of both immunity and tolerance. PMID:20619360

  13. Age-Related Instability in Spermatogenic Cell Nuclear and Mitochondrial DNA Obtained from Apex1 Heterozygous Mice

    PubMed Central

    Vogel, Kristine S.; Perez, Marissa; Momand, Jamila R.; Acevedo-Torres, Karina; Hildreth, Kim; Garcia, Rebecca A.; Torres-Ramos, Carlos A.; Ayala-Torres, Sylvette; Prihoda, Thomas J.; McMahan, C. Alex; Walter, Christi A.

    2011-01-01

    The prevalence of spontaneous mutations increases with age in the male germline; consequently, older men have an increased risk of siring children with genetic disease due to de novo mutations. The lacI transgenic mouse can be used to study paternal age effects, and in this system, the prevalence of de novo mutations increases in the male germline at old ages. Mutagenesis is linked with DNA repair capacity, and base excision repair, which can ameliorate spontaneous DNA damage, decreases in nuclear extracts of spermatogenic cells from old mice. Mice heterozygous for a null allele of the Apex1 gene, which encodes apurinic/apyrimidinic endonuclease I (APEN), an essential base excision repair enzyme, display an accelerated increase in spontaneous germline mutagenesis early in life. Here, the consequences of lifelong reduction of APEN on genetic instability in the male germline were examined, for the first time, at middle and old ages. Mutation frequency increased earlier in spermatogenic cells from Apex1+/− mice (by 6 months of age). Nuclear DNA damage increased with age in the spermatogenic lineage for both wild-type and Apex1+/− mice. By old age, mutation frequencies were similar for wild-type and APEN-deficient mice. Mitochondrial genome repair also depends on APEN, and novel analysis of mitochondrial DNA damage revealed an increase in the Apex1+/− spermatogenic cells by middle age. Thus, Apex1 heterozygosity results in accelerated damage to mitochondrial DNA and spontaneous mutagenesis, consistent with an essential role for APEN in maintaining nuclear and mitochondrial DNA integrity in spermatogenic cells throughout life. PMID:21919107

  14. Cellular and Molecular Biology of Aging Endothelial Cells

    PubMed Central

    Donato, Anthony J.; Morgan, R. Garrett; Walker, Ashley E.; Lesniewski, Lisa A.

    2015-01-01

    Cardiovascular disease (CVD) is the leading cause of death in the United States and aging is a major risk factor for CVD development. One of the major age-related arterial phenotypes thought to be responsible for the development of CVD in older adults is endothelial dysfunction. Endothelial function is modulated by traditional CVD risk factors in young adults, but advancing age is independently associated with the development of vascular endothelial dysfunction. This endothelial dysfunction results from a reduction in nitric oxide bioavailability downstream of endothelial oxidative stress and inflammation that can be further modulated by traditional CVD risk factors in older adults. Greater endothelial oxidative stress with aging is a result of augmented production from the intracellular enzymes NADPH oxidase and uncoupled eNOS, as well as from mitochondrial respiration in the absence of appropriate increases in antioxidant defenses as regulated by relevant transcription factors, such as FOXO. Interestingly, it appears that NFkB, a critical inflammatory transcription factor, is sensitive to this age-related endothelial redox change and its activation induces transcription of pro-inflammatory cytokines that can further suppress endothelial function, thus creating a vicious feed-forward cycle. This review will discuss the two macro-mechanistic processes, oxidative stress and inflammation, that contribute to endothelial dysfunction with advancing age as well as the cellular and molecular events that lead to the vicious cycle of inflammation and oxidative stress in the aged endothelium. Other potential mediators of this pro-inflammatory endothelial phenotype are increases in immune or senescent cells in the vasculature. Of note, genomic instability, telomere dysfunction or DNA damage have been shown to trigger cell senescence via the p53/p21 pathway that results in increased inflammatory signaling in arteries from older adults. This review will discuss the current

  15. Magnetically enhanced cell delivery for accelerating recovery of the endothelium in injured arteries

    PubMed Central

    Adamo, Richard F.; Fishbein, Ilia; Zhang, Kehan; Wen, Justin; Levy, Robert J.; Alferiev, Ivan S.; Chorny, Michael

