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Sample records for infected cell life-span

  1. Life span extension and neuronal cell protection by Drosophila nicotinamidase.

    PubMed

    Balan, Vitaly; Miller, Gregory S; Kaplun, Ludmila; Balan, Karina; Chong, Zhao-Zhong; Li, Faqi; Kaplun, Alexander; VanBerkum, Mark F A; Arking, Robert; Freeman, D Carl; Maiese, Kenneth; Tzivion, Guri

    2008-10-10

    The life span of model organisms can be modulated by environmental conditions that influence cellular metabolism, oxidation, or DNA integrity. The yeast nicotinamidase gene pnc1 was identified as a key transcriptional target and mediator of calorie restriction and stress-induced life span extension. PNC1 is thought to exert its effect on yeast life span by modulating cellular nicotinamide and NAD levels, resulting in increased activity of Sir2 family class III histone deacetylases. In Caenorhabditis elegans, knockdown of a pnc1 homolog was shown recently to shorten the worm life span, whereas its overexpression increased survival under conditions of oxidative stress. The function and regulation of nicotinamidases in higher organisms has not been determined. Here, we report the identification and biochemical characterization of the Drosophila nicotinamidase, D-NAAM, and demonstrate that its overexpression significantly increases median and maximal fly life span. The life span extension was reversed in Sir2 mutant flies, suggesting Sir2 dependence. Testing for physiological effectors of D-NAAM in Drosophila S2 cells, we identified oxidative stress as a primary regulator, both at the transcription level and protein activity. In contrast to the yeast model, stress factors such as high osmolarity and heat shock, calorie restriction, or inhibitors of TOR and phosphatidylinositol 3-kinase pathways do not appear to regulate D-NAAM in S2 cells. Interestingly, the expression of D-NAAM in human neuronal cells conferred protection from oxidative stress-induced cell death in a sirtuin-dependent manner. Together, our findings establish a life span extending the ability of nicotinamidase in flies and offer a role for nicotinamide-modulating genes in oxidative stress regulated pathways influencing longevity and neuronal cell survival.

  2. Increasing cell culture population doublings for long-term growth of finite life span human cell cultures

    DOEpatents

    Stampfer, Martha R; Garbe, James C

    2015-02-24

    Cell culture media formulations for culturing human epithelial cells are herein described. Also described are methods of increasing population doublings in a cell culture of finite life span human epithelial cells and prolonging the life span of human cell cultures. Using the cell culture media disclosed alone and in combination with addition to the cell culture of a compound associated with anti-stress activity achieves extended growth of pre-stasis cells and increased population doublings and life span in human epithelial cell cultures.

  3. Increasing cell culture population doublings for long-term growth of finite life span human cell cultures

    SciTech Connect

    Stampfer, Martha R.; Garbe, James C.

    2016-06-28

    Cell culture media formulations for culturing human epithelial cells are herein described. Also described are methods of increasing population doublings in a cell culture of finite life span human epithelial cells and prolonging the life span of human cell cultures. Using the cell culture media disclosed alone and in combination with addition to the cell culture of a compound associated with anti-stress activity achieves extended growth of pre-stasis cells and increased population doublings and life span in human epithelial cell cultures.

  4. Blood volume and red cell life span (M113), part C

    NASA Technical Reports Server (NTRS)

    Johnson, P. C., Jr.

    1973-01-01

    Prechamber, in-chamber, and postchamber blood samples taken from Skylab simulation crewmembers did not indicate significant shortening of the red cell life span during the mission. This does not suggest that the space simulation environment could not be associated with red cell enzyme changes. It does show that any changes in enzymes were not sufficiently great to significantly shorten red cell survival. There was no evidence of bone marrow erythropoetic suppression nor was there any evidence of increased red cell destruction.

  5. NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice.

    PubMed

    Zhang, Hongbo; Ryu, Dongryeol; Wu, Yibo; Gariani, Karim; Wang, Xu; Luan, Peiling; D'Amico, Davide; Ropelle, Eduardo R; Lutolf, Matthias P; Aebersold, Ruedi; Schoonjans, Kristina; Menzies, Keir J; Auwerx, Johan

    2016-06-17

    Adult stem cells (SCs) are essential for tissue maintenance and regeneration yet are susceptible to senescence during aging. We demonstrate the importance of the amount of the oxidized form of cellular nicotinamide adenine dinucleotide (NAD(+)) and its effect on mitochondrial activity as a pivotal switch to modulate muscle SC (MuSC) senescence. Treatment with the NAD(+) precursor nicotinamide riboside (NR) induced the mitochondrial unfolded protein response and synthesis of prohibitin proteins, and this rejuvenated MuSCs in aged mice. NR also prevented MuSC senescence in the mdx (C57BL/10ScSn-Dmd(mdx)/J) mouse model of muscular dystrophy. We furthermore demonstrate that NR delays senescence of neural SCs and melanocyte SCs and increases mouse life span. Strategies that conserve cellular NAD(+) may reprogram dysfunctional SCs and improve life span in mammals.

  6. Generation and Characterization of Telomerase-Transfected Human Lymphatic Endothelial Cells with an Extended Life Span

    PubMed Central

    Nisato, Riccardo E.; Harrison, Jillian A.; Buser, Raphaele; Orci, Lelio; Rinsch, Chris; Montesano, Roberto; Dupraz, Philippe; Pepper, Michael S.

    2004-01-01

    The study of lymphatic endothelial cells and lymphangiogenesis has, in the past, been hampered by the lack of lymphatic endothelial-specific markers. The recent discovery of several such markers has permitted the isolation of lymphatic endothelial cells (LECs) from human skin. However, cell numbers are limited and purity is variable with the different isolation procedures. To overcome these problems, we have transfected human dermal microvascular endothelial cells (HDMVECs) with a retrovirus containing the coding region of human telomerase reverse transcriptase (hTERT), and have produced a cell line, hTERT-HDLEC, with an extended lifespan. hTERT-HDLEC exhibit a typical cobblestone morphology when grown in culture, are contact-inhibited, and express endothelial cell-specific markers. hTERT-HDLEC also express the recognized lymphatic markers, Prox-1, LYVE-1 and podoplanin, as well as integrin α9, but do not express CD34. They also form tube-like structures in three-dimensional collagen gels when stimulated with vascular endothelial growth factors -A and -C. Based on these currently recognized criteria, these cells are LEC. Surprisingly, we also found that the widely studied HMEC-1 cell line expresses recognized lymphatic markers; however, these cells are also CD34-positive. In summary, the ectopic expression of hTERT increases the life span of LECs and does not affect their capacity to form tube-like structures in a collagen matrix. The production and characterization of hTERT-HDLEC will facilitate the study of the properties of lymphatic endothelium in vitro. PMID:15215158

  7. Factors controlling the proliferative rate, final cell density, and life span of bovine vascular smooth muscle cells in culture

    PubMed Central

    1981-01-01

    Low density vascular smooth muscle (VSM) cell cultures maintained on extracellular-matrix(ECM)-coated dishes and plated in the presence of either plasma or serum will proliferate actively when serum-containing medium is replaced by a synthetic medium supplemented with three factors: high density lipoprotein (HDL, 250 micrograms protein/ml); insulin (2.5 micrograms/ml) or somatomedin C (10 ng/ml); and fibroblast growth factor (FGF, 100 ng/ml) or epidermal growth factor (EGF, 50 ng/ml). The omission of any of these three factors from the synthetic medium results in a lower growth rate of the cultures, as well as in a lower final cell density once cultures reach confluence. When cells are plated in the total absence of serum, transferrin (10 micrograms/ml) is also required to induce optimal cell growth. The effects of the substrate and medium supplements on the life span of VSM cultures have also been analyzed. Cultures maintained on plastic and exposed to medium supplemented with 5% bovine serum underwent 15 generations. However, when maintained on ECM-coated dishes the serum-fed cultures had a life span of at least 88 generations. Likewise, when cultures were maintained in a synthetic medium supplemented with HDL and either FGF or EGF, an effect on the tissue culture life span by the substrate was observed. Cultures maintained on plastic underwent 24 generations, whereas those maintained on ECM-coated dishes could be passaged repeatedly for 58 generations. These experiments demonstrate the influence of the ECM-substrate only in promoting cell growth but also in increasing the longevity of the cultures. PMID:6454694

  8. Uncoupling of pathways that promote postmitotic life span and apoptosis from replicative immortality of Caenorhabditis elegans germ cells.

    PubMed

    Ahmed, Shawn

    2006-12-01

    A dichotomy exists between germ and somatic cells in most organisms, such that somatic cell lineages proliferate for a single generation, whereas the germ cell lineage has the capacity to proliferate from one generation to the next, indefinitely. Several theories have been proposed to explain the unlimited replicative life span of germ cells, including the elimination of damaged germ cells by apoptosis or expression of high levels of gene products that prevent aging in somatic cells. These theories were tested in the nematode Caenorhabditis elegans by examining the consequences of eliminating either apoptosis or the daf-16, daf-18 or sir-2.1 genes that promote longevity of postmitotic somatic cells. However, germ cells of strains deficient for these activities displayed an unlimited proliferative capacity. Thus, C. elegans germ cells retain their youthful character via alternative pathways that prevent or eliminate damage that accumulates as a consequence of cell proliferation.

  9. Cell specific radiation dosimetry in skeleton from life-span carcinogenesis studies. Final report

    SciTech Connect

    Webster, S.S.J.

    1993-04-05

    The osteogenic sarcoma is the dominant life-threatening pathology in lifespan studies of beagles exposed to alpha-emitting bone-seeking radionuclides. It was deduced from these studies that certain skeletal sites are more prone to develop tumors. This project sought to determine the bone cells at risk and their cell-specific radiation dose. The cell-specific radiation dose values are related to loss and high Ra-226 and Pu-239 induced osteogenic sarcoma sites, to test different dose response hypothesis and predict the extent of effects in humans.

  10. Cell specific radiation dosimetry in skeleton from life-span carcinogenesis studies

    SciTech Connect

    Webster, S.S.J.

    1993-04-05

    The osteogenic sarcoma is the dominant life-threatening pathology in lifespan studies of beagles exposed to alpha-emitting bone-seeking radionuclides. It was deduced from these studies that certain skeletal sites are more prone to develop tumors. This project sought to determine the bone cells at risk and their cell-specific radiation dose. The cell-specific radiation dose values are related to loss and high Ra-226 and Pu-239 induced osteogenic sarcoma sites, to test different dose response hypothesis and predict the extent of effects in humans.

  11. Sickle Cell Disease: An Opportunity for Palliative Care across the Life Span

    PubMed Central

    Johnson, Bonnye; Mack, A. Kyle; Labotka, Richard; Molokie, Robert E.

    2010-01-01

    Sickle cell disease is a chronic illness that impacts patients physically and emotionally and can do so at an early age. An ecological model of palliative care that involves improved communication among the health care team, patients, and their families can be beneficial. Open and honest communication regarding advance care planning, disease management, relief of pain and other symptoms, and bereavement and grief are all important for the patient, family, and health care team. Given the multiple acute and chronic complications of sickle cell disease, an approach to care that is holistic and comprehensive may help to improve a patient’s biological function and the perceived health, functional status, and quality of life of the patient and family. PMID:20804884

  12. Characterization of beta-adrenergic receptors through the replicative life span of IMR-90 cells

    SciTech Connect

    Scarpace, P.J.

    1987-01-01

    Beta-adrenergic receptor number and receptor affinity for isoproterenol were assessed at various in vitro ages of the human diploid fibroblast cell line IMR-90. From population doubling level (PDL) 33 to 44, there was a positive correlation between beta-adrenergic receptor density and PDL. Beta-adrenergic receptors, assessed by Scatchard analysis of (/sup 125/I)-iodocyanopindolol (ICYP) binding, increased from 15 fmol/mg protein at PDL 33 to 36 fmol/mg protein at PDL 44. In contrast, from PDL 44 to 59, there was a negative correlation between beta-adrenergic receptor density and PDL. Receptor density declined to 12 fmol/mg protein at PDL 59. When the density of beta-adrenergic receptors was expressed as receptor per cell, the findings were similar. Receptor agonist affinity for isoproterenol was determined from Hill plots of (/sup 125/I)-ICYP competition with isoproterenol. There was no change in the dissociation constant for isoproterenol with in vitro age. In humans, serum norepinephrine concentrations increase with age. This increase in serum norepinephrine may be partially responsible for the decreased beta-adrenergic receptor-agonist affinity observed with age in human lymphocytes and rat heart and lung. The present findings are consistent with the hypothesis that the decreases in receptor agonist affinity in rat and man with age are secondary to increases in catecholamine concentrations.

  13. Effect of continuous irradiation with a very low dose of gamma rays on life span and the immune system in SJL mice prone to B-cell lymphoma.

    PubMed

    Lacoste-Collin, L; Jozan, S; Cances-Lauwers, V; Pipy, B; Gasset, G; Caratero, C; Courtade-Saïdi, M

    2007-12-01

    Ionizing radiation has been shown to have dose- and dose-rate-dependent carcinogenic effects on the hematopoietic and lymphoreticular systems. We report here that continuous exposure to a low dose of gamma rays influences the course of spontaneous B-cell lymphoma in SJL mice. We studied the biological effects of 10 cGy year(-1) gamma rays on the life span of 560 4-week-old SJL/J female mice and on various parameters of the cell-mediated immune response. Life span was slightly prolonged. The mean survival was 397 days for controls and 417 days for irradiated mice that died with lymphoma (P = 0.34). In lymph nodes and spleen, lower percentages of CD4+ and CD8+ T cells were observed in irradiated mice before 32 weeks. Interestingly, the percentages of CD49+ NK cells were increased in the spleens of irradiated mice at 28 weeks (0.61 +/- 0.08% compared to 0.43 +/- 0.12% in controls, P = 0.01) and at 32 weeks (0.62 +/- 0.24% compared to 0.33 +/- 0.09%, P = 0.02), while NK cell activity remained unchanged in exposed mice. These results provide further support for the absence of harmful effects of a continuous very low dose of radiation on life span and incidence of lymphoma in SJL mice.

  14. Budding yeast SSD1-V regulates transcript levels of many longevity genes and extends chronological life span in purified quiescent cells.

    PubMed

    Li, Lihong; Lu, Yong; Qin, Li-Xuan; Bar-Joseph, Ziv; Werner-Washburne, Margaret; Breeden, Linda L

    2009-09-01

    Ssd1 is an RNA-binding protein that affects literally hundreds of different processes and is polymorphic in both wild and lab yeast strains. We have used transcript microarrays to compare mRNA levels in an isogenic pair of mutant (ssd1-d) and wild-type (SSD1-V) cells across the cell cycle. We find that 15% of transcripts are differentially expressed, but there is no correlation with those mRNAs bound by Ssd1. About 20% of cell cycle regulated transcripts are affected, and most show sharper amplitudes of oscillation in SSD1-V cells. Many transcripts whose gene products influence longevity are also affected, the largest class of which is involved in translation. Ribosomal protein mRNAs are globally down-regulated by SSD1-V. SSD1-V has been shown to increase replicative life span currency and we show that SSD1-V also dramatically increases chronological life span (CLS). Using a new assay of CLS in pure populations of quiescent prototrophs, we find that the CLS for SSD1-V cells is twice that of ssd1-d cells.

  15. Life span extension and cancer risk: myths and reality.

    PubMed

    Anisimov, V N

    2001-07-01

    A significant increase in the number of old people in the populations of developed countries was followed by an increase in morbidity and mortality resulting from main age-related diseases -- cardiovascular, cancer, neurodegenerative, diabetes mellitus, decrease in resistance to infections. Obviously, the development of the means of prevention of the premature aging of humans is crucial for the realization of this program. However, data available on such kind of means are rather scarce, contradictory and are often not reliable from the points of view of the adequacy of the experiments to current scientific requirements as well as the interpretation of the results and safety. Data available on the increase in life span and the adverse effects of the following geroprotectors were critically analyzed: antioxidants, chelate agents and lathyrogens, succinate, adaptogens and herbs, neurotropic drugs, inhibitors of monoamine oxidase, glucocorticoids, dehydroepiandrosterone, sex and growth hormones, melatonin, pineal peptide preparations, protein inhibitors, antidiabetic biguanides, thymic hormones and peptides, immunomodulators, enteroadsorbents, lypofuscin inhibitors, as well as calorie intake restriction and special diets. Most of the available results were insufficient and could not provide convincing evidence for the life span extension and the safety of the suggested geroprotectors. Drugs and means prolonging the life span could be subdivided into three groups: (a) geroprotectors prolonging the life span equally in all the members of the population: these postponed the beginning of the population's aging; (b) geroprotectors decreasing the mortality rate in a long-lived subpopulation, which raised their maximal life span: these slowed down the population's aging rate; (c) geroprotectors increasing the survival rate in a short-lived subpopulation without changes in the maximal life span: in this case, the aging rate increased. There was a high positive correlation

  16. Karyotypic instability and centrosome aberrations in the progeny of finite life-span human mammary epithelial cells exposed to sparsely or densely ionizing radiation.

    PubMed

    Sudo, Hiroko; Garbe, James; Stampfer, Martha R; Barcellos-Hoff, Mary Helen; Kronenberg, Amy

    2008-07-01

    The human breast is sensitive to radiation carcinogenesis, and genomic instability occurs early in breast cancer development. This study tests the hypothesis that ionizing radiation elicits genomic instability in finite life-span human mammary epithelial cells (HMEC) and asks whether densely ionizing radiation is a more potent inducer of instability. HMEC in a non-proliferative state were exposed to X rays or 1 GeV/nucleon iron ions followed by delayed plating. Karyotypic instability and centrosome aberrations were monitored in expanded clonal isolates. Severe karyotypic instability was common in the progeny of cells that survived X-ray or iron-ion exposure. There was a lower dose threshold for severe karyotypic instability after iron-ion exposure. More than 90% of X-irradiated colonies and >60% of iron-ion-irradiated colonies showed supernumerary centrosomes at levels above the 95% upper confidence limit of the mean for unirradiated clones. A dose response was observed for centrosome aberrations for each radiation type. There was a statistically significant association between the incidence of karyotypic instability and supernumerary centrosomes for iron-ion-exposed colonies and a weaker association for X-irradiated colonies. Thus genomic instability occurs frequently in finite life-span HMEC exposed to sparsely or densely ionizing radiation and may contribute to radiation-induced breast cancer.

  17. Cell proliferation dynamics of somatic and germline tissues during zooidal life span in the colonial tunicate Botryllus primigenus.

    PubMed

    Kawamura, Kazuo; Tachibana, Miki; Sunanaga, Takeshi

    2008-07-01

    Botryllus primigenus is a colonial tunicate in which three successive generations develop synchronously. To identify proliferation centers and possible adult stem cells during asexual reproduction, somatic and germline cells were labeled with 5-bromo-2'-deoxyuridine (BrdU). In the youngest generation, multipotent epithelial cells exhibited an average labeling index (LI) of 30% 24 hr after BrdU injection. In the middle generation, the LI of organ rudiments decreased gradually and reached zero by the beginning of the eldest generation. Exceptionally, cells of specialized tissues such as the pharyngeal inner longitudinal vessel and the posterior end of the endostyle continued DNA synthesis and mitosis even in the eldest generation. Proliferating somatic and germline cells of younger generations expressed a Botryllus myc homolog (BpMyc), but adult tissues did not. This result strongly suggests that in B. primigenus undifferentiated progenitor cells are discernible from possible adult stem cells by the presence or absence of BpMyc.

  18. Plasmid accumulation reduces life span in Saccharomyces cerevisiae.

    PubMed

    Falcón, Alaric A; Aris, John P

    2003-10-24

    Aging in the yeast Saccharomyces cerevisiae is under the control of multiple pathways. The production and accumulation of extrachromosomal rDNA circles (ERCs) is one pathway that has been proposed to bring about aging in yeast. To test this proposal, we have developed a plasmid-based model system to study the role of DNA episomes in reduction of yeast life span. Recombinant plasmids containing different replication origins, cis-acting partitioning elements, and selectable marker genes were constructed and analyzed for their effects on yeast replicative life span. Plasmids containing the ARS1 replication origin reduce life span to the greatest extent of the plasmids analyzed. This reduction in life span is partially suppressed by a CEN4 centromeric element on ARS1 plasmids. Plasmids containing a replication origin from the endogenous yeast 2 mu circle also reduce life span, but to a lesser extent than ARS1 plasmids. Consistent with this, ARS1 and 2 mu origin plasmids accumulate in approximately 7-generation-old cells, but ARS1/CEN4 plasmids do not. Importantly, ARS1 plasmids accumulate to higher levels in old cells than 2 mu origin plasmids, suggesting a correlation between plasmid accumulation and life span reduction. Reduction in life span is neither an indirect effect of increased ERC levels nor the result of stochastic cessation of growth. The presence of a fully functional 9.1-kb rDNA repeat on plasmids is not required for, and does not augment, reduction in life span. These findings support the view that accumulation of DNA episomes, including episomes such as ERCs, cause cell senescence in yeast.

  19. Insulin-like growth factor-I extends in vitro replicative life span of skeletal muscle satellite cells by enhancing G1/S cell cycle progression via the activation of phosphatidylinositol 3'-kinase/Akt signaling pathway

    NASA Technical Reports Server (NTRS)

    Chakravarthy, M. V.; Abraha, T. W.; Schwartz, R. J.; Fiorotto, M. L.; Booth, F. W.

    2000-01-01

    Interest is growing in methods to extend replicative life span of non-immortalized stem cells. Using the insulin-like growth factor I (IGF-I) transgenic mouse in which the IGF-I transgene is expressed during skeletal muscle development and maturation prior to isolation and during culture of satellite cells (the myogenic stem cells of mature skeletal muscle fibers) as a model system, we elucidated the underlying molecular mechanisms of IGF-I-mediated enhancement of proliferative potential of these cells. Satellite cells from IGF-I transgenic muscles achieved at least five additional population doublings above the maximum that was attained by wild type satellite cells. This IGF-I-induced increase in proliferative potential was mediated via activation of the phosphatidylinositol 3'-kinase/Akt pathway, independent of mitogen-activated protein kinase activity, facilitating G(1)/S cell cycle progression via a down-regulation of p27(Kip1). Adenovirally mediated ectopic overexpression of p27(Kip1) in exponentially growing IGF-I transgenic satellite cells reversed the increase in cyclin E-cdk2 kinase activity, pRb phosphorylation, and cyclin A protein abundance, thereby implicating an important role for p27(Kip1) in promoting satellite cell senescence. These observations provide a more complete dissection of molecular events by which increased local expression of a growth factor in mature skeletal muscle fibers extends replicative life span of primary stem cells than previously known.

  20. Sexual Conflict, Life Span, and Aging

    PubMed Central

    Adler, Margo I.; Bonduriansky, Russell

    2014-01-01

    The potential for sexual conflict to influence the evolution of life span and aging has been recognized for more than a decade, and recent work also suggests that variation in life span and aging can influence sexually antagonistic coevolution. However, empirical exploration of these ideas is only beginning. Here, we provide an overview of the ideas and evidence linking inter- and intralocus sexual conflicts with life span and aging. We aim to clarify the conceptual basis of this research program, examine the current state of knowledge, and suggest key questions for further investigation. PMID:24938876

  1. Stress Proteins in Aging and Life Span

    PubMed Central

    Murshid, Ayesha; Eguchi, Takanori; Calderwood, Stuart K.

    2014-01-01

    Heat shock proteins (HSP) are molecular chaperones and have been implicated in longevity and aging in many species. Their major functions include, chaperoning misfolded or newly synthesized polypeptides, protecting cells from proteotoxic stress, and processing of immunogenic agents. These proteins are expressed constitutively and can be induced by stresses such as heat, oxidative stress and many more. The induction of HSP in aging could potentially maintain protein homeostasis and longevity by refolding the damaged proteins which accumulate during aging and are toxic to cells. HSP are shown to increase life span in model organisms such as C. elegans and decrease aging related proteotoxicity. Thus, decrease in HSP in aging is associated with disruption of cellular homeostasis which causes diseases such as cancer, cell senescence and neurodegeneration. HSP levels are decreased with aging in most organs including neurons. Aging also causes attenuation or alteration of many signaling pathways as well as the expression of transcription factors such as heat shock factor (HSF). The alteration in regulation and synthesis of Forkhead box O3a (FOXO3a) family of transcription factors as well as major antioxidant enzymes [manganese superoxide dismutase (MnSOD), catalase] are also seen in aging. Among many signaling mechanisms involved in altering longevity and aging, the insulin/IGF1 pathway and the Sir2 deacetylase are highly significant. This review inquires into the role of some of these pathways in longevity/aging along with HSP. PMID:23742046

  2. Methionine restriction beyond life-span extension.

    PubMed

    Ables, Gene P; Hens, Julie R; Nichenametla, Sailendra N

    2016-01-01

    Dietary methionine restriction (MR) extends life span across species via various intracellular regulatory mechanisms. In rodents, MR induces resistance against adiposity, improves hepatic glucose metabolism, preserves cardiac function, and reduces body size, all of which can affect the onset of age-related diseases. Recent studies have shown that MR-affected biomarkers, such as fibroblast growth factor 21, adiponectin, leptin, cystathionine β synthase, and insulin-like growth factor 1, can potentially alter physiology. The beneficial effects of MR could be explained in part by its ability to reduce mitochondrial oxidative stress. Studies have revealed that MR can reduce reactive oxygen species that damage cells and promote cancer progression. It has been demonstrated that either MR or the targeting of specific genes in the methionine cycle could induce cell apoptosis while decreasing proliferation in several cancer models. The complete mechanism underlying the actions of MR on the cell cycle during cancer has not been fully elucidated. Epigenetic mechanisms, such as methylation and noncoding RNAs, are also possible downstream effectors of MR; future studies should help to elucidate some of these mechanisms. Despite evidence that changes in dietary methionine can affect epigenetics, it remains unknown whether epigenetics is a mechanism in MR. This review summarizes research on MR and its involvement in metabolism, cancer, and epigenetics.

  3. Heat stress-induced life span extension in yeast.

    PubMed

    Shama, S; Lai, C Y; Antoniazzi, J M; Jiang, J C; Jazwinski, S M

    1998-12-15

    The yeast Saccharomyces cerevisiae has a limited life span that can be measured by the number of times individual cells divide. Several genetic manipulations have been shown to prolong the yeast life span. However, environmental effects that extend longevity have been largely ignored. We have found that mild, nonlethal heat stress extended yeast life span when it was administered transiently early in life. The increased longevity was due to a reduction in the mortality rate that persisted over many cell divisions (generations) but was not permanent. The genes RAS1 and RAS2 were necessary to observe this effect of heat stress. The RAS2 gene is consistently required for maintenance of life span when heat stress is chronic or in its extension when heat stress is transient or absent altogether. RAS1, on the other hand, appears to have a role in signaling life extension induced by transient, mild heat stress, which is distinct from its life-span-curtailing effect in the absence of stress and its lack of involvement in the response to chronic heat stress. This distinction between the RAS genes may be partially related to their different effects on growth-promoting genes and stress-responsive genes. The ras2 mutation clearly hindered resumption of growth and recovery from stress, while the ras1 mutation did not. The HSP104 gene, which is largely responsible for induced thermotolerance in yeast, was necessary for life extension induced by transient heat stress. An interaction between mitochondrial petite mutations and heat stress was found, suggesting that mitochondria may be necessary for life extension by transient heat stress. The results raise the possibility that the RAS genes and mitochondria may play a role in the epigenetic inheritance of reduced mortality rate afforded by transient, mild heat stress.

  4. Spatial Abilities across the Adult Life Span

    ERIC Educational Resources Information Center

    Borella, Erika; Meneghetti, Chiara; Ronconi, Lucia; De Beni, Rossana

    2014-01-01

    The study investigates age-related effects across the adult life span on spatial abilities (testing subabilities based on a distinction between spatial visualization, mental rotation, and perspective taking) and spatial self-assessments. The sample consisted of 454 participants (223 women and 231 men) from 20 to 91 years of age. Results showed…

  5. The Cost of Uncertain Life Span*

    PubMed Central

    Edwards, Ryan D.

    2012-01-01

    A considerable amount of uncertainty surrounds the length of human life. The standard deviation in adult life span is about 15 years in the U.S., and theory and evidence suggest it is costly. I calibrate a utility-theoretic model of preferences over length of life and show that one fewer year in standard deviation is worth about half a mean life year. Differences in the standard deviation exacerbate cross-sectional differences in life expectancy between the U.S. and other industrialized countries, between rich and poor countries, and among poor countries. Accounting for the cost of life-span variance also appears to amplify recently discovered patterns of convergence in world average human well-being. This is partly for methodological reasons and partly because unconditional variance in human length of life, primarily the component due to infant mortality, has exhibited even more convergence than life expectancy. PMID:22368324

  6. Attitudes Toward Death Across the Life Span.

    ERIC Educational Resources Information Center

    Maiden, Robert; Walker, Gail

    To understand the change and development of people's attitudes toward death over the life span, a 62-item attitude questionnaire on death and dying was administered to 90 adults. Participants included five females and five males in each of nine age categories: 18-20, 20-24, 25-29, 30-34, 35-39, 40-49, 50-59, 60-64, and 65 or older. Participants…

  7. Mutant models of prolonged life span.

    PubMed

    Mahler, J F

    2001-01-01

    Aging is an important biological process that affects all creatures. For humans, age-related diseases and the question of why we age and die also have tremendous social and philosophical impact. We can therefore expect that models to study mechanisms of the aging process will always attract much interest. Until recently, the mutant model approach to study molecular mechanisms of aging has been limited to lower animals such as yeast, worms, and flies. However, given the current power of genetic technology in mammals, we can expect that phenotypes of prolonged life span will increasingly be seen in mice and subject to evaluation by pathologists. A brief review of current models is presented.

  8. The dihydrolipoamide acetyltransferase is a novel metabolic longevity factor and is required for calorie restriction-mediated life span extension.

    PubMed

    Easlon, Erin; Tsang, Felicia; Dilova, Ivanka; Wang, Chen; Lu, Shu-Ping; Skinner, Craig; Lin, Su-Ju

    2007-03-02

    Calorie restriction (CR) extends life span in a wide variety of species. Recent studies suggest that an increase in mitochondrial metabolism mediates CR-induced life span extension. Here we present evidence that Lat1 (dihydrolipoamide acetyltransferase), the E2 component of the mitochondrial pyruvate dehydrogenase complex, is a novel metabolic longevity factor in the CR pathway. Deleting the LAT1 gene abolishes life span extension induced by CR. Overexpressing Lat1 extends life span, and this life span extension is not further increased by CR. Similar to CR, life span extension by Lat1 overexpression largely requires mitochondrial respiration, indicating that mitochondrial metabolism plays an important role in CR. Interestingly, Lat1 overexpression does not require the Sir2 family to extend life span, suggesting that Lat1 mediates a branch of the CR pathway that functions in parallel to the Sir2 family. Lat1 is also a limiting longevity factor in nondividing cells in that overexpressing Lat1 extends cell survival during prolonged culture at stationary phase. Our studies suggest that Lat1 overexpression extends life span by increasing metabolic fitness of the cell. CR may therefore also extend life span and ameliorate age-associated diseases by increasing metabolic fitness through regulating central metabolic enzymes.

  9. Metformin supplementation and life span in Fischer-344 rats.

    PubMed

    Smith, Daniel L; Elam, Calvin F; Mattison, Julie A; Lane, Mark A; Roth, George S; Ingram, Donald K; Allison, David B

    2010-05-01

    Calorie restriction (CR) has been known for more than 70 years to extend life span and delay disease in rodent models. Metformin administration in rodent disease models has been shown to delay cancer incidence and progression, reduce cardiovascular disease and extend life span. To more directly test the potential of metformin supplementation (300 mg/kg/day) as a CR mimetic, life-span studies were performed in Fischer-344 rats and compared with ad libitum feeding and CR (30%). The CR group had significantly reduced food intake and body weight throughout the study. Body weight was significantly reduced in the metformin group compared with control during the middle of the study, despite similar weekly food intake. Although CR significantly extended early life span (25th quantile), metformin supplementation did not significantly increase life span at any quantile (25th, 50th, 75th, or 90th), overall or maximum life span (p > .05) compared with control.

  10. Developmental Regulation across the Life Span: Toward a New Synthesis

    ERIC Educational Resources Information Center

    Haase, Claudia M.; Heckhausen, Jutta; Wrosch, Carsten

    2013-01-01

    How can individuals regulate their own development to live happy, healthy, and productive lives? Major theories of developmental regulation across the life span have been proposed (e.g., dual-process model of assimilation and accommodation; motivational theory of life-span development; model of selection, optimization, and compensation), but they…

  11. Sir2 blocks extreme life-span extension.

    PubMed

    Fabrizio, Paola; Gattazzo, Cristina; Battistella, Luisa; Wei, Min; Cheng, Chao; McGrew, Kristen; Longo, Valter D

    2005-11-18

    Sir2 is a conserved deacetylase that modulates life span in yeast, worms, and flies and stress response in mammals. In yeast, Sir2 is required for maintaining replicative life span, and increasing Sir2 dosage can delay replicative aging. We address the role of Sir2 in regulating chronological life span in yeast. Lack of Sir2 along with calorie restriction and/or mutations in the yeast AKT homolog, Sch9, or Ras pathways causes a dramatic chronological life-span extension. Inactivation of Sir2 causes uptake and catabolism of ethanol and upregulation of many stress-resistance and sporulation genes. These changes while sufficient to extend chronological life span in wild-type yeast require severe calorie restriction or additional mutations to extend life span of sir2Delta mutants. Our results demonstrate that effects of SIR2 on chronological life span are opposite to replicatve life span and suggest that the relevant activities of Sir2-like deacetylases may also be complex in higher eukaryotes.

  12. Essential role for autophagy in life span extension

    PubMed Central

    Madeo, Frank; Zimmermann, Andreas; Maiuri, Maria Chiara; Kroemer, Guido

    2015-01-01

    Life and health span can be prolonged by calorie limitation or by pharmacologic agents that mimic the effects of caloric restriction. Both starvation and the genetic inactivation of nutrient signaling converge on the induction of autophagy, a cytoplasmic recycling process that counteracts the age-associated accumulation of damaged organelles and proteins as it improves the metabolic fitness of cells. Here we review experimental findings indicating that inhibition of the major nutrient and growth-related signaling pathways as well as the upregulation of anti-aging pathways mediate life span extension via the induction of autophagy. Furthermore, we discuss mounting evidence suggesting that autophagy is not only necessary but, at least in some cases, also sufficient for increasing longevity. PMID:25654554

  13. ω-6 Polyunsaturated fatty acids extend life span through the activation of autophagy.

    PubMed

    O'Rourke, Eyleen J; Kuballa, Petric; Xavier, Ramnik; Ruvkun, Gary

    2013-02-15

    Adaptation to nutrient scarcity depends on the activation of metabolic programs to efficiently use internal reserves of energy. Activation of these programs in abundant food regimens can extend life span. However, the common molecular and metabolic changes that promote adaptation to nutritional stress and extend life span are mostly unknown. Here we present a response to fasting, enrichment of ω-6 polyunsaturated fatty acids (PUFAs), which promotes starvation resistance and extends Caenorhabditis elegans life span. Upon fasting, C. elegans induces the expression of a lipase, which in turn leads to an enrichment of ω-6 PUFAs. Supplementing C. elegans culture media with these ω-6 PUFAs increases their resistance to starvation and extends their life span in conditions of food abundance. Supplementation of C. elegans or human epithelial cells with these ω-6 PUFAs activates autophagy, a cell recycling mechanism that promotes starvation survival and slows aging. Inactivation of C. elegans autophagy components reverses the increase in life span conferred by supplementing the C. elegans diet with these fasting-enriched ω-6 PUFAs. We propose that the salubrious effects of dietary supplementation with ω-3/6 PUFAs (fish oils) that have emerged from epidemiological studies in humans may be due to a similar activation of autophagic programs.

  14. Low auxotrophy-complementing amino acid concentrations reduce yeast chronological life span.

    PubMed

    Gomes, Pedro; Sampaio-Marques, Belém; Ludovico, Paula; Rodrigues, Fernando; Leão, Cecília

    2007-01-01

    In the yeast Saccharomyces cerevisiae, interventions resembling caloric restriction, either by reduction of glucose or non-essential amino acid content in the medium, prolong life span and retard aging. Here we have examined the role of auxotrophy-complementing amino acid supplementation of S. cerevisiae strains in determining yeast chronological life span and stress resistance. The results obtained from cells cultured in standard amino acid concentrations revealed a reduced final biomass yield and premature aging phenotypes. These included shorter life span and indicators of oxidative stress, together with a G2/M cell cycle arrest and the appearance of a sub-G0/G1 population pointing to the occurrence of a specific cell death programme under starvation of essential amino acids. In order to overcome this starvation, five times higher amino acid concentrations were supplied to the medium as has already been commonly used by few laboratories. Such cultures reached more than five-fold higher final biomass yield in stationary phase and the early aging phenotypes were abrogated. Furthermore, in a long-lived yeast strain lacking TOR1, there was no positive effect of amino acid supplementation on longevity. On the contrary, amino acid supply had a positive effect on chronological life span of RAS2 deleted cells. This study may provide novel insights into the role of essential nutrients and their effect on aging process and raises the warning that the positive effects of caloric restriction on life span maybe restricted to non-essential nutrients. Moreover, the severe consequences on cell physiology, life span and stress resistance induced by essential amino acid imbalances presents a note of caution for those still using standard amino acid concentrations for studies with auxotrophic yeast strains.

  15. Effect of deleterious mutations on life span in Drosophila melanogaster.

    PubMed

    Gong, Yi; Thompson, James N; Woodruff, R C

    2006-12-01

    Evolutionary theories of aging assume that the accumulation of deleterious mutations will reduce life span. We tested this assumption in Drosophila melanogaster by a newly designed mating scheme, in which mutations accumulate on the Binscy balancer X chromosome in heterozygous females in the absence of selection and recombination. We found that the life span of Binscy/RY(L) males from this cross decreased faster than the life span of their sibling controls over time in two of three runs, and that there was an age-specific increase in mortality in the Binscy/RY(L) males with time in one of three runs. Therefore, the accumulation of deleterious mutations can decrease life span by increasing fragility and can cause age-specific changes in mortality. These results support the evolutionary theory of aging.

  16. A Motivational Theory of Life-Span Development

    PubMed Central

    Heckhausen, Jutta; Wrosch, Carsten; Schulz, Richard

    2010-01-01

    This article had four goals. First, the authors identified a set of general challenges and questions that a life-span theory of development should address. Second, they presented a comprehensive account of their Motivational Theory of Life-Span Development. They integrated the model of optimization in primary and secondary control and the action-phase model of developmental regulation with their original life-span theory of control to present a comprehensive theory of development. Third, they reviewed the relevant empirical literature testing key propositions of the Motivational Theory of Life-Span Development. Finally, because the conceptual reach of their theory goes far beyond the current empirical base, they pointed out areas that deserve further and more focused empirical inquiry. PMID:20063963

  17. 78. VIEW SHOWING PLACEMENT OF LIFE SPAN SHOE ON PIER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    78. VIEW SHOWING PLACEMENT OF LIFE SPAN SHOE ON PIER 6, LOOKING NORTH, March 5, 1935 - Sacramento River Bridge, Spanning Sacramento River at California State Highway 275, Sacramento, Sacramento County, CA

  18. Human Needs: A Literature Review and Cognitive Life Span Model

    DTIC Science & Technology

    1992-04-01

    needs, they fail to address how needs change across the life span. Life span developmental psychologists (e.g., Erikson , Levinson) have proposed that...Erikson’s Theory of Psychosocial Development Erik Erikson’s (1963) influential theory of development proposes that personality develops through a series of...the order that Erikson suggested. Several researchers (e.g., Rosenthal, Gurney, & Moore, 1981) have developed inventories that measure Erikson’s stages

  19. Tequila Regulates Insulin-Like Signaling and Extends Life Span in Drosophila melanogaster.

    PubMed

    Huang, Cheng-Wen; Wang, Horng-Dar; Bai, Hua; Wu, Ming-Shiang; Yen, Jui-Hung; Tatar, Marc; Fu, Tsai-Feng; Wang, Pei-Yu

    2015-12-01

    The aging process is a universal phenomenon shared by all living organisms. The identification of longevity genes is important in that the study of these genes is likely to yield significant insights into human senescence. In this study, we have identified Tequila as a novel candidate gene involved in the regulation of longevity in Drosophila melanogaster. We have found that a hypomorphic mutation of Tequila (Teq(f01792)), as well as cell-specific downregulation of Tequila in insulin-producing neurons of the fly, significantly extends life span. Tequila deficiency-induced life-span extension is likely to be associated with reduced insulin-like signaling, because Tequila mutant flies display several common phenotypes of insulin dysregulation, including reduced circulating Drosophila insulin-like peptide 2 (Dilp2), reduced Akt phosphorylation, reduced body size, and altered glucose homeostasis. These observations suggest that Tequila may confer life-span extension by acting as a modulator of Drosophila insulin-like signaling.

  20. Life-span extension by a metacaspase in the yeast Saccharomyces cerevisiae.

    PubMed

    Hill, Sandra Malmgren; Hao, Xinxin; Liu, Beidong; Nyström, Thomas

    2014-06-20

    Single-cell species harbor ancestral structural homologs of caspase proteases, although the evolutionary benefit of such apoptosis-related proteins in unicellular organisms is unclear. Here, we found that the yeast metacaspase Mca1 is recruited to the insoluble protein deposit (IPOD) and juxtanuclear quality-control compartment (JUNQ) during aging and proteostatic stress. Elevating MCA1 expression counteracted accumulation of unfolded proteins and aggregates and extended life span in a heat shock protein Hsp104 disaggregase- and proteasome-dependent manner. Consistent with a role in protein quality control, genetic interaction analysis revealed that MCA1 buffers against deficiencies in the Hsp40 chaperone YDJ1 in a caspase cysteine-dependent manner. Life-span extension and aggregate management by Mca1 was only partly dependent on its conserved catalytic cysteine, which suggests that Mca1 harbors both caspase-dependent and independent functions related to life-span control.

  1. Relationship between heat shock protein 70 expression and life span in Daphnia.

    PubMed

    Schumpert, Charles; Handy, Indhira; Dudycha, Jeffry L; Patel, Rekha C

    2014-07-01

    The longevity of an organism is directly related to its ability to effectively cope with cellular stress. Heat shock response (HSR) protects the cells against accumulation of damaged proteins after exposure to elevated temperatures and also in aging cells. To understand the role of Hsp70 in regulating life span of Daphnia, we examined the expression of Hsp70 in two ecotypes that exhibit strikingly different life spans. Daphnia pulicaria, the long lived ecotype, showed a robust Hsp70 induction as compared to the shorter lived Daphnia pulex. Interestingly, the short-lived D. pulex isolates showed no induction of Hsp70 at the mid point in their life span. In contrast to this, the long-lived D. pulicaria continued to induce Hsp70 expression at an equivalent age. We further show that the Hsp70 expression was induced at transcriptional level in response to heat shock. The transcription factor responsible for Hsp70 induction, heat shock factor-1 (HSF-1), although present in aged organisms did not exhibit DNA-binding capability. Thus, the decline of Hsp70 induction in old organisms could be attributed to a decline in HSF-1's DNA-binding activity. These results for the first time, present a molecular analysis of the relationship between HSR and life span in Daphnia.

  2. Adaptive prolonged postreproductive life span in killer whales.

    PubMed

    Foster, Emma A; Franks, Daniel W; Mazzi, Sonia; Darden, Safi K; Balcomb, Ken C; Ford, John K B; Croft, Darren P

    2012-09-14

    Prolonged life after reproduction is difficult to explain evolutionarily unless it arises as a physiological side effect of increased longevity or it benefits related individuals (i.e., increases inclusive fitness). There is little evidence that postreproductive life spans are adaptive in nonhuman animals. By using multigenerational records for two killer whale (Orcinus orca) populations in which females can live for decades after their final parturition, we show that postreproductive mothers increase the survival of offspring, particularly their older male offspring. This finding may explain why female killer whales have evolved the longest postreproductive life span of all nonhuman animals.

  3. Target of rapamycin signaling regulates metabolism, growth, and life span in Arabidopsis.

    PubMed

    Ren, Maozhi; Venglat, Prakash; Qiu, Shuqing; Feng, Li; Cao, Yongguo; Wang, Edwin; Xiang, Daoquan; Wang, Jinghe; Alexander, Danny; Chalivendra, Subbaiah; Logan, David; Mattoo, Autar; Selvaraj, Gopalan; Datla, Raju

    2012-12-01

    Target of Rapamycin (TOR) is a major nutrition and energy sensor that regulates growth and life span in yeast and animals. In plants, growth and life span are intertwined not only with nutrient acquisition from the soil and nutrition generation via photosynthesis but also with their unique modes of development and differentiation. How TOR functions in these processes has not yet been determined. To gain further insights, rapamycin-sensitive transgenic Arabidopsis thaliana lines (BP12) expressing yeast FK506 Binding Protein12 were developed. Inhibition of TOR in BP12 plants by rapamycin resulted in slower overall root, leaf, and shoot growth and development leading to poor nutrient uptake and light energy utilization. Experimental limitation of nutrient availability and light energy supply in wild-type Arabidopsis produced phenotypes observed with TOR knockdown plants, indicating a link between TOR signaling and nutrition/light energy status. Genetic and physiological studies together with RNA sequencing and metabolite analysis of TOR-suppressed lines revealed that TOR regulates development and life span in Arabidopsis by restructuring cell growth, carbon and nitrogen metabolism, gene expression, and rRNA and protein synthesis. Gain- and loss-of-function Ribosomal Protein S6 (RPS6) mutants additionally show that TOR function involves RPS6-mediated nutrition and light-dependent growth and life span in Arabidopsis.

  4. Families and Drugs: A Life-Span Research Approach.

    ERIC Educational Resources Information Center

    Glynn, Thomas J.

    The study of human development and behavior from a life-span perspective is an area of growing interest, and the family is a natural laboratory for this study. Research in the area of drug abuse demonstrates that drug use is not limited to any one population segment or age group, but is pervasive across population subgroups. More and more evidence…

  5. Neuromodulation of Behavioral and Cognitive Development across the Life Span

    ERIC Educational Resources Information Center

    Li, Shu-Chen

    2012-01-01

    Among other mechanisms, behavioral and cognitive development entail, on the one hand, contextual scaffolding and, on the other hand, neuromodulation of adaptive neurocognitive representations across the life span. Key brain networks underlying cognition, emotion, and motivation are innervated by major transmitter systems (e.g., the catecholamines…

  6. Life span extension in Drosophila melanogaster induced by morphine.

    PubMed

    Dubiley, Tatyana A; Rushkevich, Yury E; Koshel, Natalya M; Voitenko, Vladimir P; Vaiserman, Alexander M

    2011-06-01

    The influence of morphine on the life span of Drosophila melanogaster fruit flies has been investigated. Morphine hydrochloride (MH) at concentrations of 0.01, 0.05 and 0.25 mg/ml was added to a medium starting from day 5 or 54 of imaginal life. Supplementation with MH starting from day 5 of imaginal life has resulted in significant increases in the mean life span of males at all concentrations studied. In females, a significant increase in life span compared with control was obtained only for those treated with 0.25 mg/ml MH. In flies with MH feeding from day 54, residual life span was significantly increased in both males and females after treatment with 0.05 mg/ml MH. The present data, together with those of our earlier study in mice (Dubiley et al. Probl Aging Longvity 9:331–332, 2000) suggest that morphine supplementation can result in life extension in both vertebrate and invertebrate animal species.

  7. Women's Spirituality across the Life Span: Implications for Counseling

    ERIC Educational Resources Information Center

    Briggs, Michele Kielty; Dixon, Andrea L.

    2013-01-01

    Women's spirituality has unique characteristics that are often ignored within the spirituality literature. The authors review the literature on women's spirituality to reveal the major themes women have identified as relevant to their spiritual journeys across the life span. Implications for counseling and ideas for practice are included after…

  8. Exceptional Cognitive Development: A Life Span Developmental Approach.

    ERIC Educational Resources Information Center

    Flom, Peter

    The belief that gifted children are more likely to have personality problems than "normal" individuals is not supported by research, but the image of the disturbed gifted child persists. This paper reviews research from a life-span developmental perspective to examine why this image persists. The paper critically examines the research of L.…

  9. Mitochondria-mediated hormetic response in life span extension of calorie-restricted Saccharomyces cerevisiae.

    PubMed

    Sharma, Praveen Kumar; Agrawal, Vineet; Roy, Nilanjan

    2011-06-01

    Calorie restriction (CR) is the only proven regimen, which confers lifespan extension benefits across the various phyla right from unicellular organisms like yeast to primates. In a bid to elucidate the mechanism of calorie-restriction-mediated life span extension, the role of mitochondria in the process was investigated. In this study, we found that the mitochondrial content in CR cells remains unaltered as compared to cells grown on nonrestricted media. However, mitochondria isolated from CR cells showed increased respiration and elevated reactive oxygen species levels without augmenting adenosine triphosphate (ATP) generation. The antioxidant defense system was amplified in CR mitochondria, and in CR cells a cross protection to hydrogen-peroxide-induced stress was also observed. Moreover, we also documented that a functional electron transport chain was vital for the life span extension benefits of calorie restriction. Altogether, our results indicate that calorie restriction elicits mitohormetic effect, which ultimately leads to longevity benefit.

  10. HSF-1-mediated cytoskeletal integrity determines thermotolerance and life span.

    PubMed

    Baird, Nathan A; Douglas, Peter M; Simic, Milos S; Grant, Ana R; Moresco, James J; Wolff, Suzanne C; Yates, John R; Manning, Gerard; Dillin, Andrew

    2014-10-17

    The conserved heat shock transcription factor-1 (HSF-1) is essential to cellular stress resistance and life-span determination. The canonical function of HSF-1 is to regulate a network of genes encoding molecular chaperones that protect proteins from damage caused by extrinsic environmental stress or intrinsic age-related deterioration. In Caenorhabditis elegans, we engineered a modified HSF-1 strain that increased stress resistance and longevity without enhanced chaperone induction. This health assurance acted through the regulation of the calcium-binding protein PAT-10. Loss of pat-10 caused a collapse of the actin cytoskeleton, stress resistance, and life span. Furthermore, overexpression of pat-10 increased actin filament stability, thermotolerance, and longevity, indicating that in addition to chaperone regulation, HSF-1 has a prominent role in cytoskeletal integrity, ensuring cellular function during stress and aging.

  11. Fundamental frequency changes of Persian speakers across the life span.

    PubMed

    Soltani, Majid; Ashayeri, Hasan; Modarresi, Yahya; Salavati, Mahyar; Ghomashchi, Hamed

    2014-05-01

    This study was designed to investigate changes in fundamental frequency (F0) across the life span in Persian speakers. Four hundred children and adults were asked to produce a sustained phonation of vowel /a/ and their voice samples were studied in 10 age groups. F0 was analyzed using the software Praat (Version 5.1.17.). The results revealed that (1) the mean F0 in both sexes decreases from childhood to adulthood; (2) significant F0 differences between boys and girls begin at the age of 12 years; and (3) the range of F0 changes in the life span is greater in men (178.38 Hz) than in women (113.57 Hz). These findings provide new data for Persian-speaking children, women, and men and could be beneficial for Iranian speech and language pathologists.

  12. Extract of North American ginseng (Panax quinquefolius), administered to leukemic, juvenile mice extends their life span.

    PubMed

    Miller, Sandra C; Delorme, Danielle; Shan, Jacqueline J

    2011-01-01

    In a recent study involving normal, juvenile mice, we showed that CVT-E002, a proprietary extract (Afexa Life Sciences, Inc.) of North American ginseng, Panax quinquefolius, significantly enhanced the absolute levels of cells acting at the first line of defense in tumor combat, i.e., natural killer (NK) cells. The present study evaluated the effect of CVT-E002, on life span when administered intraperitoneally to leukemic, infant/juvenile mice. The extract was administered to groups of mice daily for 14 days in several dosing groups up to 50mg/day from age 7 to 21 days. The tumor was administered intraperitoneally under sterile conditions, in a laminar flow hood at 7 days of age (0.5 x 10(6) leukemic cells), immediately preceding the first CVT-E002 injection for each dose group. The data revealed that CVT-E002 significantly extends the life of leukemic, young mice in a dose-specific manner, i.e., 20 mg/day was effective in extending life, while lower doses of 5, 10 mg as well as higher doses of 30, 40, 50 mg per day were completely ineffective. We have already shown that CVT-E002 significantly elevates NK cells in normal and leukemic, adult mice, as well as in normal, infant/juvenile mice, and we have also shown that CVT-E002 significantly extends the life span of leukemic, adult mice. The results of the present study did indeed show that (i) CVT-E002 extends the life span of leukemic, infant/juvenile mice, and (ii) that the dose of CVT-E002 is critical in achieving life span augmentation in these leukemic infant/juvenile mice.

  13. C. elegans VANG-1 Modulates Life Span via Insulin/IGF-1-Like Signaling

    PubMed Central

    Honnen, Sebastian J.; Büchter, Christian; Schröder, Verena; Hoffmann, Michael; Kohara, Yuji; Kampkötter, Andreas; Bossinger, Olaf

    2012-01-01

    The planar cell polarity (PCP) pathway is highly conserved from Drosophila to humans and a PCP-like pathway has recently been described in the nematode Caenorhabditis elegans. The developmental function of this pathway is to coordinate the orientation of cells or structures within the plane of an epithelium or to organize cell-cell intercalation required for correct morphogenesis. Here, we describe a novel role of VANG-1, the only C. elegans ortholog of the conserved PCP component Strabismus/Van Gogh. We show that two alleles of vang-1 and depletion of the protein by RNAi cause an increase of mean life span up to 40%. Consistent with the longevity phenotype vang-1 animals also show enhanced resistance to thermal- and oxidative stress and decreased lipofuscin accumulation. In addition, vang-1 mutants show defects like reduced brood size, decreased ovulation rate and prolonged reproductive span, which are also related to gerontogenes. The germline, but not the intestine or neurons, seems to be the primary site of vang-1 function. Life span extension in vang-1 mutants depends on the insulin/IGF-1-like receptor DAF-2 and DAF-16/FoxO transcription factor. RNAi against the phase II detoxification transcription factor SKN-1/Nrf2 also reduced vang-1 life span that might be explained by gradual inhibition of insulin/IGF-1-like signaling in vang-1. This is the first time that a key player of the PCP pathway is shown to be involved in the insulin/IGF-1-like signaling dependent modulation of life span in C. elegans. PMID:22359667

  14. Tequila Regulates Insulin-Like Signaling and Extends Life Span in Drosophila melanogaster

    PubMed Central

    Huang, Cheng-Wen; Wang, Horng-Dar; Bai, Hua; Wu, Ming-Shiang; Yen, Jui-Hung; Tatar, Marc; Fu, Tsai-Feng

    2015-01-01

    The aging process is a universal phenomenon shared by all living organisms. The identification of longevity genes is important in that the study of these genes is likely to yield significant insights into human senescence. In this study, we have identified Tequila as a novel candidate gene involved in the regulation of longevity in Drosophila melanogaster. We have found that a hypomorphic mutation of Tequila (Teq f01792), as well as cell-specific downregulation of Tequila in insulin-producing neurons of the fly, significantly extends life span. Tequila deficiency–induced life-span extension is likely to be associated with reduced insulin-like signaling, because Tequila mutant flies display several common phenotypes of insulin dysregulation, including reduced circulating Drosophila insulin-like peptide 2 (Dilp2), reduced Akt phosphorylation, reduced body size, and altered glucose homeostasis. These observations suggest that Tequila may confer life-span extension by acting as a modulator of Drosophila insulin-like signaling. PMID:26265729

  15. Meta-analysis of global metabolomic data identifies metabolites associated with life-span extension.

    PubMed

    Patti, Gary J; Tautenhahn, Ralf; Johannsen, Darcy; Kalisiak, Ewa; Ravussin, Eric; Brüning, Jens C; Dillin, Andrew; Siuzdak, Gary

    2014-08-01

    The manipulation of distinct signaling pathways and transcription factors has been shown to influence life span in a cell-non-autonomous manner in multicellular model organisms such as Caenorhabditis elegans. These data suggest that coordination of whole-organism aging involves endocrine signaling, however, the molecular identities of such signals have not yet been determined and their potential relevance in humans is unknown. Here we describe a novel metabolomic approach to identify molecules directly associated with extended life span in C. elegans that represent candidate compounds for age-related endocrine signals. To identify metabolic perturbations directly linked to longevity, we developed metabolomic software for meta-analysis that enabled intelligent comparisons of multiple different mutants. Simple pairwise comparisons of long-lived glp-1, daf-2, and isp-1 mutants to their respective controls resulted in more than 11,000 dysregulated metabolite features of statistical significance. By using meta-analysis, we were able to reduce this number to six compounds most likely to be associated with life-span extension. Mass spectrometry-based imaging studies suggested that these metabolites might be localized to C. elegans muscle. We extended the metabolomic analysis to humans by comparing quadricep muscle tissue from young and old individuals and found that two of the same compounds associated with longevity in worms were also altered in human muscle with age. These findings provide candidate compounds that may serve as age-related endocrine signals and implicate muscle as a potential tissue regulating their levels in humans.

  16. The social context of managing diabetes across the life span.

    PubMed

    Wiebe, Deborah J; Helgeson, Vicki; Berg, Cynthia A

    2016-10-01

    Diabetes self-management is crucial to maintaining quality of life and preventing long-term complications, and it occurs daily in the context of close interpersonal relationships. This article examines how social relationships are central to meeting the complex demands of managing Type I and Type 2 diabetes across the life span. The social context of diabetes management includes multiple resources, including family (parents, spouses), peers, romantic partners, and health care providers. We discuss how these social resources change across the life span, focusing on childhood and adolescence, emerging adulthood, and adulthood and aging. We review how diabetes both affects and is affected by key social relationships at each developmental period. Despite high variability in how the social context is conceptualized and measured across studies, findings converge on the characteristics of social relationships that facilitate or undermine diabetes management across the life span. These characteristics are consistent with both Interpersonal Theory and Self-Determination Theory, 2 organizing frameworks that we utilize to explore social behaviors that are related to diabetes management. Involvement and support from one's social partners, particularly family members, is consistently associated with good diabetes outcomes when characterized by warmth, collaboration, and acceptance. Underinvolvement and interactions characterized by conflict and criticism are consistently associated with poor diabetes outcomes. Intrusive involvement that contains elements of social control may undermine diabetes management, particularly when it impinges on self-efficacy. Implications for future research directions and for interventions that promote the effective use of the social context to improve diabetes self-management are discussed. (PsycINFO Database Record

  17. Dead or alive: deformed wing virus and Varroa destructor reduce the life span of winter honeybees.

    PubMed

    Dainat, Benjamin; Evans, Jay D; Chen, Yan Ping; Gauthier, Laurent; Neumann, Peter

    2012-02-01

    Elevated winter losses of managed honeybee colonies are a major concern, but the underlying mechanisms remain controversial. Among the suspects are the parasitic mite Varroa destructor, the microsporidian Nosema ceranae, and associated viruses. Here we hypothesize that pathogens reduce the life expectancy of winter bees, thereby constituting a proximate mechanism for colony losses. A monitoring of colonies was performed over 6 months in Switzerland from summer 2007 to winter 2007/2008. Individual dead workers were collected daily and quantitatively analyzed for deformed wing virus (DWV), acute bee paralysis virus (ABPV), N. ceranae, and expression levels of the vitellogenin gene as a biomarker for honeybee longevity. Workers from colonies that failed to survive winter had a reduced life span beginning in late fall, were more likely to be infected with DWV, and had higher DWV loads. Colony levels of infection with the parasitic mite Varroa destructor and individual infections with DWV were also associated with reduced honeybee life expectancy. In sharp contrast, the level of N. ceranae infection was not correlated with longevity. In addition, vitellogenin gene expression was significantly positively correlated with ABPV and N. ceranae loads. The findings strongly suggest that V. destructor and DWV (but neither N. ceranae nor ABPV) reduce the life span of winter bees, thereby constituting a parsimonious possible mechanism for honeybee colony losses.

  18. Homeless Aging Veterans in Transition: A Life-Span Perspective

    PubMed Central

    Thompson, Carla J.; Bridier, Nancy L.

    2013-01-01

    The need for counseling and career/educational services for homeless veterans has captured political and economic venues for more than 25 years. Veterans are three times more likely to become homeless than the general population if veterans live in poverty or are minority veterans. This mixed methods study emphasized a life-span perspective approach for exploring factors influencing normative aging and life-quality of 39 homeless veterans in Alabama and Florida. Seven descriptive quantitative and qualitative research questions framed the investigation. Study participants completed a quantitative survey reflecting their preferences and needs with a subset of the sample (N = 12) also participating in individual qualitative interview sessions. Thirty-two service providers and stakeholders completed quantitative surveys. Empirical and qualitative data with appropriate triangulation procedures provided interpretive information relative to a life-span development perspective. Study findings provide evidence of the need for future research efforts to address strategies that focus on the health and economic challenges of veterans before they are threatened with the possibility of homelessness. Implications of the study findings provide important information associated with the premise that human development occurs throughout life with specific characteristics influencing the individual's passage. Implications for aging/homelessness research are grounded in late-life transitioning and human development intervention considerations. PMID:24286010

  19. Exercise, brain, and cognition across the life span.

    PubMed

    Voss, Michelle W; Nagamatsu, Lindsay S; Liu-Ambrose, Teresa; Kramer, Arthur F

    2011-11-01

    This is a brief review of current evidence for the relationships between physical activity and exercise and the brain and cognition throughout the life span in non-pathological populations. We focus on the effects of both aerobic and resistance training and provide a brief overview of potential neurobiological mechanisms derived from non-human animal models. Whereas research has focused primarily on the benefits of aerobic exercise in youth and young adult populations, there is growing evidence that both aerobic and resistance training are important for maintaining cognitive and brain health in old age. Finally, in these contexts, we point out gaps in the literature and future directions that will help advance the field of exercise neuroscience, including more studies that explicitly examine the effect of exercise type and intensity on cognition, the brain, and clinically significant outcomes. There is also a need for human neuroimaging studies to adopt a more unified multi-modal framework and for greater interaction between human and animal models of exercise effects on brain and cognition across the life span.

  20. IQ and ability across the adult life span.

    PubMed

    Baxendale, Sallie

    2011-07-01

    The experience of cognitive decline can be a potent source of anxiety and concern for many people. While an IQ consistent with estimated optimal levels or previously recorded scores may indicate no significant change in cognitive function, the patient may be accurately reporting a normal age-related deterioration in actual ability. The aim of this article is to chart the age-related changes in intellectual abilities evident on the Wechsler Adult Intelligence Scales-Fourth Edition (WAIS-IV). The norms from the WAIS-IV manual were examined to plot the age-related changes in Full-Scale IQ (FSIQ) and composite scores across the adult life span, while holding actual ability level constant across the age groups. Here we present a graphical representation of the normal cognitive developments and declines in FSIQ, Verbal Comprehension, Perceptual Reasoning, Working Memory, and Processing Speed across the adult life span. This graphical representation provides a rational basis for the identification of atypical profiles/complaints of cognitive deterioration that may require further specialist neuropsychological evaluation. These graphs can be used to provide reassurance for healthy adults with concerns of cognitive decline and as an educative tool for their referring agencies.

  1. Genetic regulation of life span, metabolism, and body weight in Pohn, a new wild-derived mouse strain.

    PubMed

    Yuan, Rong; Flurkey, Kevin; Meng, Qingying; Astle, Mike C; Harrison, David E

    2013-01-01

    Quantitative trait loci (QTL) of longevity identified in human and mouse are significantly colocalized, suggesting that common mechanisms are involved. However, the limited number of strains that have been used in mouse longevity studies undermines the ability to identify longevity genes. We crossed C57BL/6J mice with a new wild-derived strain, Pohn, and identified two life span QTL-Ls1 and Ls2. Interestingly, homologous human longevity QTL colocalize with Ls1. We also defined new QTL for metabolic heat production and body weight. Both phenotypes are significantly correlated with life span. We found that large clone ratio, an in vitro indicator for cellular senescence, is not correlated with life span, suggesting that cell senescence and intrinsic aging are not always associated. Overall, by using Pohn mice, we identified new QTL for longevity-related traits, thus facilitating the exploration of the genetic regulation of aging.

  2. Genetic (Co)Variation for Life Span in Rhabditid Nematodes: Role of Mutation, Selection, and History

    PubMed Central

    Upadhyay, Ambuj; Salomon, Matthew P.; Grigaltchik, Veronica; Baer, Charles F.

    2009-01-01

    The evolutionary mechanisms maintaining genetic variation in life span, particularly post-reproductive life span, are poorly understood. We characterized the effects of spontaneous mutations on life span in the rhabditid nematodes Caenorhabditis elegans and C. briggsae and standing genetic variance for life span and correlation of life span with fitness in C. briggsae. Mutations decreased mean life span, a signature of directional selection. Mutational correlations between life span and fitness were consistently positive. The average selection coefficient against new mutations in C. briggsae was approximately 2% when homozygous. The pattern of phylogeographic variation in life span is inconsistent with global mutation–selection balance (MSB), but MSB appears to hold at the local level. Standing genetic correlations in C. briggsae reflect mutational correlations at a local scale but not at a broad phylogeographic level. At the local scale, results are broadly consistent with predictions of the “mutation accumulation” hypothesis for the evolution of aging. PMID:19671885

  3. 7 CFR 701.37 - Loss of control of the property during the practice life span.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... life span. 701.37 Section 701.37 Agriculture Regulations of the Department of Agriculture (Continued... THIS PART General § 701.37 Loss of control of the property during the practice life span. In the event... during the practice life-span, if the person or legal entity acquiring control elects not to become...

  4. 7 CFR 701.37 - Loss of control of the property during the practice life span.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... life span. 701.37 Section 701.37 Agriculture Regulations of the Department of Agriculture (Continued... THIS PART General § 701.37 Loss of control of the property during the practice life span. In the event... during the practice life-span, if the person or legal entity acquiring control elects not to become...

  5. 7 CFR 701.37 - Loss of control of the property during the practice life span.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... life span. 701.37 Section 701.37 Agriculture Regulations of the Department of Agriculture (Continued... THIS PART General § 701.37 Loss of control of the property during the practice life span. In the event... during the practice life-span, if the person or legal entity acquiring control elects not to become...

  6. 7 CFR 701.37 - Loss of control of the property during the practice life span.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... life span. 701.37 Section 701.37 Agriculture Regulations of the Department of Agriculture (Continued... the property during the practice life span. In the event of voluntary or involuntary loss of control of the land by the ECP cost-share recipient during the practice life-span, if the person...

  7. 7 CFR 701.37 - Loss of control of the property during the practice life span.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... life span. 701.37 Section 701.37 Agriculture Regulations of the Department of Agriculture (Continued... THIS PART General § 701.37 Loss of control of the property during the practice life span. In the event... during the practice life-span, if the person or legal entity acquiring control elects not to become...

  8. Ascorbic acid extends replicative life span of human embryonic fibroblast by reducing DNA and mitochondrial damages.

    PubMed

    Hwang, Won-Sang; Park, Seong-Hoon; Kim, Hyun-Seok; Kang, Hong-Jun; Kim, Min-Ju; Oh, Soo-Jin; Park, Jae-Bong; Kim, Jaebong; Kim, Sung Chan; Lee, Jae-Yong

    2007-01-01

    Ascorbic acid has been reported to extend replicative life span of human embryonic fibroblast (HEF). Since the detailed molecular mechanism of this phenomenon has not been investigated, we attempted to elucidate. Continuous treatment of HEF cells with ascorbic acid (at 200 microM) from 40 population doubling (PD) increased maximum PD numbers by 18% and lowered SA-beta-gal positive staining, an aging marker, by 2.3 folds, indicating that ascorbic acid extends replicative life span of HEF cells. Ascorbic acid treatment lowered DCFH by about 7 folds and Rho123 by about 70%, suggesting that ascorbic acid dramatically decreased ROS formation. Ascorbic acid also increased aconitase activity, a marker of mitochondrial aging, by 41%, indicating that ascorbic acid treatment restores age-related decline of mitochondrial function. Cell cycle analysis by flow cytometry revealed that ascorbic acid treatment decreased G1 population up to 12%. Further western blot analysis showed that ascorbic acid treatment decreased levels of p53, phospho-p53 at ser 15, and p21, indicating that ascorbic acid relieved senescence-related G1 arrest. Analysis of AP (apurinic/apyrimidinic) sites showed that ascorbic acid treatment decreased AP site formation by 35%. We also tested the effect of hydrogen peroxide treatment, as an additional oxidative stress. Continuous treatment of 20 microM of hydrogen peroxide from PD 40 of HEF cells resulted in premature senescence due to increased ROS level, and increased AP sites. Taken together, the results suggest that ascorbic acid extends replicative life span of HEF cells by reducing mitochondrial and DNA damages through lowering cellular ROS.

  9. Emotional Egocentricity Bias Across the Life-Span

    PubMed Central

    Riva, Federica; Triscoli, Chantal; Lamm, Claus; Carnaghi, Andrea; Silani, Giorgia

    2016-01-01

    In our daily lives, we often have to quickly estimate the emotions of our conspecifics in order to have successful social interactions. While this estimation process seems quite easy when we are ourselves in a neutral or equivalent emotional state, it has recently been shown that in case of incongruent emotional states between ourselves and the others, our judgments can be biased. This phenomenon, introduced to the literature with the term Emotional Egocentricity Bias (EEB), has been found to occur in young adults and, to a greater extent, in children. However, how the EEB changes across the life-span from adolescence to old age has been largely unexplored. In this study, we recruited 114 female participants subdivided in four cohorts (adolescents, young adults, middle-aged adults, older adults) to examine EEB age-related changes. Participants were administered with a recently developed paradigm which, by making use of visuo-tactile stimulation that elicits conflicting feelings in paired participants, allows the valid and reliable exploration of the EEB. Results highlighted a U-shape relation between age and EEB, revealing enhanced emotional egocentricity in adolescents and older adults compared to young and middle-aged adults. These results are in line with the neuroscientific literature which has recently shown that overcoming the EEB is associated with a greater activation of a portion of the parietal lobe, namely the right Supramarginal Gyrus (rSMG). This is an area that reaches full maturation by the end of adolescence and goes through an early decay. Thus, the age-related changes of the EEB could be possibly due to the life-span development of the rSMG. This study is the first one to show the quadratic relation between age and the EEB and set a milestone for further research exploring the neural correlates of the life-span development of the EEB. Future studies are needed in order to generalize these results to the male population and to explore gender

  10. Reduced Ssy1-Ptr3-Ssy5 (SPS) signaling extends replicative life span by enhancing NAD+ homeostasis in Saccharomyces cerevisiae.

    PubMed

    Tsang, Felicia; James, Christol; Kato, Michiko; Myers, Victoria; Ilyas, Irtqa; Tsang, Matthew; Lin, Su-Ju

    2015-05-15

    Attenuated nutrient signaling extends the life span in yeast and higher eukaryotes; however, the mechanisms are not completely understood. Here we identify the Ssy1-Ptr3-Ssy5 (SPS) amino acid sensing pathway as a novel longevity factor. A null mutation of SSY5 (ssy5Δ) increases replicative life span (RLS) by ∼50%. Our results demonstrate that several NAD(+) homeostasis factors play key roles in this life span extension. First, expression of the putative malate-pyruvate NADH shuttle increases in ssy5Δ cells, and deleting components of this shuttle, MAE1 and OAC1, largely abolishes RLS extension. Next, we show that Stp1, a transcription factor of the SPS pathway, directly binds to the promoter of MAE1 and OAC1 to regulate their expression. Additionally, deletion of SSY5 increases nicotinamide riboside (NR) levels and phosphate-responsive (PHO) signaling activity, suggesting that ssy5Δ increases NR salvaging. This increase contributes to NAD(+) homeostasis, partially ameliorating the NAD(+) deficiency and rescuing the short life span of the npt1Δ mutant. Moreover, we observed that vacuolar phosphatase, Pho8, is partially required for ssy5Δ-mediated NR increase and RLS extension. Together, our studies present evidence that supports SPS signaling is a novel NAD(+) homeostasis factor and ssy5Δ-mediated life span extension is likely due to concomitantly increased mitochondrial and vacuolar function. Our findings may contribute to understanding the molecular basis of NAD(+) metabolism, cellular life span, and diseases associated with NAD(+) deficiency and aging.

  11. Memory plasticity across the life span: uncovering children's latent potential.

    PubMed

    Brehmer, Yvonne; Li, Shu-Chen; Müller, Viktor; von Oertzen, Timo; Lindenberger, Ulman

    2007-03-01

    Memory plasticity, or the ability to improve one's memory performance through instruction and training, is known to decline during adulthood. However, direct comparisons among middle childhood, adulthood, and old age are lacking. The authors examined memory plasticity in an age-comparative multisession training study. One hundred and eight participants ages 9-10, 11-12, 20-25, and 65-78 years learned and practiced an imagery-based mnemonic technique to encode and retrieve words by location cues. Individuals of all ages were able to acquire and optimize use of the technique. Older adults and children showed similar baseline performance and improvement through mnemonic instruction. However, in line with tenets from life-span psychology (P. B. Baltes, 1987), children profited more from mnemonic practice and reached higher levels of final performance than did older adults.

  12. Life span extension of Caenorhabditis elegans by novel pyridoperimidine derivative.

    PubMed

    Sayed, Ahmed A R; El-Shaieb, Kamal M; Mourad, Aboul-Fetouh E

    2012-01-01

    Zwitterions formed from the addition of triphenylphosphine to dialky acetylene-dicarboxylates attack the nucleus of both 1H-perimidine (1) and 1H-benzo[d]imidazole (9) to form novel pyrido[1,2,3-cd]perimidine and imidazo[4,5,1-ij]quinoline derivatives in moderate yields (64-72%). The biological activity of the products has been studied. Compound 3a was found to extend life span of wild type Caenorhabditis elegans under standard laboratory conditions. Both heat stress and induced chemical stress resistance of wild type C. elegans were improved in a reverse dose-dependent manner due to 3a treatment. In addition, treatment of worms with compound 3a significantly attenuated the formation of advanced glycation end products in a reverse dose-dependent manner.

  13. eRapa Restores A Normal Life Span in a FAP Mouse Model

    PubMed Central

    Hasty, Paul; Livi, Carolina B.; Dodds, Sherry G.; Jones, Diane; Strong, Randy; Javors, Martin; Fischer, Kathleen E.; Sloane, Lauren; Murthy, Kruthi; Hubbard, Gene; Sun, Lishi; Hurez, Vincent; Curiel, Tyler J.; Sharp, Zelton Dave

    2014-01-01

    Mutation of a single copy of the adenomatous polyposis coli (APC) gene results in familial adenomatous polyposis (FAP), which confers an extremely high risk for colon cancer. ApcMin/+ mice exhibit multiple intestinal neoplasia (MIN) that causes anemia and death from bleeding by 6 months. Mechanistic target of rapamycin complex 1 (mTORC1) inhibitors were shown to improve ApcMin/+ mouse survival when administered by oral gavage or added directly to the chow, but these mice still died from neoplasia well short of a natural life span. The National Institute of Aging Intervention Testing Program showed that enterically targeted rapamycin (eRapa) extended life span for wild type genetically heterogeneous mice in part by inhibiting age-associated cancer. We hypothesized that eRapa would be effective in preventing neoplasia and extend survival of ApcMin/+ mice. We show that eRapa improved survival for ApcMin/+ mice in a dose-dependent manner. Remarkably, and in contrast to previous reports, most of the ApcMin/+ mice fed 42 ppm eRapa lived beyond the median life span reported for wild type syngeneic mice. Furthermore, chronic eRapa did not cause detrimental immune effects in mouse models of cancer, infection or autoimmunity; thus, assuaging concerns that chronic rapamycin treatment suppresses immunity. Our studies suggest that a novel formulation (enteric targeting) of a well-known and widely used drug (rapamycin) can dramatically improve its efficacy in targeted settings. eRapa or other mTORC1 inhibitors could serve as effective cancer preventatives for people with FAP without suppressing the immune system, thus reducing the dependency on surgery as standard therapy. PMID:24282255

  14. Life-span cognitive activity, neuropathologic burden, and cognitive aging

    PubMed Central

    Boyle, Patricia A.; Yu, Lei; Barnes, Lisa L.; Schneider, Julie A.; Bennett, David A.

    2013-01-01

    Objective: To test the hypothesis that cognitive activity across the life span is related to late-life cognitive decline not linked to common neuropathologic disorders. Methods: On enrollment, older participants in a longitudinal clinical-pathologic cohort study rated late-life (i.e., current) and early-life participation in cognitively stimulating activities. After a mean of 5.8 years of annual cognitive function testing, 294 individuals had died and undergone neuropathologic examination. Chronic gross infarcts, chronic microscopic infarcts, and neocortical Lewy bodies were identified, and measures of β-amyloid burden and tau-positive tangle density in multiple brain regions were derived. Results: In a mixed-effects model adjusted for age at death, sex, education, gross and microscopic infarction, neocortical Lewy bodies, amyloid burden, and tangle density, more frequent late-life cognitive activity (estimate = 0.028, standard error [SE] = 0.008, p < 0.001) and early-life cognitive activity (estimate = 0.034, SE = 0.013, p = 0.008) were each associated with slower cognitive decline. The 2 measures together accounted for 14% of the residual variability in cognitive decline not related to neuropathologic burden. The early-life–activity association was attributable to cognitive activity in childhood (estimate = 0.027, SE = 0.012, p = 0.026) and middle age (estimate = 0.029, SE = 0.013, p = 0.025) but not young adulthood (estimate = −0.020, SE = 0.014, p = 0.163). Conclusions: More frequent cognitive activity across the life span has an association with slower late-life cognitive decline that is independent of common neuropathologic conditions, consistent with the cognitive reserve hypothesis. PMID:23825173

  15. Knock out of the NADPH oxidase Nox4 has no impact on life span in mice.

    PubMed

    Rezende, Flavia; Schürmann, Christoph; Schütz, Susanne; Harenkamp, Sabine; Herrmann, Eva; Seimetz, Michael; Weißmann, Norbert; Schröder, Katrin

    2017-04-01

    The free radical theory of aging suggests reactive oxygen species as a main reason for accumulation of damage events eventually leading to aging. Nox4, a member of the family of NADPH oxidases constitutively produces ROS and therefore has the potential to be a main driver of aging. Herein we analyzed the life span of Nox4 deficient mice and found no difference when compared to their wildtype littermates. Accordingly neither Tert expression nor telomere length was different in cells isolated from those animals. In fact, Nox4 mRNA expression in lungs of wildtype mice dropped with age. We conclude that Nox4 has no influence on lifespan of healthy mice.

  16. Shorter Life Span of Microorganisms and Plants as a Consequence of Shielded Magnetic Environment

    NASA Astrophysics Data System (ADS)

    Dobrota, C.; Piso, I. M.; Bathory, D.

    The geomagnetic field is an essential environmental factor for life and health on this planet. In order to survey how magnetic fields affect the life span and the nitrogenase (an iron-sulphur enzyme) activity of Azotobacter chroococcum as well as the life span, the main organic synthesis and the water balance of plants (22 species), the biological tests were incubated under shielded magnetic field and also in normal geo-magnetic environment. The shielding level was about 10-6 of the terrestrial magnetic field.Life cycles of all organisms require the co-ordinated control of a complex set of interlocked physiological processes and metabolic pathways. Such processes are likely to be regulated by a large number of genes. Our researches suggest that the main point in biological structures, which seems to be affected by the low magnetic environment, is the water molecule. Magnetic field induces a molecular alignment. Under shielded conditions, unstructured water molecules with fewer hydrogen bonds, which are producing a more reactive environment, are occurring. As compared to control, the life span of both microorganisms and plants was shorter in shielded environment. A higher nitrogenase affinity for the substrate was recorded in normal geo-magnetic field compared to low magnetic field. The synthesis of carbohydrates, lipids, proteins and enzymes was modified under experimental conditions. The stomatal conductance was higher between 158 and 300% in shielded environment indicating an important water loss from the plant cells.Our results support the idea that the shielded magnetic environment induces different reactions depending on the time of exposure and on the main metabolic pathways of the cells.

  17. Increased iron supplied through Fet3p results in replicative life span extension of Saccharomyces cerevisiae under conditions requiring respiratory metabolism.

    PubMed

    Botta, Gabriela; Turn, Christina S; Quintyne, Nicholas J; Kirchman, Paul A

    2011-10-01

    We have previously shown that copper supplementation extends the replicative life span of Saccharomyces cerevisiae when grown under conditions forcing cells to respire. We now show that copper's effect on life span is through Fet3p, a copper containing enzyme responsible for high affinity transport of iron into yeast cells. Life span extensions can also be obtained by supplementing the growth medium with 1mM ferric chloride. Extension by high iron levels is still dependent on the presence of Fet3p. Life span extension by iron or copper requires growth on media containing glycerol as the sole carbon source, which forces yeast to respire. Yeast grown on glucose containing media supplemented with iron show no extension of life span. The iron associated with cells grown in media supplemented with copper or iron is 1.4-1.8 times that of cells grown without copper or iron supplementation. As with copper supplementation, iron supplementation partially rescues the life span of superoxide dismutase mutants. Cells grown with copper supplementation display decreased production of superoxide as measured by dihydroethidium staining.

  18. The life span-prolonging effect of sirtuin-1 is mediated by autophagy.

    PubMed

    Morselli, Eugenia; Maiuri, Maria Chiara; Markaki, Maria; Megalou, Evgenia; Pasparaki, Angela; Palikaras, Konstantinos; Criollo, Alfredo; Galluzzi, Lorenzo; Malik, Shoaib Ahmad; Vitale, Ilio; Michaud, Mickael; Madeo, Frank; Tavernarakis, Nektarios; Kroemer, Guido

    2010-01-01

    The life span of various model organisms can be extended by caloric restriction as well as by autophagy-inducing pharmacological agents. Life span-prolonging effects have also been observed in yeast cells, nematodes and flies upon the overexpression of the deacetylase Sirtuin-1. Intrigued by these observations and by the established link between caloric restriction and Sirtuin-1 activation, we decided to investigate the putative implication of Sirtuin-1 in the response of human cancer cells and Caenorhabditis elegans to multiple triggers of autophagy. Our data indicate that the activation of Sirtuin-1 (by the pharmacological agent resveratrol and/or genetic means) per se ignites autophagy, and that Sirtuin-1 is required for the autophagic response to nutrient deprivation, in both human and nematode cells, but not for autophagy triggered by downstream signals such as the inhibition of mTOR or p53. Since the life spanextending effects of Sirtuin-1 activators are lost in autophagy-deficient C. elegans, our results suggest that caloric restriction and resveratrol extend longevity, at least in experimental settings, by activating autophagy.

  19. Chromosomal aberrations, reproductive success, life span, and mortality in irradiated Neanthes arenaceodentata (polychaeta)

    SciTech Connect

    Anderson, S.L.; Harrison, F.L.; Chan, G.; Moore, D.H. II

    1987-10-01

    The polychaete worm Neanthes arenaceodentata ws used in experiments to determine possible relationships between short-term genotoxicity tests and reproductive and lethal consequences of exposure to ionizing radiation. Groups of juvenile N. arenaceodentata received one of four different radiation doses (2, 4, 8, and 16 Gy) to determine dose-effect estimates for chromosomal aberration induction, and groups of both adult and juveniles received one of seven different radiation doses (1, 4, 8.4, 46, 102, 500, and 1000 Gy) to determine dose-effect estimates for reproduction, mortality, and life span. Effects on reproduction and genetic material were observed at the lowest doses and in the same range; detrimental reproductive effects were observed at 1 to 4 Gy, and the frequency of chromosomal aberrations were significantly increased at 2 Gy. Only high doses resulted in acute mortality (>500 Gy) and decreased life span (>100 Gy). Dose-effect estimates for chromosomal aberration induction were dependant on radiation dose and on the stage of the cell cycle at the time of irradiation. Dose-effect estimates for reproduction were dependant on dose and the potential for repopulation of gonadal tissue. Such knowledge is required because factors, such as cell-cycle effects, may modify dose-effect estimates. It is concluded that short-term genotoxicity tests can be predictive of detrimental reproductive effects in those model systems for which basic cell kinetics and reproductive parameters are well known. 4 refs., 11 figs., 13 tabs.

  20. Oxidative Stress Tolerance, Adenylate Cyclase, and Autophagy Are Key Players in the Chronological Life Span of Saccharomyces cerevisiae during Winemaking

    PubMed Central

    Orozco, Helena; Matallana, Emilia

    2012-01-01

    Most grape juice fermentation takes place when yeast cells are in a nondividing state called the stationary phase. Under such circumstances, we aimed to identify the genetic determinants controlling longevity, known as the chronological life span. We identified commercial strains with both short (EC1118) and long (CSM) life spans in laboratory growth medium and compared them under diverse conditions. Strain CSM shows better tolerance to stresses, including oxidative stress, in the stationary phase. This is reflected during winemaking, when this strain has an increased maximum life span. Compared to EC1118, CSM overexpresses a mitochondrial rhodanese gene-like gene, RDL2, whose deletion leads to increased reactive oxygen species production at the end of fermentation and a correlative loss of viability at this point. EC1118 shows faster growth and higher expression of glycolytic genes, and this is related to greater PKA activity due to the upregulation of the adenylate cyclase gene. This phenotype has been linked to the presence of a δ element in its promoter, whose removal increases the life span. Finally, EC1118 exhibits a higher level of protein degradation by autophagy, which might help achieve fast growth at the expense of cellular structures and may be relevant for long-term survival under winemaking conditions. PMID:22327582

  1. Childhood Self-Control and Unemployment Throughout the Life Span

    PubMed Central

    Delaney, Liam; Egan, Mark; Baumeister, Roy F.