    2015-01-01

    Arterial injury and disruption of the endothelial layer are an inevitable consequence of interventional procedures used for treating obstructive vascular disease. The slow and often incomplete endothelium regrowth after injury is the primary cause of serious short- and long-term complications, including thrombosis, restenosis and neoatherosclerosis. Rapid endothelium restoration has the potential to prevent these sequelae, providing a rationale for developing strategies aimed at accelerating the reendothelialization process. The present studies focused on magnetically guided delivery of endothelial cells (EC) functionalized with biodegradable magnetic nanoparticles (MNP) as an experimental approach for achieving rapid and stable cell homing and expansion in stented arteries. EC laden with polylactide-based MNP exhibited strong magnetic responsiveness, capacity for cryopreservation and rapid expansion, and the ability to disintegrate internalized MNP in both proliferating and contact-inhibited states. Intracellular decomposition of BODIPY558/568-labeled MNP monitored non-invasively based on assembly state-dependent changes in the emission spectrum demonstrated cell proliferation rate-dependent kinetics (average disassembly rates: 6.6 ± 0.8% and 3.6 ± 0.4% per day in dividing and contact-inhibited EC, respectively). With magnetic guidance using a transient exposure to a uniform 1-kOe field, stable localization and subsequent propagation of MNP-functionalized EC, markedly enhanced in comparison to non-magnetic delivery conditions, were observed in stented rat carotid arteries. In conclusion, magnetically guided delivery is a promising experimental strategy for accelerating endothelial cell repopulation of stented blood vessels after angioplasty. PMID:26704936

  16. Aging disrupts cell subpopulation dynamics and diminishes the function of mesenchymal stem cells

    PubMed Central

    Duscher, Dominik; Rennert, Robert C.; Januszyk, Michael; Anghel, Ersilia; Maan, Zeshaan N.; Whittam, Alexander J.; Perez, Marcelina G.; Kosaraju, Revanth; Hu, Michael S.; Walmsley, Graham G.; Atashroo, David; Khong, Sacha; Butte, Atul J.; Gurtner, Geoffrey C.

    2014-01-01

    Advanced age is associated with an increased risk of vascular morbidity, attributable in part to impairments in new blood vessel formation. Mesenchymal stem cells (MSCs) have previously been shown to play an important role in neovascularization and deficiencies in these cells have been described in aged patients. Here we utilize single cell transcriptional analysis to determine the effect of aging on MSC population dynamics. We identify an age-related depletion of a subpopulation of MSCs characterized by a pro-vascular transcriptional profile. Supporting this finding, we demonstrate that aged MSCs are also significantly compromised in their ability to support vascular network formation in vitro and in vivo. Finally, aged MSCs are unable to rescue age-associated impairments in cutaneous wound healing. Taken together, these data suggest that age-related changes in MSC population dynamics result in impaired therapeutic potential of aged progenitor cells. These findings have critical implications for therapeutic cell source decisions (autologous versus allogeneic) and indicate the necessity of strategies to improve functionality of aged MSCs. PMID:25413454

  17. Inhibition of a solid phase reaction among excipients that accelerates drug release from a solid dispersion with aging.

    PubMed

    Mizuno, Masayasu; Hirakura, Yutaka; Yamane, Ikuro; Miyanishi, Hideo; Yokota, Shoji; Hattori, Munetaka; Kajiyama, Atsushi