    2015-01-01

    The capacity for self-control may underlie successful labor-force entry and job retention, particularly in times of economic uncertainty. Analyzing unemployment data from two nationally representative British cohorts (N = 16,780), we found that low self-control in childhood was associated with the emergence and persistence of unemployment across four decades. On average, a 1-SD increase in self-control was associated with a reduction in the probability of unemployment of 1.4 percentage points after adjustment for intelligence, social class, and gender. From labor-market entry to middle age, individuals with low self-control experienced 1.6 times as many months of unemployment as those with high self-control. Analysis of monthly unemployment data before and during the 1980s recession showed that individuals with low self-control experienced the greatest increases in unemployment during the recession. Our results underscore the critical role of self-control in shaping life-span trajectories of occupational success and in affecting how macroeconomic conditions affect unemployment levels in the population. PMID:25870404

  2. Coping strategies: gender differences and development throughout life span.

    PubMed

    Meléndez, Juan Carlos; Mayordomo, Teresa; Sancho, Patricia; Tomás, José Manuel

    2012-11-01

    Development during life-span implies to cope with stressful events, and this coping may be done with several strategies. It could be useful to know if these coping strategies differ as a consequence of personal characteristics. This work uses the Coping with Stress Questionnaire with this aim using a sample of 400 participants. Specifically, the effects of gender and age group (young people, middle age and elderly), as well as its interaction on coping strategies is studied. With regard to age, on one hand, it is hypothesised a decrement in the use of coping strategies centred in problem solving and social support seeking as age increases. On the other hand, the use of emotional coping is hypothesised to increase with age. With respect to gender, it is hypothesised a larger use of emotional coping and social support seeking within women, and a larger use of problem solving within men. A MANOVA found significant effects for the two main effects (gender and age) as well as several interactions. Separate ANOVAs allowed us to test for potential differences in each of the coping strategies measured in the CAE. These results partially supported the hypotheses. Results are discussed in relation to scientific literature on coping, age and gender.

  3. Programmed life span in the context of evolvability.

    PubMed

    Mitteldorf, Joshua; Martins, André C R

    2014-09-01

    Population turnover is necessary for progressive evolution. In the context of a niche with fixed carrying capacity, aging contributes to the rate of population turnover. Theoretically, a population in which death is programmed on a fixed schedule can evolve more rapidly than one in which population turnover is left to a random death rate. Could aging evolve on this basis? Quantitative realization of this idea is problematic, since the short-term individual fitness cost is likely to eliminate any hypothetical gene for programmed death before the long-term benefit can be realized. In 2011, one of us proposed the first quantitative model based on this mechanism that robustly evolves a finite, programmed life span. That model was based on a viscous population in a rapidly changing environment. Here, we strip this model to its essence and eliminate the assumption of environmental change. We conclude that there is no obvious way in which this model is unrealistic, and that it may indeed capture an important principle of nature's workings. We suggest aging may be understood within the context of the emerging science of evolvability.

  4. The Life Span Model of Suicide and Its Neurobiological Foundation

    PubMed Central

    Ludwig, Birgit; Roy, Bhaskar; Wang, Qingzhong; Birur, Badari; Dwivedi, Yogesh

    2017-01-01

    The very incomprehensibility of the suicidal act has been occupying the minds of researchers and health professionals for a long time. Several theories of suicide have been proposed since the beginning of the past century, and a myriad of neurobiological studies have been conducted over the past two decades in order to elucidate its pathophysiology. Both neurobiology and psychological theories tend to work in parallel lines that need behavioral and empirical data respectively, to confirm their hypotheses. In this review, we are proposing a “Life Span Model of Suicide” with an attempt to integrate the “Stress-Diathesis Model” and the “Interpersonal Model of Suicide” into a neurobiological narrative and support it by providing a thorough compilation of related genetic, epigenetic, and gene expression findings. This proposed model comprises three layers, forming the capability of suicide: genetic factors as the predisposing Diathesis on one side and Stress, characterized by epigenetic marks on the other side, and in between gene expression and gene function which are thought to be influenced by Diathesis and Stress components. The empirical evidence of this model is yet to be confirmed and further research, specifically epigenetic studies in particular, are needed to support the presence of a life-long, evolving capability of suicide and identify its neurobiological correlates. PMID:28261051

  5. Colour constancy across the life span: evidence for compensatory mechanisms.

    PubMed

    Wuerger, Sophie

    2013-01-01

    It is well known that the peripheral visual system declines with age: the yellowing of the lens causes a selective reduction of short-wavelength light and sensitivity losses occur in the cone receptor mechanisms. At the same time, our subjective experience of colour does not change with age. The main purpose of this large-scale study (n = 185) covering a wide age range of colour-normal observers (18-75 years of age) was to assess the extent to which the human visual system is able to compensate for the changes in the optical media and at which level of processing this compensation is likely to occur. We report two main results: (1) Supra-threshold parafoveal colour perception remains largely unaffected by the age-related changes in the optical media (yellowing of the lens) whereas our ability to discriminate between small colour differences is compromised with an increase in age. (2) Significant changes in colour appearance are only found for unique green settings under daylight viewing condition which is consistent with the idea that the yellow-blue mechanism is most affected by an increase in age due to selective attenuation of short-wavelength light. The data on the invariance of hue perception, in conjunction with the age-related decline in chromatic sensitivity, provides evidence for compensatory mechanisms that enable colour-normal human observers a large degree of colour constancy across the life span. These compensatory mechanisms are likely to originate at cortical sites.

  6. Counting the calories: the role of specific nutrients in extension of life span by food restriction.

    PubMed

    Piper, Matthew D W; Mair, William; Partridge, Linda

    2005-05-01

    Reduction of food intake without malnourishment extends life span in many different organisms. The majority of work in this field has been performed in rodents where it has been shown that both restricting access to the entire diet and restricting individual dietary components can cause life-span extension. Thus, for insights into the mode of action of this intervention, it is of great interest to investigate the aspects of diet that are critical for life span extension. Further studies on the mechanisms of how food components modify life span are well suited to the model organism Drosophila melanogaster because of its short life span and ease of handling and containment. Therefore, we summarize practical aspects of implementing dietary restriction in this organism, as well as highlight the major advances already made. Delineation of the nutritional components that are critical for life-span extension will help to reveal the mechanisms by which it operates.

  7. AMPKalpha1 deletion shortens erythrocyte life span in mice: role of oxidative stress.

    PubMed

    Wang, Shaobin; Dale, George L; Song, Ping; Viollet, Benoit; Zou, Ming-Hui

    2010-06-25

    AMP-activated protein kinase (AMPK) is an energy sensor essential for maintaining cellular energy homeostasis. Here, we report that AMPKalpha1 is the predominant isoform of AMPK in murine erythrocytes and mice globally deficient in AMPKalpha1 (AMPKalpha1(-/-)), but not in those lacking AMPKalpha2, and the mice had markedly enlarged spleens with dramatically increased proportions of Ter119-positive erythroid cells. Blood tests revealed significantly decreased erythrocyte and hemoglobin levels with increased reticulocyte counts and elevated plasma erythropoietin concentrations in AMPKalpha1(-/-) mice. The life span of erythrocytes from AMPKalpha1(-/-) mice was less than that in wild-type littermates, and the levels of reactive oxygen species and oxidized proteins were significantly increased in AMPKalpha1(-/-) erythrocytes. In keeping with the elevated oxidative stress, treatment of AMPKalpha1(-/-) mice with the antioxidant, tempol, resulted in decreased reticulocyte counts and improved erythrocyte survival. Furthermore, the expression of Foxo3 and reactive oxygen species scavenging enzymes was significantly decreased in erythroblasts from AMPKalpha1(-/-) mice. Collectively, these results establish an essential role for AMPKalpha1 in regulating oxidative stress and life span in erythrocytes.

  8. CALHM1 Deletion in Mice Affects Glossopharyngeal Taste Responses, Food Intake, Body Weight, and Life Span.

    PubMed

    Hellekant, Göran; Schmolling, Jared; Marambaud, Philippe; Rose-Hellekant, Teresa A

    2015-07-01

    Stimulation of Type II taste receptor cells (TRCs) with T1R taste receptors causes sweet or umami taste, whereas T2Rs elicit bitter taste. Type II TRCs contain the calcium channel, calcium homeostasis modulator protein 1 (CALHM1), which releases adenosine triphosphate (ATP) transmitter to taste fibers. We have previously demonstrated with chorda tympani nerve recordings and two-bottle preference (TBP) tests that mice with genetically deleted Calhm1 (knockout [KO]) have severely impaired perception of sweet, bitter, and umami compounds, whereas their sour and salty tasting ability is unaltered. Here, we present data from KO mice of effects on glossopharyngeal (NG) nerve responses, TBP, food intake, body weight, and life span. KO mice have no NG response to sweet and a suppressed response to bitter compared with control (wild-type [WT]) mice. KO mice showed some NG response to umami, suggesting that umami taste involves both CALHM1- and non-CALHM1-modulated signals. NG responses to sour and salty were not significantly different between KO and WT mice. Behavioral data conformed in general with the NG data. Adult KO mice consumed less food, weighed significantly less, and lived almost a year longer than WT mice. Taken together, these data demonstrate that sweet taste majorly influences food intake, body weight, and life span.

  9. CALHM1 Deletion in Mice Affects Glossopharyngeal Taste Responses, Food Intake, Body Weight, and Life Span

    PubMed Central

    Schmolling, Jared; Marambaud, Philippe; Rose-Hellekant, Teresa A.

    2015-01-01

    Stimulation of Type II taste receptor cells (TRCs) with T1R taste receptors causes sweet or umami taste, whereas T2Rs elicit bitter taste. Type II TRCs contain the calcium channel, calcium homeostasis modulator protein 1 (CALHM1), which releases adenosine triphosphate (ATP) transmitter to taste fibers. We have previously demonstrated with chorda tympani nerve recordings and two-bottle preference (TBP) tests that mice with genetically deleted Calhm1 (knockout [KO]) have severely impaired perception of sweet, bitter, and umami compounds, whereas their sour and salty tasting ability is unaltered. Here, we present data from KO mice of effects on glossopharyngeal (NG) nerve responses, TBP, food intake, body weight, and life span. KO mice have no NG response to sweet and a suppressed response to bitter compared with control (wild-type [WT]) mice. KO mice showed some NG response to umami, suggesting that umami taste involves both CALHM1- and non-CALHM1-modulated signals. NG responses to sour and salty were not significantly different between KO and WT mice. Behavioral data conformed in general with the NG data. Adult KO mice consumed less food, weighed significantly less, and lived almost a year longer than WT mice. Taken together, these data demonstrate that sweet taste majorly influences food intake, body weight, and life span. PMID:25855639

  10. CTT1 overexpression increases life span of calorie-restricted Saccharomyces cerevisiae deficient in Sod1.

    PubMed

    Rona, Germana; Herdeiro, Ricardo; Mathias, Cristiane Juliano; Torres, Fernando Araripe; Pereira, Marcos Dias; Eleutherio, Elis

    2015-06-01

    Studies using different organisms revealed that reducing calorie intake, without malnutrition, known as calorie restriction (CR), increases life span, but its mechanism is still unkown. Using the yeast Saccharomyces cerevisiae as eukaryotic model, we observed that Cu, Zn-superoxide dismutase (Sod1p) is required to increase longevity, as well as to confer protection against lipid and protein oxidation under CR. Old cells of sod1 strain also presented a premature induction of apoptosis. However, when CTT1 (which codes for cytosolic catalase) was overexpressed, sod1 and WT strains showed similar survival rates. Furthermore, CTT1 overexpression decreased lipid peroxidation and delayed the induction of apoptotic process. Superoxide is rapidly converted to hydrogen peroxide by superoxide dismutase, but it also undergoes spontaneous dismutation albeit at a slower rate. However, the quantity of peroxide produced from superoxide in this way is two-fold higher. Peroxide degradation, catalyzed by catalase, is of vital importance, because in the presence of a reducer transition metal peroxide is reduced to the highly reactive hydroxyl radical, which reacts indiscriminately with most cellular constituents. These findings might explain why overexpression of catalase was able to overcome the deficiency of Sod1p, increasing life span in response to CR.

  11. Deleting the 14-3-3 protein Bmh1 extends life span in Saccharomyces cerevisiae by increasing stress response.

    PubMed

    Wang, Chen; Skinner, Craig; Easlon, Erin; Lin, Su-Ju

    2009-12-01

    Enhanced stress response has been suggested to promote longevity in many species. Calorie restriction (CR) and conserved nutrient-sensing target of rapamycin (TOR) and protein kinase A (PKA) pathways have also been suggested to extend life span by increasing stress response, which protects cells from age-dependent accumulation of oxidative damages. Here we show that deleting the yeast 14-3-3 protein, Bmh1, extends chronological life span (CLS) by activating the stress response. 14-3-3 proteins are highly conserved chaperone-like proteins that play important roles in many cellular processes. bmh1Delta-induced heat resistance and CLS extension require the general stress-response transcription factors Msn2, Msn4, and Rim15. The bmh1Delta mutant also displays a decreased reactive oxygen species level and increased heat-shock-element-driven transcription activity. We also show that BMH1 genetically interacts with CR and conserved nutrient-sensing TOR- and PKA-signaling pathways to regulate life span. Interestingly, the level of phosphorylated Ser238 on Bmh1 increases during chronological aging, which is delayed by CR or by reduced TOR activities. In addition, we demonstrate that PKA can directly phosphorylate Ser238 on Bmh1. The status of Bmh1 phosphorylation is therefore likely to play important roles in life-span regulation. Together, our studies suggest that phosphorylated Bmh1 may cause inhibitory effects on downstream longevity factors, including stress-response proteins. Deleting Bmh1 may eliminate the inhibitory effects of Bmh1 on these longevity factors and therefore extends life span.

  12. Angiotensin Converting Enzyme (ACE) Inhibitor Extends Caenorhabditis elegans Life Span.

    PubMed

    Kumar, Sandeep; Dietrich, Nicholas; Kornfeld, Kerry

    2016-02-01

    Animal aging is characterized by progressive, degenerative changes in many organ systems. Because age-related degeneration is a major contributor to disability and death in humans, treatments that delay age-related degeneration are desirable. However, no drugs that delay normal human aging are currently available. To identify drugs that delay age-related degeneration, we used the powerful Caenorhabditis elegans model system to screen for FDA-approved drugs that can extend the adult lifespan of worms. Here we show that captopril extended mean lifespan. Captopril is an angiotensin-converting enzyme (ACE) inhibitor used to treat high blood pressure in humans. To explore the mechanism of captopril, we analyzed the acn-1 gene that encodes the C. elegans homolog of ACE. Reducing the activity of acn-1 extended the mean life span. Furthermore, reducing the activity of acn-1 delayed age-related degenerative changes and increased stress resistance, indicating that acn-1 influences aging. Captopril could not further extend the lifespan of animals with reduced acn-1, suggesting they function in the same pathway; we propose that captopril inhibits acn-1 to extend lifespan. To define the relationship with previously characterized longevity pathways, we analyzed mutant animals. The lifespan extension caused by reducing the activity of acn-1 was additive with caloric restriction and mitochondrial insufficiency, and did not require sir-2.1, hsf-1 or rict-1, suggesting that acn-1 functions by a distinct mechanism. The interactions with the insulin/IGF-1 pathway were complex, since the lifespan extensions caused by captopril and reducing acn-1 activity were additive with daf-2 and age-1 but required daf-16. Captopril treatment and reducing acn-1 activity caused similar effects in a wide range of genetic backgrounds, consistent with the model that they act by the same mechanism. These results identify a new drug and a new gene that can extend the lifespan of worms and suggest new

  13. Boundaries of life: estimating the life span of the biosphere

    NASA Astrophysics Data System (ADS)

    Franck, S.; Bounama, C.; von Bloh, W.

    We present a minimal model for the global carbon cycle of the Earth containing the reservoirs mantle ocean floor continental crust continental biosphere and the Kerogen as well as the aggregated reservoir ocean and atmosphere and obtain reasonable values for the present distribution of carbon in the surface reservoirs of the Earth The Earth system model for the long-term carbon cycle is specified by introducing three different types of biosphere prokaryotes eucaryotes and complex multicellular life They are characterized by different global temperature tolerance windows prokaryotes 2oC 100oC eucaryotes 5oC 45oC complex multicellular life 0oC 30oC From the Archaean to the future there always exists a prokaryotic biosphere 2 Gyr ago eucaryotic life first appears because the global surface temperature reaches the tolerance window for eucaryotes The emergence of complex multicellular life is connected with an explosive increase in biomass and a strong decrease in Cambrian global surface temperature at about 0 54 Gyr ago In the long-term future the three types of biosphere will die out in reverse sequence of their appearance For realistic values of the biotic enhancement of weathering there is no bistability in the future solutions for complex life Therefore complex organisms will not extinct by an implosion in comparison to the Cambrian explosion Eucaryotes and complex life become extinct because of too high surface temperatures in the future The ultimate life span of the biosphere is defined by the extinction of procaryotes in about 1 6 Gyr

  14. The malate-aspartate NADH shuttle components are novel metabolic longevity regulators required for calorie restriction-mediated life span extension in yeast.

    PubMed

    Easlon, Erin; Tsang, Felicia; Skinner, Craig; Wang, Chen; Lin, Su-Ju

    2008-04-01

    Recent studies suggest that increased mitochondrial metabolism and the concomitant decrease in NADH levels mediate calorie restriction (CR)-induced life span extension. The mitochondrial inner membrane is impermeable to NAD (nicotinamide adenine dinucleotide, oxidized form) and NADH, and it is unclear how CR relays increased mitochondrial metabolism to multiple cellular pathways that reside in spatially distinct compartments. Here we show that the mitochondrial components of the malate-aspartate NADH shuttle (Mdh1 [malate dehydrogenase] and Aat1 [aspartate amino transferase]) and the glycerol-3-phosphate shuttle (Gut2, glycerol-3-phosphate dehydrogenase) are novel longevity factors in the CR pathway in yeast. Overexpressing Mdh1, Aat1, and Gut2 extend life span and do not synergize with CR. Mdh1 and Aat1 overexpressions require both respiration and the Sir2 family to extend life span. The mdh1Deltaaat1Delta double mutation blocks CR-mediated life span extension and also prevents the characteristic decrease in the NADH levels in the cytosolic/nuclear pool, suggesting that the malate-aspartate shuttle plays a major role in the activation of the downstream targets of CR such as Sir2. Overexpression of the NADH shuttles may also extend life span by increasing the metabolic fitness of the cells. Together, these data suggest that CR may extend life span and ameliorate age-associated metabolic diseases by activating components of the NADH shuttles.

  15. Poly(ADP-ribose) polymerase activity in mononuclear leukocytes of 13 mammalian species correlates with species-specific life span.

    PubMed Central

    Grube, K; Bürkle, A

    1992-01-01

    Poly(ADP-ribosyl)ation is a eukaryotic posttranslational modification of proteins that is strongly induced by the presence of DNA strand breaks and plays a role in DNA repair and the recovery of cells from DNA damage. We compared poly(ADP-ribose) polymerase (PARP; EC 2.4.2.30) activities in Percoll gradient-purified, permeabilized mononuclear leukocytes from mammalian species of different maximal life span. Saturating concentrations of a double-stranded octameric oligonucleotide were applied to provide a direct and maximal stimulation of PARP. Our results on 132 individuals from 13 different species yield a strong positive correlation between PARP activity and life span (r = 0.84; P << 0.001), with human cells displaying approximately 5 times the activity of rat cells. Intraspecies comparisons with both rat and human cells from donors of all age groups revealed some decline of PARP activity with advancing age, but it was only weakly correlated. No significant polymer degradation was detectable under our assay conditions, ruling out any interference by poly(ADP-ribose) glycohydrolase activity. By Western blot analysis of mononuclear leukocytes from 11 species, using a crossreactive antiserum directed against the extremely well-conserved NAD-binding domain, no correlation between the amount of PARP protein and the species' life spans was found, suggesting a greater specific enzyme activity in longer-lived species. We propose that a higher poly(ADP-ribosyl)ation capacity in cells from long-lived species might contribute to the efficient maintenance of genome integrity and stability over their longer life span. Images PMID:1465394

  16. Implications for Research of a Life-Span Approach to Teacher Development.

    ERIC Educational Resources Information Center

    Sutton, Rosemary E.; Peters, Donald L.

    This paper examines the life-span approach to developmental psychology as it relates to teacher development research and presents some empirical results demonstrating the potential of the approach for increasing understanding of teacher development. Five assumptions of the life-span orientation as applied to the study of teacher development are…

  17. Exploratory and problem-solving consumer behavior across the life span.

    PubMed

    Lesser, J A; Kunkel, S R

    1991-09-01

    Different cognitive functioning, social, and personality changes appear to occur systematically during the adult life span. This article synthesizes research on life span changes in order to develop age-specific models of shopping behavior. The models are tested within a naturalistic field study of shoppers.

  18. The Time of Our Lives: Life Span Development of Timing and Event Tracking

    ERIC Educational Resources Information Center

    McAuley, J. Devin; Jones, Mari Riess; Holub, Shayla; Johnston, Heather M.; Miller, Nathaniel S.

    2006-01-01

    Life span developmental profiles were constructed for 305 participants (ages 4-95) for a battery of paced and unpaced perceptual-motor timing tasks that included synchronize-continue tapping at a wide range of target event rates. Two life span hypotheses, derived from an entrainment theory of timing and event tracking, were tested. A preferred…

  19. Qualitative Exploration of Acculturation and Life-Span Issues of Elderly Asian Americans

    ERIC Educational Resources Information Center

    Lee, Jee Hyang; Heo, Nanseol; Lu, Junfei; Portman, Tarrell Awe Agahe

    2013-01-01

    Awareness of aging issues across diverse populations begins the journey toward counselors becoming culturally competent across client life spans. Understanding the life-span experiences of cultural groups is important for helping professionals. The purpose of this research was to gain insight into the qualitative experiences of Asian American…

  20. The Rate of Source Memory Decline across the Adult Life Span

    ERIC Educational Resources Information Center

    Cansino, Selene; Estrada-Manilla, Cinthya; Hernandez-Ramos, Evelia; Martinez-Galindo, Joyce Graciela; Torres-Trejo, Frine; Gomez-Fernandez, Tania; Ayala-Hernandez, Mariana; Osorio, David; Cedillo-Tinoco, Melisa; Garces-Flores, Lissete; Gomez-Melgarejo, Sandra; Beltran-Palacios, Karla; Guadalupe Garcia-Lazaro, Haydee; Garcia-Gutierrez, Fabiola; Cadena-Arenas, Yadira; Fernandez-Apan, Luisa; Bartschi, Andrea; Resendiz-Vera, Julieta; Rodriguez-Ortiz, Maria Dolores

    2013-01-01

    Previous studies have suggested that the ability to remember contextual information related to specific episodic experiences declines with advancing age; however, the exact moment in the adult life span when this deficit begins is still controversial. Source memory for spatial information was tested in a life span sample of 1,500 adults between…

  1. [Effect of peptide bioregulators and cytokines on life span and age-related changes of hemostasis].

    PubMed

    Khavinson, V Kh; Kuznik, B I; Linkova, N S; Pronyaeva, V E

    2013-01-01

    The review considers literature data and own results of research of cytokines functions and their effects on hemostatic system and life span. The data of age-related changes in the hemostatic system is presented in this article. A big part of the review is devoted to the action of regulatory peptides (RP) on various body systems. It is established that the RP can normalize the expression of cytokine genes in humans and animals with stress and pathological conditions. Effect of RP on the cytokines has geroprotective action, which is based on anti-oxidant, anti-inflammatory action, stimulation of cell proliferation and differentiation, as well as a normalizing effect on the immune system and hemostasis.

  2. Mitochondrial respiratory thresholds regulate yeast chronological life span and its extension by caloric restriction.

    PubMed

    Ocampo, Alejandro; Liu, Jingjing; Schroeder, Elizabeth A; Shadel, Gerald S; Barrientos, Antoni

    2012-07-03

    We have explored the role of mitochondrial function in aging by genetically and pharmacologically modifying yeast cellular respiration production during the exponential and/or stationary growth phases and determining how this affects chronological life span (CLS). Our results demonstrate that respiration is essential during both growth phases for standard CLS, but that yeast have a large respiratory capacity, and only deficiencies below a threshold (~40% of wild-type) significantly curtail CLS. Extension of CLS by caloric restriction also required respiration above a similar threshold during exponential growth and completely alleviated the need for respiration in the stationary phase. Finally, we show that supplementation of media with 1% trehalose, a storage carbohydrate, restores wild-type CLS to respiratory-null cells. We conclude that mitochondrial respiratory thresholds regulate yeast CLS and its extension by caloric restriction by increasing stress resistance, an important component of which is the optimal accumulation and mobilization of nutrient stores.

  3. Altered Lipid Synthesis by Lack of Yeast Pah1 Phosphatidate Phosphatase Reduces Chronological Life Span.

    PubMed

    Park, Yeonhee; Han, Gil-Soo; Mileykovskaya, Eugenia; Garrett, Teresa A; Carman, George M

    2015-10-16

    In Saccharomyces cerevisiae, Pah1 phosphatidate phosphatase, which catalyzes the dephosphorylation of phosphatidate to yield diacylglycerol, plays a crucial role in the synthesis of the storage lipid triacylglycerol. This evolutionarily conserved enzyme also plays a negative regulatory role in controlling de novo membrane phospholipid synthesis through its consumption of phosphatidate. We found that the pah1Δ mutant was defective in the utilization of non-fermentable carbon sources but not in oxidative phosphorylation; the mutant did not exhibit major changes in oxygen consumption rate, mitochondrial membrane potential, F1F0-ATP synthase activity, or gross mitochondrial morphology. The pah1Δ mutant contained an almost normal complement of major mitochondrial phospholipids with some alterations in molecular species. Although oxidative phosphorylation was not compromised in the pah1Δ mutant, the cellular levels of ATP in quiescent cells were reduced by 2-fold, inversely correlating with a 4-fold increase in membrane phospholipids. In addition, the quiescent pah1Δ mutant cells had 3-fold higher levels of mitochondrial superoxide and cellular lipid hydroperoxides, had reduced activities of superoxide dismutase 2 and catalase, and were hypersensitive to hydrogen peroxide. Consequently, the pah1Δ mutant had a shortened chronological life span. In addition, the loss of Tsa1 thioredoxin peroxidase caused a synthetic growth defect with the pah1Δ mutation. The shortened chronological life span of the pah1Δ mutant along with its growth defect on non-fermentable carbon sources and hypersensitivity to hydrogen peroxide was suppressed by the loss of Dgk1 diacylglycerol kinase, indicating that the underpinning of pah1Δ mutant defects was the excess synthesis of membrane phospholipids.

  4. Nup100 regulates Saccharomyces cerevisiae replicative life span by mediating the nuclear export of specific tRNAs.

    PubMed

    Lord, Christopher L; Ospovat, Ophir; Wente, Susan R

    2017-03-01

    Nuclear pore complexes (NPCs), which are composed of nucleoporins (Nups) and regulate transport between the nucleus and cytoplasm, significantly impact the replicative life span (RLS) of Saccharomyces cerevisiae We previously reported that deletion of the nonessential gene NUP100 increases RLS, although the molecular basis for this effect was unknown. In this study, we find that nuclear tRNA accumulation contributes to increased longevity in nup100Δ cells. Fluorescence in situ hybridization (FISH) experiments demonstrate that several specific tRNAs accumulate in the nuclei of nup100Δ mutants. Protein levels of the transcription factor Gcn4 are increased when NUP100 is deleted, and GCN4 is required for the elevated life spans of nup100Δ mutants, similar to other previously described tRNA export and ribosomal mutants. Northern blots indicate that tRNA splicing and aminoacylation are not significantly affected in nup100Δ cells, suggesting that Nup100 is largely required for nuclear export of mature, processed tRNAs. Distinct tRNAs accumulate in the nuclei of nup100Δ and msn5Δ mutants, while Los1-GFP nucleocytoplasmic shuttling is unaffected by Nup100. Thus, we conclude that Nup100 regulates tRNA export in a manner distinct from Los1 or Msn5. Together, these experiments reveal a novel Nup100 role in the tRNA life cycle that impacts the S. cerevisiae life span.

  5. Life span extension and H(2)O(2) resistance elicited by caloric restriction require the peroxiredoxin Tsa1 in Saccharomyces cerevisiae.

    PubMed

    Molin, Mikael; Yang, Junsheng; Hanzén, Sarah; Toledano, Michel B; Labarre, Jean; Nyström, Thomas

    2011-09-02

    Caloric restriction (CR) extends the life span of organisms ranging from yeast to primates. Here, we show that the thiol-dependent peroxiredoxin Tsa1 and its partner sulfiredoxin, Srx1, are required for CR to extend the replicative life span of yeast cells. Tsa1 becomes hyperoxidized/inactive during aging, and CR mitigates such oxidation by elevating the levels of Srx1, which is required to reduce/reactivate hyperoxidized Tsa1. CR, by lowering cAMP-PKA activity, enhances Gcn2-dependent SRX1 translation, resulting in increased resistance to H(2)O(2) and life span extension. Moreover, an extra copy of the SRX1 gene is sufficient to extend the life span of cells grown in high glucose concentrations by 20% in a Tsa1-dependent and Sir2-independent manner. The data demonstrate that Tsa1 is required to ensure yeast longevity and that CR extends yeast life span, in part, by counteracting age-induced hyperoxidation of this peroxiredoxin.

  6. The Influence of Dietary Fat Source on Life Span in Calorie Restricted Mice.

    PubMed

    López-Domínguez, José A; Ramsey, Jon J; Tran, Dianna; Imai, Denise M; Koehne, Amanda; Laing, Steven T; Griffey, Stephen M; Kim, Kyoungmi; Taylor, Sandra L; Hagopian, Kevork; Villalba, José M; López-Lluch, Guillermo; Navas, Plácido; McDonald, Roger B

    2015-10-01

    Calorie restriction (CR) without malnutrition extends life span in several animal models. It has been proposed that a decrease in the amount of polyunsaturated fatty acids (PUFAs), and especially n-3 fatty acids, in membrane phospholipids may contribute to life span extension with CR. Phospholipid PUFAs are sensitive to dietary fatty acid composition, and thus, the purpose of this study was to determine the influence of dietary lipids on life span in CR mice. C57BL/6J mice were assigned to four groups (a 5% CR control group and three 40% CR groups) and fed diets with soybean oil (high in n-6 PUFAs), fish oil (high in n-3 PUFAs), or lard (high in saturated and monounsaturated fatty acids) as the primary lipid source. Life span was increased (p < .05) in all CR groups compared to the Control mice. Life span was also increased (p < .05) in the CR lard mice compared to animals consuming either the CR fish or soybean oil diets. These results indicate that dietary lipid composition can influence life span in mice on CR, and suggest that a diet containing a low proportion of PUFAs and high proportion of monounsaturated and saturated fats may maximize life span in animals maintained on CR.

  7. Blade life span, structural investment, and nutrient allocation in giant kelp.

    PubMed

    Rodriguez, Gabriel E; Reed, Daniel C; Holbrook, Sally J

    2016-10-01

    The turnover of plant biomass largely determines the amount of energy flowing through an ecosystem and understanding the processes that regulate turnover has been of interest to ecologists for decades. Leaf life span theory has proven useful in explaining patterns of leaf turnover in relation to resource availability, but the predictions of this theory have not been tested for macroalgae. We measured blade life span, size, thickness, nitrogen content, pigment content, and maximum photosynthetic rate (P max) in the giant kelp (Macrocystis pyrifera) along a strong resource (light) gradient to test whether the predictions of leaf life span theory applied to this alga. We found that shorter blade life spans and larger blade areas were associated with increased light availability. In addition, nitrogen and P max decreased with blade age, and their decrease was greater in shorter lived blades. These observations are generally consistent with patterns observed for higher plants and the prevailing theory of leaf life span. By contrast, variation observed in pigments of giant kelp was inconsistent with that predicted by leaf life span theory, as blades growing in the most heavily shaded portion of the forest had the lowest chlorophyll content. This result may reflect the dual role of macroalgal blades in carbon fixation and nutrient absorption and the ability of giant kelp to modify blade physiology to optimize the acquisition of light and nutrients. Thus, the marine environment may place demands on resource acquisition and allocation that have not been previously considered with respect to leaf life span optimization.

  8. Life-span plasticity of the brain and cognition: from questions to evidence and back.

    PubMed

    Raz, Naftali; Lindenberger, Ulman

    2013-11-01

    Experience-related changes induced by modification of environment, physical exercise, or cognitive training affect brain structure and function. Research on brain plasticity and its relationship to experiential changes gathers momentum and attracts significant public interest. This collection of papers is based on presentation at the First International Conference on Life-Span Plasticity of Brain and Behavior: A Cognitive Neuroscience Perspective that took place in Detroit, MI, on October 12-14, 2011. The conference honored Margret M. and Paul B. Baltes, the pioneers of life-span developmental psychology who initiated some of the first studies on experience- and training-related changes in cognition across the life span.

  9. Bax-induced apoptosis shortens the life span of DNA repair defect Ku70-knockout mice by inducing emphysema.

    PubMed

    Matsuyama, Shigemi; Palmer, James; Bates, Adam; Poventud-Fuentes, Izmarie; Wong, Kelvin; Ngo, Justine; Matsuyama, Mieko

    2016-06-01

    Cells with DNA damage undergo apoptosis or cellular senescence if the damage cannot be repaired. Recent studies highlight that cellular senescence plays a major role in aging. However, age-associated diseases, including emphysema and neurodegenerative disorders, are caused by apoptosis of lung alveolar epithelial cells and neurons, respectively. Therefore, enhanced apoptosis also promotes aging and shortens the life span depending on the cell type. Recently, we reported that ku70(-) (/) (-)bax(-) (/) (-) and ku70(-) (/) (-)bax(+/) (-) mice showed significantly extended life span in comparison with ku70(-) (/) (-)bax(+/+) mice. Ku70 is essential for non-homologous end joining pathway for DNA double strand break repair, and Bax plays an important role in apoptosis. Our study suggests that Bax-induced apoptosis has a significant impact on shortening the life span of ku70(-) (/) (-) mice, which are defective in one of DNA repair pathways. The lung alveolar space gradually enlarges during aging, both in mouse and human, and this age-dependent change results in the decrease of respiration capacity during aging that can lead to emphysema in more severe cases. We found that emphysema occurred in ku70(-) (/) (-) mice at the age of three-months old, and that Bax deficiency was able to suppress it. These results suggest that Bax-mediated apoptosis induces emphysema in ku70(-) (/) (-) mice. We also found that the number of cells, including bronchiolar epithelial cells and type 2 alveolar epithelial cells, shows a higher DNA double strand break damage response in ku70 KO mouse lung than in wild type. Recent studies suggest that non-homologous end joining activity decreases with increased age in mouse and rat model. Together, we hypothesize that the decline of Ku70-dependent DNA repair activity in lung alveolar epithelial cells is one of the causes of age-dependent decline of lung function resulting from excess Bax-mediated apoptosis of lung alveolar epithelial cells (and their

  10. Life-Span Differences in Semantic Integration of Pictures and Sentences in Memory.

    ERIC Educational Resources Information Center

    Pezdek, Kathy

    1980-01-01

    Examines life-span developmental differences in spontaneous integration of semantically relevant material presented in pictures and sentences. Elementary school students, high school students, and adults were tested. (Author/SS)

  11. Herbal Supplement Extends Life Span Under Some Environmental Conditions and Boosts Stress Resistance

    PubMed Central

    Villeponteau, Bryant; Matsagas, Kennedy; Nobles, Amber C.; Rizza, Cristina; Horwitz, Marc; Benford, Gregory; Mockett, Robin J.

    2015-01-01

    Genetic studies indicate that aging is modulated by a great number of genetic pathways. We have used Drosophila longevity and stress assays to test a multipath intervention strategy. To carry out this strategy, we supplemented the flies with herbal extracts (SC100) that are predicted to modulate the expression of many genes involved in aging and stress resistance, such as mTOR, NOS, NF-KappaB, and VEGF. When flies were housed in large cages with SC100 added, daily mortality rates of both male and female flies were greatly diminished in mid to late life. Surprisingly, SC100 also stabilized midlife mortality rate increases so as to extend the maximum life span substantially beyond the limits previously reported for D. melanogaster. Under these conditions, SC100 also promoted robust resistance to partial starvation stress and to heat stress. Fertility was the same initially in both treated and control flies, but it became significantly higher in treated flies at older ages as the fertility of control flies declined. Mean and maximum life spans of flies in vials at the same test site were also extended by SC100, but the life spans were short in absolute terms. In contrast, at an independent test site where stress was minimized, the flies exhibited much longer mean life spans, but the survival curves became highly rectangular and the effects of SC100 on both mean and maximum life spans declined greatly or were abolished. The data indicate that SC100 is a novel herbal mix with striking effects on enhancing Drosophila stress resistance and life span in some environments, while minimizing mid to late life mortality rates. They also show that the environment and other factors can have transformative effects on both the length and distribution of survivorship, and on the ability of SC100 to extend the life span. PMID:25879540

  12. Telomerase-mediated life-span extension of human primary fibroblasts by human artificial chromosome (HAC) vector

    SciTech Connect

    Shitara, Shingo; Kakeda, Minoru; Nagata, Keiko; Hiratsuka, Masaharu; Sano, Akiko; Osawa, Kanako; Okazaki, Akiyo; Katoh, Motonobu; Kazuki, Yasuhiro; Oshimura, Mitsuo; Tomizuka, Kazuma

    2008-05-09

    Telomerase-mediated life-span extension enables the expansion of normal cells without malignant transformation, and thus has been thought to be useful in cell therapies. Currently, integrating vectors including the retrovirus are used for human telomerase reverse transcriptase (hTERT)-mediated expansion of normal cells; however, the use of these vectors potentially causes unexpected insertional mutagenesis and/or activation of oncogenes. Here, we established normal human fibroblast (hPF) clones retaining non-integrating human artificial chromosome (HAC) vectors harboring the hTERT expression cassette. In hTERT-HAC/hPF clones, we observed the telomerase activity and the suppression of senescent-associated SA-{beta}-galactosidase activity. Furthermore, the hTERT-HAC/hPF clones continued growing beyond 120 days after cloning, whereas the hPF clones retaining the silent hTERT-HAC senesced within 70 days. Thus, hTERT-HAC-mediated episomal expression of hTERT allows the extension of the life-span of human primary cells, implying that gene delivery by non-integrating HAC vectors can be used to control cellular proliferative capacity of primary cultured cells.

  13. Age-associated molecular changes are deleterious and may modulate life span through diet

    PubMed Central

    Lee, Sang-Goo; Kaya, Alaattin; Avanesov, Andrei S.; Podolskiy, Dmitriy I.; Song, Eun Ju; Go, Du-Min; Jin, Gwi-Deuk; Hwang, Jae Yeon; Kim, Eun Bae; Kim, Dae-Yong; Gladyshev, Vadim N.

    2017-01-01

    Transition through life span is accompanied by numerous molecular changes, such as dysregulated gene expression, altered metabolite levels, and accumulated molecular damage. These changes are thought to be causal factors in aging; however, because they are numerous and are also influenced by genotype, environment, and other factors in addition to age, it is difficult to characterize the cumulative effect of these molecular changes on longevity. We reasoned that age-associated changes, such as molecular damage and tissue composition, may influence life span when used in the diet of organisms that are closely related to those that serve as a dietary source. To test this possibility, we used species-specific culture media and diets that incorporated molecular extracts of young and old organisms and compared the influence of these diets on the life span of yeast, fruitflies, and mice. In each case, the “old” diet or medium shortened the life span for one or both sexes. These findings suggest that age-associated molecular changes, such as cumulative damage and altered dietary composition, are deleterious and causally linked with aging and may affect life span through diet. PMID:28232953

  14. Repeated intraspecific divergence in life span and aging of African annual fishes along an aridity gradient.

    PubMed

    Blažek, Radim; Polačik, Matej; Kačer, Petr; Cellerino, Alessandro; Řežucha, Radomil; Methling, Caroline; Tomášek, Oldřich; Syslová, Kamila; Terzibasi Tozzini, Eva; Albrecht, Tomáš; Vrtílek, Milan; Reichard, Martin

    2017-02-01

    Life span and aging are substantially modified by natural selection. Across species, higher extrinsic (environmentally related) mortality (and hence shorter life expectancy) selects for the evolution of more rapid aging. However, among populations within species, high extrinsic mortality can lead to extended life span and slower aging as a consequence of condition-dependent survival. Using within-species contrasts of eight natural populations of Nothobranchius fishes in common garden experiments, we demonstrate that populations originating from dry regions (with short life expectancy) had shorter intrinsic life spans and a greater increase in mortality with age, more pronounced cellular and physiological deterioration (oxidative damage, tumor load), and a faster decline in fertility than populations from wetter regions. This parallel intraspecific divergence in life span and aging was not associated with divergence in early life history (rapid growth, maturation) or pace-of-life syndrome (high metabolic rates, active behavior). Variability across four study species suggests that a combination of different aging and life-history traits conformed with or contradicted the predictions for each species. These findings demonstrate that variation in life span and functional decline among natural populations are linked, genetically underpinned, and can evolve relatively rapidly.

  15. Age-associated molecular changes are deleterious and may modulate life span through diet.

    PubMed

    Lee, Sang-Goo; Kaya, Alaattin; Avanesov, Andrei S; Podolskiy, Dmitriy I; Song, Eun Ju; Go, Du-Min; Jin, Gwi-Deuk; Hwang, Jae Yeon; Kim, Eun Bae; Kim, Dae-Yong; Gladyshev, Vadim N

    2017-02-01

    Transition through life span is accompanied by numerous molecular changes, such as dysregulated gene expression, altered metabolite levels, and accumulated molecular damage. These changes are thought to be causal factors in aging; however, because they are numerous and are also influenced by genotype, environment, and other factors in addition to age, it is difficult to characterize the cumulative effect of these molecular changes on longevity. We reasoned that age-associated changes, such as molecular damage and tissue composition, may influence life span when used in the diet of organisms that are closely related to those that serve as a dietary source. To test this possibility, we used species-specific culture media and diets that incorporated molecular extracts of young and old organisms and compared the influence of these diets on the life span of yeast, fruitflies, and mice. In each case, the "old" diet or medium shortened the life span for one or both sexes. These findings suggest that age-associated molecular changes, such as cumulative damage and altered dietary composition, are deleterious and causally linked with aging and may affect life span through diet.