    2005-11-23

    Hydrophobic drug substances can be formulated as a solid dispersion or solution using macromolecular matrices with high glass transition temperatures to attain satisfactory dissolution. However, very few marketed products have previously relied on solid dispersion technology due to physical and chemical instability problems, and processing difficulties. In the present study, a modified release product of a therapeutic drug for hypertension, Barnidipine hydrochloride, was developed. The drug product consisted of solid dispersion based on a matrix of carboxymethylethylcellulose (CMEC), which was produced using the spray-coating method. An enteric coat layer was sprayed on the surface of the solid dispersion to control drug release. Interestingly, the release rate accelerated as the drug product aged, while there were no indications of deceleration of the release rate which was due to crystallization of the drug substance. To prevent changes in the dissolution kinetics during storage periods, a variety of processing conditions were tried. It was found that not only use of non-aqueous solvents but also a reduction in coating temperatures consistently resulted in stable solid dispersions. The molecular bases of dissolution of the drug substance from those matrices were investigated. The molecular weight of CMEC was found to be a dominant factor that determined dissolution kinetics, which followed zero-order release, suggesting an involvement of an osmotic pumping mechanism. While dissolution was faster using a higher molecular weight CMEC, the molecular weight of CMEC in the drug product slowly increased with aging (solid phase reaction) depending on the processing conditions, causing the time-induced elevation of dissolution. While no crystalline components were found in the solid dispersion, the amorphous structure maintained a degree of non-equilibrium by nature. Plasticization by water in the coating solution relaxed the amorphous system and facilitated phase

  18. Friend or foe: the dichotomous impact of T cells on neuro-de/re-generation during aging.

    PubMed

    Coder, Brandon; Wang, Weikan; Wang, Liefeng; Wu, Zhongdao; Zhuge, Qichuan; Su, Dong-Ming

    2017-01-24

    The interaction between T cells and the central nervous system (CNS) in homeostasis and injury has been recognized being both pathogenic (CD4+ T-helper 1 - Th1, Th17 and γδT) and ameliorative (Th2 and regulatory T cells - Tregs). However, in-depth studies aimed to elucidate the precise in the aged microenvironment and the dichotomous role of Tregs have just begun and many aspects remain unclear. This is due, not only to a mutual dependency and reciprocal causation of alterations and diseases between the nervous and T cell immune systems, but also to an inconsistent aging of the two systems, which dynamically changes with CNS injury/recovery and/or aging process. Cellular immune system aging, particularly immunosenescence and T cell aging initiated by thymic involution - sources of chronic inflammation in the elderly (termed inflammaging), potentially induces an acceleration of brain aging and memory loss. In turn, aging of the brain via neuro-endocrine-immune network drives total body systemic aging, including that of the immune system. Therefore, immunotherapeutics including vaccination and "protective autoimmunity" provide promising means to rejuvenate neuro-inflammatory disorders and repair CNS acute injury and chronic neuro-degeneration. We review the current understanding and recent discoveries linking the aging immune system with CNS injury and neuro-degeneration. Additionally, we discuss potential recovery and rejuvenation strategies, focusing on targeting the aging T cell immune system in an effort to alleviate acute brain injury and chronic neuro-degeneration during aging, via the "thymus-inflammaging-neurodegeneration axis".

  19. Friend or foe: the dichotomous impact of T cells on neuro-de/re-generation during aging

    PubMed Central

    Wang, Liefeng; Wu, Zhongdao; Zhuge, Qichuan; Su, Dong-Ming

    2017-01-01

    The interaction between T cells and the central nervous system (CNS) in homeostasis and injury has been recognized being both pathogenic (CD4+ T-helper 1 - Th1, Th17 and γδT) and ameliorative (Th2 and regulatory T cells - Tregs). However, in-depth studies aimed to elucidate the precise in the aged microenvironment and the dichotomous role of Tregs have just begun and many aspects remain unclear. This is due, not only to a mutual dependency and reciprocal causation of alterations and diseases between the nervous and T cell immune systems, but also to an inconsistent aging of the two systems, which dynamically changes with CNS injury/recovery and/or aging process. Cellular immune system aging, particularly immunosenescence and T cell aging initiated by thymic involution - sources of chronic inflammation in the elderly (termed inflammaging), potentially induces an acceleration of brain aging and memory loss. In turn, aging of the brain via neuro-endocrine-immune network drives total body systemic aging, including that of the immune system. Therefore, immunotherapeutics including vaccination and “protective autoimmunity” provide promising means to rejuvenate neuro-inflammatory disorders and repair CNS acute injury and chronic neuro-degeneration. We review the current understanding and recent discoveries linking the aging immune system with CNS injury and neuro-degeneration. Additionally, we discuss potential recovery and rejuvenation strategies, focusing on targeting the aging T cell immune system in an effort to alleviate acute brain injury and chronic neuro-degeneration during aging, via the “thymus-inflammaging-neurodegeneration axis”. PMID:27738345