  16. Life span of common marmoset (Callithrix jacchus) at CLEA Japan breeding colony.

    PubMed

    Nishijima, Kazutoshi; Saitoh, Ryoichi; Tanaka, Shin; Ohsato-Suzuki, Motoko; Ohno, Tamio; Kitajima, Shuji

    2012-08-01

    The life span and survival parameters of the common marmoset (Callithrix jacchus) in a breeding colony at CLEA Japan, Inc. were investigated. The average life span of male marmosets was 148.5 ± 6.1 (mean ± SE) months of age (M), which was significantly longer (P < 0.01) than that of females (111.7 ± 6.0 M). Additionally, the male population reached 25-, 50-, 75- and 90 %-mortality at an older age than the female population. However, the maximum life span in males (259.9 M) was shorter than in females (262.5 M). The survival of females shows a relatively continuous decline; however, the male marmosets show a slight decline in survival during the first 7-9 years and then a dramatic decrease and another slight decline after 14-16 year of age in survival, i.e., a lifespan curve similar to what is observed in colonies of aging rodents and humans. The sex-associated difference in life span was caused by reproductive burden on the females. The present study reported a longer than expected life span of the marmoset, and a long-lived animal can be a powerful model for senescence and longevity sciences.

  17. Balance between macronutrients affects life span and functional senescence in fruit fly Drosophila melanogaster.

    PubMed

    Lushchak, Oleh V; Gospodaryov, Dmytro V; Rovenko, Bohdana M; Glovyak, Andriy D; Yurkevych, Ihor S; Klyuba, Vira P; Shcherbij, Maria V; Lushchak, Volodymyr I

    2012-02-01

    It has recently been demonstrated that as the ratio of protein to carbohydrate (P:C) in the diet declines, life span increases in Drosophila. Here we explored how extremely low dietary ratios of protein to carbohydrate affected longevity and a selection of variables associated with functional senescence. An increase in P:C ratio from 1:57 to 1:20 shortened life span by increasing age-dependent mortality; whereas a further decline in P:C from 1:57 to 1:95 caused a modest decrease in life span. Female flies consuming the 1:20 and 1:38 diets laid more eggs than those consuming the lower P:C diets. Flies fed diets with higher ratios were more resistant to heat stress. Flies consuming the diets with lowest P:C ratios needed more time to restore activity after paralysis. Our study has therefore extended to very low P:C ratios available data demonstrating that dietary P:C ratio affects life span, fecundity and heat stress resistance, with fecundity and heat stress responses showing the opposite trend to life span.

  18. From yeast to human: exploring the comparative biology of methionine restriction in extending eukaryotic life span.

    PubMed

    McIsaac, R Scott; Lewis, Kaitlyn N; Gibney, Patrick A; Buffenstein, Rochelle

    2016-01-01

    Methionine restriction is a widely reported intervention for increasing life span in several model organisms. Low circulating levels of methionine are evident in the long-lived naked mole-rat, suggesting that it naturally presents with a life-extending phenotype akin to that observed in methionine-restricted animals. Similarly, long-lived dwarf mice also appear to have altered methionine metabolism. The mechanisms underlying methionine-restriction effects on life-span extension, however, remain unknown, as do their potential connections with caloric restriction, another well-established intervention for prolonging life span. Paradoxically, methionine is enriched in proteins expressed in mitochondria and may itself serve an important role in the detoxification of reactive oxygen species and may thereby contribute to delayed aging. Collectively, we highlight the evidence that modulation of the methionine metabolic network can extend life span-from yeast to humans-and explore the evidence that sulfur amino acids and the concomitant transsulfuration pathway play a privileged role in this regard. However, systematic studies in single organisms (particularly those that exhibit extreme longevity) are still required to distinguish the fundamental principles concerning the role of methionine and other amino acids in regulating life span.

  19. Bone marrow transplantation prolongs life span and ameliorates neurologic manifestations in Sandhoff disease mice.

    PubMed Central

    Norflus, F; Tifft, C J; McDonald, M P; Goldstein, G; Crawley, J N; Hoffmann, A; Sandhoff, K; Suzuki, K; Proia, R L

    1998-01-01

    The GM2 gangliosidoses are a group of severe, neurodegenerative conditions that include Tay-Sachs disease, Sandhoff disease, and the GM2 activator deficiency. Bone marrow transplantation (BMT) was examined as a potential treatment for these disorders using a Sandhoff disease mouse model. BMT extended the life span of these mice from approximately 4.5 mo to up to 8 mo and slowed their neurologic deterioration. BMT also corrected biochemical deficiencies in somatic tissues as indicated by decreased excretion of urinary oligosaccharides, and lower glycolipid storage and increased levels of beta-hexosaminidase activity in visceral organs. Even with neurologic improvement, neither clear reduction of brain glycolipid storage nor improvement in neuronal pathology could be detected, suggesting a complex pathogenic mechanism. Histological analysis revealed beta-hexosaminidase-positive cells in the central nervous system and visceral organs with a concomitant reduction of colloidal iron-positive macrophages. These results may be important for the design of treatment approaches for the GM2 gangliosidoses. PMID:9576752

  20. Control of protein life-span by N-terminal methionine excision

    PubMed Central

    Giglione, Carmela; Vallon, Olivier; Meinnel, Thierry

    2003-01-01

    Peptide deformylases (PDFs) have been discovered recently in eukaryotic genomes, and it appears that N-terminal methionine excision (NME) is a conserved pathway in all compartments where protein synthesis occurs. This work aimed at uncovering the function(s) of NME in a whole proteome, using the chloroplast-encoded proteins of both Arabidopsis thaliana and Chlamydomonas reinhardtii as model systems. Dis ruption of PDF1B in A.thaliana led to an albino phenotype, and an extreme sensitivity to the PDF- specific inhibitor actinonin. In contrast, a knockout line for PDF1A exhibited no apparent phenotype. Photosystem II activity in C.reinhardtii cells was substantially reduced by the presence of actinonin. Pulse–chase experiments revealed that PDF inhibi tion leads to destabilization of a crucial subset of chloroplast-encoded photosystem II components in C.reinhardtii. The same proteins were destabilized in pdf1b. Site-directed substitutions altering NME of the most sensitive target, subunit D2, resulted in similar effects. Thus, plastid NME is a critical mechanism specifically influencing the life-span of photosystem II polypeptides. A general role of NME in modulating the half-life of key subsets of proteins is suggested. PMID:12505980

  1. Connecting Life Span Development with the Sociology of the Life Course: A New Direction.

    PubMed

    Gilleard, Chris; Higgs, Paul

    2016-04-01

    The life course has become a topic of growing interest within the social sciences. Attempts to link this sub-discipline with life span developmental psychology have been called for but with little sign of success. In this paper, we seek to address three interlinked issues concerning the potential for a more productive interchange between life course sociology and life span psychology. The first is to try to account for the failure of these two sub-disciplines to achieve any deepening engagement with each other, despite the long-expressed desirability of that goal; the second is to draw attention to the scope for enriching the sociology of the life course through Erik Erikson's model of life span development; and the last is the potential for linking Eriksonian theory with current debates within mainstream sociology about the processes involved in 'individualisation' and 'self-reflexivity' as an alternative entry point to bring together these two fields of work.

  2. Survival Analysis of Life Span Quantitative Trait Loci in Drosophila melanogaster

    PubMed Central

    Nuzhdin, Sergey V.; Khazaeli, Aziz A.; Curtsinger, James W.

    2005-01-01

    We used quantitative trait loci (QTL) mapping to evaluate the age specificity of naturally segregating alleles affecting life span. Estimates of age-specific mortality rates were obtained from observing 51,778 mated males and females from a panel of 144 recombinant inbred lines (RILs). Twenty-five QTL were found, having 80 significant effects on life span and weekly mortality rates. Generation of RILs from heterozygous parents enabled us to contrast effects of QTL alleles with the means of RIL populations. Most of the low-frequency alleles increased mortality, especially at younger ages. Two QTL had negatively correlated effects on mortality at different ages, while the remainder were positively correlated. Chromosomal positions of QTL were roughly concordant with estimates from other mapping populations. Our findings are broadly consistent with a mix of transient deleterious mutations and a few polymorphisms maintained by balancing selection, which together contribute to standing genetic variation in life span. PMID:15834144

  3. Genetic manipulation of longevity-related genes as a tool to regulate yeast life span and metabolite production during winemaking

    PubMed Central

    2013-01-01

    Background Yeast viability and vitality are essential for different industrial processes where the yeast Saccharomyces cerevisiae is used as a biotechnological tool. Therefore, the decline of yeast biological functions during aging may compromise their successful biotechnological use. Life span is controlled by a variety of molecular mechanisms, many of which are connected to stress tolerance and genomic stability, although the metabolic status of a cell has proven a main factor affecting its longevity. Acetic acid and ethanol accumulation shorten chronological life span (CLS), while glycerol extends it. Results Different age-related gene classes have been modified by deletion or overexpression to test their role in longevity and metabolism. Overexpression of histone deacetylase SIR2 extends CLS and reduces acetate production, while overexpression of SIR2 homolog HST3 shortens CLS, increases the ethanol level, and reduces acetic acid production. HST3 overexpression also enhances ethanol tolerance. Increasing tolerance to oxidative stress by superoxide dismutase SOD2 overexpression has only a moderate positive effect on CLS. CLS during grape juice fermentation has also been studied for mutants on several mRNA binding proteins that are regulators of gene expression at the posttranscriptional level; we found that NGR1 and UTH4 deletions decrease CLS, while PUF3 and PUB1 deletions increase it. Besides, the pub1Δ mutation increases glycerol production and blocks stress granule formation during grape juice fermentation. Surprisingly, factors relating to apoptosis, such as caspase Yca1 or apoptosis-inducing factor Aif1, play a positive role in yeast longevity during winemaking as their deletions shorten CLS. Conclusions Manipulation of regulators of gene expression at both transcriptional (i.e., sirtuins) and posttranscriptional (i.e., mRNA binding protein Pub1) levels allows to modulate yeast life span during its biotechnological use. Due to links between aging and

  4. Bmi-1 extends the life span of normal human oral keratinocytes by inhibiting the TGF-{beta} signaling

    SciTech Connect

    Kim, Reuben H.; Lieberman, Mark B.; Lee, Rachel; Shin, Ki-Hyuk; Mehrazarin, Shebli; Oh, Ju-Eun; Park, No-Hee; Kang, Mo K.

    2010-10-01

    We previously demonstrated that Bmi-1 extended the in vitro life span of normal human oral keratinocytes (NHOK). We now report that the prolonged life span of NHOK by Bmi-1 is, in part, due to inhibition of the TGF-{beta} signaling pathway. Serial subculture of NHOK resulted in replicative senescence and terminal differentiation and activation of TGF-{beta} signaling pathway. This was accompanied with enhanced intracellular and secreted TGF-{beta}1 levels, phosphorylation of Smad2/3, and increased expression of p15{sup INK4B} and p57{sup KIP2}. An ectopic expression of Bmi-1 in NHOK (HOK/Bmi-1) decreased the level of intracellular and secreted TGF-{beta}1 induced dephosphorylation of Smad2/3, and diminished the level of p15{sup INK4B} and p57{sup KIP2}. Moreover, Bmi-1 expression led to the inhibition of TGF-{beta}-responsive promoter activity in a dose-specific manner. Knockdown of Bmi-1 in rapidly proliferating HOK/Bmi-1 and cancer cells increased the level of phosphorylated Smad2/3, p15{sup INK4B}, and p57{sup KIP2}. In addition, an exposure of senescent NHOK to TGF-{beta} receptor I kinase inhibitor or anti-TGF-{beta} antibody resulted in enhanced replicative potential of cells. Taken together, these data suggest that Bmi-1 suppresses senescence of cells by inhibiting the TGF-{beta} signaling pathway in NHOK.

  5. Foraging across the life span: is there a reduction in exploration with aging?

    PubMed Central

    Mata, Rui; Wilke, Andreas; Czienskowski, Uwe

    2013-01-01

    Does foraging change across the life span, and in particular, with aging? We report data from two foraging tasks used to investigate age differences in search in external environments as well as internal search in memory. Overall, the evidence suggests that foraging behavior may undergo significant changes across the life span across internal and external search. In particular, we find evidence of a trend toward reduced exploration with increased age. We discuss these findings in light of theories that postulate a link between aging and reductions in novelty seeking and exploratory behavior. PMID:23616741

  6. C. elegans as Model for the Study of High Glucose– Mediated Life Span Reduction

    PubMed Central

    Schlotterer, Andreas; Kukudov, Georgi; Bozorgmehr, Farastuk; Hutter, Harald; Du, Xueliang; Oikonomou, Dimitrios; Ibrahim, Youssef; Pfisterer, Friederike; Rabbani, Naila; Thornalley, Paul; Sayed, Ahmed; Fleming, Thomas; Humpert, Per; Schwenger, Vedat; Zeier, Martin; Hamann, Andreas; Stern, David; Brownlee, Michael; Bierhaus, Angelika; Nawroth, Peter; Morcos, Michael

    2009-01-01

    OBJECTIVE Establishing Caenorhabditis elegans as a model for glucose toxicity–mediated life span reduction. RESEARCH DESIGN AND METHODS C. elegans were maintained to achieve glucose concentrations resembling the hyperglycemic conditions in diabetic patients. The effects of high glucose on life span, glyoxalase-1 activity, advanced glycation end products (AGEs), and reactive oxygen species (ROS) formation and on mitochondrial function were studied. RESULTS High glucose conditions reduced mean life span from 18.5 ± 0.4 to 16.5 ± 0.6 days and maximum life span from 25.9 ± 0.4 to 23.2 ± 0.4 days, independent of glucose effects on cuticle or bacterial metabolization of glucose. The formation of methylglyoxal-modified mitochondrial proteins and ROS was significantly increased by high glucose conditions and reduced by mitochondrial uncoupling and complex IIIQo inhibition. Overexpression of the methylglyoxal–detoxifying enzyme glyoxalase-1 attenuated the life-shortening effect of glucose by reducing AGE accumulation (by 65%) and ROS formation (by 50%) and restored mean (16.5 ± 0.6 to 20.6 ± 0.4 days) and maximum life span (23.2 ± 0.4 to 27.7 ± 2.3 days). In contrast, inhibition of glyoxalase-1 by RNAi further reduced mean (16.5 ± 0.6 to 13.9 ± 0.7 days) and maximum life span (23.2 ± 0.4 to 20.3 ± 1.1 days). The life span reduction by glyoxalase-1 inhibition was independent from the insulin signaling pathway because high glucose conditions also affected daf-2 knockdown animals in a similar manner. CONCLUSIONS C. elegans is a suitable model organism to study glucose toxicity, in which high glucose conditions limit the life span by increasing ROS formation and AGE modification of mitochondrial proteins in a daf-2 independent manner. Most importantly, glucose toxicity can be prevented by improving glyoxalase-1–dependent methylglyoxal detoxification or preventing mitochondrial dysfunction. PMID:19675139

  7. Quantitative proteomics of rat livers shows that unrestricted feeding is stressful for proteostasis with implications on life span

    PubMed Central

    Pinto, Galit; Quadroni, Manfredo; Shtaif, Biana; Goloubinoff, Pierre

    2016-01-01

    Studies in young mammals on the molecular effects of food restriction leading to prolong adult life are scares. Here, we used high-throughput quantitative proteomic analysis of whole rat livers to address the molecular basis for growth arrest and the apparent life-prolonging phenotype of the food restriction regimen. Over 1800 common proteins were significantly quantified in livers of ad libitum, restriction- and re-fed rats, which summed up into 92% of the total protein mass of the cells. Compared to restriction, ad libitum cells contained significantly less mitochondrial catabolic enzymes and more cytosolic and ER HSP90 and HSP70 chaperones, which are hallmarks of heat- and chemically-stressed tissues. Following re-feeding, levels of HSPs nearly reached ad libitum levels. The quantitative and qualitative protein values indicated that the restriction regimen was a least stressful condition that used minimal amounts of HSP-chaperones to maintain optimal protein homeostasis and sustain optimal life span. In contrast, the elevated levels of HSP-chaperones in ad libitum tissues were characteristic of a chronic stress, which in the long term could lead to early aging and shorter life span. PMID:27508340

  8. Sparing of the Extraocular Muscles in mdx Mice with Absent or Reduced Utrophin Expression: A Life Span Analysis

    PubMed Central

    McDonald, Abby A.; Hebert, Sadie L.; McLoon, Linda K.

    2015-01-01

    Sparing of the extraocular muscles in muscular dystrophy is controversial. To address the potential role of utrophin in this sparing, mdx:utrophin+/− and mdx:utrophin−/− mice were examined for changes in myofiber size, central nucleation, and Pax7-positive and MyoD-positive cell density at intervals over their life span. Known to be spared in the mdx mouse, and contrary to previous reports, the extraocular muscles from both the mdx:utrophin+/− and mdx:utrophin−/− mice were also morphologically spared. In the mdx:utrophin+/− mice, which have a normal life span compared to the mdx:utrophin−/− mice, the myofibers were larger at 3 and 12 months than the wild type age-matched eye muscles. While there was a significant increase in central nucleation in the extraocular muscles from all mdx:utrophin+/− mice, the levels were still very low compared to age-matched limb skeletal muscles. Pax7- and MyoD-positive myogenic precursor cell populations were retained and similar to age-matched wild type controls. These results support the hypothesis that utrophin is not involved in extraocular muscle sparing in these genotypes. In addition, it appears these muscles retain the myogenic precursors that would allow them to maintain their regenerative capacity and normal morphology over a lifetime even in these more severe models of muscular dystrophy. PMID:26429098

  9. Sparing of the extraocular muscles in mdx mice with absent or reduced utrophin expression: A life span analysis.

    PubMed

    McDonald, Abby A; Hebert, Sadie L; McLoon, Linda K

    2015-11-01

    Sparing of the extraocular muscles in muscular dystrophy is controversial. To address the potential role of utrophin in this sparing, mdx:utrophin(+/-) and mdx:utrophin(-/-) mice were examined for changes in myofiber size, central nucleation, and Pax7-positive and MyoD-positive cell density at intervals over their life span. Known to be spared in the mdx mouse, and contrary to previous reports, the extraocular muscles from both the mdx:utrophin(+/-) and mdx:utrophin(-/-) mice were also morphologically spared. In the mdx:utrophin(+/)(-) mice, which have a normal life span compared to the mdx:utrophin(-/-) mice, the myofibers were larger at 3 and 12 months than the wild type age-matched eye muscles. While there was a significant increase in central nucleation in the extraocular muscles from all mdx:utrophin(+/)(-) mice, the levels were still very low compared to age-matched limb skeletal muscles. Pax7- and MyoD-positive myogenic precursor cell populations were retained and were similar to age-matched wild type controls. These results support the hypothesis that utrophin is not involved in extraocular muscle sparing in these genotypes. In addition, it appears that these muscles retain the myogenic precursors that would allow them to maintain their regenerative capacity and normal morphology over a lifetime even in these more severe models of muscular dystrophy.

  10. Attachment and the Processing of Social Information across the Life Span: Theory and Evidence

    ERIC Educational Resources Information Center

    Dykas, Matthew J.; Cassidy, Jude

    2011-01-01

    Researchers have used J. Bowlby's (1969/1982, 1973, 1980, 1988) attachment theory frequently as a basis for examining whether experiences in close personal relationships relate to the processing of social information across childhood, adolescence, and adulthood. We present an integrative life-span-encompassing theoretical model to explain the…

  11. Psychopathology in Williams Syndrome: The Effect of Individual Differences across the Life Span

    ERIC Educational Resources Information Center

    Dodd, Helen F.; Porter, Melanie A.

    2009-01-01

    This research aimed to comprehensively explore psychopathology in Williams syndrome (WS) across the life span and evaluate the relationship between psychopathology and age category (child or adult), gender, and cognitive ability. The parents of 50 participants with WS, ages 6-50 years, were interviewed using the Schedule for Affective Disorders…

  12. Abilities and Competencies in Adulthood: Life-Span Perspectives on Workplace Skills.

    ERIC Educational Resources Information Center

    Smith, Jacqui; Marsiske, Michael

    This report presents a framework for considering general and work-related adult cognitive performance that is drawn from current theory and research on life-span developmental and cognitive psychology. The first section considers the concept of basic skills and the classical distinction between achievement and aptitude. By drawing linkages between…

  13. Like cognitive function, decision making across the life span shows profound age-related changes

    PubMed Central

    Tymula, Agnieszka; Rosenberg Belmaker, Lior A.; Ruderman, Lital; Glimcher, Paul W.; Levy, Ifat

    2013-01-01

    It has long been known that human cognitive function improves through young adulthood and then declines across the later life span. Here we examined how decision-making function changes across the life span by measuring risk and ambiguity attitudes in the gain and loss domains, as well as choice consistency, in an urban cohort ranging in age from 12 to 90 y. We identified several important age-related patterns in decision making under uncertainty: First, we found that healthy elders between the ages of 65 and 90 were strikingly inconsistent in their choices compared with younger subjects. Just as elders show profound declines in cognitive function, they also show profound declines in choice rationality compared with their younger peers. Second, we found that the widely documented phenomenon of ambiguity aversion is specific to the gain domain and does not occur in the loss domain, except for a slight effect in older adults. Finally, extending an earlier report by our group, we found that risk attitudes across the life span show an inverted U-shaped function; both elders and adolescents are more risk-averse than their midlife counterparts. Taken together, these characterizations of decision-making function across the life span in this urban cohort strengthen the conclusions of previous reports suggesting a profound impact of aging on cognitive function in this domain. PMID:24082105

  14. The Status of Number and Quantity Conservation Concepts Across the Life-span.

    ERIC Educational Resources Information Center

    Papalia, Diane E.

    Conservation performance during childhood to portions of the life span beyond adolescence is examined, with existing data replicated on subjects ranging from the preschool to middle-childhood years. Age differences in performance are studied for the typical Piagetian paired-stimulus equivalence conservation of number, substance, weight, and volume…

  15. Age, growth and size interact with stress to determine life span and mortality

    PubMed Central

    Roach, Deborah Ann

    2012-01-01

    Individuals in a large experimental field population, of the short-lived perennial species Plantago lanceolata, were followed to determine the sources of variation that influence mortality and life span. The design included multiple age groups with initially similar genetic structure, which made it possible to separate age effects from period effects and to identify the genetic component to variation in life span. During a period of stress, individuals of all ages showed parallel increases in mortality but different cohorts experienced this period of high mortality at different ages. This then influenced the distribution of life spans across cohorts. Age and size-age interactions influenced mortality during the period of stress. Smaller individuals died but only if they were old. Additionally, growth and age interacted with stress such that older individuals had negative growth and high mortality whereas younger individuals had positive growth and relatively lower mortality during stress. The results of this study show that it is not simply the environment that can have a major impact on demography in natural populations, rather, age, size and growth can interact with the environment to influence mortality and life span when the environment is stressful. PMID:22664575

  16. Gains and Losses in Creative Personality as Perceived by Adults across the Life Span

    ERIC Educational Resources Information Center

    Hui, Anna N. N.; Yeung, Dannii Y.; Sue-Chan, Christina; Chan, Kara; Hui, Desmond C. K.; Cheng, Sheung-Tak

    2014-01-01

    In this study, we used a life span model to study the subjective perception of creative personality (CP) in emerging, young, middle-aged, and older Hong Kong Chinese adults. We also asked participants to estimate the approximate age by which people develop and lose CP across adulthood. We expected an interesting interplay between internalized age…

  17. Effects of a Short Strategy Training on Metacognitive Monitoring across the Life-Span

    ERIC Educational Resources Information Center

    von der Linden, Nicole; Löffler, Elisabeth; Schneider, Wolfgang

    2015-01-01

    The present study was conducted to explore the potential positive influence of a short strategy training on metacognitive monitoring competencies covering a life-span approach. Participants of four age groups (3rd-grade children, adolescents, younger and older adults) concluded a paired-associate learning task. Additionally, they gave delayed…

  18. Expression of a Single-Copy hsp-16.2 Reporter Predicts Life span

    PubMed Central

    Tedesco, Patricia M.; Taylor, Larry D.; Lowe, Anita; Cypser, James R.; Johnson, Thomas E.

    2012-01-01

    The level of green fluorescent protein expression from an hsp-16.2–based transcriptional reporter predicts life span and thermotolerance in Caenorhabditis elegans. The initial report used a high-copy number reporter integrated into chromosome IV. There was concern that the life-span prediction power of this reporter was not attributable solely to hsp-16.2 output. Specifically, prediction power could stem from disruption of some critical piece of chromatin on chromosome IV by the gpIs1 insertion, a linked mutation from the process used to create the reporter, or from an artifact of transgene regulation (multicopy transgenes are subject to regulation by C elegans chromatin surveillance machinery). Here we determine if the ability to predict life span and thermotolerance is specific to the gpIs1 insertion or a general property of hsp-16.2–based reporters. New single-copy hsp-16.2–based reporters predict life span and thermotolerance. We conclude that prediction power of hsp-16.2–based transcriptional reporters is not an artifact of any specific transgene configuration or chromatin surveillance mechanism. PMID:22227523

  19. The Use of Digital Technologies across the Adult Life Span in Distance Education

    ERIC Educational Resources Information Center

    Jelfs, Anne; Richardson, John T. E.

    2013-01-01

    In June 2010, a survey was carried out to explore access to digital technology, attitudes to digital technology and approaches to studying across the adult life span in students taking courses with the UK Open University. In total, 7000 people were surveyed, of whom more than 4000 responded. Nearly all these students had access to a computer and…

  20. The Impact of Drug Use on Earnings: A Life-Span Perspective.

    ERIC Educational Resources Information Center

    Kandel, Denise; And Others

    1995-01-01

    Among a longitudinal cohort of 400 employed males, illicit drug use had a positive impact on wages up to age 28-29 and a negative impact by the mid-30s. A life-span perspective emphasizes differential short- and long-term impacts of education, training, and job changes on users' and nonusers' incomes. Contains 57 references. (Author/SV)

  1. Age Differences and Educational Attainment across the Life Span on Three Generations of Wechsler Adult Scales

    ERIC Educational Resources Information Center

    Kaufman, A. S.; Salthouse, T. A.; Scheiber, C.; Chen, H.

    2016-01-01

    Patterns of maintenance of ability across the life span have been documented on tests of knowledge ("Gc"), as have patterns of steady decline on measures of reasoning ("Gf/Gv"), working memory ("Gsm"), and speed ("Gs"). Whether these patterns occur at the same rate for adults from different educational…

  2. Female Early Adolescent Sex Role Attitude and Behavior Development: A Life Span, Ecosystem Approach.

    ERIC Educational Resources Information Center

    Nelson, Christine Seipke; Keith, Joanne

    Theory and research related to early adolescent sex role development needs to be addressed from both a life-span and an ecological perspective. A study was conducted to examine the development of female early adolescent sex role attitudes and behaviors in an ecological context as defined by Urie Bronfenbrenner. Data were the results of a…

  3. Extending the Human Life Span: An Exploratory Study of Pro- and Anti-Longevity Attitudes

    ERIC Educational Resources Information Center

    Kogan, Nathan; Tucker, Jennifer; Porter, Matthew

    2011-01-01

    Successful efforts by biologists to substantially increase the life span of non-human animals has raised the possibility of extrapolation to humans, which in turn has given rise to bioethical argumentation, pro and con. The present study converts these arguments into pro- and anti-longevity items on a questionnaire and examines the structure and…

  4. Influence of Domain Knowledge on Monitoring Performance across the Life Span

    ERIC Educational Resources Information Center

    Löffler, Elisabeth; von der Linden, Nicole; Schneider, Wolfgang

    2016-01-01

    Two studies were conducted to investigate effects of domain knowledge on metacognitive monitoring across the life span in materials of different complexity. Participants from 4 age groups (3rd-grade children, adolescents, younger and older adults) were compared using an expert-novice paradigm. In Study 1, soccer experts' and novices'…

  5. Adults' Diaries: Changes Made to Written Narratives across the Life Span.

    ERIC Educational Resources Information Center

    Kemper, Susan

    1990-01-01

    Examines diaries kept by 8 adults (born between 1856 and 1876) over a 70-year period of their lives. Analyzes the complexity of the narrative structure and the cohesion of the text. Finds that the diarists' narratives became structurally more complex across the life span, although they became less cohesive as ambiguous anaphors increased. (KEH)

  6. Integrating the Life Course and Life-Span: Formulating Research Questions with Dual Points of Entry.

    ERIC Educational Resources Information Center

    Shanahan, Michael J.; Porfelli, Erik

    2002-01-01

    Life-span research typically begins with personal characteristics, life-course research with social context and roles. Using both points of entry will encourage interdisciplinary work as well as the study of person-context interactions. (Contains 30 references.) (SK)

  7. Developmental Change in Proactive Interference across the Life Span: Evidence from Two Working Memory Tasks

    ERIC Educational Resources Information Center

    Loosli, Sandra V.; Rahm, Benjamin; Unterrainer, Josef M.; Weiller, Cornelius; Kaller, Christoph P.

    2014-01-01

    Working memory (WM) as the ability to temporarily maintain and manipulate various kinds of information is known to be affected by proactive interference (PI) from previously relevant contents, but studies on developmental changes in the susceptibility to PI are scarce. In the present study, we investigated life span development of item-specific…

  8. Assimilation of endogenous nicotinamide riboside is essential for calorie restriction-mediated life span extension in Saccharomyces cerevisiae.

    PubMed

    Lu, Shu-Ping; Kato, Michiko; Lin, Su-Ju

    2009-06-19

    NAD(+) (nicotinamide adenine dinucleotide) is an essential cofactor involved in various biological processes including calorie restriction-mediated life span extension. Administration of nicotinamide riboside (NmR) has been shown to ameliorate deficiencies related to aberrant NAD(+) metabolism in both yeast and mammalian cells. However, the biological role of endogenous NmR remains unclear. Here we demonstrate that salvaging endogenous NmR is an integral part of NAD(+) metabolism. A balanced NmR salvage cycle is essential for calorie restriction-induced life span extension and stress resistance in yeast. Our results also suggest that partitioning of the pyridine nucleotide flux between the classical salvage cycle and the NmR salvage branch might be modulated by the NAD(+)-dependent Sir2 deacetylase. Furthermore, two novel deamidation steps leading to nicotinic acid mononucleotide and nicotinic acid riboside production are also uncovered that further underscore the complexity and flexibility of NAD(+) metabolism. In addition, utilization of extracellular nicotinamide mononucleotide requires prior conversion to NmR mediated by a periplasmic phosphatase Pho5. Conversion to NmR may thus represent a strategy for the transport and assimilation of large nonpermeable NAD(+) precursors. Together, our studies provide a molecular basis for how NAD(+) homeostasis factors confer metabolic flexibility.

  9. 20S proteasome activation promotes life span extension and resistance to proteotoxicity in Caenorhabditis elegans

    PubMed Central

    Chondrogianni, Niki; Georgila, Konstantina; Kourtis, Nikos; Tavernarakis, Nektarios; Gonos, Efstathios S.

    2015-01-01

    Protein homeostasis (proteostasis) is one of the nodal points that need to be preserved to retain physiologic cellular/organismal balance. The ubiquitin-proteasome system (UPS) is responsible for the removal of both normal and damaged proteins, with the proteasome being the downstream effector. The proteasome is the major cellular protease with progressive impairment of function during aging and senescence. Despite the documented age-retarding properties of proteasome activation in various cellular models, simultaneous enhancement of the 20S core proteasome content, assembly, and function have never been reported in any multicellular organism. Consequently, the possible effects of the core proteasome modulation on organismal life span are elusive. In this study, we have achieved activation of the 20S proteasome at organismal level. We demonstrate enhancement of proteasome levels, assembly, and activity in the nematode Caenorhabditis elegans, resulting in life span extension and increased resistance to stress. We also provide evidence that the observed life span extension is dependent on the transcriptional activity of Dauer formation abnormal/Forkhead box class O (DAF-16/FOXO), skinhead-1 (SKN-1), and heat shock factor-1 (HSF-1) factors through regulation of downstream longevity genes. We further show that the reported beneficial effects are not ubiquitous but they are dependent on the genetic context. Finally, we provide evidence that proteasome core activation might be a potential strategy to minimize protein homeostasis deficiencies underlying aggregation-related diseases, such as Alzheimer’s disease (AD) or Huntington’s disease (HD). In summary, this is the first report demonstrating that 20S core proteasome up-regulation in terms of both content and activity is feasible in a multicellular eukaryotic organism and that in turn this modulation promotes extension of organismal health span and life span.—Chondrogianni, N., Georgila, K., Kourtis, N

  10. Dietary restriction: critical co-factors to separate health span from life span benefits.

    PubMed

    Mendelsohn, Andrew R; Larrick, James W

    2012-10-01

    Dietary restriction (DR), typically a 20%-40% reduction in ad libitum or "normal" nutritional energy intake, has been reported to extend life span in diverse organisms, including yeast, nematodes, spiders, fruit flies, mice, rats, and rhesus monkeys. The magnitude of the life span enhancement appears to diminish with increasing organismal complexity. However, the extent of life span extension has been notoriously inconsistent, especially in mammals. Recently, Mattison et al. reported that DR does not extend life span in rhesus monkeys in contrast to earlier work of Colman et al. Examination of these papers identifies multiple potential confounding factors. Among these are the varied genetic backgrounds and composition of the "normal" and DR diets. In monkeys, the correlation of DR with increased health span is stronger than that seen with life span and indeed may be separable. Recent mechanistic studies in Drosophila implicate non-genetic co-factors such as level of physical activity and muscular fatty acid metabolism in the benefits of DR. These results should be followed up in mammals. Perhaps levels of physical activity among the cohorts of rhesus monkeys contribute to inconsistent DR effects. To understand the maximum potential benefits from DR requires differentiating fundamental effects on aging at the cellular and molecular levels from suppression of age-associated diseases, such as cancer. To that end, it is important that investigators carefully evaluate the effects of DR on biomarkers of molecular aging, such as mutation rate and epigenomic alterations. Several short-term studies show that humans may benefit from DR in as little as 6 months, by achieving lowered fasting insulin levels and improved cardiovascular health. Optimized health span engineering will require a much deeper understanding of DR.

  11. Human adipose tissue derived pericytes increase life span in Utrn (tm1Ked) Dmd (mdx) /J mice.

    PubMed

    Valadares, M C; Gomes, J P; Castello, G; Assoni, A; Pellati, M; Bueno, C; Corselli, M; Silva, H; Bartolini, P; Vainzof, M; Margarido, P F; Baracat, E; Péault, B; Zatz, M

    2014-12-01

    Duchenne muscular dystrophy (DMD) is still an untreatable lethal X-linked disorder, which affects 1 in 3500 male births. It is caused by the absence of muscle dystrophin due to mutations in the dystrophin gene. The potential regenerative capacity as well as immune privileged properties of mesenchymal Stem Cells (MSC) has been under investigation for many years in an attempt to treat DMD. One of the questions to be addressed is whether stem cells from distinct sources have comparable clinical effects when injected in murine or canine muscular dystrophy animal models. Many studies comparing different stem cells from various sources were reported but these cells were obtained from different donors and thus with different genetic backgrounds. Here we investigated whether human pericytes obtained from 4 different tissues (muscle, adipose tissue, fallopian tube and endometrium) from the same donor have a similar clinical impact when injected in double mutant Utrn (tm1Ked) Dmd (mdx) /J mice, a clinically relevant model for DMD. After a weekly regimen of intraperitoneal injections of 10(6) cells per 8 weeks we evaluated the motor ability as well as the life span of the treated mice as compared to controls. Our experiment showed that only adipose tissue derived pericytes are able to increase significantly (39 days on average) the life span of affected mice. Microarray analysis showed an inhibition of the interferon pathway by adipose derived pericytes. Our results suggest that the clinical benefit associated with intraperitoneal injections of these adult stem cells is related to immune modulation rather than tissue regeneration.

  12. Notwithstanding Circumstantial Alibis, Cytotoxic T Cells Can Be Major Killers of HIV-1-Infected Cells

    PubMed Central

    Gadhamsetty, Saikrishna; Coorens, Tim

    2016-01-01

    ABSTRACT Several experiments suggest that in the chronic phase of human immunodeficiency virus type 1 (HIV-1) infection, CD8+ cytotoxic T lymphocytes (CTL) contribute very little to the death of productively infected cells. First, the expected life span of productively infected cells is fairly long, i.e., about 1 day. Second, this life span is hardly affected by the depletion of CD8+ T cells. Third, the rate at which mutants escaping a CTL response take over the viral population tends to be slow. Our main result is that all these observations are perfectly compatible with killing rates that are much faster than one per day once we invoke the fact that infected cells proceed through an eclipse phase of about 1 day before they start producing virus. Assuming that the major protective effect of CTL is cytolytic, we demonstrate that mathematical models with an eclipse phase account for the data when the killing is fast and when it varies over the life cycle of infected cells. Considering the steady state corresponding to the chronic phase of the infection, we find that the rate of immune escape and the rate at which the viral load increases following CD8+ T cell depletion should reflect the viral replication rate, ρ. A meta-analysis of previous data shows that viral replication rates during chronic infection vary between 0.5 ≤ ρ ≤ 1 day−1. Balancing such fast viral replication requires killing rates that are several times larger than ρ, implying that most productively infected cells would die by cytolytic effects. IMPORTANCE Most current data suggest that cytotoxic T cells (CTL) mediate their control of human immunodeficiency virus type 1 (HIV-1) infection by nonlytic mechanisms; i.e., the data suggest that CTL hardly kill. This interpretation of these data has been based upon the general mathematical model for HIV infection. Because this model ignores the eclipse phase between the infection of a target cell and the start of viral production by that cell, we

  13. Effect of habitat preference on frond life span in three Cyathea tree ferns

    NASA Astrophysics Data System (ADS)

    Chiu, Tzu Yun; Wang, Hsiang Hua; Lun Kuo, Yao; Kume, Tomonori

    2013-04-01

    It has been reported that plants living in various geographical areas had different physiological forms, as factors of microenvironment have strong impacts on physiological characters. However, the physiological characters of fronds have been scarcely reported in ferns. In this study, we investigated physiological differences in response to the habitat preference in the three tree ferns in northeast Taiwan, Cyathea lepifera, C. spinulosa, and C. podophylla, prefer to open site, edge of forest, and interior forest, respectively. The canopy openness above the individuals of C. lepifera, C. spinulosa and C. podophylla were 29.2 ± 14.10 , 7.0 ± 3.07 and 5.0 ± 2.24 %, respectively. Among three species, C. podophylla had the longest frond life span (13.0 ± 4.12 months) than the two others (C. lepifera (6.8 ± 1.29 months) and C. spinulosa (7.3 ±1.35 months). Our result supported the general patterns that shade intolerant species have a shorter leaf life span than shade tolerant species. The maximum net CO2 assimilation of C. lepifera, C. spinulosa and C. podophylla were 11.46 ± 1.34, 8.27 ± 0.69, and 6.34 ± 0.54 μmol CO2 m-2 s-1, respectively. As well, C. lepifera had the highest photosynthetic light saturation point (LSP), while C. podophylla had the lowest LSP among these three tree ferns. These suggested that C. lepifera could be more efficient for capturing and utilizing light resources under the larger canopy openness condition than the other two species. We also found that frond C : N ratio were positively correlated with frond life span among species. C. podophylla, with the longest frond life span, had the highest frond C : N ratio (22.17 ± 1.95), which was followed by C. spinulosa (18.58 ± 1.37) and C. lepifera (18.68 ± 2.63) with shorter frond life span. The results were consistent to the theory that the fronds and leaves of shade intolerant species have high photosynthetic abilities with low C : N ratio. Key words: Canopy openness, frond life span

  14. [THE ANALYSIS OF LIFE SPAN AND MORTALITY OF PATIENTS WITH SPINOCEREBELLAR ATAXIA TYPE I].

    PubMed

    Tikhonov, D G; Goldfarb, L G; Neustroeva, T S; Yakovleva, N V; Timofeev, L F; Luckan, I P; Platonov, F A

    2015-01-01

    The article presents results of investigation of certain unclear aspects of mortality of patients with spinocerebellar ataxia type I including patients with the same number of CAG-repetitions. The analysis of mortality of patients observed from 1993 to nowadays was implemented. Sampling included 112 patients during that period 53 patients died. The comparative analysis was implemented concerning received data and results of analysis of mortality of patients died prior to 1980. According received data, average value of CAG-repetitions of normal allele was equal to 30.2, and ofpathologic allele--48.7. The average life span made up to 52.8 years, average age of disease onset--38 years and natural duration of disease--14.8 years. The analysis of life span of patients with equal length of repetitions demonstrated that range of life span of patients makes up to from 8 to 23 years. It is established that life of patients becomes shorter because of accidents, cancer and concomitant diseases of cardiovascular system. The presence of such concomitant disease as tuberculosis of lungs results in no shortening of life of patients. The comparative analysis of mortality during the period over 34 years demonstrated that age of disease onset turned out to be more conservative and stable indicator of morbidity. Despite of lacking of effective methods of treatment of disease, the natural duration of disease increased statistically reliable up to 1.8 times during period of observation. The analysis of life span ofpatients with spinocerebellar ataxia type I demonstrated that their life span except length of CAG-expansion depends on a number of factors accelerating and retarding development of disease. At that, life span of patients with the same number of CAG-repetitions can significantly differ The malignant neoplasms, diseases of cardiovascular system and external causes are to be referred to factors accelerating and retarding development of main disease. The addition oftuberculosis

  15. Loss of Ubp3 increases silencing, decreases unequal recombination in rDNA, and shortens the replicative life span in Saccharomyces cerevisiae.

    PubMed

    Oling, David; Masoom, Rehan; Kvint, Kristian

    2014-06-15

    Ubp3 is a conserved ubiquitin protease that acts as an antisilencing factor in MAT and telomeric regions. Here we show that ubp3∆ mutants also display increased silencing in ribosomal DNA (rDNA). Consistent with this, RNA polymerase II occupancy is lower in cells lacking Ubp3 than in wild-type cells in all heterochromatic regions. Moreover, in a ubp3∆ mutant, unequal recombination in rDNA is highly suppressed. We present genetic evidence that this effect on rDNA recombination, but not silencing, is entirely dependent on the silencing factor Sir2. Further, ubp3∆ sir2∆ mutants age prematurely at the same rate as sir2∆ mutants. Thus our data suggest that recombination negatively influences replicative life span more so than silencing. However, in ubp3∆ mutants, recombination is not a prerequisite for aging, since cells lacking Ubp3 have a shorter life span than isogenic wild-type cells. We discuss the data in view of different models on how silencing and unequal recombination affect replicative life span and the role of Ubp3 in these processes.

  16. Toward an integrative science of life-span development and aging.

    PubMed

    Hofer, Scott M; Piccinin, Andrea M

    2010-05-01

    The study of aging demands an integrative life-span developmental framework, involving interdisciplinary collaborations and multiple methodological approaches for understanding how and why individuals change, in both normative and idiosyncratic ways. We highlight and summarize some of the issues encountered when conducting integrative research for understanding aging-related change, including, the integration of results across different levels of analysis; the integration of theory, design, and analysis; and the synthesis of results across studies of aging. We emphasize the necessity of longitudinal designs for understanding development and aging and discuss methodological issues that should be considered for achieving reproducible research on within-person processes. It will be important that current and future studies permit opportunities for quantitative comparison across populations given the extent to which historical shifts and cultural differences influence life-span processes and aging-related outcomes.

  17. C. elegans miro-1 Mutation Reduces the Amount of Mitochondria and Extends Life Span.

    PubMed

    Shen, Yanqing; Ng, Li Fang; Low, Natarie Pei Wen; Hagen, Thilo; Gruber, Jan; Inoue, Takao

    2016-01-01

    Mitochondria play a critical role in aging, however, the underlying mechanism is not well understood. We found that a mutation disrupting the C. elegans homolog of Miro GTPase (miro-1) extends life span. This phenotype requires simultaneous loss of miro-1 from multiple tissues including muscles and neurons, and is dependent on daf-16/FOXO. Notably, the amount of mitochondria in the miro-1 mutant is reduced to approximately 50% of the wild-type. Despite this reduction, oxygen consumption is only weakly reduced, suggesting that mitochondria of miro-1 mutants are more active than wild-type mitochondria. The ROS damage is slightly reduced and the mitochondrial unfolded protein response pathway is weakly activated in miro-1 mutants. Unlike previously described long-lived mitochondrial electron transport chain mutants, miro-1 mutants have normal growth rate. These results suggest that the reduction in the amount of mitochondria can affect the life span of an organism through activation of stress pathways.

  18. Evolutionary entropy: a predictor of body size, metabolic rate and maximal life span.

    PubMed

    Demetrius, Lloyd; Legendre, Stéphane; Harremöes, Peter

    2009-05-01

    Body size of organisms spans 24 orders of magnitude, and metabolic rate and life span present comparable differences across species. This article shows that this variation can be explained in terms of evolutionary entropy, a statistical parameter which characterizes the robustness of a population, and describes the uncertainty in the age of the mother of a randomly chosen newborn. We show that entropy also has a macroscopic description: It is linearly related to the logarithm of the variables body size, metabolic rate, and life span. Furthermore, entropy characterizes Darwinian fitness, the efficiency with which a population acquires and converts resources into viable offspring. Accordingly, entropy predicts the outcome of natural selection in populations subject to different classes of ecological constraints. This predictive property, when integrated with the macroscopic representation of entropy, is the basis for enormous differences in morphometric and life-history parameters across species.

  19. C. elegans miro-1 Mutation Reduces the Amount of Mitochondria and Extends Life Span

    PubMed Central

    Shen, Yanqing; Ng, Li Fang; Low, Natarie Pei Wen; Hagen, Thilo; Gruber, Jan; Inoue, Takao

    2016-01-01

    Mitochondria play a critical role in aging, however, the underlying mechanism is not well understood. We found that a mutation disrupting the C. elegans homolog of Miro GTPase (miro-1) extends life span. This phenotype requires simultaneous loss of miro-1 from multiple tissues including muscles and neurons, and is dependent on daf-16/FOXO. Notably, the amount of mitochondria in the miro-1 mutant is reduced to approximately 50% of the wild-type. Despite this reduction, oxygen consumption is only weakly reduced, suggesting that mitochondria of miro-1 mutants are more active than wild-type mitochondria. The ROS damage is slightly reduced and the mitochondrial unfolded protein response pathway is weakly activated in miro-1 mutants. Unlike previously described long-lived mitochondrial electron transport chain mutants, miro-1 mutants have normal growth rate. These results suggest that the reduction in the amount of mitochondria can affect the life span of an organism through activation of stress pathways. PMID:27064409

  20. Demography of Genotypes: Failure of the Limited Life-Span Paradigm in Drosophila melanogaster

    NASA Astrophysics Data System (ADS)

    Curtsinger, James W.; Fukui, Hidenori H.; Townsend, David R.; Vaupel, James W.

    1992-10-01

    Experimental systems that are amenable to genetic manipulation can be used to address fundamental questions about genetic and nongenetic determinants of longevity. Analysis of large cohorts of ten genotypes of Drosophila melanogaster raised under conditions that favored extended survival has revealed variation between genotypes in both the slope and location of age-specific mortality curves. More detailed examination of a single genotype showed that the mortality trajectory was best fit by a two-stage Gompertz model, with no age-specific increase in mortality rates beyond 30 days after emergence. These results are contrary to the limited life-span paradigm, which postulates well-defined, genotype-specific limits on life-span and brief periods of intense and rapidly accelerating mortality rates at the oldest ages.

  1. Basic traits predict the prevalence of personality disorder across the life span: the example of psychopathy.

    PubMed

    Vachon, David D; Lynam, Donald R; Widiger, Thomas A; Miller, Joshua D; McCrae, Robert R; Costa, Paul T

    2013-05-01

    Personality disorders (PDs) may be better understood in terms of dimensions of general personality functioning rather than as discrete categorical conditions. Personality-trait descriptions of PDs are robust across methods and settings, and PD assessments based on trait measures show good construct validity. The study reported here extends research showing that basic traits (e.g., impulsiveness, warmth, straightforwardness, modesty, and deliberation) can re-create the epidemiological characteristics associated with PDs. Specifically, we used normative changes in absolute trait levels to simulate age-related differences in the prevalence of psychopathy in a forensic setting. Results demonstrated that trait information predicts the rate of decline for psychopathy over the life span; discriminates the decline of psychopathy from that of a similar disorder, antisocial PD; and accurately predicts the differential decline of subfactors of psychopathy. These findings suggest that basic traits provide a parsimonious account of PD prevalence across the life span.

  2. Oral treatment with desipramine improves breathing and life span in Rett syndrome mouse model.

    PubMed

    Zanella, Sébastien; Mebarek, Saida; Lajard, Anne-Marie; Picard, Nathalie; Dutschmann, Mathias; Hilaire, Gérard

    2008-01-01

    Rett syndrome is a neurodevelopmental disease due to Mecp2 gene mutations that is associated to complex neurological symptoms, with bioaminergic deficits and life-threatening apneas related to sudden and unexpected death. In male mice, Mecp2-deficiency similarly induces medullary bioaminergic deficits, severe apneas and short life span. Here, we show that long-term oral treatment of Mecp2-deficient male mice with desipramine, an old drug of clinical use known to block norepinephrine uptake and to strengthen its synaptic effects, significantly alleviates their breathing symptoms and prolongs their life span. Although these mouse results identify desipramine as the first oral pharmacological treatment potentially able to alleviate breathing symptoms of Rett syndrome, we recommend further studies of desipramine effects in Mecp2-deficient mice before attempting any clinical trials in Rett patients.

  3. Verminoside mediates life span extension and alleviates stress in Caenorhabditis elegans.

    PubMed

    Pant, A; Asthana, J; Yadav, A K; Rathor, L; Srivastava, S; Gupta, M M; Pandey, R

    2015-01-01

    The discovery of bioactive molecules modulating aging in living organism promotes development of natural therapeutics for curing age-related afflictions. The progression in age-related disorders can be attributed to increment in intracellular reactive oxygen species (ROS) and oxidative stress level. To this end, we isolated an iridoid verminoside (VMS) from Stereospermum suaveolens (Roxb.) DC. and evaluated its effect on Caenorhabditis elegans. The present study delineates VMS-mediated alteration of intracellular ROS, oxidative stress, and life span in C. elegans. The different tested doses of VMS (5 μM, 25 μM, and 50 μM) were able to enhance ROS scavenging and extend mean life span in C. elegans. The maximal life span extension was observed in 25 μM VMS, that is, 20.79% (P < 0.0001) followed by 9.84% (P < 0.0001) in 5 μM VMS and 8.54% (P < 0.0001) in 50 μM VMS. VMS was able to alleviate juglone-induced oxidative stress and enhanced thermotolerance in worms. The stress-modulating and ROS-scavenging potential of VMS was validated by increment in mean survival by 29.54% (P < 0.0001) in VMS-treated oxidative stress hypersensitive mev-1 mutant strain. Furthermore, VMS modulates expression of DAF-16 (a FoxO transcription factor) promoting stress resistance and longevity. Altogether, our results suggest that VMS attenuates intracellular ROS and stress (oxidative and thermal) level promoting longevity. The longevity and stress modulation can be attributed to VMS-mediated alterations in daf-16 expression which regulates insulin signaling pathway. This study opens doors for development of phytomolecule-based therapeutics for prolonging life span and managing age-related severe disorders.

  4. 20S proteasome activation promotes life span extension and resistance to proteotoxicity in Caenorhabditis elegans.

    PubMed

    Chondrogianni, Niki; Georgila, Konstantina; Kourtis, Nikos; Tavernarakis, Nektarios; Gonos, Efstathios S

    2015-02-01

    Protein homeostasis (proteostasis) is one of the nodal points that need to be preserved to retain physiologic cellular/organismal balance. The ubiquitin-proteasome system (UPS) is responsible for the removal of both normal and damaged proteins, with the proteasome being the downstream effector. The proteasome is the major cellular protease with progressive impairment of function during aging and senescence. Despite the documented age-retarding properties of proteasome activation in various cellular models, simultaneous enhancement of the 20S core proteasome content, assembly, and function have never been reported in any multicellular organism. Consequently, the possible effects of the core proteasome modulation on organismal life span are elusive. In this study, we have achieved activation of the 20S proteasome at organismal level. We demonstrate enhancement of proteasome levels, assembly, and activity in the nematode Caenorhabditis elegans, resulting in life span extension and increased resistance to stress. We also provide evidence that the observed life span extension is dependent on the transcriptional activity of Dauer formation abnormal/Forkhead box class O (DAF-16/FOXO), skinhead-1 (SKN-1), and heat shock factor-1 (HSF-1) factors through regulation of downstream longevity genes. We further show that the reported beneficial effects are not ubiquitous but they are dependent on the genetic context. Finally, we provide evidence that proteasome core activation might be a potential strategy to minimize protein homeostasis deficiencies underlying aggregation-related diseases, such as Alzheimer's disease (AD) or Huntington's disease (HD). In summary, this is the first report demonstrating that 20S core proteasome up-regulation in terms of both content and activity is feasible in a multicellular eukaryotic organism and that in turn this modulation promotes extension of organismal health span and life span.

  5. On the need for a life-span approach to health campaign evaluation.

    PubMed

    Southwell, Brian G

    2010-09-01

    Campaign evaluation researchers should investigate age not just as an audience segmentation variable but also as a potentially valuable moderator of measure validity and campaign effects. Although researchers interested in physician-patient interaction and family communication have long considered aging dynamics, media campaign evaluation research has insufficiently addressed changes over the life span. In this article, I summarize some examples illustrating the importance of such work and propose additional theoretical possibilities.

  6. Life-Span Differences in the Uses and Gratifications of Tablets: Implications for Older Adults

    PubMed Central

    Magsamen-Conrad, Kate; Dowd, John; Abuljadail, Mohammad; Alsulaiman, Saud; Shareefi, Adnan

    2015-01-01

    This study extends Uses and Gratifications theory by examining the uses and gratifications of a new technological device, the tablet computer, and investigating the differential uses and gratifications of tablet computers across the life-span. First, we utilized a six-week tablet training intervention to adapt and extend existing measures to the tablet as a technological device. Next, we used paper-based and online surveys (N=847), we confirmed four main uses of tablets: 1) Information Seeking, 2) Relationship Maintenance, 3) Style, 4) Amusement and Killing time, and added one additional use category 5) Organization. We discovered differences among the five main uses of tablets across the life-span, with older adults using tablets the least overall. Builders, Boomers, GenX and GenY all reported the highest means for information seeking. Finally, we used a structural equation model to examine how uses and gratifications predicts hours of tablet use. The study provides limitations and suggestions for future research and marketers. In particular, this study offers insight to the relevancy of theory as it applies to particular information and communication technologies and consideration of how different periods in the life-span affect tablet motivations. PMID:26113769

  7. Causes and consequences of variation in conifer leaf life-span

    SciTech Connect

    Reich, P.B.; Koike, T.; Gower, S.T.; Schoettle, A.W.

    1995-07-01

    Species with mutually supporting traits, such as high N{sub mass}, SLA, and A{sub mass}, and short leaf life-span, tend to inhabit either generally resource-rich environments or spatial and/or temporal microhabitats that are resource-rich in otherwise more limited habitats (e.g., {open_quotes}precipitation{close_quotes} ephemerals in warm deserts or spring ephemerals in the understory of temperate deciduous forests). In contrast, species with long leaf life-span often support foliage with low SLA, N{sub mass}, and A{sub mass}, and often grow in low-temperature limited, dry, and/or nutrient-poor environments. The contrast between evergreen and deciduous species, and the implications that emerge from such comparisons, can be considered a paradigm of modern ecological theory. However, based on the results of Reich et al. (1992) and Gower et al. (1993), coniferous species with foliage that persists for 9-10 years are likely to assimilate and allocate carbon and nutrients differently than other evergreen conifers that retain foliage for 2-3 years. Thus, attempts to contrast ecophysiological or ecosystem characteristics of evergreen versus deciduous life forms may be misleading, and pronounced differences among evergreen conifers may be ignored. Clearly, the deciduous-evergreen contrast, although useful in several ways, should be viewed from the broader perspective of a gradient in leaf life-span.

  8. Determination of the cost of worker reproduction via diminished life span in the ant Diacamma sp.

    PubMed

    Tsuji, Kazuki; Kikuta, Noritsugu; Kikuchi, Tomonori

    2012-05-01

    Workers of social Hymenoptera can usually produce male offspring, but rarely do so in the presence of a queen despite the potential individual fitness benefit. Various mechanisms have been hypothesized to regulate worker reproduction, including avoiding the colony-level cost of worker reproduction. However, firm quantitative evidence is lacking to support that hypothesis. Here, we accurately quantified this cost by studying an ant species (Diacamma sp.) in which worker reproduction is rare in the presence of the gamergate (the functional queen). A series of experiments to manipulate worker-gamergate contact revealed that short-term brood-production efficiency is not changed by the presence of worker reproduction. However, when workers reproduce, their average life span is reduced to between 74% and 88% of that in the absence of reproduction, indicating a long-term cost to the colony. In theory, this cost can explain the policing of worker reproduction under a queen-single mating system, but the cost does not appear to be high enough to stop worker reproduction. When contact with the gamergate is lost, it is only the nonreproductive workers whose life span was reduced; the reproductive workers lived as long as nonorphaned workers. We suggest that an increased workload can account for the reduction in life span better than a trade-off between reproduction and longevity.

  9. Connecting Life Span Development with the Sociology of the Life Course: A New Direction

    PubMed Central

    Gilleard, Chris; Higgs, Paul

    2015-01-01

    The life course has become a topic of growing interest within the social sciences. Attempts to link this sub-discipline with life span developmental psychology have been called for but with little sign of success. In this paper, we seek to address three interlinked issues concerning the potential for a more productive interchange between life course sociology and life span psychology. The first is to try to account for the failure of these two sub-disciplines to achieve any deepening engagement with each other, despite the long-expressed desirability of that goal; the second is to draw attention to the scope for enriching the sociology of the life course through Erik Erikson’s model of life span development; and the last is the potential for linking Eriksonian theory with current debates within mainstream sociology about the processes involved in ‘individualisation’ and ‘self-reflexivity’ as an alternative entry point to bring together these two fields of work. PMID:27041774

  10. Does Dietary Restriction Reduce Life Span in Male Fruit-feeding Butterflies?

    PubMed Central

    Molleman, Freerk; Ding, Jimin; Boggs, Carol L.; Carey, James R.; Arlet, Małgorzata E.

    2009-01-01

    Male life history and resource allocation is not frequently studied in aging and life span research. Here we verify that males of long-lived fruit-feeding butterfly species have reduced longevity on restricted diets (Beck 2007 Oecologia), in contrast to the common finding of longevity extension in dietary restriction experiments in Drosophila and some other organisms. Males of some of the most long-lived species of fruit-feeding butterflies were collected from Kibale Forest, Uganda, and kept on diets of either sugar or mashed banana. Seven out of eight species had non-significantly longer life spans on mashed banana diets. Data analysis using a time-varying Cox-model with species as covariate showed that males had reduced survival on the sugar diet during the first 35 days of captive life, but the effect was absent or reversed at more advanced ages. These results challenge the generality of dietary restriction as a way to extend life span in animals. We argue that such studies on males are promising tools for better understanding life history evolution and aging because males display a wider variety of tactics for obtaining reproductive success than females. PMID:19580860

  11. Indy gene variation in natural populations confers fitness advantage and life span extension through transposon insertion.

    PubMed

    Zhu, Chen-Tseh; Chang, Chengyi; Reenan, Robert A; Helfand, Stephen L

    2014-01-01

    Natural selection acts to maximize reproductive fitness. However, antagonism between life span and reproductive success frequently poses a dilemma pitting the cost of fecundity against longevity. Here, we show that natural populations of Drosophila melanogaster harbor a Hoppel transposon insertion variant in the longevity gene Indy (I'm not dead yet), which confers both increased reproduction and longevity through metabolic changes. Heterozygosity for this natural long-lived variant has been maintained in isolates despite long-term inbreeding under laboratory conditions and advantageously confers increased fecundity. DNA sequences of variant chromosome isolates show evidence of selective sweep acting on the advantageous allele, suggesting that natural selection acts to maintain this variant. The transposon insertion also regulates Indy expression level, which has experimentally been shown to affect life span and fecundity. Thus, in the wild, evolution reaffirms that the mechanism of heterozygote advantage has acted upon the Indy gene to assure increased reproductive fitness and, coincidentally, longer life span through regulatory transposon mutagenesis.

  12. Life-Span Differences in the Uses and Gratifications of Tablets: Implications for Older Adults.

    PubMed

    Magsamen-Conrad, Kate; Dowd, John; Abuljadail, Mohammad; Alsulaiman, Saud; Shareefi, Adnan

    2015-11-01

    This study extends Uses and Gratifications theory by examining the uses and gratifications of a new technological device, the tablet computer, and investigating the differential uses and gratifications of tablet computers across the life-span. First, we utilized a six-week tablet training intervention to adapt and extend existing measures to the tablet as a technological device. Next, we used paper-based and online surveys (N=847), we confirmed four main uses of tablets: 1) Information Seeking, 2) Relationship Maintenance, 3) Style, 4) Amusement and Killing time, and added one additional use category 5) Organization. We discovered differences among the five main uses of tablets across the life-span, with older adults using tablets the least overall. Builders, Boomers, GenX and GenY all reported the highest means for information seeking. Finally, we used a structural equation model to examine how uses and gratifications predicts hours of tablet use. The study provides limitations and suggestions for future research and marketers. In particular, this study offers insight to the relevancy of theory as it applies to particular information and communication technologies and consideration of how different periods in the life-span affect tablet motivations.

  13. Life span decrements in fluid intelligence and processing speed predict mortality risk.

    PubMed

    Aichele, Stephen; Rabbitt, Patrick; Ghisletta, Paolo

    2015-09-01

    We examined life span changes in 5 domains of cognitive performance as predictive of mortality risk. Data came from the Manchester Longitudinal Study of Cognition, a 20-plus-year investigation of 6,203 individuals ages 42-97 years. Cognitive domains were general crystallized intelligence, general fluid intelligence, verbal memory, visuospatial memory, and processing speed. Life span decrements were evident across these domains, controlling for baseline performance at age 70 and adjusting for retest effects. Survival analyses stratified by sex and conducted independently by cognitive domain showed that lower baseline performance levels in all domains-and larger life span decrements in general fluid intelligence and processing speed-were predictive of increased mortality risk for both women and men. Critically, analyses of the combined predictive power of cognitive performance variables showed that baseline levels of processing speed (in women) and general fluid intelligence (in men), and decrements in processing speed (in women and in men) and general fluid intelligence (in women), accounted for most of the explained variation in mortality risk. In light of recent evidence from brain-imaging studies, we speculate that cognitive abilities closely linked to cerebral white matter integrity (such as processing speed and general fluid intelligence) may represent particularly sensitive markers of mortality risk. In addition, we presume that greater complexity in cognition-survival associations observed in women (in analyses incorporating all cognitive predictors) may be a consequence of longer and more variable cognitive declines in women relative to men.

  14. Leaf life span spectrum of tropical woody seedlings: effects of light and ontogeny and consequences for survival

    PubMed Central

    Kitajima, Kaoru; Cordero, Roberto A.; Wright, S. Joseph

    2013-01-01

    Background and Aims Leaf life span is widely recognized as a key life history trait associated with herbivory resistance, but rigorous comparative data are rare for seedlings. The goal of this study was to examine how light environment affects leaf life span, and how ontogenetic development during the first year may influence leaf fracture toughness, lamina density and stem density that are relevant for herbivory resistance, leaf life span and seedling survival. Methods Data from three experiments encompassing 104 neotropical woody species were combined. Leaf life span, lamina and vein fracture toughness, leaf and stem tissue density and seedling survival were quantified for the first-year seedlings at standardized ontogenetic stages in shade houses and common gardens established in gaps and shaded understorey in a moist tropical forest in Panama. Mortality of naturally recruited seedlings till 1 year later was quantified in 800 1-m2 plots from 1994 to 2011. Key Results Median leaf life span ranged widely among species, always greater in shade (ranging from 151 to >1790 d in the understorey and shade houses) than in gaps (115–867 d), but with strong correlation between gaps and shade. Leaf and stem tissue density increased with seedling age, whereas leaf fracture toughness showed only a weak increase. All these traits were positively correlated with leaf life span. Leaf life span and stem density were negatively correlated with seedling mortality in shade, while gap mortality showed no correlation with these traits. Conclusions The wide spectrum of leaf life span and associated functional traits reflects variation in shade tolerance of first-year seedlings among coexisting trees, shrubs and lianas in this neotropical forest. High leaf tissue density is important in enhancing leaf toughness, a known physical defence, and leaf life span. Both seedling leaf life span and stem density should be considered as key functional traits that contribute to seedling survival

  15. Resveratrol induces mitochondrial dysfunction and decreases chronological life span of Saccharomyces cerevisiae in a glucose-dependent manner.

    PubMed

    Ramos-Gomez, Minerva; Olivares-Marin, Ivanna Karina; Canizal-García, Melina; González-Hernández, Juan Carlos; Nava, Gerardo M; Madrigal-Perez, Luis Alberto

    2017-04-11

    A broad range of health benefits have been attributed to resveratrol (RSV) supplementation in mammalian systems, including the increases in longevity. Nonetheless, despite the growing number of studies performed with RSV, the molecular mechanism by which it acts still remains unknown. Recently, it has been proposed that inhibition of the oxidative phosphorylation activity is the principal mechanism of RSV action. This mechanism suggests that RSV might induce mitochondrial dysfunction resulting in oxidative damage to cells with a concomitant decrease of cell viability and cellular life span. To prove this hypothesis, the chronological life span (CLS) of Saccharomyces cerevisiae was studied as it is accepted as an important model of oxidative damage and aging. In addition, oxygen consumption, mitochondrial membrane potential, and hydrogen peroxide (H2O2) release were measured in order to determine the extent of mitochondrial dysfunction. The results demonstrated that the supplementation of S. cerevisiae cultures with 100 μM RSV decreased CLS in a glucose-dependent manner. At high-level glucose, RSV supplementation increased oxygen consumption during the exponential phase yeast cultures, but inhibited it in chronologically aged yeast cultures. However, at low-level glucose, oxygen consumption was inhibited in yeast cultures in the exponential phase as well as in chronologically aged cultures. Furthermore, RSV supplementation promoted the polarization of the mitochondrial membrane in both cultures. Finally, RSV decreased the release of H2O2 with high-level glucose and increased it at low-level glucose. Altogether, this data supports the hypothesis that RSV supplementation decreases CLS as a result of mitochondrial dysfunction and this phenotype occurs in a glucose-dependent manner.

  16. Poor growth prior to early childhood: decreased health and life-span in the adult.

    PubMed

    Clark, G A; Hall, N R; Armelagos, G J; Borkan, G A; Panjabi, M M; Wetzel, F T

    1986-06-01

    Previous studies in animal populations have shown that stunted neural and thymolymphatic growth early in development may result in permanently impaired neural and immune function, decreased body growth, vertebral wedging, and decreased life-span. In the human adult, small vertebral neural canal (VNC) diameters may reflect early stunted neural and immune development and impaired function that leads to decreased health (inferred by greater vertebral wedging) and life-span in the adult. VNC, which complete their growth by early childhood (age 4), are markers of early development in adults. On the other hand, features following general body growth, such as height, weight (represented here by vertebral body height) continues to grow until young adulthood. They are less reliable, because they readily experience catch-up growth (even in chronically stressed populations) and, unlike VNC, may mask poor early growth. To test associations between early growth and adult health and life-span in humans, we measured 2,060 VNC, vertebral heights, vertebral wedging, nerve-root tunnel lengths, severity of vertebral osteophytosis, and ages at death in 90 adult (aged 15-55 years) prehistoric skeletons (950-1300 A.D.). Tibial lengths were also measured in a subsample (n = 30). Multivariate, bivariate, and nonparametric analyses showed that small VNC are significantly associated with greater vertebral wedging and decreased life-span (P less than 0.05-0.00001). VNC are independent of vertebral body heights and tibial lengths (general body growth). VNC, but not statural components, are useful in predicting adult health, presumably because they reflect neural and immune development and do not readily experience catch-up growth. Thus, longitudinal retrospective measures of early growth and adult health were systematically linked within individuals regardless of confounding factors operating over the 350-year time period. Since this research was completed, this model has repeatedly been

  17. Extension of Health Span and Life Span in Drosophila by S107 Requires the calstabin Homologue FK506-BP2.

    PubMed

    Kreko-Pierce, Tabita; Azpurua, Jorge; Mahoney, Rebekah E; Eaton, Benjamin A

    2016-12-09

    The accumulation of oxidative damage is strongly linked to age-dependent declines in cell function, but the contribution of oxidative damage to morbidity is still debated. Many organisms seem to tolerate oxidative damage, and the extension of health span and life span by augmenting antioxidant activity has been inconsistent. Here we use the Drosophila model system to investigate the relationship among oxidative stress, health span, and life span. The oxidation-dependent dissociation of the Calstabin protein from the ryanodine receptor has been shown to result in reduced muscle function in mammals. The S107 molecule is able to reestablish this binding resulting in improved muscle function. We find that S107 is able to restore motor function in aging Drosophila to young levels, and this effect of S107 is absent in calstabin (FK506-BP2) mutants. Interestingly, FK506-BP2 mutant flies have reduced sensitivity to the effects of age and oxidative stress on motor function between 7 and 35 days of age. Muscle expression of FK506-BP2 in FK506-BP2 mutants completely restores the sensitivity of motor function to both age and oxidative stress, supporting the idea that the age-dependent decline in motor function in Drosophila requires FK506-BP2 function within the muscle. Although FK506-BP2 mutant flies are found to have less sensitivity to oxidative stress, FK506-BP2 mutants do not live longer than wild type. These results demonstrate that the deleterious effects of oxidation on motor function early in life are the result of a singular event that does not compromise survival.

  18. Comparative transcriptional pathway bioinformatic analysis of dietary restriction, Sir2, p53 and resveratrol life span extension in Drosophila.

    PubMed

    Antosh, Michael; Whitaker, Rachel; Kroll, Adam; Hosier, Suzanne; Chang, Chengyi; Bauer, Johannes; Cooper, Leon; Neretti, Nicola; Helfand, Stephen L

    2011-03-15

    A multiple comparison approach using whole genome transcriptional arrays was used to identify genes and pathways involved in calorie restriction/dietary restriction (DR) life span extension in Drosophila. Starting with a gene centric analysis comparing the changes in common between DR and two DR related molecular genetic life span extending manipulations, Sir2 and p53, lead to a molecular confirmation of Sir2 and p53's similarity with DR and the identification of a small set of commonly regulated genes. One of the identified upregulated genes, takeout, known to be involved in feeding and starvation behavior, and to have sequence homology with Juvenile Hormone (JH) binding protein, was shown to directly extend life span when specifically overexpressed. Here we show that a pathway centric approach can be used to identify shared physiological pathways between DR and Sir2, p53 and resveratrol life span extending interventions. The set of physiological pathways in common among these life span extending interventions provides an initial step toward defining molecular genetic and physiological changes important in life span extension. The large overlap in shared pathways between DR, Sir2, p53 and resveratrol provide strong molecular evidence supporting the genetic studies linking these specific life span extending interventions.

  19. ATM-dependent phosphorylation of SNEVhPrp19/hPso4 is involved in extending cellular life span and suppression of apoptosis

    PubMed Central

    Dellago, Hanna; Khan, Abdulhameed; Nussbacher, Monika; Gstraunthaler, Anna; Lämmermann, Ingo; Schosserer, Markus; Mück, Christoph; Anrather, Dorothea; Scheffold, Annika; Ammerer, Gustav; Jansen-Dürr, Pidder; Rudolph, Karl Lenhard; Voglauer-Grillari, Regina; Grillari, Johannes

    2012-01-01

    Defective DNA repair is widely acknowledged to negatively impact on healthy aging, since mutations in DNA repair factors lead to accelerated and premature aging. However, the opposite, namely if improved DNA repair will also increase the life or health span is less clear, and only few studies have tested if overexpression of DNA repair factors modulates life and health span in cells or organisms. Recently, we identified and characterized SNEVhPrp19/hPso4, a protein that plays a role in DNA repair and pre-mRNA splicing, and observed a doubling of the replicative life span upon ectopic overexpression, accompanied by lower basal DNA damage and apoptosis levels as well as an increased resistance to oxidative stress. Here we find that SNEVhPrp19/hPso4 is phosphorylated at S149 in an ataxia telangiectasia mutated protein (ATM)-dependent manner in response to oxidative stress and DNA double strand break inducing agents. By overexpressing wild-type SNEVhPrp19/hPso4 and a phosphorylation-deficient point-mutant, we found that S149 phosphorylation is necessary for mediating the resistance to apoptosis upon oxidative stress and is partially necessary for elongating the cellular life span. Therefore, ATM dependent phosphorylation of SNEVhPrp19/hPso4 upon DNA damage or oxidative stress might represent a novel axis capable of modulating cellular life span. PMID:22529335

  20. Age at Menopause, Reproductive Life Span, and Type 2 Diabetes Risk

    PubMed Central

    Brand, Judith S.; van der Schouw, Yvonne T.; Onland-Moret, N. Charlotte; Sharp, Stephen J.; Ong, Ken K.; Khaw, Kay-Tee; Ardanaz, Eva; Amiano, Pilar; Boeing, Heiner; Chirlaque, Maria-Dolores; Clavel-Chapelon, Françoise; Crowe, Francesca L.; de Lauzon-Guillain, Blandine; Duell, Eric J.; Fagherazzi, Guy; Franks, Paul W.; Grioni, Sara; Groop, Leif C.; Kaaks, Rudolf; Key, Timothy J.; Nilsson, Peter M.; Overvad, Kim; Palli, Domenico; Panico, Salvatore; Quirós, J. Ramón; Rolandsson, Olov; Sacerdote, Carlotta; Sánchez, María-José; Slimani, Nadia; Teucher, Birgit; Tjonneland, Anne; Tumino, Rosario; van der A, Daphne L.; Feskens, Edith J.M.; Langenberg, Claudia; Forouhi, Nita G.; Riboli, Elio; Wareham, Nicholas J.

    2013-01-01

    OBJECTIVE Age at menopause is an important determinant of future health outcomes, but little is known about its relationship with type 2 diabetes. We examined the associations of menopausal age and reproductive life span (menopausal age minus menarcheal age) with diabetes risk. RESEARCH DESIGN AND METHODS Data were obtained from the InterAct study, a prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition. A total of 3,691 postmenopausal type 2 diabetic case subjects and 4,408 subcohort members were included in the analysis, with a median follow-up of 11 years. Prentice weighted Cox proportional hazards models were adjusted for age, known risk factors for diabetes, and reproductive factors, and effect modification by BMI, waist circumference, and smoking was studied. RESULTS Mean (SD) age of the subcohort was 59.2 (5.8) years. After multivariable adjustment, hazard ratios (HRs) of type 2 diabetes were 1.32 (95% CI 1.04–1.69), 1.09 (0.90–1.31), 0.97 (0.86–1.10), and 0.85 (0.70–1.03) for women with menopause at ages <40, 40–44, 45–49, and ≥55 years, respectively, relative to those with menopause at age 50–54 years. The HR per SD younger age at menopause was 1.08 (1.02–1.14). Similarly, a shorter reproductive life span was associated with a higher diabetes risk (HR per SD lower reproductive life span 1.06 [1.01–1.12]). No effect modification by BMI, waist circumference, or smoking was observed (P interaction all > 0.05). CONCLUSIONS Early menopause is associated with a greater risk of type 2 diabetes. PMID:23230098

  1. Gender, Race, and Age: The Content of Compound Stereotypes Across the Life Span.

    PubMed

    Andreoletti, Carrie; Leszczynski, Jennifer P; Disch, William B

    2015-07-01

    While stereotypes about gender, race, and age (particularly old age) have been studied independently, few have examined the content of compound stereotypes that consider the intersection of gender, race, and age. Using a within-subjects design, we examined stereotypes as a function of target gender (male, female), race (Black, White), and age across the life span (adolescent, young adult, middle-aged, young-old, and old-old). Participants rated 20 target groups on 10 attributes representative of either an agentic (e.g., ambitious) or communal (e.g., considerate) orientation. Participants were presented only with categorical information (e.g., Black, 85-year-old, males), and ordering of categorical information and target groups was counterbalanced across participants. We hypothesized differential effects of target gender and race as a function of age. Multivariate analyses of variance on each attribute revealed significant main effects that supported traditional stereotype research, but significant interactions revealed a more complicated picture. Overall, results showed that while gender stereotypes about agency and communion generally hold up across the life span, they are more applicable to White than Black targets. Results also supported the notion that we hold unique stereotypes based on multiple social categories rather than simply perceiving one social category as more salient than another, which was best exemplified in the case of Black female targets that were less likely to be perceived in gender stereotypic ways across the life span. We suggest stereotype research needs to shift to accommodate for the complexity and diversity of real people.

  2. Sexual orientation across the life span: introduction to the special section.

    PubMed

    Patterson, Charlotte J

    2008-01-01

    What impact does sexual orientation have on human development over the life span? As questions related to sexual orientation have become increasingly topics of public discussion and debate in recent years, psychological study of the issues has also burgeoned. What was once a new frontier for research has matured into a large, complex, and rapidly growing area of knowledge. Important research is being conducted on many issues, by diverse investigators, from a number of theoretical perspectives, in many parts of the world. The articles in this special section provide only a sampling of current research, but they begin to suggest the vitality and excitement of a field that is coming into its own.

  3. Psychosocial stressors and the short life spans of legendary jazz musicians.

    PubMed

    Patalano, F

    2000-04-01

    Mean age at death of 168 legendary jazz musicians and 100 renowned classical musicians were compared to examine whether psychosocial stressors such as severe substance abuse, haphazard working conditions, lack of acceptance of jazz as an art form in the United States, marital and family discord, and a vagabond life style may have contributed to shortened life spans for the jazz musicians. Analysis indicated that the jazz musicians died at an earlier age (57.2 yr.) than the classical musicians (73.3 yr.).

  4. Provenance, life span, and phylogeny do not affect grass species' responses to nitrogen and phosphorus.

    PubMed

    Seabloom, Eric W; Benfield, Cara D; Borer, Elizabeth T; Stanley, Amanda G; Kaye, Thomas N; Dunwiddie, Peter W

    2011-09-01

    Successful conservation management requires an understanding of how species respond to intervention. Native and exotic species may respond differently to management interventions due to differences arising directly from their origin (i.e., provenance) or indirectly due to biased representations of different life history types (e.g., annual vs. perennial life span) or phylogenetic lineages among provenance (i.e., native or exotic origin) groups. Thus, selection of a successful management regime requires knowledge of the life history and provenance-bias in the local flora and an understanding of the interplay between species characteristics across existing environmental gradients in the landscape. Here we tested whether provenance, phylogeny, and life span interact to determine species distributions along natural gradients of soil chemistry (e.g., soil nitrogen and phosphorus) in 10 upland prairie sites along a 600-km latitudinal transect running from southern Vancouver Island in British Columbia, Canada, to the Willamette Valley in Oregon, USA. We found that soil nitrate, phosphorus, and pH exerted strong control over community composition. However, species distributions along environmental gradients were unrelated to provenance, life span, or phylogenetic groupings. We then used a greenhouse experiment to more precisely measure the response of common grass species to nitrogen and phosphorus supply. As with the field data, species responses to nutrient additions did not vary as a function of provenance, life span, or phylogeny. Native and exotic species differed strongly in the relationship between greenhouse-measured tolerance of low nutrients and field abundance. Native species with the greatest ability to maintain biomass production at low nutrient supply rates were most abundant in field surveys, as predicted by resource competition theory. In contrast, there was no relationship between exotic-species biomass at low nutrient levels and field abundance. The

  5. Holistic Life-Span Health Outcomes Among Elite Intercollegiate Student–Athletes

    PubMed Central

    Sorenson, Shawn C.; Romano, Russell; Scholefield, Robin M.; Martin, Brandon E.; Gordon, James E.; Azen, Stanley P.; Schroeder, E. Todd; Salem, George J.

    2014-01-01

    Context: Competitive sports are recognized as having unique health benefits and risks, and the effect of sports on life-span health among elite athletes has received increasing attention. However, supporting scientific data are sparse and do not represent modern athletes. Objective: To assess holistic life-span health and health-related quality-of-life (HRQL) among current and former National Collegiate Athletic Association student–athletes (SAs). Design: Cross-sectional study. Setting: A large Division I university. Patients or Other Participants: Population-based sample of 496 university students and alumni (age 17–84 years), including SAs and an age-matched and sex-matched nonathlete (NA) control group. Main Outcome Measure(s): Participants completed anonymous, self-report questionnaires. We measured the Short-Form 12 (SF-12) physical and mental component HRQL scores and cumulative lifetime experience and relative risk of treatment for joint, cardiopulmonary, and psychosocial health concerns. Results: Older alumni (age 43+ years) SAs reported greater joint health concerns than NAs (larger joint summary scores; P = .04; Cohen d = 0.69; probability of clinically important difference [pCID] = 77%; treatment odds ratio [OR] = 14.0, 95% confidence interval [CI] = 1.6, 126). Joint health for current and younger alumni SAs was similar to that for NAs. Older alumni reported greater cardiopulmonary health concerns than younger alumni (summary score P < .001; d = 1.05; pCID = 85%; OR = 5.8, 95% CI = 2.0, 16) and current students (P < .001; d = 2.25; pCID >99.5%; OR = 7.1, 95% CI = 3.3, 15), but the risk was similar for SAs and NAs. Current SAs demonstrated evidence of better psychosocial health (summary score P = .006; d = −0.52; pCID = 40%) and mental component HRQL (P = .008; d = 0.50; pCID = 48%) versus NAs but similar psychosocial treatment odds (OR = 0.87, 95% CI = 0.39, 1.9). Psychosocial health and mental component HRQL were similar between alumni SAs and NAs

  6. Caffeine extends life span, improves healthspan, and delays age-associated pathology in Caenorhabditis elegans

    PubMed Central

    2012-01-01

    Background The longevity of an organism is influenced by both genetic and environmental factors. With respect to genetic factors, a significant effort is being made to identify pharmacological agents that extend life span by targeting pathways with a defined role in the aging process. On the environmental side, the molecular mechanisms responsible for the positive influence of interventions such as dietary restriction are being explored. The environment experienced by humans in modern societies already contains countless compounds that may influence longevity. Understanding the role played by common compounds that substantially affect the aging process will be critical for predicting and interpreting the outcome of introducing new interventions. Caffeine is the most widely used psychoactive drug worldwide. Prior studies in flies, worms, and mice indicate that caffeine may positively impact age-associated neurodegenerative pathology, such as that observed in Alzheimer’s disease. Results Here we report that caffeine is capable of extending life span and improving healthspan in Caenorhabditis elegans, a finding that is in agreement with a recently published screen looking for FDA-approved compounds capable of extending worm life span. Life span extension using caffeine displays epistatic interaction with two known longevity interventions: dietary restriction and reduced insulin signaling. Caffeine treatment also delays pathology in a nematode model of polyglutamine disease. Conclusions The identification of caffeine as a relevant factor in aging and healthspan in worms, combined with prior work in both humans and rodents linking caffeine consumption to reduced risk of age-associated disease, suggests that caffeine may target conserved longevity pathways. Further, it may be important to consider caffeine consumption when developing clinical interventions, particularly those designed to mimic dietary restriction or modulate insulin/IGF-1-like signaling. The positive

  7. Targeting caspases in intracellular protozoan infections.

    PubMed

    Guillermo, Landi V C; Pereira, Wânia F; De Meis, Juliana; Ribeiro-Gomes, Flavia L; Silva, Elisabeth M; Kroll-Palhares, Karina; Takiya, Christina M; Lopes, Marcela F

    2009-06-01

    Caspases are cysteine aspartases acting either as initiators (caspases 8, 9, and 10) or executioners (caspases 3, 6, and 7) to induce programmed cell death by apoptosis. Parasite infections by certain intracellular protozoans increase host cell life span by targeting caspase activation. Conversely, caspase activation, followed by apoptosis of lymphocytes and other cells, prevents effective immune responses to chronic parasite infection. Here we discuss how pharmacological inhibition of caspases might affect the immunity to protozoan infections, by either blocking or delaying apoptosis.

  8. Life-span development of visual working memory: when is feature binding difficult?

    PubMed

    Cowan, Nelson; Naveh-Benjamin, Moshe; Kilb, Angela; Saults, J Scott

    2006-11-01

    We asked whether the ability to keep in working memory the binding between a visual object and its spatial location changes with development across the life span more than memory for item information. Paired arrays of colored squares were identical or differed in the color of one square, and in the latter case, the changed color was unique on that trial (item change) or was duplicated elsewhere in the array (color-location binding change). Children (8-10 and 11-12 years old) and older adults (65-85 years old) showed deficits relative to young adults. These were only partly simulated by dividing attention in young adults. The older adults had an additional deficiency, specifically in binding information, which was evident only when item- and binding-change trials were mixed together. In that situation, the older adults often overlooked the more subtle, binding-type changes. Some working memory processes related to binding undergo life-span development in an inverted-U shape, whereas other, bias- and salience-related processes that influence the use of binding information seem to develop monotonically.