  20. Microglial cell dysregulation in brain aging and neurodegeneration.

    PubMed

    von Bernhardi, Rommy; Eugenín-von Bernhardi, Laura; Eugenín, Jaime

    2015-01-01

    Aging is the main risk factor for neurodegenerative diseases. In aging, microglia undergoes phenotypic changes compatible with their activation. Glial activation can lead to neuroinflammation, which is increasingly accepted as part of the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). We hypothesize that in aging, aberrant microglia activation leads to a deleterious environment and neurodegeneration. In aged mice, microglia exhibit an increased expression of cytokines and an exacerbated inflammatory response to pathological changes. Whereas LPS increases nitric oxide (NO) secretion in microglia from young mice, induction of reactive oxygen species (ROS) predominates in older mice. Furthermore, there is accumulation of DNA oxidative damage in mitochondria of microglia during aging, and also an increased intracellular ROS production. Increased ROS activates the redox-sensitive nuclear factor kappa B, which promotes more neuroinflammation, and can be translated in functional deficits, such as cognitive impairment. Mitochondria-derived ROS and cathepsin B, are also necessary for the microglial cell production of interleukin-1β, a key inflammatory cytokine. Interestingly, whereas the regulatory cytokine TGFβ1 is also increased in the aged brain, neuroinflammation persists. Assessing this apparent contradiction, we have reported that TGFβ1 induction and activation of Smad3 signaling after inflammatory stimulation are reduced in adult mice. Other protective functions, such as phagocytosis, although observed in aged animals, become not inducible by inflammatory stimuli and TGFβ1. Here, we discuss data suggesting that mitochondrial and endolysosomal dysfunction could at least partially mediate age-associated microglial cell changes, and, together with the impairment of the TGFβ1-Smad3 pathway, could result in the reduction of protective activation and the facilitation of cytotoxic activation of microglia, resulting in the promotion of

  1. Microglial cell dysregulation in brain aging and neurodegeneration

    PubMed Central

    von Bernhardi, Rommy; Eugenín-von Bernhardi, Laura; Eugenín, Jaime

    2015-01-01

    Aging is the main risk factor for neurodegenerative diseases. In aging, microglia undergoes phenotypic changes compatible with their activation. Glial activation can lead to neuroinflammation, which is increasingly accepted as part of the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD). We hypothesize that in aging, aberrant microglia activation leads to a deleterious environment and neurodegeneration. In aged mice, microglia exhibit an increased expression of cytokines and an exacerbated inflammatory response to pathological changes. Whereas LPS increases nitric oxide (NO) secretion in microglia from young mice, induction of reactive oxygen species (ROS) predominates in older mice. Furthermore, there is accumulation of DNA oxidative damage in mitochondria of microglia during aging, and also an increased intracellular ROS production. Increased ROS activates the redox-sensitive nuclear factor kappa B, which promotes more neuroinflammation, and can be translated in functional deficits, such as cognitive impairment. Mitochondria-derived ROS and cathepsin B, are also necessary for the microglial cell production of interleukin-1β, a key inflammatory cytokine. Interestingly, whereas the regulatory cytokine TGFβ1 is also increased in the aged brain, neuroinflammation persists. Assessing this apparent contradiction, we have reported that TGFβ1 induction and activation of Smad3 signaling after inflammatory stimulation are reduced in adult mice. Other protective functions, such as phagocytosis, although observed in aged animals, become not inducible by inflammatory stimuli and TGFβ1. Here, we discuss data suggesting that mitochondrial and endolysosomal dysfunction could at least partially mediate age-associated microglial cell changes, and, together with the impairment of the TGFβ1-Smad3 pathway, could result in the reduction of protective activation and the facilitation of cytotoxic activation of microglia, resulting in the promotion of

  2. Novel Role for Decay-Accelerating Factor in Coxsackievirus A21-Mediated Cell Infectivity

    PubMed Central

    Newcombe, Nicole G.; Beagley, Leone G.; Christiansen, Dale; Loveland, Bruce E.; Johansson, E. Susanne; Beagley, Ken W.; Barry, Richard D.; Shafren, Darren R.