  9. Hippocampal volume varies with educational attainment across the life-span

    PubMed Central

    Noble, Kimberly G.; Grieve, Stuart M.; Korgaonkar, Mayuresh S.; Engelhardt, Laura E.; Griffith, Erica Y.; Williams, Leanne M.; Brickman, Adam M.

    2012-01-01

    Socioeconomic disparities—and particularly differences in educational attainment—are associated with remarkable differences in cognition and behavior across the life-span. Decreased educational attainment has been linked to increased exposure to life stressors, which in turn have been associated with structural differences in the hippocampus and the amygdala. However, the degree to which educational attainment is directly associated with anatomical differences in these structures remains unclear. Recent studies in children have found socioeconomic differences in regional brain volume in the hippocampus and amygdala across childhood and adolescence. Here we expand on this work, by investigating whether disparities in hippocampal and amygdala volume persist across the life-span. In a sample of 275 individuals from the BRAINnet Foundation database ranging in age from 17 to 87, we found that socioeconomic status (SES), as operationalized by years of educational attainment, moderates the effect of age on hippocampal volume. Specifically, hippocampal volume tended to markedly decrease with age among less educated individuals, whereas age-related reductions in hippocampal volume were less pronounced among more highly educated individuals. No such effects were found for amygdala volume. Possible mechanisms by which education may buffer age-related effects on hippocampal volume are discussed. PMID:23162453

  10. Minocycline, but not ascorbic acid, increases motor activity and extends the life span of Drosophila melanogaster.

    PubMed

    Mora, Marylhi; Medina-Leendertz, Shirley J; Bonilla, Ernesto; Terán, Raikelin E; Paz, Milagros C; Arcaya, José Luis

    2013-06-01

    In the present study we compared the effects of minocycline and ascorbic acid in the life span, motor activity and lipid peroxidation of Drosophila melanogaster, in an effort to find a substance capable of providing protection against oxidative stress in aging. In the flies treated with minocycline a very significant increase in the life span (101 +/- 1.33 days) was observed when compared to those treated with ascorbic acid and controls (42.3% and 38.4%, respectively). The motor activity of minocycline treated flies also increased significantly with respect to control and ascorbic acid fed flies, from the 3rd to the 9th week of treatment. With regard to lipid peroxidation, it was found that the levels of malondialdehyde (MDA) in flies treated with minocycline showed no statistical differences to the control on the first day of treatment, but a significantly lower content on the day of 50% survival. In contrast, in flies treated with ascorbic acid significantly elevated levels of MDA compared to control and minocycline treated flies were detected throughout. These results suggest a protective effect of minocycline against oxidative stress and aging in D. melanogaster. An inhibitory effect on reactive oxygen species production may be an important contributing factor.

  11. Transformations in the couplings among intellectual abilities and constituent cognitive processes across the life span.

    PubMed

    Li, Shu-Chen; Lindenberger, Ulman; Hommel, Bernhard; Aschersleben, Gisa; Prinz, Wolfgang; Baltes, Paul B

    2004-03-01

    Two-component theories of intellectual development over the life span postulate that fluid abilities develop earlier during child development and decline earlier during aging than crystallized abilities do, and that fluid abilities support or constrain the acquisition and expression of crystallized abilities. Thus, maturation and senescence compress the structure of intelligence by imposing age-specific constraints upon its constituent processes. Hence, the couplings among different intellectual abilities and cognitive processes are expected to be strong in childhood and old age. Findings from a population-based study of 291 individuals aged 6 to 89 years support these predictions. Furthermore, processing robustness, a frequently overlooked aspect of processing, predicted fluid intelligence beyond processing speed in old age but not in childhood, suggesting that the causes of more compressed functional organization of intelligence differ between maturation and senescence. Research on developmental changes in functional brain circuitry may profit from explicitly recognizing transformations in the organization of intellectual abilities and their underlying cognitive processes across the life span.

  12. Relation of behaviour and macrophage function to life span in a murine model of premature immunosenescence.

    PubMed

    Guayerbas, Noelia; Catalán, Marina; Víctor, Víctor M; Miquel, Jaime; De la Fuente, Mónica

    2002-08-21

    According to our previous work, mice of the same strain and age show striking inter-individual differences in behaviour when exposed to a T-maze test. Further, the animals exploring the maze slowly (slow mice) or staying at the starting point (freezing behaviour), which show high levels of emotionality/anxiety in other standard behavioural tests, have a less competent immune system (earlier immunosenescence) than those which explore it quickly (fast mice). The present longitudinal study on OF-1 Swiss female mice confirms and extends the above findings. Thus, the animals showing a lower performance in the T-test (slow mice) which is accompanied by a poor neuromuscular coordination in a tightrope test, have a shorter life span than the good performers (fast mice). Moreover, the slow mice have a less competent immune system as regards the following functions of peritoneal macrophages: adherence to substrate, chemotaxis, ingestion of particles and superoxide anion production. This suggests that, at the same chronological age and as regards their immune competence, the slow mice are biologically older than the fast mice. This agrees with current ideas on the close functional relationship between the nervous and the immune system in the physiological adaptation to stress, and supports the concept that an optimum level of performance of these two systems is needed to attain a long life span.

  13. The life span of Drosophila melanogaster is affected by melatonin and thioctic acid.

    PubMed

    Terán, Raikelin; Bonilla, Ernesto; Medina-Leendertz, Shirley; Mora, Marylú; Villalobos, Virginia; Paz, Milagros; Arcaya, José L

    2012-09-01

    Aging and reduced longevity are due in part to the action of free radicals (FR). Melatonin (Mel) and thioctic acid (TA) are effective in protecting against the damage caused by FR. In this study, the effect of Mel and TA on the life cycle of Drosophila melanogaster was determined. We used a control group of flies, another group that was provided with Mel (0.43 mM) throughout their life cycle (Mel-c), a third group received Mel upon reaching adulthood (Mel-a) and two groups were fed with TA (2.15 mM) in the same manner (TA-c and TA-a). The number of eclosed, survival, phenotype changes, motor activity and the content of malondialdehyde (MDA) was evaluated in each group. Mel-c increased the eclosion rate and the motor activity of the flies. Mel-c and Mel-a increased the life span and decreased the concentrations of MDA. By contrast, TA-c diminished the eclosion rate, produced phenotypic changes and increased MDA levels and motor activity of the flies. TA-a extended the life span of flies, and did not alter MDA levels and motor activity when compared with the control group. In conclusion, Mel mitigated the effects caused by FR generated during aging, while TA-c increased lipid peroxidation and altered the phenotype of flies.

  14. Genetic Determinants of Human Health Span and Life Span: Progress and New Opportunities

    PubMed Central

    Martin, George M; Bergman, Aviv; Barzilai, Nir

    2007-01-01

    We review three approaches to the genetic analysis of the biology and pathobiology of human aging. The first and so far the best-developed is the search for the biochemical genetic basis of varying susceptibilities to major geriatric disorders. These include a range of progeroid syndromes. Collectively, they tell us much about the genetics of health span. Given that the major risk factor for virtually all geriatric disorders is biological aging, they may also serve as markers for the study of intrinsic biological aging. The second approach seeks to identify allelic contributions to exceptionally long life spans. While linkage to a locus on Chromosome 4 has not been confirmed, association studies have revealed a number of significant polymorphisms that impact upon late-life diseases and life span. The third approach remains theoretical. It would require longitudinal studies of large numbers of middle-aged sib-pairs who are extremely discordant or concordant for their rates of decline in various physiological functions. We can conclude that there are great opportunities for research on the genetics of human aging, particularly given the huge fund of information on human biology and pathobiology, and the rapidly developing knowledge of the human genome. PMID:17677003

  15. New tetradecyltrimethylammonium-selective electrodes: surface composition and topography as correlated with electrode's life span.

    PubMed

    Marafie, Hayat M; Al-Shammari, Tahani F; Shoukry, Adel F

    2012-03-15

    Two conventional plastic membrane electrodes that are selective for the tetradecyltrimethylammonium cation (TTA) have been prepared. The ion exchangers of these sensors were the ion associate, TTA-PT, and the ion aggregate, TTA-PSS, where PT and PSS are phosphotungstate and polystyrene sulfonate, respectively. The following performance characteristics of the TTA-PT- and TTA-PSS-containing electrodes were found: conditioning time of 30 and 20 min; potential response of 58.2 and 61.1 mV/TTA concentration decade; rectilinear concentration ranges of 2.0 × 10(-5)-5.0 × 10(-2) and 1.5 × 10(-5)-7.9 × 10(-2) mol L(-1); average working pH ranges of 4.0-10.5 and 3.8-10.7; life spans of 20 and 28 weeks, and isothermal temperature coefficients of 4.44 × 10(-4) and 6.10 × 10(-4)V/°C, respectively. Both electrodes exhibited high selectivity for TTA with an increasing number of inorganic and quaternary ammonium surfactant cations. These electrodes have been successfully applied to assay an antiseptic formulation containing TTA. Surface analyses using electron microscopy and X-ray photoelectron spectroscopy were used to determine the cause of the limited life span of plastic membrane electrodes.

  16. NRF2 deficiency reduces life span of mice administered thoracic irradiation.

    PubMed

    Travis, Elizabeth L; Rachakonda, Girish; Zhou, Xinhui; Korhonen, Katrina; Sekhar, Konjeti R; Biswas, Swati; Freeman, Michael L

    2011-09-15

    Subsets of cancer survivors who have been subjected to thoracic irradiation face the prospect of developing pulmonary injury. Radiation-induced pulmonary fibrosis is an insidious injury that presents 6 to 24 months after irradiation and continues to progress over a period of years. TGF-β and reactive oxygen species contribute significantly to the pathogenesis of this injury. The transcription factor NRF2 controls antioxidant gene expression and therefore regulates the cellular oxidant burden. This work demonstrates an additional paradigm for NRF2: suppression of TGF-β-mediated signaling, assessed by measuring expression of a surrogate TGF-β1 target gene (PAI-1) in lung fibroblasts. Thoracic irradiation of Nfe2l2(-/-) mice resulted in rapid expression of PAI-1 and FSP-1 compared to irradiated wild-type mice. Examination of lung tissue 16 weeks after thoracic irradiation of Nfe2l2(-/-) mice revealed the presence of distended alveoli and decreased numbers of alveoli compared to wild-type mice. Suppression of NRF2 expression shortened life span in mice administered 16 Gy to the thorax. Nfe2l2(+/-) and Nfe2l2(-/-) mice exhibited a mean life span of 176 days compared to wild-type mice, which lived an average of 212 days. These novel results identify NRF2 as a susceptibility factor for the development of late tissue injury.

  17. Linking Peroxiredoxin and Vacuolar-ATPase Functions in Calorie Restriction-Mediated Life Span Extension.

    PubMed

    Molin, Mikael; Demir, Ayse Banu

    2014-01-01

    Calorie restriction (CR) is an intervention extending the life spans of many organisms. The mechanisms underlying CR-dependent retardation of aging are still poorly understood. Despite mechanisms involving conserved nutrient signaling pathways proposed, few target processes that can account for CR-mediated longevity have so far been identified. Recently, both peroxiredoxins and vacuolar-ATPases were reported to control CR-mediated retardation of aging downstream of conserved nutrient signaling pathways. In this review, we focus on peroxiredoxin-mediated stress-defence and vacuolar-ATPase regulated acidification and pinpoint common denominators between the two mechanisms proposed for how CR extends life span. Both the activities of peroxiredoxins and vacuolar-ATPases are stimulated upon CR through reduced activities in conserved nutrient signaling pathways and both seem to stimulate cellular resistance to peroxide-stress. However, whereas vacuolar-ATPases have recently been suggested to control both Ras-cAMP-PKA- and TORC1-mediated nutrient signaling, neither the physiological benefits of a proposed role for peroxiredoxins in H2O2-signaling nor downstream targets regulated are known. Both peroxiredoxins and vacuolar-ATPases do, however, impinge on mitochondrial iron-metabolism and further characterization of their impact on iron homeostasis and peroxide-resistance might therefore increase our understanding of the beneficial effects of CR on aging and age-related diseases.

  18. Life span and reproductive cost explain interspecific variation in the optimal onset of reproduction.

    PubMed

    Mourocq, Emeline; Bize, Pierre; Bouwhuis, Sandra; Bradley, Russell; Charmantier, Anne; de la Cruz, Carlos; Drobniak, Szymon M; Espie, Richard H M; Herényi, Márton; Hötker, Hermann; Krüger, Oliver; Marzluff, John; Møller, Anders P; Nakagawa, Shinichi; Phillips, Richard A; Radford, Andrew N; Roulin, Alexandre; Török, János; Valencia, Juliana; van de Pol, Martijn; Warkentin, Ian G; Winney, Isabel S; Wood, Andrew G; Griesser, Michael

    2016-02-01

    Fitness can be profoundly influenced by the age at first reproduction (AFR), but to date the AFR-fitness relationship only has been investigated intraspecifically. Here, we investigated the relationship between AFR and average lifetime reproductive success (LRS) across 34 bird species. We assessed differences in the deviation of the Optimal AFR (i.e., the species-specific AFR associated with the highest LRS) from the age at sexual maturity, considering potential effects of life history as well as social and ecological factors. Most individuals adopted the species-specific Optimal AFR and both the mean and Optimal AFR of species correlated positively with life span. Interspecific deviations of the Optimal AFR were associated with indices reflecting a change in LRS or survival as a function of AFR: a delayed AFR was beneficial in species where early AFR was associated with a decrease in subsequent survival or reproductive output. Overall, our results suggest that a delayed onset of reproduction beyond maturity is an optimal strategy explained by a long life span and costs of early reproduction. By providing the first empirical confirmations of key predictions of life-history theory across species, this study contributes to a better understanding of life-history evolution.

  19. Estrogens maintain bone mass by regulating expression of genes controlling function and life span in mature osteoclasts.

    PubMed

    Imai, Yuuki; Youn, Ming-Young; Kondoh, Shino; Nakamura, Takashi; Kouzmenko, Alexander; Matsumoto, Takahiro; Takada, Ichiro; Takaoka, Kunio; Kato, Shigeaki

    2009-09-01

    Estrogens play a key role in regulation of bone mass and strength by controlling activity of bone-forming osteoblasts and bone-resorbing osteoclasts. Cellular effects of estrogens are mediated predominantly by the action of estrogen receptor alpha (ERalpha). In earlier studies, ablation of the ERalpha gene in mice did not result in osteoporotic phenotypes due to systemic endocrine disturbance and compensatory effects of elevated levels of testosterone. Despite the relatively well-established effects in osteoblasts, little is known about the direct action of estrogen in osteoclasts. Development in the last decade of more sophisticated genetic manipulation approaches opened new possibilities to explore cell-specific roles of nuclear receptors in bone tissue. Recently, we have generated osteoclast-specific ERalpha gene knockout mice and shown that in vivo estrogens directly regulate the life span of mature osteoclasts by inducing the expression of pro-apoptotic Fas ligand (FasL). Inhibitory effects of estrogens on osteoclast function were further studied in vitro. We observed sufficiently detectable ERalpha expression in osteoclasts differentiating from primary bone marrow cells or RAW264 cells, although levels of ERalpha were decreasing during progression of the differentiation into mature osteoclasts. Treatment with estrogens led to reduction in expression of osteoclast-specific genes controlling bone resorption activity. However, estrogens did not affect the size of multinucleated osteoclasts or number of nuclei in a mature osteoclast. In conclusion, in osteoclasts, estrogens function to inhibit bone resorption activity and vitality rather than differentiation.

  20. Life spans of a Bellman-Harris branching process with immigration

    SciTech Connect

    Badalbaev, I.S.; Mashrabbaev, A.

    1987-09-10

    One considers two schemes of the Bellman-Harris process with immigration when a) the lifetime of the particles is an integral-valued random variable and the immigration is defined by a sequence of independent random variables; b) the distribution of the lifetime of the particles is nonlattice and the immigration is a process with continuous time. One investigates the properties of the life spans of such processes. The results obtained here are a generalization to the case of Bellman-Harris processes of the results of A.M. Zubkov, obtained for Markov branching processes. For the proof one makes use in an essential manner of the known inequalities of Goldstein, estimating the generating function of the Bellman-Harris process in terms of the generating functions of the imbedded Galton-Watson process.

  1. Invited commentary: missing doses in the life span study of Japanese atomic bomb survivors.

    PubMed

    Ozasa, K; Grant, E J; Cullings, H M; Shore, R E

    2013-03-15

    The Life Span Study is a long-term epidemiologic cohort study of survivors of the atomic bombs dropped on Hiroshima and Nagasaki, Japan. In this issue of the Journal, Richardson et al. (Am J Epidemiol. 2013;177(6):562-568) suggest that those who died in the earliest years of follow-up were more likely to have a missing dose of radiation exposure assigned, leading to a bias in the radiation risk estimates. We show that nearly all members of the cohort had shielding information recorded before the beginning of follow-up and that much of the alleged bias that Richardson et al. describe simply reflects the geographic distribution of shielding conditions for which reliable dosimetry was impossible.

  2. Age and sex differences in strategies of coping and defense across the life span.

    PubMed

    Diehl, M; Coyle, N; Labouvie-Vief, G

    1996-03-01

    Age and sex differences in the use of coping and defense strategies were examined in life-span sample of 381 individuals. Participants responded to 2 self-report measures assessing mechanisms of coping and defense and measures assessing their level of cognitive complexity. Older adults used a combination of coping and defense strategies indicative of greater impulse control and the tendency to positively appraise conflict situations. Adolescents and younger adults used strategies that were outwardly aggressive and psychologically undifferentiated, indicating lower levels of impulse control and self-awareness. Women used more internalizing defenses than men and used coping strategies that flexibly integrated intra-and interpersonal aspects of conflict situations. Taken together, findings provide evidence for the age- and sex-specific use of strategies of coping and defense, suggesting that men and women may face different developmental tasks in the process toward maturity in adulthood.

  3. Exposure To Harmful Workplace Practices Could Account For Inequality In Life Spans Across Different Demographic Groups.

    PubMed

    Goh, Joel; Pfeffer, Jeffrey; Zenios, Stefanos

    2015-10-01

    The existence of important socioeconomic disparities in health and mortality is a well-established fact. Many pathways have been adduced to explain inequality in life spans. In this article we examine one factor that has been somewhat neglected: People with different levels of education get sorted into jobs with different degrees of exposure to workplace attributes that contribute to poor health. We used General Social Survey data to estimate differential exposures to workplace conditions, results from a meta-analysis that estimated the effect of workplace conditions on mortality, and a model that permitted us to estimate the overall effects of workplace practices on health. We conclude that 10-38 percent of the difference in life expectancy across demographic groups can be explained by the different job conditions their members experience.

  4. Partner preferences across the life span: online dating by older adults.

    PubMed

    Alterovitz, Sheyna Sears-Roberts; Mendelsohn, Gerald A

    2009-06-01

    Stereotypes of older adults as withdrawn or asexual fail to recognize that romantic relationships in later life are increasingly common. The authors analyzed 600 Internet personal ads from 4 age groups: 20-34, 40-54, 60-74, and 75+ years. Predictions from evolutionary theory held true in later life, when reproduction is no longer a concern. Across the life span, men sought physical attractiveness and offered status-related information more than women; women were more selective than men and sought status more than men. With age, men desired women increasingly younger than themselves, whereas women desired older men until ages 75 and over, when they sought men younger than themselves.

  5. The Verriest Lecture: Short-wave-sensitive cone pathways across the life span

    PubMed Central

    Werner, John S.

    2017-01-01

    Structurally and functionally, the short-wave-sensitive (S) cone pathways are thought to decline more rapidly with normal aging than the middle- and long-wave-sensitive cone pathways. This would explain the celebrated results by Verriest and others demonstrating that the largest age-related color discrimination losses occur for stimuli on a tritan axis. Here, we challenge convention, arguing from psychophysical data that selective S-cone pathway losses do not cause declines in color discrimination. We show substantial declines in chromatic detection and discrimination, as well as in temporal and spatial vision tasks, that are mediated by S-cone pathways. These functional losses are not, however, unique to S-cone pathways. Finally, despite reduced photon capture by S cones, their postreceptoral pathways provide robust signals for the visual system to renormalize itself to maintain nearly stable color perception across the life span. PMID:26974914

  6. Expert Panel Recommendations on Lower Urinary Tract Health of Women Across Their Life Span

    PubMed Central

    Losada, Liliana; Amundsen, Cindy L.; Ashton-Miller, James; Chai, Toby; Close, Clare; Damaser, Margot; DiSanto, Michael; Dmochowski, Roger; Fraser, Matthew O.; Kielb, Stephanie J.; Kuchel, George; Mueller, Elizabeth R.; Parker-Autry, Candace; Wolfe, Alan J.

    2016-01-01

    Abstract Urologic and kidney problems are common in women across their life span and affect their daily life, including physical activity, sexual relations, social life, and future health. Urological health in women is still understudied and the underlying mechanisms of female urological dysfunctions are not fully understood. The Society for Women's Health Research (SWHR®) recognized the need to have a roundtable discussion where researchers and clinicians would define the current state of knowledge, gaps, and recommendations for future research directions to transform women's urological health. This report summarizes the discussions, which focused on epidemiology, clinical presentation, basic science, prevention strategies, and efficacy of current therapies. Experts around the table agreed on a set of research, education, and policy recommendations that have the potential to dramatically increase awareness and improve women's urological health at all stages of life. PMID:27285829

  7. Materialism across the life span: An age-period-cohort analysis.

    PubMed

    Jaspers, Esther D T; Pieters, Rik G M

    2016-09-01

    This research examined the development of materialism across the life span. Two initial studies revealed that (a) lay beliefs were that materialism declines with age and (b) previous research findings also implied a modest, negative relationship between age and materialism. Yet, previous research has considered age only as a linear control variable, thereby precluding the possibility of more intricate relationships between age and materialism. Moreover, prior studies have relied on cross-sectional data and thus confound age and cohort effects. To improve on this, the main study used longitudinal data from 8 waves spanning 9 years of over 4,200 individuals (16 to 90 years) to examine age effects on materialism while controlling for cohort and period effects. Using a multivariate multilevel latent growth model, it found that materialism followed a curvilinear trajectory across the life span, with the lowest levels at middle age and higher levels before and after that. Thus, in contrast to lay beliefs, materialism increased in older age. Moreover, age effects on materialism differed markedly between 3 core themes of materialism: acquisition centrality, possession-defined success, and acquisition as the pursuit of happiness. In particular, acquisition centrality and possession-defined success were higher at younger and older age. Independent of these age effects, older birth cohorts were oriented more toward possession-defined success, whereas younger birth cohorts were oriented more toward acquisition centrality. The economic downturn since 2008 led to a decrease in acquisition as the pursuit of happiness and in desires for personal growth, but to an increase in desires for achievement. (PsycINFO Database Record

  8. Rapamycin extends life span of Rb1+/− mice by inhibiting neuroendocrine tumors

    PubMed Central

    Livi, Carolina B.; Hardman, Rulon L.; Christy, Barbara A.; Dodds, Sherry G.; Jones, Diane; Williams, Charnae; Strong, Randy; Bokov, Alex; Javors, Martin A.; Ikeno, Yuji; Hubbard, Gene; Hasty, Paul; Sharp, Zelton Dave

    2013-01-01

    Chronic treatment of mice with an enterically released formulation of rapamycin (eRapa) extends median and maximum life span, partly by attenuating cancer. The mechanistic basis of this response is not known. To gain a better understanding of these in vivo effects, we used a defined preclinical model of neuroendocrine cancer, Rb1+/− mice. Previous results showed that diet restriction (DR) had minimal or no effect on the lifespan of Rb1+/− mice, suggesting that the beneficial response to DR is dependent on pRb1. Since long-term eRapa treatment may at least partially mimic chronic DR in lifespan extension, we predicted that it would have a minimal effect in Rb1+/− mice. Beginning at 9 weeks of age until death, we fed Rb1+/− mice a diet without or with eRapa at 14 mg/kg food, which results in an approximate dose of 2.24 mg/kg body weight per day, and yielded rapamycin blood levels of about 4 ng/ml. Surprisingly, we found that eRapa dramatically extended life span of both female and male Rb1+/− mice, and slowed the appearance and growth of pituitary and decreased the incidence of thyroid tumors commonly observed in these mice. In this model, eRapa appears to act differently than DR, suggesting diverse mechanisms of action on survival and anti-tumor effects. In particular the beneficial effects of rapamycin did not depend on the dose of Rb1. PMID:23454836

  9. Stability and change: Stress responses and the shaping of behavioral phenotypes over the life span.

    PubMed

    Hennessy, Michael B; Kaiser, Sylvia; Tiedtke, Tobias; Sachser, Norbert

    2015-01-01

    In mammals, maternal signals conveyed via influences on hypothalamic-pituitary-adrenal (HPA) activity may shape behavior of the young to be better adapted for prevailing environmental conditions. However, the mother's influence extends beyond classic stress response systems. In guinea pigs, several hours (h) of separation from the mother activates not only the HPA axis, but also the innate immune system, which effects immediate behavioral change, as well as modifies behavioral responsiveness in the future. Moreover, the presence of the mother potently suppresses the behavioral consequences of this innate immune activation. These findings raise the possibility that long-term adaptive behavioral change can be mediated by the mother's influence on immune-related activity of her pups. Furthermore, the impact of social partners on physiological stress responses and their behavioral outcomes are not limited to the infantile period. A particularly crucial period for social development in male guinea pigs is that surrounding the attainment of sexual maturation. At this time, social interactions with adults can dramatically affect circulating cortisol concentrations and social behavior in ways that appear to prepare the male to best cope in its likely future social environment. Despite such multiple social influences on the behavior of guinea pigs at different ages, inter-individual differences in the magnitude of the cortisol response remain surprisingly stable over most of the life span. Together, it appears that throughout the life span, physiological stress responses may be regulated by social stimuli. These influences are hypothesized to adjust behavior for predicted environmental conditions. In addition, stable individual differences might provide a means of facilitating adaptation to less predictable conditions.

  10. Niacin-bound chromium increases life span in Zucker Fatty Rats.

    PubMed

    Preuss, Harry G; Echard, Bobby; Clouatre, Dallas; Bagchi, Debasis; Perricone, Nicholas V

    2011-10-01

    Avoiding insulin resistance (IR) associated with aging might lengthen life span based on previous studies using caloric-restricted animals. We assessed whether consuming niacin-bound chromium (NBC) alone or in a formula containing other so-called "insulin sensitizers" would overcome various manifestations of aging and extend life span in Zucker Fatty Rats (ZFR). We compared many metabolic parameters of ZFR fed NBC alone (n=12) or NBC in a unique formula (n=10) to a control group (n=10). In addition to NBC, the formula contained Allium sativum, Momordica charantia, Trigonella foenum-graecum and Gymnema sylvestre. The formula group received roughly 1/2 as much NBC daily as the NBC group. At week 44, all rats still lived, and no abnormalities in blood count (CBC), renal, or liver functions were found. In the two treatment groups compared to control, circulating glucose levels were significantly lower, with a trend toward lower HbA1C. Relatively elevated cholesterol and triglyceride concentrations occurred in the formula group. Compared to control, the NBC group had increased average lifespan (21.8%), median lifespan (14.1%), 30th percentile survival (19.6%), and maximum lifespan (22%). Despite similar beneficial effects on the glucose and blood pressure systems, a difference in aging was also found when the NBC group was compared to the formula group. When all rats in the other two groups had died, four in the NBC group continued to live at least a month longer. We attribute lack of a similar aging effect in the formula group to either lower dosing of NBC and/or that various ingredients in the formula counteracted the antiaging effect(s) of NBC.

  11. Virtual navigation strategies from childhood to senescence: evidence for changes across the life span

    PubMed Central

    Bohbot, Veronique D.; McKenzie, Sam; Konishi, Kyoko; Fouquet, Celine; Kurdi, Vanessa; Schachar, Russel; Boivin, Michel; Robaey, Philippe

    2012-01-01

    This study sought to investigate navigational strategies across the life span, by testing 8-years old children to 80-years old healthy older adults on the 4 on 8 virtual maze (4/8VM). The 4/8VM was previously developed to assess spontaneous navigational strategies, i.e., hippocampal-dependent spatial strategies (navigation by memorizing relationships between landmarks) versus caudate nucleus-dependent response strategies (memorizing a series of left and right turns from a given starting position). With the 4/8VM, we previously demonstrated greater fMRI activity and gray matter in the hippocampus of spatial learners relative to response learners. A sample of 599 healthy participants was tested in the current study. Results showed that 84.4% of children, 46.3% of young adults, and 39.3% of older adults spontaneously used spatial strategies (p < 0.0001). Our results suggest that while children predominantly use spatial strategies, the proportion of participants using spatial strategies decreases across the life span, in favor of response strategies. Factors promoting response strategies include repetition, reward and stress. Since response strategies can result from successful repetition of a behavioral pattern, we propose that the increase in response strategies is a biological adaptive mechanism that allows for the automatization of behavior such as walking in order to free up hippocampal-dependent resources. However, the down-side of this shift from spatial to response strategies occurs if people stop building novel relationships, which occurs with repetition and routine, and thereby stop stimulating their hippocampus. Reduced fMRI activity and gray matter in the hippocampus were shown to correlate with cognitive deficits in normal aging. Therefore, these results have important implications regarding factors involved in healthy and successful aging. PMID:23162463

  12. Metal-based superoxide dismutase and catalase mimics reduce oxidative stress biomarkers and extend life span of Saccharomyces cerevisiae.

    PubMed

    Ribeiro, Thales de P; Fonseca, Fernanda L; de Carvalho, Mariana D C; Godinho, Rodrigo M da C; de Almeida, Fernando Pereira; Saint'Pierre, Tatiana D; Rey, Nicolás A; Fernandes, Christiane; Horn, Adolfo; Pereira, Marcos D

    2017-01-15

    Aging is a natural process characterized by several biological changes. In this context, oxidative stress appears as a key factor that leads cells and organisms to severe dysfunctions and diseases. To cope with reactive oxygen species and oxidative-related damage, there has been increased use of superoxide dismutase (SOD)/catalase (CAT) biomimetic compounds. Recently, we have shown that three metal-based compounds {[Fe(HPClNOL)Cl2]NO3, [Cu(HPClNOL)(CH3CN)](ClO4)2 and Mn(HPClNOL)(Cl)2}, harboring in vitro SOD and/or CAT activities, were critical for protection of yeast cells against oxidative stress. In this work, treating Saccharomyces cerevisiae with these SOD/CAT mimics (25.0 µM/1 h), we highlight the pivotal role of these compounds to extend the life span of yeast during chronological aging. Evaluating lipid and protein oxidation of aged cells, it becomes evident that these mimics extend the life expectancy of yeast mainly due to the reduction in oxidative stress biomarkers. In addition, the treatment of yeast cells with these mimics regulated the amounts of lipid droplet occurrence, consistent with the requirement and protection of lipids for cell integrity during aging. Concerning SOD/CAT mimics uptake, using inductively coupled plasma mass spectrometry, we add new evidence that these complexes, besides being bioabsorbed by S. cerevisiae cells, can also affect metal homeostasis. Finally, our work presents a new application for these SOD/CAT mimics, which demonstrate a great potential to be employed as antiaging agents. Taken together, these promising results prompt future studies concerning the relevance of administration of these molecules against the emerging aging-related diseases such as Parkinson's, Alzheimer's and Huntington's.

  13. Metabotypes with properly functioning mitochondria and anti-inflammation predict extended productive life span in dairy cows

    PubMed Central

    Huber, K.; Dänicke, S.; Rehage, J.; Sauerwein, H.; Otto, W.; Rolle-Kampczyk, U.; von Bergen, M.

    2016-01-01

    The failure to adapt metabolism to the homeorhetic demands of lactation is considered as a main factor in reducing the productive life span of dairy cows. The so far defined markers of production performance and metabolic health in dairy cows do not predict the length of productive life span satisfyingly. This study aimed to identify novel pathways and biomarkers related to productive life in dairy cows by means of (targeted) metabolomics. In a longitudinal study from 42 days before up to 100 days after parturition, we identified metabolites such as long-chain acylcarnitines and biogenic amines associated with extended productive life spans. These metabolites are mainly secreted by the liver and depend on the functionality of hepatic mitochondria. The concentrations of biogenic amines and some acylcarnitines differed already before the onset of lactation thus indicating their predictive potential for continuation or early ending of productive life. PMID:27089826

  14. A life-span, relational, public health model of self-regulation: impact on individual and community health.

    PubMed

    Maniar, Swapnil; Zaff, Jonathan F

    2011-01-01

    In this chapter, the authors extend the ideas around the development of self-regulation and its impact on development by proposing a life-span, relational, public health model. They propose that the role of self-regulation should be understood across transitions from childhood to adulthood and through an individual and community perspective, including the relational process between the individual, the community, and contextual factors, such as the social determinants of health. These contextual factors may mediate or moderate the development of self-regulatory capacity across one's life span, influencing both individual and community health. Therefore, to ensure proper self-regulatory development, we must address the myriad external factors that undermine the development of self-regulation across the life span.

  15. Low Six4 and Six5 gene dosage improves dystrophic phenotype and prolongs life span of mdx mice.

    PubMed

    Yajima, Hiroshi; Kawakami, Kiyoshi

    2016-08-01

    Muscle regeneration is an important process for skeletal muscle growth and recovery. Repair of muscle damage is exquisitely programmed by cellular mechanisms inherent in myogenic stem cells, also known as muscle satellite cells. We demonstrated previously the involvement of homeobox transcription factors, SIX1, SIX4 and SIX5, in the coordinated proliferation and differentiation of isolated satellite cells in vitro. However, their roles in adult muscle regeneration in vivo remain elusive. To investigate SIX4 and SIX5 functions during muscle regeneration, we introduced knockout alleles of Six4 and Six5 into an animal model of Duchenne Muscular Dystrophy (DMD), mdx (Dmd(mdx) /Y) mice, characterized by frequent degeneration-regeneration cycles in muscles. A lower number of small myofibers, higher number of thick ones and lower serum creatine kinase and lactate dehydrogenase activities were noted in 50-week-old Six4(+/-) 5(+/-) Dmd(mdx) /Y mice than Dmd(mdx) /Y mice, indicating improvement of dystrophic phenotypes of Dmd(mdx) /Y mice. Higher proportions of cells positive for MYOD1 and MYOG (markers of regenerating myonuclei) and SIX1 (a marker of regenerating myoblasts and newly regenerated myofibers) in 12-week-old Six4(+/-) 5(+/-) Dmd(mdx) /Y mice suggested enhanced regeneration, compared with Dmd(mdx) /Y mice. Although grip strength was comparable in Six4(+/-) 5(+/-) Dmd(mdx) /Y and Dmd(mdx) /Y mice, treadmill exercise did not induce muscle weakness in Six4(+/-) 5(+/-) Dmd(mdx) /Y mice, suggesting higher regeneration capacity. In addition, Six4(+/-) 5(+/-) Dmd(mdx) /Y mice showed 33.8% extension of life span. The results indicated that low Six4 and Six5 gene dosage improved dystrophic phenotypes of Dmd(mdx) /Y mice by enhancing muscle regeneration, and suggested that SIX4 and SIX5 are potentially useful de novo targets in therapeutic applications against muscle disorders, including DMD.

  16. Resting-State Network Topology Differentiates Task Signals across the Adult Life Span

    PubMed Central

    Alhazmi, Fahd H.; Savalia, Neil K.

    2017-01-01

    Brain network connectivity differs across individuals. For example, older adults exhibit less segregated resting-state subnetworks relative to younger adults (Chan et al., 2014). It has been hypothesized that individual differences in network connectivity impact the recruitment of brain areas during task execution. While recent studies have described the spatial overlap between resting-state functional correlation (RSFC) subnetworks and task-evoked activity, it is unclear whether individual variations in the connectivity pattern of a brain area (topology) relates to its activity during task execution. We report data from 238 cognitively normal participants (humans), sampled across the adult life span (20–89 years), to reveal that RSFC-based network organization systematically relates to the recruitment of brain areas across two functionally distinct tasks (visual and semantic). The functional activity of brain areas (network nodes) were characterized according to their patterns of RSFC: nodes with relatively greater connections to nodes in their own functional system (“non-connector” nodes) exhibited greater activity than nodes with relatively greater connections to nodes in other systems (“connector” nodes). This “activation selectivity” was specific to those brain systems that were central to each of the tasks. Increasing age was accompanied by less differentiated network topology and a corresponding reduction in activation selectivity (or differentiation) across relevant network nodes. The results provide evidence that connectional topology of brain areas quantified at rest relates to the functional activity of those areas during task. Based on these findings, we propose a novel network-based theory for previous reports of the “dedifferentiation” in brain activity observed in aging. SIGNIFICANCE STATEMENT Similar to other real-world networks, the organization of brain networks impacts their function. As brain network connectivity patterns

  17. Environmental enrichment improves age-related immune system impairment: long-term exposure since adulthood increases life span in mice.

    PubMed

    Arranz, Lorena; De Castro, Nuria M; Baeza, Isabel; Maté, Ianire; Viveros, Maria Paz; De la Fuente, Mónica

    2010-08-01

    Age-related changes in immunity have been shown to highly influence morbidity and mortality. The aim of the present work was to study the effects of environmental enrichment (EE) (8-16 weeks) on several functions and oxidative stress parameters of peritoneal leukocytes, previously described as health and longevity markers, in mice at different ages, namely adult (44 +/- 4 weeks), old (69 +/- 4 weeks), and very old (92 +/- 4 weeks). Mortality rates were monitored in control and enriched animals, and effects on survival of long-term exposure to EE until natural death were determined. The results showed that exposure to EE was efficient in improving the function (i.e., macrophage chemotaxis and phagocytosis, lymphocyte chemotaxis and proliferation, natural killer cell activity, interleukin-2 and tumor necrosis factor-alpha levels) and decreasing the oxidative-inflammatory stress (i.e., lowered oxidized glutathione content, xanthine oxidase activity, expression of Toll-like receptors 2 and 4 on CD4 and CD8 cells, and increased reduced glutathione and glutathione peroxidase and catalase activities) of immune cells. These positive effects of EE were especially remarkable in animals at older ages. Importantly, long-term exposure to EE from adult age and until natural death stands out as a useful strategy to extend longevity. Thus, the present work confirms the importance of maintaining active mental and/or physical activity aiming to improve quality of life in terms of immunity, and demonstrates that this active life must be initiated at early stages of the aging process and preserved until death to improve life span.

  18. The frequency of 4 common gene polymorphisms in nonagenarians, centenarians, and average life span individuals.

    PubMed

    Kolovou, Genovefa; Kolovou, Vana; Vasiliadis, Ioannis; Giannakopoulou, Vasiliki; Mihas, Constantinos; Bilianou, Helen; Kollia, Aikaterini; Papadopoulou, Evaggelia; Marvaki, Apostolia; Goumas, Georgos; Kalogeropoulos, Petros; Limperi, Sotiria; Katsiki, Niki; Mavrogeni, Sophie

    2014-03-01

    Single nucleotide polymorphisms of angiotensin-converting enzyme (ACE) such as rs1799752, nuclear factor kappa B (NFkB) such as rs28362491 and cholesteryl ester transport protein (CETP) such as rs708272 (TaqB1) and rs5882 (I405V) were evaluated in nonagenarians, centenarians, and average life span individuals (controls). The study population (n = 307; 190 nonagenarians, 12 centenarians and 105 middle-aged controls) was genotyped for ACE, NFkB, and CETP genetic variants. The age of nonagenarian and centenarian group ranged between 90 and 111 years; centenarians and controls age ranged from 99 to 111, and from 18 to 80 years, respectively. The I carriers of ACE I/D gene were fewer in nonagenarians compared to centenarians (37.6% vs 62.5%, P = .016). The I carriers of ACE gene were more frequent in centenarians compared to controls (62% vs 41%, P = .045). No differences in frequency of common NFkB and CETP genotypes between patients with exceptional longevity and middle-aged patients were observed.

  19. Childhood self-control and unemployment throughout the life span: evidence from two British cohort studies.

    PubMed

    Daly, Michael; Delaney, Liam; Egan, Mark; Baumeister, Roy F

    2015-06-01

    The capacity for self-control may underlie successful labor-force entry and job retention, particularly in times of economic uncertainty. Analyzing unemployment data from two nationally representative British cohorts (N = 16,780), we found that low self-control in childhood was associated with the emergence and persistence of unemployment across four decades. On average, a 1-SD increase in self-control was associated with a reduction in the probability of unemployment of 1.4 percentage points after adjustment for intelligence, social class, and gender. From labor-market entry to middle age, individuals with low self-control experienced 1.6 times as many months of unemployment as those with high self-control. Analysis of monthly unemployment data before and during the 1980s recession showed that individuals with low self-control experienced the greatest increases in unemployment during the recession. Our results underscore the critical role of self-control in shaping life-span trajectories of occupational success and in affecting how macroeconomic conditions affect unemployment levels in the population.

  20. Octopamine controls starvation resistance, life span and metabolic traits in Drosophila

    PubMed Central

    Li, Yong; Hoffmann, Julia; Li, Yang; Stephano, Flora; Bruchhaus, Iris; Fink, Christine; Roeder, Thomas

    2016-01-01

    The monoamines octopamine (OA) and tyramine (TA) modulate numerous behaviours and physiological processes in invertebrates. Nevertheless, it is not clear whether these invertebrate counterparts of norepinephrine are important regulators of metabolic and life history traits. We show that flies (Drosophila melanogaster) lacking OA are more resistant to starvation, while their overall life span is substantially reduced compared with control flies. In addition, these animals have increased body fat deposits, reduced physical activity and a reduced metabolic resting rate. Increasing the release of OA from internal stores induced the opposite effects. Flies devoid of both OA and TA had normal body fat and metabolic rates, suggesting that OA and TA act antagonistically. Moreover, OA-deficient flies show increased insulin release rates. We inferred that the OA-mediated control of insulin release accounts for a substantial proportion of the alterations observed in these flies. Apparently, OA levels control the balance between thrifty and expenditure metabolic modes. Thus, changes in OA levels in response to external and internal signals orchestrate behaviour and metabolic processes to meet physiological needs. Moreover, chronic deregulation of the corresponding signalling systems in humans may be associated with metabolic disorders, such as obesity or diabetes. PMID:27759117

  1. Speech rate effects on the processing of conversational speech across the adult life span.

    PubMed

    Koch, Xaver; Janse, Esther

    2016-04-01

    This study investigates the effect of speech rate on spoken word recognition across the adult life span. Contrary to previous studies, conversational materials with a natural variation in speech rate were used rather than lab-recorded stimuli that are subsequently artificially time-compressed. It was investigated whether older adults' speech recognition is more adversely affected by increased speech rate compared to younger and middle-aged adults, and which individual listener characteristics (e.g., hearing, fluid cognitive processing ability) predict the size of the speech rate effect on recognition performance. In an eye-tracking experiment, participants indicated with a mouse-click which visually presented words they recognized in a conversational fragment. Click response times, gaze, and pupil size data were analyzed. As expected, click response times and gaze behavior were affected by speech rate, indicating that word recognition is more difficult if speech rate is faster. Contrary to earlier findings, increased speech rate affected the age groups to the same extent. Fluid cognitive processing ability predicted general recognition performance, but did not modulate the speech rate effect. These findings emphasize that earlier results of age by speech rate interactions mainly obtained with artificially speeded materials may not generalize to speech rate variation as encountered in conversational speech.

  2. Life span alteration after irradiation in Drosophila melanogaster strains with mutations of Hsf and Hsps.

    PubMed

    Moskalev, A; Shaposhnikov, M; Turysheva, E

    2009-02-01

    The life span alteration after gamma-irradiation and/or paraquat treatment in Drosophila in wild type strain Canton-S and strains with mutations of heat shock factor (1-4 alleles) and heat shock proteins (Hsp70Ba ( 304 ), Hsp83 ( e6A ), Hsp22 ( EY09909 ), Hsp67Bb ( EY099099 )) was investigated. Chronic low-dose rate gamma-irradiation (0.017 and 0.17 cGy/h) on pre-imago stages was used as a priming dose (absorbed doses were 4 and 40 cGy). Paraquat, a free radical inducing agent, was a challenging factor (20 mM for 1 day). It was shown that chronic irradiation led to adaptive response in both sexes except homozygous males and females with mutations of Hsf ( 4 ) and Hsp70Ba ( 304 ). The gender-specific differences in stress response were discovered in wild type strain Canton-S, Hsp22 ( EY09909 ) Hsp67Bb ( EY09909 ) homozygotes and Hsp83 ( e6A ) heterozygotes: the adaptive response persisted in males, but not in females. Thus, Drosophila Hsp and Hsf mutation homozygotes did not demonstrate the adaptive response in the majority of cases, implying an important role of those genes in radiation hormesis and adaptation to stresses.

  3. A structural-developmental psychodynamic approach to psychopathology: two polarities of experience across the life span.

    PubMed

    Blatt, Sidney J; Luyten, Patrick

    2009-01-01

    Consistent with principles of developmental psychopathology, this paper presents a broad psychodynamic structural developmental perspective that establishes conceptual continuities between processes of normal personality development, personality organization, concepts of psychopathology, and processes of therapeutic change. The major assumption of this approach is that personality development proceeds in a dialectic synergistic interaction between the development of capacities for interpersonal relatedness and the development of self-definition or identity. Extensive research demonstrates that these two dimensions define two broad types of personality organization, each with a particular experiential mode; preferred forms of cognition, defense, and adaptation; unique qualities of interpersonal relatedness and specific types of object and self-representation. Severe disruptions of this normal dialectic developmental process result in various forms of psychopathology organized in two basic configurations in which there is distorted defensive preoccupation, at different developmental levels, with one of these polarities (relatedness or self-definition) at the expense of the development of the other dimension. This paper reviews empirical findings supporting this approach to normal and disrupted personality development throughout the life cycle and considers its relationship to the internalizing-externalizing distinction in childhood and adolescence, attachment theory, and research on the interaction between biological and psychosocial factors in development across the life span. Finally, we discuss the implications of this approach for intervention and prevention.

  4. Exposure to anabolic-androgenic steroids shortens life span of male mice.

    PubMed

    Bronson, F H; Matherne, C M

    1997-05-01

    Adult male laboratory mice were exposed for 6 months to a combination of four anabolic-androgenic steroids of the kinds and at the relative levels to which human athletes and body builders expose themselves. The four steroids included testosterone, two 17-alkylated steroids, and an ester, and they were given at doses that totaled either 5 or 20 times normal androgenic maintenance levels for mice. By the time the survivors were 20 months old (1 yr after the termination of steroid exposure), 52% of the mice given the high dose of steroids had died compared with 35% of the mice given the low dose and only 12% of the control mice given no exogenous hormones (P < 0.001). Autopsy of the steroid-treated mice typically revealed tumors in the liver or kidney, other kinds of damage to these two organs, broadly invase lymphosarcomas, or heart damage, and usually more than one of these conditions. It can be concluded that the life span of male mice is decreased dramatically by exposing them for 6 months to the kinds and relative levels of anabolic steroids used by many athletes and body builders.

  5. Radiation effects on cancer risks in the Life Span Study cohort.

    PubMed

    Kodama, Kazunori; Ozasa, Kotaro; Katayama, Hiroaki; Shore, Roy E; Okubo, Toshiteru

    2012-10-01

    To determine late health effects of radiation in atomic bomb survivors, the Radiation Effects Research Foundation has been conducting studies on the Life Span Study (LSS) population, which consists of 93,000 atomic bomb survivors and 27,000 controls. A recent report on the incidence of solid cancers estimates that at the age of 70 y, after exposure at the age of 30 y, solid-cancer rates increase by about 35% per Gy for men and 58% per Gy for women. The age-at-exposure is an important risk modifier. Furthermore, it seems that radiation-associated increases in cancer rates persist throughout life. In addition, radiation has similar effects upon first-primary and second-primary cancer risks. A recent report on leukemia mortality suggested that the effect of radiation on leukemia mortality persisted for more than five decades. In addition, a significant dose-response for myelodysplastic syndrome is found in Nagasaki LSS members 40-60 y after radiation exposure. In view of the nature of the continuing increase in solid cancers, the LSS should continue to provide important new information on cancer risks, as most survivors still alive today were exposed to the atomic bomb radiation under the age of 20 y and are now entering their cancer-prone years.

  6. Aging Theories for Establishing Safe Life Spans of Airborne Critical Structural Components

    NASA Technical Reports Server (NTRS)

    Ko, William L.

    2003-01-01

    New aging theories have been developed to establish the safe life span of airborne critical structural components such as B-52B aircraft pylon hooks for carrying air-launch drop-test vehicles. The new aging theories use the equivalent-constant-amplitude loading spectrum to represent the actual random loading spectrum with the same damaging effect. The crack growth due to random loading cycling of the first flight is calculated using the half-cycle theory, and then extrapolated to all the crack growths of the subsequent flights. The predictions of the new aging theories (finite difference aging theory and closed-form aging theory) are compared with the classical flight-test life theory and the previously developed Ko first- and Ko second-order aging theories. The new aging theories predict the number of safe flights as considerably lower than that predicted by the classical aging theory, and slightly lower than those predicted by the Ko first- and Ko second-order aging theories due to the inclusion of all the higher order terms.

  7. β-N-Methylamino-L-alanine Induces Neurological Deficits and Shortened Life Span in Drosophila

    PubMed Central

    Zhou, Xianchong; Escala, Wilfredo; Papapetropoulos, Spyridon; Zhai, R. Grace

    2010-01-01

    The neurotoxic non-protein amino acid, β-N-methylamino-L-alanine (BMAA), was first associated with the high incidence of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) in Guam. Recently, BMAA has been implicated as a fierce environmental factor that contributes to the etiology of Alzheimer’s and Parkinson’s diseases, in addition to ALS. However, the toxicity of BMAA in vivo has not been clearly demonstrated. Here we report our investigation of the neurotoxicity of BMAA in Drosophila. We found that dietary intake of BMAA reduced life span, locomotor functions, and learning and memory abilities in flies. The severity of the alterations in phenotype is correlated with the concentration of BMAA detected in flies. Interestingly, developmental exposure to BMAA had limited impact on survival rate, but reduced fertility in females, and caused delayed neurological impairment in aged adults. Our studies indicate that BMAA exposure causes chronic neurotoxicity, and that Drosophila serves as a useful model in dissecting the pathogenesis of ALS/PDC. PMID:22069570

  8. Mixed emotions across the adult life span in the United States

    PubMed Central

    Schneider, Stefan; Stone, Arthur A.

    2015-01-01

    Mixed emotions involve the co-occurrence of positive and negative affect, such that people feel happy and sad at the same time. The purpose of the present study was to investigate age-related differences in the experience of mixed emotions across the adult life span in two nationally representative samples of U.S. residents. Data collected by the Princeton Affect and Time Survey (PATS, n = 3,948) and by the 2010 Wellbeing Module of the American Time Use Survey (ATUS, n = 12,828) were analyzed. In both surveys, respondents (aged 15 years or older) provided a detailed time diary about the preceding day and rated their happiness and sadness for three of the day's episodes. From these reports, three different indices of mixed emotions were derived. Results indicated small, but robust, increases in mixed emotions with age. Linear age increases were consistently evident in both PATS and ATUS, and replicated across the different indices of mixed emotions. There was no significant evidence for curvilinear age trends in either study. Several sociodemographic factors that could plausibly explain age-differences in mixed emotions (e.g., retirement, disability) did not alter the age-effects. The present study adds to the growing literature documenting vital changes in the complexity of emotional experience over the lifespan. PMID:25894487

  9. Childhood Adversity, Self-Esteem, and Diurnal Cortisol Profiles Across the Life Span.

    PubMed

    Zilioli, Samuele; Slatcher, Richard B; Chi, Peilian; Li, Xiaoming; Zhao, Junfeng; Zhao, Guoxiang

    2016-09-01

    Childhood adversity is associated with poor health outcomes in adulthood; the hypothalamic-pituitary-adrenal (HPA) axis has been proposed as a crucial biological intermediary of these long-term effects. Here, we tested whether childhood adversity was associated with diurnal cortisol parameters and whether this link was partially explained by self-esteem. In both adults and youths, childhood adversity was associated with lower levels of cortisol at awakening, and this association was partially driven by low self-esteem. Further, we found a significant indirect pathway through which greater adversity during childhood was linked to a flatter cortisol slope via self-esteem. Finally, youths who had a caregiver with high self-esteem experienced a steeper decline in cortisol throughout the day compared with youths whose caregiver reported low self-esteem. We conclude that self-esteem is a plausible psychological mechanism through which childhood adversity may get embedded in the activity of the HPA axis across the life span.

  10. Expressions of ecological identity across the life span of eight environmental exemplars

    NASA Astrophysics Data System (ADS)

    Seydel, Jennifer

    While there is a substantial body of literature looking at various aspects of ecological identity and factors that influence it, there has been less work done on how an individual's ecological identity changes with time. Much of that work is limited to short segments of the life span (e.g. the impact of wilderness experiences). This dissertation attempts to address this perceived gap by investigating how the ecological identity of eight environmental exemplars changed during the course of his or her life. What has emerged from this qualitative grounded theory investigation of the lives and works of Charles Darwin, John Muir, Aldo Leopold, Marjory Stoneman Douglas, Hazel Wolf, Rachel Carson, James Lovelock and E.O. Wilson are five sequential expressions of ecological identity. These 'stages' serve as a framework to explain ecological identity as a developmental process, both fluid and continuous, rather than at) end product. The development of an ecological identity is traced, through the development of five cognitive foundations and their alignment with five emotional foundations that reflect a progression from a sensory interaction and a kinship bond with nature into a deep understanding of the interconnectedness of all aspects of the planet. The findings reveal the evolution of an ecological identity and suggest the importance of looking beyond content knowledge in the nurturing of ecological attitudes, values, and lifestyles.

  11. Expected value information improves financial risk taking across the adult life span.

    PubMed

    Samanez-Larkin, Gregory R; Wagner, Anthony D; Knutson, Brian

    2011-04-01

    When making decisions, individuals must often compensate for cognitive limitations, particularly in the face of advanced age. Recent findings suggest that age-related variability in striatal activity may increase financial risk-taking mistakes in older adults. In two studies, we sought to further characterize neural contributions to optimal financial risk taking and to determine whether decision aids could improve financial risk taking. In Study 1, neuroimaging analyses revealed that individuals whose mesolimbic activation correlated with the expected value estimates of a rational actor made more optimal financial decisions. In Study 2, presentation of expected value information improved decision making in both younger and older adults, but the addition of a distracting secondary task had little impact on decision quality. Remarkably, provision of expected value information improved the performance of older adults to match that of younger adults at baseline. These findings are consistent with the notion that mesolimbic circuits play a critical role in optimal choice, and imply that providing simplified information about expected value may improve financial risk taking across the adult life span.

  12. Life span extension by targeting a link between metabolism and histone acetylation in Drosophila.

    PubMed

    Peleg, Shahaf; Feller, Christian; Forne, Ignasi; Schiller, Evelyn; Sévin, Daniel C; Schauer, Tamas; Regnard, Catherine; Straub, Tobias; Prestel, Matthias; Klima, Caroline; Schmitt Nogueira, Melanie; Becker, Lore; Klopstock, Thomas; Sauer, Uwe; Becker, Peter B; Imhof, Axel; Ladurner, Andreas G

    2016-03-01

    Old age is associated with a progressive decline of mitochondrial function and changes in nuclear chromatin. However, little is known about how metabolic activity and epigenetic modifications change as organisms reach their midlife. Here, we assessed how cellular metabolism and protein acetylation change during early aging in Drosophila melanogaster. Contrary to common assumptions, we find that flies increase oxygen consumption and become less sensitive to histone deacetylase inhibitors as they reach midlife. Further, midlife flies show changes in the metabolome, elevated acetyl-CoA levels, alterations in protein-notably histone-acetylation, as well as associated transcriptome changes. Based on these observations, we decreased the activity of the acetyl-CoA-synthesizing enzyme ATP citrate lyase (ATPCL) or the levels of the histone H4 K12-specific acetyltransferase Chameau. We find that these targeted interventions both alleviate the observed aging-associated changes and promote longevity. Our findings reveal a pathway that couples changes of intermediate metabolism during aging with the chromatin-mediated regulation of transcription and changes in the activity of associated enzymes that modulate organismal life span.

  13. Multimodal neuroimaging of male and female brain structure in health and disease across the life span

    PubMed Central

    Thompson, Paul M.

    2016-01-01

    Sex differences in brain development and aging are important to identify, as they may help to understand risk factors and outcomes in brain disorders that are more prevalent in one sex compared with the other. Brain imaging techniques have advanced rapidly in recent years, yielding detailed structural and functional maps of the living brain. Even so, studies are often limited in sample size, and inconsistent findings emerge, one example being varying findings regarding sex differences in the size of the corpus callosum. More recently, large‐scale neuroimaging consortia such as the Enhancing Neuro Imaging Genetics through Meta Analysis Consortium have formed, pooling together expertise, data, and resources from hundreds of institutions around the world to ensure adequate power and reproducibility. These initiatives are helping us to better understand how brain structure is affected by development, disease, and potential modulators of these effects, including sex. This review highlights some established and disputed sex differences in brain structure across the life span, as well as pitfalls related to interpreting sex differences in health and disease. We also describe sex‐related findings from the ENIGMA consortium, and ongoing efforts to better understand sex differences in brain circuitry. © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc. PMID:27870421

  14. Chips in black boxes? Convenience life span, parafood, brandwidth, families, and co-creation.

    PubMed

    Jacobs, Marc

    2015-11-01

    Any consumer who opens a bag of potato or corn chips (or crisps in the UK) knows there is no time to waste to enjoy or share them. The convenience life span of chips is limited: it is the shelf or storage life and a very limited time once outside the bag. Many technologies converge to generate the desired effect as a black box, not only of the packaging but also of the chips themselves. The concept of paratext can be applied to printed messages on the package, including the brand name and other texts like advertising (epitexts), which can be expanded into the concept of parafood. These concepts help to discuss technological developments and interpret why this has recently become a negotiation zone for co-creation (see the Do us a flavor campaigns). They are symptoms of changing relations between production, research and development, marketing, and consumption. This paper pays special attention to back stories, underdog brand biographies and narratives about origin. The concept of brandwidth is introduced to sensitize about the limits of combining different stories about chips. A recent brand biography, a family history and a cookery book are used to discuss the phenomenon of cooking with Fritos. Together with the concepts of parafood, brandwidth and black boxes, more reflection and dialogue about the role of history and heritage in marketing put new challenging perspectives on the agenda.

  15. Atomic Bomb Survivors Life-Span Study: Insufficient Statistical Power to Select Radiation Carcinogenesis Model.

    PubMed

    Socol, Yehoshua; Dobrzyński, Ludwik

    2015-01-01

    The atomic bomb survivors life-span study (LSS) is often claimed to support the linear no-threshold hypothesis (LNTH) of radiation carcinogenesis. This paper shows that this claim is baseless. The LSS data are equally or better described by an s-shaped dependence on radiation exposure with a threshold of about 0.3 Sievert (Sv) and saturation level at about 1.5 Sv. A Monte-Carlo simulation of possible LSS outcomes demonstrates that, given the weak statistical power, LSS cannot provide support for LNTH. Even if the LNTH is used at low dose and dose rates, its estimation of excess cancer mortality should be communicated as 2.5% per Sv, i.e., an increase of cancer mortality from about 20% spontaneous mortality to about 22.5% per Sv, which is about half of the usually cited value. The impact of the "neutron discrepancy problem" - the apparent difference between the calculated and measured values of neutron flux in Hiroshima - was studied and found to be marginal. Major revision of the radiation risk assessment paradigm is required.

  16. A fasting-responsive signaling pathway that extends life span in C. elegans.

    PubMed

    Uno, Masaharu; Honjoh, Sakiko; Matsuda, Mitsuhiro; Hoshikawa, Haruka; Kishimoto, Saya; Yamamoto, Tomohito; Ebisuya, Miki; Yamamoto, Takuya; Matsumoto, Kunihiro; Nishida, Eisuke

    2013-01-31

    Intermittent fasting is one of the most effective dietary restriction regimens that extend life span in C. elegans and mammals. Fasting-stimulus responses are key to the longevity response; however, the mechanisms that sense and transduce the fasting stimulus remain largely unknown. Through a comprehensive transcriptome analysis in C. elegans, we find that along with the FOXO transcription factor DAF-16, AP-1 (JUN-1/FOS-1) plays a central role in fasting-induced transcriptional changes. KGB-1, one of the C. elegans JNKs, acts as an activator of AP-1 and is activated in response to fasting. KGB-1 and AP-1 are involved in intermittent fasting-induced longevity. Fasting-induced upregulation of the components of the SCF E3 ubiquitin ligase complex via AP-1 and DAF-16 enhances protein ubiquitination and reduces protein carbonylation. Our results thus identify a fasting-responsive KGB-1/AP-1 signaling pathway, which, together with DAF-16, causes transcriptional changes that mediate longevity, partly through regulating proteostasis.

  17. Effects of kaolin particle films on the life span of an orb-weaver spider.

    PubMed

    Benhadi-Marín, Jacinto; Pereira, José Alberto; Santos, Sónia A P

    2016-02-01

    Araniella cucurbitina (Araneae: Araneidae) is a widespread orb-weaver spider commonly found in agroecosystems. Mineral particle films such as kaolin, due to their protective or anti-feeding action, can represent an alternative to pesticides, especially in organic farming systems, but little is known about its effects on A. cucurbitina. Therefore, we tested the effect of kaolin sprays on the life span of A. cucurbitina under laboratory conditions. Four treatments were tested encompassing different exposure routes. Thus, kaolin sprays were applied on (i) the surface, (ii) the prey (fly), (iii) the spider and (iv) both spider & prey. A control group was tested with water in each treatment. Results showed that sprays of kaolin significantly affected the survival of A. curcubitina when applications were done on the surface and on both spider & prey registering a reduction of 48% and 56%, respectively. Spiders in control obtained higher probability of reaching alive at the end of the assay than those treated with kaolin. Differences observed can be explained by the feeding behavior of the species and may depend on the consumption of the web by the spider and the ratio spider/fly for body size.

  18. Dietary intake of Curcuma longa and Emblica officinalis increases life span in Drosophila melanogaster.

    PubMed

    Rawal, Shilpa; Singh, Pavneet; Gupta, Ayush; Mohanty, Sujata

    2014-01-01

    Intake of food and nutrition plays a major role in affecting aging process and longevity. However, the precise mechanisms underlying the ageing process are still unclear. To this respect, diet has been considered to be a determinant of ageing process. In order to better illustrate this, we used Drosophila melanogaster as a model and fed them orally with different concentrations of two commonly used Indian medicinal plant products, Curcuma longa (rhizome) and Emblica officinalis (fruit). The results revealed significant increase in life span of Drosophila flies on exposure to both the plant products, more efficiently by C. Longa than by E. officinalis. In order to understand whether the increase in lifespan was due to high-antioxidant properties of these medicinal plants, we performed enzymatic assays to assess the SOD and catalase activities in case of both treated and control Drosophila flies. Interestingly, the results support the free radical theory of aging as both these plant derivatives show high reactive oxygen species (ROS) scavenging activities.

  19. Studying the Motivated Agent Through Time: Personal Goal Development During the Adult Life Span.

    PubMed

    Dunlop, William L; Bannon, Brittany L; McAdams, Dan P

    2017-04-01

    This research examined the rank-order and mean-level consistency of personal goals at two periods in the adult life span. Personal goal continuity was considered among a group of young adults (N = 145) who reported their goals three times over a 3-year period and among a group of midlife adults (N = 163) who specified their goals annually over a 4-year period. Goals were coded for a series of motive-based (viz., achievement, affiliation, intimacy, power) and domain-based (viz., finance, generativity, health, travel) categories. In both samples, we noted a moderate degree of rank-order consistency across assessment periods. In addition, the majority of goal categories exhibited a high degree of mean-level consistency. The results of this research suggest that (a) the content of goals exhibits a modest degree of rank-order consistency and a substantial degree of mean-level consistency over time, and (b) considering personality continuity and development as manifest via goals represents a viable strategy for personality psychologists.

  20. Deletion of Brca2 exon 27 causes hypersensitivity to DNA crosslinks, chromosomal instability, and reduced life span in mice

    NASA Technical Reports Server (NTRS)

    Donoho, Greg; Brenneman, Mark A.; Cui, Tracy X.; Donoviel, Dorit; Vogel, Hannes; Goodwin, Edwin H.; Chen, David J.; Hasty, Paul

    2003-01-01

    The Brca2 tumor-suppressor gene contributes to genomic stability, at least in part by a role in homologous recombinational repair. BRCA2 protein is presumed to function in homologous recombination through interactions with RAD51. Both exons 11 and 27 of Brca2 code for domains that interact with RAD51; exon 11 encodes eight BRC motifs, whereas exon 27 encodes a single, distinct interaction domain. Deletion of all RAD51-interacting domains causes embryonic lethality in mice. A less severe phenotype is seen with BRAC2 truncations that preserve some, but not all, of the BRC motifs. These mice can survive beyond weaning, but are runted and infertile, and die very young from cancer. Cells from such mice show hypersensitivity to some genotoxic agents and chromosomal instability. Here, we have analyzed mice and cells with a deletion of only the RAD51-interacting region encoded by exon 27. Mice homozygous for this mutation (called brca2(lex1)) have a shorter life span than that of control littermates, possibly because of early onsets of cancer and sepsis. No other phenotype was observed in these animals; therefore, the brca2(lex1) mutation is less severe than truncations that delete some BRC motifs. However, at the cellular level, the brca2(lex1) mutation causes reduced viability, hypersensitivity to the DNA interstrand crosslinking agent mitomycin C, and gross chromosomal instability, much like more severe truncations. Thus, the extreme carboxy-terminal region encoded by exon 27 is important for BRCA2 function, probably because it is required for a fully functional interaction between BRCA2 and RAD51. Copyright 2003 Wiley-Liss, Inc.

  1. Accessing Data Resources in the Mouse Phenome Database for Genetic Analysis of Murine Life Span and Health Span

    PubMed Central

    Peters, Luanne L.; Paigen, Beverly; Korstanje, Ron; Yuan, Rong; Ackert-Bicknell, Cheryl; Grubb, Stephen C.; Churchill, Gary A.; Chesler, Elissa J.

    2016-01-01

    Understanding the source of genetic variation in aging and using this variation to define the molecular mechanisms of healthy aging require deep and broad quantification of a host of physiological, morphological, and behavioral endpoints. The murine model is a powerful system in which to understand the relations across age-related phenotypes and to identify research models with variation in life span and health span. The Jackson Laboratory Nathan Shock Center of Excellence in the Basic Biology of Aging has performed broad characterization of aging in genetically diverse laboratory mice and has placed these data, along with data from several other major aging initiatives, into the interactive Mouse Phenome Database. The data may be accessed and analyzed by researchers interested in finding mouse models for specific aging processes, age-related health and disease states, and for genetic analysis of aging variation and trait covariation. We expect that by placing these data in the hands of the aging community that there will be (a) accelerated genetic analyses of aging processes, (b) discovery of genetic loci regulating life span, (c) identification of compelling correlations between life span and susceptibility for age-related disorders, and (d) discovery of concordant genomic loci influencing life span and aging phenotypes between mouse and humans. PMID:25533306

  2. Osteopenia is present at an early age and worsens across the life span in girls and women with Rett syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Girls and women with Rett syndrome (RTT) are at increased risk for osteopenia and skeletal fractures. Our objective was to characterize the natural history of bone mineralization in RTT girls and women across their life span and to identify genetic, nutritional, physical, hormonal, or inflammatory ...

  3. Self-Esteem Development across the Life Span: A Longitudinal Study with a Large Sample from Germany

    ERIC Educational Resources Information Center

    Orth, Ulrich; Maes, Jürgen; Schmitt, Manfred

    2015-01-01

    The authors examined the development of self-esteem across the life span. Data came from a German longitudinal study with 3 assessments across 4 years of a sample of 2,509 individuals ages 14 to 89 years. The self-esteem measure used showed strong measurement invariance across assessments and birth cohorts. Latent growth curve analyses indicated…

  4. Changes in Acoustic Characteristics of the Voice across the Life Span: Measures from Individuals 4-93 Years of Age

    ERIC Educational Resources Information Center

    Stathopoulos, Elaine T.; Huber, Jessica E.; Sussman, Joan E.

    2011-01-01

    Purpose: The purpose of the present investigation was to examine acoustic voice changes across the life span. Previous voice production investigations used small numbers of participants, had limited age ranges, and produced contradictory results. Method: Voice recordings were made from 192 male and female participants 4-93 years of age. Acoustic…

  5. Tor1/Sch9-regulated carbon source substitution is as effective as calorie restriction in life span extension.

    PubMed

    Wei, Min; Fabrizio, Paola; Madia, Federica; Hu, Jia; Ge, Huanying; Li, Lei M; Longo, Valter D

    2009-05-01

    The effect of calorie restriction (CR) on life span extension, demonstrated in organisms ranging from yeast to mice, may involve the down-regulation of pathways, including Tor, Akt, and Ras. Here, we present data suggesting that yeast Tor1 and Sch9 (a homolog of the mammalian kinases Akt and S6K) is a central component of a network that controls a common set of genes implicated in a metabolic switch from the TCA cycle and respiration to glycolysis and glycerol biosynthesis. During chronological survival, mutants lacking SCH9 depleted extracellular ethanol and reduced stored lipids, but synthesized and released glycerol. Deletion of the glycerol biosynthesis genes GPD1, GPD2, or RHR2, among the most up-regulated in long-lived sch9Delta, tor1Delta, and ras2Delta mutants, was sufficient to reverse chronological life span extension in sch9Delta mutants, suggesting that glycerol production, in addition to the regulation of stress resistance systems, optimizes life span extension. Glycerol, unlike glucose or ethanol, did not adversely affect the life span extension induced by calorie restriction or starvation, suggesting that carbon source substitution may represent an alternative to calorie restriction as a strategy to delay aging.

  6. Living the Dream? A Qualitative Retrospective Study Exploring the Role of Adolescent Aspirations across the Life Span

    ERIC Educational Resources Information Center

    Ashby, Julie S.; Schoon, Ingrid

    2012-01-01

    There is a lack of longitudinal research linking adolescent career aspirations to adult outcomes other than career and income attainment. Drawing on Nurmi's (2004) and Salmela-Aro, Aunola, and Nurmi's (2007) life-span model of motivation and using quantitative survey data at ages 16, 23, 33, 42, and 50 years, combined with retrospective interview…

  7. Modeling Life-Span Growth Curves of Cognition Using Longitudinal Data with Multiple Samples and Changing Scales of Measurement

    ERIC Educational Resources Information Center

    McArdle, John J.; Grimm, Kevin J.; Hamagami, Fumiaki; Bowles, Ryan P.; Meredith, William

    2009-01-01

    The authors use multiple-sample longitudinal data from different test batteries to examine propositions about changes in constructs over the life span. The data come from 3 classic studies on intellectual abilities in which, in combination, 441 persons were repeatedly measured as many as 16 times over 70 years. They measured cognitive constructs…

  8. Low-Dose-Rate Irradiation for 1 Hour Induces Protection Against Lethal Radiation Doses but Does Not Affect Life Span of DBA/2 Mice

    PubMed Central

    Altaner, Čestmír; Altanerova, Veronika; Ebbesen, Peter; Pettersen, Erik O.

    2016-01-01

    Prior findings showed that serum from DBA/2 mice that had been given whole-body irradiation for 1 hour at a low dose rate (LDR) of 30 cGy/h induced protection against radiation in reporter cells by a mechanism depending on transforming growth factor β3 and inducible nitric oxide synthase activity. In the present study, the effect of the 1 hour of LDR irradiation on the response of the preirradiated mice to a subsequent lethal dose and on the life span is examined. These DBA/2 mice were prime irradiated for 1 hour at 30 cGy/h. Two experiments with 9 and 9.5 Gy challenge doses given 6 weeks after priming showed increased survival in primed mice compared to unprimed mice followed up to 225 and 81 days after challenge irradiation, respectively. There was no overall significant difference in life span between primed and unprimed mice when no challenge irradiation was given. The males seemed to have a slight increase in lifespan after priming while the opposite was seen for the females. PMID:27867323

  9. Transcriptional remodeling in response to transfer upon carbon-limited or metformin-supplemented media in S. cerevisiae and its effect on chronological life span.

    PubMed

    Borklu-Yucel, Esra; Eraslan, Serpil; Ulgen, Kutlu O

    2015-08-01

    One of the factors affecting chronological life span (CLS) in budding yeast is nutrient, especially carbon limitation. Aside from metabolites in the growth medium such as glucose, amino acids, and acetic acid, many pharmaceuticals have also been proven to alter CLS. Besides their impact on life span, these drugs are also prospective chemicals to treat the age-associated diseases, so the identification of their action mechanism and their potential side effects is of crucial importance. In this study, the effects of caloric restriction and metformin, a dietary mimetic pharmaceutical, on yeast CLS are compared. Saccharomyces cerevisiae cells grown in synthetic dextrose complete (SDC) up to mid-exponential phase were either treated with metformin or were subjected to glucose limitation. The impacts of these perturbations were analyzed via transcriptomics, and the common (stimulation of glucose uptake, induction of mitochondrial maintenance, and reduction of protein translation) and divergent (stimulation of aerobic respiration and reprogramming of respiratory electron transport chain (ETC)) cellular responses specific to each treatment were determined. These results revealed that both glucose limitation and metformin treatment stimulate CLS extension and involve the mitochondrial function, probably by creating an efficient mitochondria-to-nucleus signaling of either aerobic respiration or ETC signaling stimulation, respectively.

  10. Life-span extension by dietary restriction is mediated by NLP-7 signaling and coelomocyte endocytosis in C. elegans

    PubMed Central

    Park, Sang-Kyu; Link, Christopher D.; Johnson, Thomas E.

    2010-01-01

    Recent studies have shown that the rate of aging can be modulated by diverse interventions. Dietary restriction is the most widely used intervention to promote longevity; however, the mechanisms underlying the effect of dietary restriction remain elusive. In a previous study, we identified two novel genes, nlp-7 and cup-4, required for normal longevity in Caenorhabditis elegans. nlp-7 is one of a set of neuropeptide-like protein genes; cup-4 encodes an ion-channel involved in endocytosis by coelomocytes. Here, we assess whether nlp-7 and cup-4 mediate longevity increases by dietary restriction. RNAi of nlp-7 or cup-4 significantly reduces the life span of the eat-2 mutant, a genetic model of dietary restriction, but has no effect on the life span of long-lived mutants resulting from reduced insulin/IGF-1 signaling or dysfunction of the mitochondrial electron transport chain. The life-span extension observed in wild-type N2 worms by dietary restriction using bacterial dilution is prevented significantly in nlp-7 and cup-4 mutants. RNAi knockdown of genes encoding candidate receptors of NLP-7 and genes involved in endocytosis by coelomocytes also specifically shorten the life span of the eat-2 mutant. We conclude that two novel pathways, NLP-7 signaling and endocytosis by coelomocytes, are required for life extension under dietary restriction in C. elegans.—Park, S.-K., Link, C. D., Johnson, T. E. Life-span extension by dietary restriction is mediated by NLP-7 signaling and coelomocyte endocytosis in C. elegans. PMID:19783783

  11. Missing doses in the life span study of Japanese atomic bomb survivors.

    PubMed

    Richardson, David B; Wing, Steve; Cole, Stephen R

    2013-03-15

    The Life Span Study of atomic bomb survivors is an important source of risk estimates used to inform radiation protection and compensation. Interviews with survivors in the 1950s and 1960s provided information needed to estimate radiation doses for survivors proximal to ground zero. Because of a lack of interview or the complexity of shielding, doses are missing for 7,058 of the 68,119 proximal survivors. Recent analyses excluded people with missing doses, and despite the protracted collection of interview information necessary to estimate some survivors' doses, defined start of follow-up as October 1, 1950, for everyone. We describe the prevalence of missing doses and its association with mortality, distance from hypocenter, city, age, and sex. Missing doses were more common among Nagasaki residents than among Hiroshima residents (prevalence ratio = 2.05; 95% confidence interval: 1.96, 2.14), among people who were closer to ground zero than among those who were far from it, among people who were younger at enrollment than among those who were older, and among males than among females (prevalence ratio = 1.22; 95% confidence interval: 1.17, 1.28). Missing dose was associated with all-cancer and leukemia mortality, particularly during the first years of follow-up (all-cancer rate ratio = 2.16, 95% confidence interval: 1.51, 3.08; and leukemia rate ratio = 4.28, 95% confidence interval: 1.72, 10.67). Accounting for missing dose and late entry should reduce bias in estimated dose-mortality associations.

  12. Missing Doses in the Life Span Study of Japanese Atomic Bomb Survivors

    PubMed Central

    Richardson, David B.; Wing, Steve; Cole, Stephen R.

    2013-01-01

    The Life Span Study of atomic bomb survivors is an important source of risk estimates used to inform radiation protection and compensation. Interviews with survivors in the 1950s and 1960s provided information needed to estimate radiation doses for survivors proximal to ground zero. Because of a lack of interview or the complexity of shielding, doses are missing for 7,058 of the 68,119 proximal survivors. Recent analyses excluded people with missing doses, and despite the protracted collection of interview information necessary to estimate some survivors' doses, defined start of follow-up as October 1, 1950, for everyone. We describe the prevalence of missing doses and its association with mortality, distance from hypocenter, city, age, and sex. Missing doses were more common among Nagasaki residents than among Hiroshima residents (prevalence ratio = 2.05; 95% confidence interval: 1.96, 2.14), among people who were closer to ground zero than among those who were far from it, among people who were younger at enrollment than among those who were older, and among males than among females (prevalence ratio = 1.22; 95% confidence interval: 1.17, 1.28). Missing dose was associated with all-cancer and leukemia mortality, particularly during the first years of follow-up (all-cancer rate ratio = 2.16, 95% confidence interval: 1.51, 3.08; and leukemia rate ratio = 4.28, 95% confidence interval: 1.72, 10.67). Accounting for missing dose and late entry should reduce bias in estimated dose-mortality associations. PMID:23429722

  13. Implicit Motor Sequence Learning and Working Memory Performance Changes Across the Adult Life Span

    PubMed Central

    Meissner, Sarah Nadine; Keitel, Ariane; Südmeyer, Martin; Pollok, Bettina

    2016-01-01

    Although implicit motor sequence learning is rather well understood in young adults, effects of aging on this kind of learning are controversial. There is first evidence that working memory (WM) might play a role in implicit motor sequence learning in young adults as well as in adults above the age of 65. However, the knowledge about the development of these processes across the adult life span is rather limited. As the average age of our population continues to rise, a better understanding of age-related changes in motor sequence learning and potentially mediating cognitive processes takes on increasing significance. Therefore, we investigated aging effects on implicit motor sequence learning and WM. Sixty adults (18–71 years) completed verbal and visuospatial n-back tasks and were trained on a serial reaction time task (SRTT). Randomly varying trials served as control condition. To further assess consolidation indicated by off-line improvement and reduced susceptibility to interference, reaction times (RTs) were determined 1 h after initial learning. Young and older but not middle-aged adults showed motor sequence learning. Nine out of 20 older adults (compared to one young/one middle-aged) exhibited some evidence of sequence awareness. After 1 h, young and middle-aged adults showed off-line improvement. However, RT facilitation was not specific to sequence trials. Importantly, susceptibility to interference was reduced in young and older adults indicating the occurrence of consolidation. Although WM performance declined in older participants when load was high, it was not significantly related to sequence learning. The data reveal a decline in motor sequence learning in middle-aged but not in older adults. The use of explicit learning strategies in older adults might account for the latter result. PMID:27199736

  14. Derived Trail Making Test indices: demographics and cognitive background variables across the adult life span.

    PubMed

    Christidi, Foteini; Kararizou, Evangelia; Triantafyllou, Nikolaos; Anagnostouli, Maria; Zalonis, Ioannis

    2015-01-01

    We examined the contribution of demographics and cognitive background variables (processing speed, visuospatial skill, working memory, and interference control) on derived Trail Making Test (TMT) scores in a large sample of Greek healthy participants. We included 775 participants and administered the TMT (TMT-A and TMT-B) and the Wechsler Intelligence Adult Scale (WAIS). Direct (TMT-A & TMT-B time-to-completion) and derived [difference TMT-(B - A) & ratio TMT-(B/A)] scores were calculated. Demographics (age, age(2), education, and gender) and WAIS Full Intelligence Quotient significantly predicted the direct TMT-A (R(2) = 0.426) and TMT-B (R(2) = 0.593) scores and to a lesser extent, the derived TMT-(B - A) (R(2) = 0.343) and TMT-(B/A) (R(2) = 0.088) scores. In a subsample of 537 healthy participants who also completed the Stroop Neuropsychological Screening Test (SNST), demographics (age and education), WAIS Digit Symbol, Block Design, Arithmetic, and SNST accounted for 44.8% and 59.7% of the variance on TMT-A and TMT-B, and 32.5% and 9.6% of the variance on TMT-(B - A) and TMT-(B/A), respectively. We found minimal influence of Block Design and Arithmetic on TMT-(B - A) and an absence of significant influence of any cognitive variable on TMT-(B/A) score. Concluding, derived TMT scores are suggested as indices to detect impairment in cognitive flexibility across the adult life span, since they minimize the effect of demographics and other cognitive background variables.

  15. The genetic architecture of life span and mortality rates: gender and species differences in inbreeding load of two seed-feeding beetles.

    PubMed

    Fox, Charles W; Scheibly, Kristy L; Wallin, William G; Hitchcock, Lisa J; Stillwell, R Craig; Smith, Benjamin P

    2006-10-01

    We examine the inbreeding load for adult life span and mortality rates of two seed beetle species, Callosobruchus maculatus and Stator limbatus. Inbreeding load differs substantially between males and females in both study populations of C. maculatus--life span of inbred females was 9-13% shorter than the life span of outbred females, whereas the life span of inbred males did not differ from the life span of outbred males. The effect of inbreeding on female life span was largely due to an increase in the slope of the mortality curve. In contrast, inbreeding had only a small effect on the life span of S. limbatus--life spans of inbred beetles were approximately 5% shorter than those of outbred beetles, and there was no difference in inbreeding load between the sexes. The inbreeding load for mean life span was approximately 0.4-0.6 lethal equivalents per haploid gamete for female C. maculatus and approximately 0.2-0.3 for both males and females of S. limbatus, all within the range of estimates commonly obtained for Drosophila. However, contrary to the predictions of mutation-accumulation models, inbreeding load for loci affecting mortality rates did not increase with age in either species, despite an effect of inbreeding on the initial rate of increase in mortality. This was because mortality rates decelerated with age and converged to a mortality plateau for both outbred and inbred beetles.

  16. Sex-specific Tradeoffs With Growth and Fitness Following Life-span Extension by Rapamycin in an Outcrossing Nematode, Caenorhabditis remanei.

    PubMed

    Lind, Martin I; Zwoinska, Martyna K; Meurling, Sara; Carlsson, Hanne; Maklakov, Alexei A

    2016-07-01

    Rapamycin inhibits the nutrient-sensing TOR pathway and extends life span in a wide range of organisms. Although life-span extension usually differs between the sexes, the reason for this is poorly understood. Because TOR influences growth, rapamycin likely affects life-history traits such as growth and reproduction. Sexes have different life-history strategies, and theory predicts that they will resolve the tradeoffs between growth, reproduction, and life span differently. Specifically, in taxa with female-biased sexual size dimorphism, reduced growth may have smaller effects on male fitness. We investigated the effects of juvenile, adult, or life-long rapamycin treatment on growth, reproduction, life span, and individual fitness in the outcrossing nematode Caenorhabditis remanei Life-long exposure to rapamycin always resulted in the strongest response, whereas postreproductive exposure did not affect life span. Although rapamycin resulted in longer life span and smaller size in males, male individual fitness was not affected. In contrast, size and fitness were negatively affected in females, whereas life span was only extended under high rapamycin concentrations. Our results support the hypothesis that rapamycin affects key life-history traits in a sex-specific manner. We argue that the fitness cost of life-span extension will be sex specific and propose that the smaller sex generally pay less while enjoying stronger life-span increase.

  17. Dietary supplementation with Lovaza and krill oil shortens the life span of long-lived F1 mice.

    PubMed

    Spindler, Stephen R; Mote, Patricia L; Flegal, James M

    2014-06-01

    Marine oils rich in ω-3 polyunsaturated fatty acids have been recommended as a preventive treatment for patients at risk for cardiovascular diseases. These oils also are the third most consumed dietary supplement in the USA. However, evidence for their health benefits is equivocal. We tested the daily, isocaloric administration of krill oil (1.17 g oil/kg diet) and Lovaza (Omacor; 4.40 g/kg diet), a pharmaceutical grade fish oil, beginning at 12 months of age, on the life span and mortality-related pathologies of long-lived, male, B6C3F1 mice. The oils were incorporated into the chemically defined American Institute of Nutrition (AIN)-93 M diet. An equivalent volume of soybean oil was removed. Krill oil was 3 % and Lovaza 11 % of the oil in the diets. When their effects were analyzed together, the marine oils significantly shortened life span by 6.6 % (P = 0.0321; log-rank test) relative to controls. Individually, Lovaza and krill oil non-significantly shortened median life span by 9.8 and 4.7 %, respectively. Lovaza increased the number of enlarged seminal vesicles (7.1-fold). Lovaza and krill oil significantly increased lung tumors (4.1- and 8.2-fold) and hemorrhagic diathesis (3.9- and 3.1-fold). Analysis of serum from treated mice found that Lovaza slightly increased blood urea nitrogen, while krill oil modestly increased bilirubin, triglycerides, and blood glucose levels. Taken together, the results do not support the idea that the consumption of isolated ω-3 fatty acid-rich oils will increase the life span or health of initially healthy individuals.