    2004-01-01

    Decay-accelerating factor (DAF) is involved in the cell membrane attachment of many human enteroviruses. Presently, further specific active roles of DAF in mediating productive cell infection and in the pathogenesis of natural enterovirus infection are poorly understood. In an attempt to more fully understand the role of DAF in lytic cell infection we examined the specific interactions of the prototype strain of coxsackievirus A21 (CVA21) with surface-expressed DAF. Investigations into discrete DAF-CVA21 interactions focused on viral binding; viral particle elution with respect to the parameters of time, temperature, and pH; and subsequent cell infection. Radiolabeled-virus binding assays revealed that peak elution of CVA21 from DAF occurred within 15 min of initial attachment and that the DAF-eluted virus increased in a linear fashion with respect to temperature and pH. CVA21 eluted from endogenous surface-expressed DAF was highly infectious, in contrast to CVA21 eluted from intercellular adhesion molecule 1 (ICAM-1), which retained little to no infectivity. Using an adenovirus transduction system, we demonstrate that CVA21 can remain infectious for up to 24 h after DAF binding and is capable of initiating a multicycle lytic infection upon delayed ICAM-1 surface expression. Taken together, the data suggest that a major role of DAF in cell infection by the prototype strain of CVA21 is to provide membrane concentration of infectious virions, effectively increasing viral interactions with endogenous or induced ICAM-1. PMID:15507656

  3. Activation of calcium-sensing receptor accelerates apoptosis in hyperplastic parathyroid cells

    SciTech Connect

    Mizobuchi, Masahide; Ogata, Hiroaki Hatamura, Ikuji; Saji, Fumie; Koiwa, Fumihiko; Kinugasa, Eriko; Koshikawa, Shozo; Akizawa, Tadao

    2007-10-12

    Calcimimetic compounds inhibit not only parathyroid hormone (PTH) synthesis and secretion, but also parathyroid cell proliferation. The aim of this investigation is to examine the effect of the calcimimetic compound NPS R-568 (R-568) on parathyroid cell death in uremic rats. Hyperplastic parathyroid glands were obtained from uremic rats (subtotal nephrectomy and high-phosphorus diet), and incubated in the media only or the media which contained high concentration of R-568 (10{sup -4} M), or 10% cyclodextrin, for 6 h. R-568 treatment significantly suppressed medium PTH concentration compared with that of the other two groups. R-568 treatment not only increased the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay-positive cells, but also induced the morphologic changes of cell death determined by light or electron microscopy. These results suggest that CaR activation by R-568 accelerates parathyroid cell death, probably through an apoptotic mechanism in uremic rats in vitro.

  4. CD133+ cancer stem cells promoted by VEGF accelerate the recurrence of hepatocellular carcinoma

    PubMed Central

    Liu, Kai; Hao, Meijun; Ouyang, Yabo; Zheng, Jiasheng; Chen, Dexi

    2017-01-01

    The role of cancer stem cells (CSCs) in inducing the recurrence of hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) remains unclear. Here, we found that a dramatic increase in plasma vascular endothelial growth factor (VEGF) and an induction of local CD133+ CSCs are associated with early HCC recurrence, suggesting that VEGF expression and tumour stemness contribute to the relapse. In vitro studies demonstrated that VEGF, via activation of VEGFR2, increased the number of CD133+ CSCs and enhanced their capacity for self-renewal by inducing the expression of Nanog. In vivo studies further demonstrated that VEGF-treated CD133+ CSCs formed tumours larger than those developing from unstimulated cells and VEGF pre-treatment increased the tumorigenic cell frequency of primary HCC cells dependently on the presence of Nanog and VEGFR2. In HCC tissue derived from patients with early recurrence, almost all CD133+ cells were Nanog and p-VEGFR2 positive, suggesting that activation of VEGFR2 is critical for RFA-induced tumour stemness in HCC. In summary, RFA-induced VEGF promotes tumour stemness and accelerates tumourigenesis in HCC in a manner dependent on Nanog and VEGFR2, which is valuable for the prediction of HCC recurrence after RFA and the development of novel therapeutics. PMID:28134312

  5. Acceleration of a Particle-in-Cell Code for Space Plasma Simulations with OpenACC

    NASA Astrophysics Data System (ADS)

    Peng, Ivy Bo; Markidis, Stefano; Vaivads, Andris; Vencels, Juris; Deca, Jan; Lapenta, Giovanni; Hart, Alistair; Laure, Erwin

    2015-04-01

    We simulate space plasmas with the Particle-in-cell (PIC) method that uses computational particles to mimic electrons and protons in solar wind and in Earth magnetosphere. The magnetic and electric fields are computed by solving the Maxwell's equations on a computational grid. In each PIC simulation step, there are four major phases: interpolation of fields to particles, updating the location and velocity of each particle, interpolation of particles to grids and solving the Maxwell's equations on the grid. We use the iPIC3D code, which was implemented in C++, using both MPI and OpenMP, for our case study. By November 2014, heterogeneous systems using hardware accelerators such as Graphics Processing Unit (GPUs) and the Many Integrated Core (MIC) coprocessors for high performance computing continue growth in the top 500 most powerful supercomputers world wide. Scientific applications for numerical simulations need to adapt to using accelerators to achieve portability and scalability in the coming exascale systems. In our work, we conduct a case study of using OpenACC to offload the computation intensive parts: particle mover and interpolation of particles to grids, in a massively parallel Particle-in-Cell simulation code, iPIC3D, to multi-GPU systems. We use MPI for inter-node communication for halo exchange and communicating particles. We identify the most promising parts suitable for GPUs accelerator by profiling using CrayPAT. We implemented manual deep copy to address the challenges of porting C++ classes to GPU. We document the necessary changes in the exiting algorithms to adapt for GPU computation. We present the challenges and findings as well as our methodology for porting a Particle-in-Cell code to multi-GPU systems using OpenACC. In this work, we will present the challenges, findings and our methodology of porting a Particle-in-Cell code for space applications as follows: We profile the iPIC3D code by Cray Performance Analysis Tool (CrayPAT) and identify

  6. Transvers Impedance Measurements of the Modified DARHT-2Accelerator Cell Design

    SciTech Connect

    Briggs, Dick; Waldron, Will

    2005-11-30

    The DARHT-2 accelerator cells have been redesigned to make their high voltage performance more robust. At the outset of the DARHT-2 development program about 8 years ago, an extensive campaign was mounted to minimize the transverse impedance of the original cell design. Since the initial spec on the machine was a beam current of 4 kA, the control of beam-breakup (BBU) amplification with a 2 microsecond pulse length was considered to be one the most critical issues in the design. Even after advances in detector technology allowed the beam current requirement to be lowered to 2 kA, the goal for the standard cell impedance was kept at {approx}300 ohms/meter to allow for the possibility of future beam current upgrades to 4 kA without any modifications in the cells. The results of this campaign to minimize the transverse impedance are described in detail in Reference 1. After several iterations in the design of ferrite dampers and the anode finger stock shape, the measured (peak) impedance of the original standard cell was determined to be about 280 ohms/meter. (As a reference point, the measured impedance of the DARHT-1 cell is about 880 ohms/meter). This impedance provided such a wide safety margin against BBU amplification at 2 kA that it was felt that the cell redesign could focus on voltage holding without any detailed considerations of impacts on the transverse impedance. Now that a baseline design for the DARHT-2 cell has been established and tested, however, it was felt that a measurement of its impedance would be prudent. The results of these impedance measurements are presented in this note. The objective was mainly to do a ''quick check'' to ensure that there were no surprises, and to provide an estimate of the BBU frequencies and growth rates to the experimental test program.

  7. 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.

  8. Tumor growth accelerated by chemotherapy-induced senescent cells is suppressed by treatment with IL-12 producing cellular vaccines

    PubMed Central

    Simova, Jana; Sapega, Olena; Imrichova, Terezie; Stepanek, Ivan; Kyjacova, Lenka; Mikyskova, Romana; Indrova, Marie; Bieblova, Jana; Bubenik, Jan; Bartek, Jiri; Hodny, Zdenek; Reinis, Milan

    2016-01-01

    Standard-of-care chemo- or radio-therapy can induce, besides tumor cell death, also tumor cell senescence. While senescence is considered to be a principal barrier against tumorigenesis, senescent cells can survive in the organism for protracted periods of time and they can promote tumor development. Based on this emerging concept, we hypothesized that elimination of such potentially cancer-promoting senescent cells could offer a therapeutic benefit. To assess this possibility, here we first show that tumor growth of proliferating mouse TC-1 HPV-16-associated cancer cells in syngeneic mice becomes accelerated by co-administration of TC-1 or TRAMP-C2 prostate cancer cells made senescent by pre-treatment with the anti-cancer drug docetaxel, or lethally irradiated. Phenotypic analyses of tumor-explanted cells indicated that the observed acceleration of tumor growth was attributable to a protumorigenic environment created by the co-injected senescent and proliferating cancer cells rather than to escape of the docetaxel-treated cells from senescence. Notably, accelerated tumor growth was effectively inhibited by cell immunotherapy using irradiated TC-1 cells engineered to produce interleukin IL-12. Collectively, our data document that immunotherapy, such as the IL-12 treatment, can provide an effective strategy for elimination of the detrimental effects caused by bystander senescent tumor cells in vivo. PMID:27448982

  9. Disruption of TGF-β signaling in T cells accelerates atherosclerosis

    PubMed Central

    Robertson, Anna-Karin L.; Rudling, Mats; Zhou, Xinghua; Gorelik, Leonid; Flavell, Richard A.; Hansson, Göran K.

    2003-01-01

    Increasing evidence suggests that atherosclerosis is an inflammatory disease promoted by hypercholesterolemia. The role of adaptive immunity has been controversial, however. We hypothesized that proatherogenic T cells are controlled by immunoregulatory cytokines. Among them, TGF-β has been implied in atherosclerosis, but its mechanism of action remains unclear. We crossed atherosclerosis-prone ApoE-knockout mice with transgenic mice carrying a dominant negative TGF-β receptor II in T cells. The ApoE-knockout mice with disrupted TGF-β signaling in T cells exhibited a sixfold increase in aortic lesion surface area, a threefold increase in aortic root lesion size, and a 125-fold increase in aortic IFN-γ mRNA when compared with age-matched ApoE-knockout littermates. When comparing size-matched lesions, those of mice with T cell–specific blockade of TGF-β signaling displayed increased T cells, activated macrophages, and reduced collagen, consistent with a more vulnerable phenotype. Ab’s to oxidized LDL, circulating T cell cytokines, and spleen T cell activity were all increased in ApoE-knockout mice with dominant negative TGF-β receptors in T cells. Taken together, these results show that abrogation of TGF-β signaling in T cells increases atherosclerosis and suggest that TGF-β reduces atherosclerosis by dampening T cell activation. Inhibition of T cell activation may therefore represent a strategy for antiatherosclerotic therapy. PMID:14568988

  10. Reprogramming aging and progeria.

    PubMed

    Freije, José M P; López-Otín, Carlos

    2012-12-01

    The aging rate of an organism depends on the ratio of tissue degeneration to tissue repair. As a consequence, molecular alterations that tip this balance toward degeneration cause accelerated aging. Conversely, interventions can be pursued to reduce tissue degeneration or to increase tissue repair with the aim of delaying the onset of age-associated manifestations. Recent studies on the biology of stem cells in aging have revealed the influence of systemic factors on their functionality and demonstrated the feasibility of reprogramming aged and progeroid cells. These results illustrate the reversibility of some aspects of the aging process and encourage the search for new anti-aging and anti-progeria interventions.

  11. Progeria, rapamycin and normal aging: recent breakthrough.

    PubMed

    Blagosklonny, Mikhail V

    2011-07-01

    A recent discovery that rapamycin suppresses a pro-senescent phenotype in progeric cells not only suggests a non-toxic therapy for progeria but also implies its similarity with normal aging. For one, rapamycin is also known to suppress aging of regular human cells. Here I discuss four potential scenarios, comparing progeria with both normal and accelerated aging. This reveals further indications of rapamycin both for accelerated aging in obese and for progeria.

  12. Continuous delivery of stromal cell-derived factor-1 from alginate scaffolds accelerates wound healing.

    PubMed

    Rabbany, Sina Y; Pastore, Joseph; Yamamoto, Masaya; Miller, Tim; Rafii, Shahin; Aras, Rahul; Penn, Marc

    2010-01-01

    Proper wound diagnosis and management is an increasingly important clinical challenge and is a large and growing unmet need. Pressure ulcers, hard-to-heal wounds, and problematic surgical incisions are emerging at increasing frequencies. At present, the wound-healing industry is experiencing a paradigm shift towards innovative treatments that exploit nanotechnology, biomaterials, and biologics. Our study utilized an alginate hydrogel patch to deliver stromal cell-derived factor-1 (SDF-1), a naturally occurring chemokine that is rapidly overexpressed in response to tissue injury, to assess the potential effects SDF-1 therapy on wound closure rates and scar formation. Alginate patches were loaded with either purified recombinant human SDF-1 protein or plasmid expressing SDF-1 and the kinetics of SDF-1 release were measured both in vitro and in vivo in mice. Our studies demonstrate that although SDF-1 plasmid- and protein-loaded patches were able to release therapeutic product over hours to days, SDF-1 protein was released faster (in vivo K(d) 0.55 days) than SDF-1 plasmid (in vivo K(d) 3.67 days). We hypothesized that chronic SDF-1 delivery would be more effective in accelerating the rate of dermal wound closure in Yorkshire pigs with acute surgical wounds, a model that closely mimics human wound healing. Wounds treated with SDF-1 protein (n = 10) and plasmid (n = 6) loaded patches healed faster than sham (n = 4) or control (n = 4). At day 9, SDF-1-treated wounds significantly accelerated wound closure (55.0 +/- 14.3% healed) compared to nontreated controls (8.2 +/- 6.0%, p < 0.05). Furthermore, 38% of SDF-1-treated wounds were fully healed at day 9 (vs. none in controls) with very little evidence of scarring. These data suggest that patch-mediated SDF-1 delivery may ultimately provide a novel therapy for accelerating healing and reducing scarring in clinical wounds.

  13. Evaluation of laser desorption mass spectrometry and UV accelerated aging of dyes on paper as tools for the evaluation of a questioned document.

    PubMed

    Grim, Donzna M; Siegel, Jay; Allison, John

    2002-11-01

    Laser desorption mass spectrometry (LDMS) may be used for the detection and identification of dyes found in inks. Naturally-aged and artificially-aged blue and black ballpoint pen inks containing the cationic dye methyl violet were analyzed on paper. The average molecular weight of the dye sample was calculated from LD mass spectral data and plotted versus time. The resulting aging curves demonstrate that, as dye degradation increases, the average molecular weight of the dye decreases. Typical variables involved in ink aging, such as the type of paper and ink formulation, were investigated. Results show that these variables influence the rate of dye degradation. Furthermore, UV accelerated aging has been developed and tested as an alternative to thermal approaches.

  14. Knockout of Endothelial Cell-Derived Endothelin-1 Attenuates Skin Fibrosis but Accelerates Cutaneous Wound Healing

    PubMed Central

    Makino, Katsunari; Jinnin, Masatoshi; Aoi, Jun; Kajihara, Ikko; Makino, Takamitsu; Fukushima, Satoshi; Sakai, Keisuke; Nakayama, Kazuhiko; Emoto, Noriaki; Yanagisawa, Masashi; Ihn, Hironobu

    2014-01-01

    Endothelin (ET)-1 is known for the most potent vasoconstrictive peptide that is released mainly from endothelial cells. Several studies have reported ET-1 signaling is involved in the process of wound healing or fibrosis as well as vasodilation. However, little is known about the role of ET-1 in these processes. To clarify its mechanism, we compared skin fibrogenesis and wound repair between vascular endothelial cell-specific ET-1 knockout mice and their wild-type littermates. Bleomycin-injected fibrotic skin of the knockout mice showed significantly decreased skin thickness and collagen conte