  18. Effects of shortened host life span on the evolution of parasite life history and virulence in a microbial host-parasite system

    PubMed Central

    Nidelet, Thibault; Koella, Jacob C; Kaltz, Oliver

    2009-01-01

    Background Ecological factors play an important role in the evolution of parasite exploitation strategies. A common prediction is that, as shorter host life span reduces future opportunities of transmission, parasites compensate with an evolutionary shift towards earlier transmission. They may grow more rapidly within the host, have a shorter latency time and, consequently, be more virulent. Thus, increased extrinsic (i.e., not caused by the parasite) host mortality leads to the evolution of more virulent parasites. To test these predictions, we performed a serial transfer experiment, using the protozoan Paramecium caudatum and its bacterial parasite Holospora undulata. We simulated variation in host life span by killing hosts after 11 (early killing) or 14 (late killing) days post inoculation; after killing, parasite transmission stages were collected and used for a new infection cycle. Results After 13 cycles (≈ 300 generations), parasites from the early-killing treatment were less infectious, but had shorter latency time and higher virulence than those from the late-killing treatment. Overall, shorter latency time was associated with higher parasite loads and thus presumably with more rapid within-host replication. Conclusion The analysis of the means of the two treatments is thus consistent with theory, and suggests that evolution is constrained by trade-offs between virulence, transmission and within-host growth. In contrast, we found little evidence for such trade-offs across parasite selection lines within treatments; thus, to some extent, these traits may evolve independently. This study illustrates how environmental variation (experienced by the host) can lead to the evolution of distinct parasite strategies. PMID:19320981

  19. A Novel Analytic Technique to Measure Associations Between Circulating Biomarkers and Physical Performance Across the Adult Life Span.

    PubMed

    Peterson, Matthew J; Thompson, Dana K; Pieper, Carl F; Morey, Miriam C; Kraus, Virginia B; Kraus, William E; Sullivan, Patrick; Fillenbaum, Gerda; Cohen, Harvey J

    2016-02-01

    Understanding associations between circulating biomarkers and physical performance across the adult life span could aid in better describing mechanistic pathways leading to disability. We hypothesized that high concentrations of circulating biomarkers would be associated with lower functioning across study populations representing the adult life span. The data were from four intervention and two observational studies with ages ranging 22-89 years. Biomarkers assayed included inflammatory, coagulation, and endothelial function markers. Physical performance was measured either by VO2peak (studies of young and middle-aged adults) or usual gait speed (studies of older adults). Partialled (by age, body mass index, race, and sex) and weighted common correlations were calculated between biomarkers and physical performance. Homogeneity of the associations was also assessed. Interleukin-6 (weighted r = -.22), tumor necrosis factor receptor 2 (weighted r = -.19), D-dimer (weighted r = -.16), tumor necrosis factor receptor 1 (weighted r = -.15), granulocyte colony-stimulating factor (weighted r = -.14), and tumor necrosis factor alpha (weighted r = -.10) were all significantly inversely correlated with physical performance (p < .05). All significant correlations were homogeneous across studies. In summary, we observed consistent inverse associations between six circulating biomarkers and objective measures of physical performance. These results suggest that these serum biomarkers may be broadly applicable for detection, trajectory, and treatment monitoring of physical function across the life span or possibly for midlife predictors of functionally deleterious conditions.

  20. rBmαTX14 Increases the Life Span and Promotes the Locomotion of Caenorhabditis Elegans

    PubMed Central

    Xu, Jie; Wan, Lu; Teng, Kaixuan; Xiang, Jin; Zhang, Rui; Huang, Zebo; Liu, Yongmei; Li, Wenhua; Liu, Xin

    2016-01-01

    The scorpion has been extensively used in various pharmacological profiles or as food supplies. The exploration of scorpion venom has been reported due to the presence of recombinant peptides. rBmαTX14 is an α-neurotoxin extracted from the venom gland of the East Asian scorpion Buthus martensii Karsch and can affect ion channel conductance. Here, we investigated the functions of rBmαTX14 using the Caenorhabditis elegans model. Using western blot analysis, rBmαTX14 was shown to be expressed both in the cytoplasm and inclusion bodies in the E.coli Rosetta (DE3) strain. Circular dichroism spectroscopy analysis demonstrated that purified rBmαTX14 retained its biological structures. Next, feeding nematodes with E.coli Rosetta (DE3) expressing rBmαTX14 caused extension of the life span and promoted the locomotion of the nematodes. In addition, we identified several genes that play various roles in the life span and locomotion of C. elegans through microarray analysis and quantitative real-time PCR. Furthermore, if the amino acid site H15 of rBmαTX14 was mutated, rBmαTX14 no longer promoted the C. elegans life span. In conclusion, the results not only demonstrated the functions and mechanism of rBmαTX14 in C. elegans, but also provided the new sight in the utility of recombinant peptides from scorpion venom. PMID:27611314

  1. An approach to give prospective life-span of the copper/low-density-polyethylene nanocomposite intrauterine device.

    PubMed

    Xia, Xianping; Tang, Ying; Xie, Changsheng; Wang, Yun; Cai, Shuizhou; Zhu, Changhong

    2011-07-01

    As a novel copper-containing intrauterine device (IUD), the prospective life-span of the copper/low-density-polyethylene (Cu/LDPE) nanocomposite IUD is very important for the future clinical use and should be given in advance. Here a novel approach, cupric ions accelerated release in diluted nitric acid solution and cupric ions concentration release in various volume of simulated uterine solution (SUS), is reported to verify the type of cupric ions release model of the cylindrical matrix-type nanocomposite IUD, and to obtain the minimal cupric ions release rate that need to ensure contraceptive efficacy and the thickness of copper particles exhausted layer of the cylindrical matrix-type nanocomposite IUD within two difficult immersion durations in experimental volume of SUS, respectively. Using these results, the prospective life-span of the cylindrical matrix-type nanocomposite IUD can be obtained. For instance, the prospective life-span of the novel γ-shape nanocomposite IUD with 25 wt% of copper nanoparticles and 2 mm of diameter and a total weight of 285 mg can be given in advance and it is about 5 years in the future clinical use.

  2. Solid Cancer Incidence among the Life Span Study of Atomic Bomb Survivors: 1958-2009.

    PubMed

    Grant, Eric J; Brenner, Alina; Sugiyama, Hiromi; Sakata, Ritsu; Sadakane, Atsuko; Utada, Mai; Cahoon, Elizabeth K; Milder, Caitlin M; Soda, Midori; Cullings, Harry M; Preston, Dale L; Mabuchi, Kiyohiko; Ozasa, Kotaro

    2017-03-20

    This is the third analysis of solid cancer incidence among the Life Span Study (LSS) cohort of atomic bomb survivors in Hiroshima and Nagasaki, adding eleven years of follow-up data since the previously reported analysis. For this analysis, several changes and improvements were implemented, including updated dose estimates (DS02R1) and adjustment for smoking. Here, we focus on all solid cancers in aggregate. The eligible cohort included 105,444 subjects who were alive and had no known history of cancer at the start of follow-up. A total of 80,205 subjects had individual dose estimates and 25,239 were not in either city at the time of the bombings. The follow-up period was 1958-2009, providing 3,079,484 person-years of follow-up. Cases were identified by linkage with population-based Hiroshima and Nagasaki Cancer Registries. Poisson regression methods were used to elucidate the nature of the radiation-associated risks per Gy of weighted absorbed colon dose using both excess relative risk (ERR) and excess absolute risk (EAR) models adjusted for smoking. Risk estimates were reported for a person exposed at age 30 years with attained age of 70 years. In this study, 22,538 incident first primary solid cancer cases were identified, of which 992 were associated with radiation exposure. There were 5,918 cases (26%) that occurred in the 11 years (1999-2009) since the previously reported study. For females, the dose response was consistent with linearity with an estimated ERR of 0.64 per Gy (95% CI: 0.52 to 0.77). For males, significant upward curvature over the full dose range as well as restricted dose ranges was observed and therefore, a linear-quadratic model was used, which resulted in an ERR of 0.20 (95% CI: 0.12 to 0.28) at 1 Gy and an ERR of 0.010 (95% CI: -0.0003 to 0.021) at 0.1 Gy. The shape of the ERR dose response was significantly different among males and females (P = 0.02). While there was a significant decrease in the ERR with increasing attained age, this

  3. Sex differences in aging, life span and spontaneous tumorigenesis in 129/Sv mice neonatally exposed to metformin

    PubMed Central

    Anisimov, Vladimir N; Popovich, Irina G; Zabezhinski, Mark A; Egormin, Peter A; Yurova, Maria N; Semenchenko, Anna V; Tyndyk, Margarita L; Panchenko, Andrey V; Trashkov, Alexandr P; Vasiliev, Andrey G; Khaitsev, Nikolai V

    2015-01-01

    The perinatal (prenatal and early neonatal) period is a critical stage for hypothalamic programming of sexual differentiation as well as for the development of energy and metabolic homeostasis. We hypothesized that neonatal treatment with antidiabetic drug biguanide metformin would positively modify regulation of growth hormone – IGF-1 – insulin signaling pathway slowing down aging and improving cancer preventive patterns in rodents. To test this hypothesis male and female 129/Sv mice were s.c. injected with metformin (100 mg/kg) at the 3rd, 5th and 7th days after birth. Metformin-treated males consumed less food and water and their body weight was decreased as compared with control mice practically over their entire lifespan. There were no significant differences in age-related dynamics of food and water consumption in females and they were heavier than controls. The fraction of mice with regular estrous cycles decreased with age and demonstrated a tendency to decrease in the females neonatally treated with metformin. Neonatal exposure to metformin practically failed to change the extent of hormonal and metabolic parameters in blood serum of male and female mice. In males, neonatal metformin treatment significantly increased the mean life span (+20%, P < 0.05) and slightly increased the maximum life span (+3.5%). In females, the mean life span and median in metformin-treated groups were slightly decreased (−9.1% and −13.8% respectively, P > 0.05) in comparison to controls, whereas mean life span of last 10% survivors and maximum life span were the same as in controls. Almost half (45%) of control male mice and 71.8% male mice neonatally exposed to metformin survived up to 800 d of age, the same age was achieved by 54.3% of mice in control female group and 30% of metformin-treated females (P < 0.03). Thus, neonatal metformin exposure slows down aging and prolongs lifespan in male but not in female mice. PMID:25483062

  4. Life-Span Extension by Caloric Restriction Is Determined by Type and Level of Food Reduction and by Reproductive Mode in Brachionus manjavacas (Rotifera)

    PubMed Central

    2013-01-01

    We measured life span and fecundity of three reproductive modes in a clone of the monogonont rotifer Brachionus manjavacas subjected to chronic caloric restriction (CCR) over a range of food concentrations or to intermittent fasting (IF). IF increased life span 50%–70% for all three modes, whereas CCR increased life span of asexual females derived from sexually or asexually produced eggs, but not that of sexual females. The main effect of CR on both asexual modes was to delay death at young ages, rather than to prevent death at middle ages or to greatly extend maximum life span; in contrast CR in sexual females greatly increased the life span of a few long-lived individuals. Lifetime fecundity did not decrease with CCR, suggesting a lack of resource allocation trade-off between somatic maintenance and reproduction. Multiple outcomes for a clonal lineage indicate that different responses are established through epigenetic programming, whereas differences in life-span allocations suggest that multiple genetic mechanisms mediate life-span extension. PMID:22904096

  5. Life-span extension by caloric restriction is determined by type and level of food reduction and by reproductive mode in Brachionus manjavacas (Rotifera).

    PubMed

    Gribble, Kristin E; Welch, David B Mark

    2013-04-01

    We measured life span and fecundity of three reproductive modes in a clone of the monogonont rotifer Brachionus manjavacas subjected to chronic caloric restriction (CCR) over a range of food concentrations or to intermittent fasting (IF). IF increased life span 50%-70% for all three modes, whereas CCR increased life span of asexual females derived from sexually or asexually produced eggs, but not that of sexual females. The main effect of CR on both asexual modes was to delay death at young ages, rather than to prevent death at middle ages or to greatly extend maximum life span; in contrast CR in sexual females greatly increased the life span of a few long-lived individuals. Lifetime fecundity did not decrease with CCR, suggesting a lack of resource allocation trade-off between somatic maintenance and reproduction. Multiple outcomes for a clonal lineage indicate that different responses are established through epigenetic programming, whereas differences in life-span allocations suggest that multiple genetic mechanisms mediate life-span extension.

  6. Marine collagen peptides prepared from chum salmon (Oncorhynchus keta) skin extend the life span and inhibit spontaneous tumor incidence in Sprague-Dawley Rats.

    PubMed

    Liang, Jiang; Pei, Xin-Rong; Wang, Nan; Zhang, Zhao-Feng; Wang, Jun-Bo; Li, Yong

    2010-08-01

    To observe the effects of marine collagen peptides (MCPs) prepared from chum salmon (Oncorhynchus keta) skin on life span and spontaneous tumor incidence, Sprague-Dawley rats were fed diets supplemented with MCP at concentrations of 0%, 2.25%, 4.5%, and 9% (wt/wt) from the age of 4 weeks until natural death. There were 40 rats in each group (male:female ratio = 1:1). The results showed that the MCP did not significantly influence body weight or food consumption of rats of either sex throughout the life span; it did dose-dependently inhibit the age-related decrease in the activities of antioxidant enzymes and the age-related increase in the levels of lipid peroxidation product in both sexes. MCP notably increased the mean life span, the life span of the last 30% of the survivors, and the maximal life span; it decreased overall spontaneous tumor incidence of both sexes with significance in the 4.5% and 9% MCP-treated male groups and 9% MCP-treated female group. Compared to the control group, the incidence of death from tumors was decreased in MCP groups in comparison with the control group of both sexes. Therefore, we concluded that MCPs dose-dependently increase life span and decrease spontaneous tumor incidence in Sprague-Dawley rats. Moreover, the antioxidative property of MCPs may be responsible for the increased life span and protection against tumor development.

  7. TSG (2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside) from the Chinese Herb Polygonum multiflorum Increases Life Span and Stress Resistance of Caenorhabditis elegans

    PubMed Central

    Büchter, Christian; Zhao, Liang; Fritz, Gerhard; Proksch, Peter

    2015-01-01

    2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG) was isolated from Polygonum multiflorum, a plant which is traditionally used as an anti-ageing drug. We have analysed ageing-related effects of TSG in the model organism C. elegans in comparison to resveratrol. TSG exerted a high antioxidative capacity both in a cell-free assay and in the nematode. The antioxidative capacity was even higher compared to resveratrol. Presumably due to its antioxidative effects, treatment with TSG decreased the juglone-mediated induction of the antioxidative enzyme SOD-3; the induction of the GST-4 by juglone was diminished slightly. TSG increased the resistance of C. elegans against lethal thermal stress more prominently than resveratrol (50 μM TSG increased mean survival by 22.2%). The level of the ageing pigment lipofuscin was decreased after incubation with the compound. TSG prolongs the mean, median, and maximum adult life span of C. elegans by 23.5%, 29.4%, and 7.2%, respectively, comparable to the effects of resveratrol. TSG-mediated extension of life span was not abolished in a DAF-16 loss-of-function mutant strain showing that this ageing-related transcription factor is not involved in the effects of TSG. Our data show that TSG possesses a potent antioxidative capacity, enhances the stress resistance, and increases the life span of the nematode C. elegans. PMID:26075030

  8. Circadian clocks govern calorie restriction-mediated life span extension through BMAL1- and IGF-1-dependent mechanisms.

    PubMed

    Patel, Sonal A; Chaudhari, Amol; Gupta, Richa; Velingkaar, Nikkhil; Kondratov, Roman V

    2016-04-01

    Calorie restriction (CR) increases longevity in many species by unknown mechanisms. The circadian clock was proposed as a potential mediator of CR. Deficiency of the core component of the circadian clock-transcriptional factor BMAL1 (brain and muscle ARNT [aryl hydrocarbon receptor nuclear translocator]-like protein 1)-results in accelerated aging. Here we investigated the role of BMAL1 in mechanisms of CR. The 30% CR diet increased the life span of wild-type (WT) mice by 20% compared to mice on anad libitum(AL) diet but failed to increase life span ofBmal1(-/-)mice. BMAL1 deficiency impaired CR-mediated changes in the plasma levels of IGF-1 and insulin. We detected a statistically significantly reduction of IGF-1 in CRvs.AL by 50 to 70% in WT mice at several daily time points tested, while inBmal1(-/-)the reduction was not significant. Insulin levels in WT were reduced by 5 to 9%, whileBmal1(-/-)induced it by 10 to 35% at all time points tested. CR up-regulated the daily average expression ofBmal1(by 150%) and its downstream target genesPeriods(by 470% forPer1and by 130% forPer2). We propose that BMAL1 is an important mediator of CR, and activation of BMAL1 might link CR mechanisms with biologic clocks.-Patel, S. A., Chaudhari, A., Gupta, R., Velingkaar, N., Kondratov, R. V. Circadian clocks govern calorie restriction-mediated life span extension through BMAL1- and IGF-1-dependent mechanisms.

  9. Extension of life span by impaired glucose metabolism in Caenorhabditis elegans is accompanied by structural rearrangements of the transcriptomic network.

    PubMed

    Priebe, Steffen; Menzel, Uwe; Zarse, Kim; Groth, Marco; Platzer, Matthias; Ristow, Michael; Guthke, Reinhard

    2013-01-01

    Glucose restriction mimicked by feeding the roundworm Caenorhabditis elegans with 2-deoxy-D-glucose (DOG) - a glucose molecule that lacks the ability to undergo glycolysis - has been found to increase the life span of the nematodes considerably. To facilitate understanding of the molecular mechanisms behind this life extension, we analyzed transcriptomes of DOG-treated and untreated roundworms obtained by RNA-seq at different ages. We found that, depending on age, DOG changes the magnitude of the expression values of about 2 to 24 percent of the genes significantly, although our results reveal that the gross changes introduced by DOG are small compared to the age-induced changes. We found that 27 genes are constantly either up- or down-regulated by DOG over the whole life span, among them several members of the cytochrome P450 family. The monotonic change with age of the temporal expression patterns of the genes was investigated, leading to the result that 21 genes reverse their monotonic behaviour under impaired glycolysis. Put simply, the DOG-treatment reduces the gross transcriptional activity but increases the interconnectedness of gene expression. However, a detailed analysis of network parameters discloses that the introduced changes differ remarkably between individual signalling pathways. We found a reorganization of the hubs of the mTOR pathway when standard diet is replaced by DOG feeding. By constructing correlation based difference networks, we identified those signalling pathways that are most vigorously changed by impaired glycolysis. Taken together, we have found a number of genes and pathways that are potentially involved in the DOG-driven extension of life span of C. elegans. Furthermore, our results demonstrate how the network structure of ageing-relevant signalling pathways is reorganised under impaired glycolysis.

  10. The effect of developmental nutrition on life span and fecundity depends on the adult reproductive environment in Drosophila melanogaster

    PubMed Central

    May, Christina M; Doroszuk, Agnieszka; Zwaan, Bas J

    2015-01-01

    Both developmental nutrition and adult nutrition affect life-history traits; however, little is known about whether the effect of developmental nutrition depends on the adult environment experienced. We used the fruit fly to determine whether life-history traits, particularly life span and fecundity, are affected by developmental nutrition, and whether this depends on the extent to which the adult environment allows females to realize their full reproductive potential. We raised flies on three different developmental food levels containing increasing amounts of yeast and sugar: poor, control, and rich. We found that development on poor or rich larval food resulted in several life-history phenotypes indicative of suboptimal conditions, including increased developmental time, and, for poor food, decreased adult weight. However, development on poor larval food actually increased adult virgin life span. In addition, we manipulated the reproductive potential of the adult environment by adding yeast or yeast and a male. This manipulation interacted with larval food to determine adult fecundity. Specifically, under two adult conditions, flies raised on poor larval food had higher reproduction at certain ages – when singly mated this occurred early in life and when continuously mated with yeast this occurred during midlife. We show that poor larval food is not necessarily detrimental to key adult life-history traits, but does exert an adult environment-dependent effect, especially by affecting virgin life span and altering adult patterns of reproductive investment. Our findings are relevant because (1) they may explain differences between published studies on nutritional effects on life-history traits; (2) they indicate that optimal nutritional conditions are likely to be different for larvae and adults, potentially reflecting evolutionary history; and (3) they urge for the incorporation of developmental nutritional conditions into the central life-history concept of

  11. Biological approaches to mechanistically understand the healthy life span extension achieved by calorie restriction and modulation of hormones.

    PubMed

    Barzilai, Nir; Bartke, Andrzej

    2009-02-01

    Calorie restriction and reduced somatotropic (growth hormone and insulin-like growth factor-1) signaling have a widespread though not universal ability to extend life. These interventions are considered central tools to understanding the downstream events that lead to the increase in healthy life span. As these approaches have been validated, the animals phenotyped, and the mechanisms proposed, many challenges have emerged. In this article, we give several examples and propose several considerations, opportunities, and approaches that may identify major mechanisms through which these interventions exert their effects, and which may lead to drug therapy to increase "health span."

  12. Allometric dependence of the life span of mammal erythrocytes on thermal stability and sphingomyelin content of plasma membranes.

    PubMed

    Ivanov, Ivan Tanev

    2007-08-01

    Thermal stability of erythrocyte membrane is a measure for its ability to maintain permeability barrier at deleterious conditions. Hence, it could impact the resistance of erythrocytes against detrimental factors in circulation. In this study the thermostability of erythrocyte membranes was expressed by the temperature, T(go), at which the transmembrane gradient of ion concentration rapidly dissipated during transient heating. T(go) is the inducing temperature of the membrane transition that activated passive ion permeability at hyperthermia causing thermal hemolysis. A good allometric correlation of T(go) to the resistance against thermal hemolysis and the life span of erythrocytes were found for 13 mammals; sheep, cow, goat, dog, horse, man, rabbit, pig, cat, hamster, guinea pig, rat, and mouse. For the same group, the values of T(go) were strictly related to the sphingomyelin content of erythrocyte membranes. The residual ion permeability, P, was temperature activated from 38 to 57 degrees C with activation energy of 250+/-15 kJ/mol that strongly differed from that below 37 degrees C. The projected value of P at 37 degrees C was about half that of residual physiological permeability for Na+ and K+ that build ground for possible explanation of the life span vs membrane thermostability allometric correlation.

  13. Knockdown of the Drosophila FIG4 induces deficient locomotive behavior, shortening of motor neuron, axonal targeting aberration, reduction of life span and defects in eye development.

    PubMed

    Kyotani, Akane; Azuma, Yumiko; Yamamoto, Itaru; Yoshida, Hideki; Mizuta, Ikuko; Mizuno, Toshiki; Nakagawa, Masanori; Tokuda, Takahiko; Yamaguchi, Masamitsu

    2016-03-01

    Mutations in Factor-Induced-Gene 4 (FIG4) gene have been identified in Charcot-Marie-Tooth disease type 4J (CMT4J), Yunis-Varon syndrome and epilepsy with polymicrogyria. FIG4 protein regulates a cellular abundance of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), a signaling lipid on the cytosolic surface of membranes of the late endosomal compartment. PI(3,5)P2 is required for retrograde membrane trafficking from lysosomal and late endosomal compartments to the Golgi. However, it is still unknown how the neurodegeneration that occurs in these diseases is related to the loss of FIG4 function. Drosophila has CG17840 (dFIG4) as a human FIG4 homolog. Here we specifically knocked down dFIG4 in various tissues, and investigated their phenotypes. Neuron-specific knockdown of dFIG4 resulted in axonal targeting aberrations of photoreceptor neurons, shortened presynaptic terminals of motor neurons in 3rd instar larvae and reduced climbing ability in adulthood and life span. Fat body-specific knockdown of dFIG4 resulted in enlarged lysosomes in cells that were detected by staining with LysoTracker. In addition, eye imaginal disk-specific knockdown of dFIG4 disrupted differentiation of pupal ommatidial cell types, such as cone cells and pigment cells, suggesting an additional role of dFIG4 during eye development.

  14. Infantile onset Vanishing White Matter disease associated with a novel EIF2B5 variant, remarkably long life span, severe epilepsy, and hypopituitarism.

    PubMed

    Woody, April L; Hsieh, David T; McIver, Harkirtin K; Thomas, Linda P; Rohena, Luis

    2015-04-01

    Vanishing White Matter disease (VWM) is an inherited progressive leukoencephalopathy caused by mutations in the genes EIF2B1-5, which encode for the 5 subunits of the eukaryotic initiation factor 2B (eIF2B), a regulator of protein synthesis. VWM typically presents with acute neurological decline following febrile infections or minor head trauma, and subsequent progressive neurological and cognitive regression. There is a varied clinical spectrum of VWM, with earlier onset associated with more severe phenotypes. Brain magnetic resonance imaging is usually diagnostic with diffusely abnormal white matter, progressing over time to cystic degeneration. We are reporting on a patient with infantile onset VWM associated with three heterozygous missense variants in EIF2B5, including a novel missense variant on exon 6 of EIF2B5 (D262N), as well as an interstitial duplication at 7q21.12. In addition, our case is unusual because of a severe epilepsy course, a novel clinical finding of hypopituitarism manifested by hypothyroidism and adrenal insufficiency, and a prolonged life span with current age of survival of 4 years and 11 months.

  15. Minocycline increases the life span and motor activity and decreases lipid peroxidation in manganese treated Drosophila melanogaster.

    PubMed

    Bonilla, E; Contreras, R; Medina-Leendertz, S; Mora, M; Villalobos, V; Bravo, Y

    2012-03-29

    The objective of this study was to investigate the effect of Minocycline in the life span, motor activity, and lipid peroxidation of Drosophila melanogaster treated with manganese. Two days after emerging from the pupa male wild-type D. melanogaster were fed for 13 days with corn media containing 15 mM manganese. Then, they were divided in six groups of 300 flies each: group (a) remained treated with manganese (Mn group); group (b) began treatment with Minocycline (0.05 mM) (Mn-Minocycline group); group (c) received no additional treatment (Mn-no treatment group); group (d) simultaneously fed with manganese and Minocycline (Mn+Minocycline group). Additionally, a control (group e) with no treatment and another group (f) fed only with Minocycline after emerging from the pupa were added. All the manganese treated flies (group a) were dead on the 25th day. The life span in group f (101.66±1.33 days, mean S.E.M.) and of group b (97.00±3.46 days) were similar, but in both cases it was significantly higher than in group e (68.33±1.76 days), group c (67.05±2.30 days) and in those of group d (37.33±0.88). Manganese (groups a and d) decreased motor activity in D. melanogaster. In the Minocycline fed flies (groups b and f) a higher motor activity was detected. In Mn-Minocycline and Mn+Minocycline treated flies a significant decrease of MDA levels was detected when compared to the Minocycline group indicating that Minocycline and Mn appear to have a synergistic effect. In conclusion, Minocycline increased the life span and motor activity and decreased MDA formation of manganese treated D. melanogaster, probably by an inhibition of the production of reactive oxygen species. Manganese also exerted an antioxidant effect as shown by the significant decrease of MDA levels when compared to control flies.

  16. [Psychoneuroimmunology of the life span: impact of childhood stress on immune dysregulation and inflammatory disease in later life].

    PubMed

    Schubert, Christian

    2014-05-01

    Studies have shown clearly that childhood mistreatment, abuse and neglect are associated with severe inflammatory disease in adulthood (e. g. cancer, heart disease, autoimmune disorder) and shortened life span. This review deals with the psychoneuroimmunological pathways of this connection. It shows that chronic stressors interfere very early in life with those protective mechanisms of the biological stress system that normally down-regulate potentially harmful inflammation. In the long term, serious inflammatory diseases, such as allergic asthma, can result. In this review, the pathogenetic connections between allergic asthma and early stress and stress system dysfunction are discussed. As our understanding of the dysfunctional psychophysiological mechanisms of inflammatory disease increases, psychodiagnostic and psychotherapeutic intervention in the treatment of physical disease will become more specific.

  17. Protein:carbohydrate ratios explain life span patterns found in Queensland fruit fly on diets varying in yeast:sugar ratios.

    PubMed

    Fanson, Benjamin G; Taylor, Phillip W

    2012-12-01

    Dietary restriction extends life span across a vast diversity of taxa, but significant challenges remain in elucidating the underlying mechanisms. Distinguishing between caloric and nutrient effects is an essential step. Recent studies with Drosophila and tephritid fruit flies have reported increased life span as dietary yeast-to-sugar ratios decreased and these effects have been attributed to changes in protein-to-carbohydrate (P:C) ratios of the diets rather than calories. However, yeast is a complex mix of macronutrients and micronutrients, and hence changes in yeast content of the diet necessarily alters other nutrients in lockstep. To explicitly test whether studies using yeast are justified in attributing results to diet protein content rather than correlated nutrients, we developed a chemically defined diet allowing manipulation of just the ratio of protein (free amino acids) to carbohydrate (sucrose) levels of diets while holding other nutrients constant. Mated, female Queensland fruit flies (Q-flies) were fed 1 of 18 diets varying in P:C ratios and diet concentration. Diet consumption, egg production, and life span were recorded for each fly. In close concordance with recent studies using yeast diets, flies had increased life span as P:C ratios decreased, and caloric restriction did not extend life span. Similarly, egg production was maximized on high P:C ratios, but lifetime egg production was maximized on intermediate P:C ratios, indicating a life history trade-off between life span and egg production rate. Finally, Q-flies adjusted their diet intake in response to P:C ratios and diet concentration. Our results substantiate recent claims that P:C ratios significantly modulate life span in flies.

  18. Life-Span Exposure to Low Doses of Aspartame Beginning during Prenatal Life Increases Cancer Effects in Rats

    PubMed Central

    Soffritti, Morando; Belpoggi, Fiorella; Tibaldi, Eva; Esposti, Davide Degli; Lauriola, Michelina

    2007-01-01

    Background In a previous study conducted at the Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation (CMCRC/ERF), we demonstrated for the first time that aspartame (APM) is a multipotent carcinogenic agent when various doses are administered with feed to Sprague-Dawley rats from 8 weeks of age throughout the life span. Objective The aim of this second study is to better quantify the carcinogenic risk of APM, beginning treatment during fetal life. Methods We studied groups of 70–95 male and female Sprague-Dawley rats administered APM (2,000, 400, or 0 ppm) with feed from the 12th day of fetal life until natural death. Results Our results show a) a significant dose-related increase of malignant tumor–bearing animals in males (p < 0.01), particularly in the group treated with 2,000 ppm APM (p < 0.01); b) a significant increase in incidence of lymphomas/leukemias in males treated with 2,000 ppm (p < 0.05) and a significant dose-related increase in incidence of lymphomas/leukemias in females (p < 0.01), particularly in the 2,000-ppm group (p < 0.01); and c) a significant dose-related increase in incidence of mammary cancer in females (p < 0.05), particularly in the 2,000-ppm group (p < 0.05). Conclusions The results of this carcinogenicity bioassay confirm and reinforce the first experimental demonstration of APM’s multipotential carcinogenicity at a dose level close to the acceptable daily intake for humans. Furthermore, the study demonstrates that when life-span exposure to APM begins during fetal life, its carcinogenic effects are increased. PMID:17805418

  19. Carbon dynamics in aboveground biomass of co-dominant plant species: related rather to leaf life span than to species

    NASA Astrophysics Data System (ADS)

    Ostler, Ulrike; Schleip, Inga; Lattanzi, Fernando A.; Schnyder, Hans

    2016-04-01

    This study investigates the role of individual organisms in whole ecosystem carbon (C) fluxes. It is currently unknown if different plant community members share the same or different kinetics of C pools in aboveground biomass, thereby adding (or not) variability to the first steps in ecosystem C cycling. We assessed the residence times in metabolic and non-metabolic (or structural) C pools and the allocation pattern of assimilated C in aboveground plant parts of four co-existing, co-dominant species from different functional groups in a temperate grassland community. For this purpose continuous, 14-16 day long 13CO2/12CO2-labeling experiments were performed in Sept. 2006, May 2007 and Sept. 2007, and the tracer kinetics were analysed with compartmental modeling. In all experimental periods, the species shared vastly similar residence times in metabolic C (5-8 d). In contrast, the residence times in non-metabolic C ranged from 20 to 58 d (except one outlier) and the fraction of fixed C allocated to the non-metabolic pool from 7 to 45%. These variations in non-metabolic C kinetics were not systematically associated with species or experimental periods, but exhibited close relationships with (independent estimates of) leaf life span, particularly in the grasses. This adds new meaning to leaf life span as a functional trait in the leaf and plant economics spectrum and its implication for C cycle studies in grassland and also forest systems. As the four co-dominant species accounted for ~80% of total community shoot biomass, we should also expect that the observed similarities in pool kinetics and allocation will scale up to similar relationships at the community level.

  20. Calorie restriction, post-reproductive life span, and programmed aging: a plea for rigor.

    PubMed

    De Grey, Aubrey D N J

    2007-11-01

    All scientists are acutely aware of the profound challenge that they face when communicating scientific findings to nonscientists, especially when great uncertainty is involved and when the topic is of personal interest to the general public. Simplification of the issues--sometimes extending to a degree of oversimplification--is a sad but generally recognized necessity. It is not, however, a necessity when scientists communicate with each other, and when that happens, the explanation may lie elsewhere: either in the speaker's vested interests or in overconfidence on the speaker's part in the extent to which he or she has grasped the topic under discussion. Both these explanations are serious allegations and must not be made without good reason, not least because an alternative explanation is often the entirely legitimate preference for scientific "shorthand." However, when a general tendency toward oversimplification emerges within an expert community, not only in informal interactions but in learned publications, the field in question can suffer a loss of reputation for rigor, which may especially infect younger scientists joining that field (or contemplating joining it). I feel that this has occurred to a dangerous degree within biogerontology in respect of the way in which the effect of the environment on the rate of aging-whether that of an individual organism or of a lineage-is described. There are still important controversies in that area, but I refer here strictly to issues concerning which a thorough consensus exists. In this essay I highlight some fundamental tenets of biogerontology that are frequently, and to my mind problematically, mis-stated by many in this field in their printed pronouncements. Greater precision on these points will, I believe, benefit biogerontology at many levels, avoiding confusion among biogerontologists, among other biologists, and among the general public.

  1. Feeding into old age: long-term effects of dietary fatty acid supplementation on tissue composition and life span in mice

    PubMed Central

    Ruf, Thomas

    2010-01-01

    Smaller mammals, such as mice, possess tissues containing more polyunsaturated fatty acids (PUFAs) than larger mammals, while at the same time live shorter lives. These relationships have been combined in the ‘membrane pacemaker hypothesis of aging’. It suggests that membrane PUFA content might determine an animal’s life span. PUFAs in general and certain long-chain PUFAs in particular, are highly prone to lipid peroxidation which brings about a high rate of reactive oxygen species (ROS) production. We hypothesized that dietary supplementation of either n-3 or n-6 PUFAs might affect (1) membrane phospholipid composition of heart and liver tissues and (2) life span of the animals due to the altered membrane composition, and subsequent effects on lipid peroxidation. Therefore, we kept female laboratory mice from the C57BL/6 strain on three diets (n-3 PUFA rich, n-6 PUFA rich, control) and assessed body weights, life span, heart, and liver phospholipid composition after the animals had died. We found that while membrane phospholipid composition clearly differed between feeding groups, life span was not directly affected. However, we were able to observe a positive correlation between monounsaturated fatty acids in cardiac muscle and life span. PMID:20981551

  2. Amino acid sources in the adult diet do not affect life span and fecundity in the fruit-feeding butterfly Bicyclus anynana.

    PubMed

    Molleman, Freerk; Ding, Jimin; Wang, Jane-Ling; Brakefield, Paul M; Carey, James R; Zwaan, Bas J

    2008-08-01

    1. In tropical forests, the adults of many butterfly species feed on fruits rather than nectar from flowers and have long life spans. Rotting fruit and nectar differ from each other in many respects, including sources of amino acids and microbial life. If amino acids in the adult diet can be used for reproduction, this may have facilitated the evolution of extended life spans in this guild.2. This issue was addressed by investigating effects of banana, yeast, and amino acids in the adult diet of the fruit-feeding butterfly Bicyclus anynana (Lepidoptera) on longevity and female reproductive output in two experiments.3. Results showed that in the fruit-feeding butterfly B. anynana: (i) banana juice, but not sliced banana or added amino acids extend life span compared with a sugar solution of similar composition; (ii) compared with this sugar solution, other cohorts (banana juice-amino acid enriched) did not have significantly higher reproductive outputs; (iii) yeast does not represent a valuable source of nutrients; (iv) caloric restriction may cause decreased life span and rate of reproduction; and (v) increased rates of reproduction have a life span cost.

  3. Environmental effects on the expression of life span and aging: an extreme contrast between wild and captive cohorts of Telostylinus angusticollis (Diptera: Neriidae).

    PubMed

    Kawasaki, Noriyoshi; Brassil, Chad E; Brooks, Robert C; Bonduriansky, Russell

    2008-09-01

    Most research on life span and aging has been based on captive populations of short-lived animals; however, we know very little about the expression of these traits in wild populations of such organisms. Because life span and aging are major components of fitness, the extent to which the results of many evolutionary studies in the laboratory can be generalized to natural settings depends on the degree to which the expression of life span and aging differ in natural environments versus laboratory environments and whether such environmental effects interact with phenotypic variation. We investigated life span and aging in Telostylinus angusticollis in the wild while simultaneously estimating these parameters under a range of conditions in a laboratory stock that was recently established from the same wild population. We found that males live less than one-fifth as long and age at least twice as rapidly in the wild as do their captive counterparts. In contrast, we found no evidence of aging in wild females. These striking sex-specific differences between captive and wild flies support the emerging view that environment exerts a profound influence on the expression of life span and aging. These findings have important implications for evolutionary gerontology and, more generally, for the interpretation of fitness estimates in captive populations.

  4. The Effect of ACP₁-ADA₁ Genetic Interaction on Human Life Span.

    PubMed

    Lucarini, Nazzareno; Napolioni, Valerio; Magrini, Andrea; Gloria, Fulvia

    2012-12-01

    Acid phosphatase (ACP₁) is a polymorphic enzyme that catalyzes the conversion of flavin-mononucleotide (FMN) to riboflavin and regulates the cellular concentration of flavin-adenine-dinucleotide (FAD) and, consequently, energy metabolism. Its activity is modulated by adenosine deaminase locus 1 (ADA₁) genotype. The aim of our work is to verify whether individuals with a high proportion of ACP₁ f-isozyme and carrying the ADA₁*2 allele, displaying the highest phosphatase activity, may have a higher life expectancy. Genomic DNA was extracted from the peripheral blood of 569 females and 509 males (18 to 106 years of age) randomly recruited from Central Italy. These samples were subdivided into three sex-specific age groups (the ages of women are in square bracket): Class 1: age <66 [<73]; Class 2: ages 66 to 88 [73 to 91]; Class 3: age >88 [>91]. ACP₁and ADA₁ singlenucleotide polymorphisms (SNPs) were genotyped by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) methods and statistical analyses were performed with SPSS 14.0. The results showed a larger proportion of Class 3 individuals displaying high ACP₁ f-isozyme concentration and carrying the ADA₁*2 allele than those individuals of Class 2 and Class 2 plus Class 1. Thus, we postulate that in Class 3 individuals the high phosphatase activity, resulting from the combined presence of high ACP₁ f-isozyme concentration and the ADA₁*2 allele, lowers the rate of glycolysis that may reduce the amount of metabolic calories and, in turn, activate Sirtuin genes that protect cells against age-related diseases.

  5. Biomarkers of aging, life span and spontaneous carcinogenesis in the wild type and HER-2 transgenic FVB/N female mice.

    PubMed

    Panchenko, Andrey V; Popovich, Irina G; Trashkov, Alexandr P; Egormin, Peter A; Yurova, Maria N; Tyndyk, Margarita L; Gubareva, Ekaterina A; Artyukin, Ilia N; Vasiliev, Andrey G; Khaitsev, Nikolai V; Zabezhinski, Mark A; Anisimov, Vladimir N

    2016-04-01

    FVB/N wild type and transgenic HER-2/neu FVB/N female mice breed at N.N. Petrov Research Institute of Oncology were under observation until natural death without any special treatment. Age-related dynamics of body weight, food consumption and parameters of carbohydrate and lipid metabolism, level of nitric oxide, malonic dialdehyde, catalase, Cu, Zn-superoxide dismutase, vascular endothelial growth factor were studied in both mice strains. The parameters of life span and tumor pathology were studied as well. Cancer-prone transgenic HER-2/neu mice developed in 100 % multiple mammary adenocarcinomas and died before the age of 1 year. Forty tree percent of long-lived wild type mice survived the age of 2 years and 19 %-800 days. The total tumor incidence in wild type mice was 34 %. The age-associated changes in the level of serum IGF-1, glucose and insulin started much earlier in transgene HER-2/neu mice as compared with wild type FVB/N mice. It was suggested that transgenic HER-2/neu involves in initiation of malignization of mammary epithelial cells but also in acceleration of age-related hormonal and metabolic changes in turn promoting mammary carcinogenesis.

  6. Evaluation of Resveratrol, Green Tea Extract, Curcumin, Oxaloacetic Acid, and Medium-Chain Triglyceride Oil on Life Span of Genetically Heterogeneous Mice

    PubMed Central

    Miller, Richard A.; Astle, Clinton M.; Baur, Joseph A.; de Cabo, Rafael; Fernandez, Elizabeth; Guo, Wen; Javors, Martin; Kirkland, James L.; Nelson, James F.; Sinclair, David A.; Teter, Bruce; Williams, David; Zaveri, Nurulain; Nadon, Nancy L.; Harrison, David E.

    2013-01-01

    The National Institute on Aging Interventions Testing Program (ITP) was established to evaluate agents that are hypothesized to increase life span and/or health span in genetically heterogeneous mice. Each compound is tested in parallel at three test sites. It is the goal of the ITP to publish all results, negative or positive. We report here on the results of lifelong treatment of mice, beginning at 4 months of age, with each of five agents, that is, green tea extract (GTE), curcumin, oxaloacetic acid, medium-chain triglyceride oil, and resveratrol, on the life span of genetically heterogeneous mice. Each agent was administered beginning at 4 months of age. None of these five agents had a statistically significant effect on life span of male or female mice, by log-rank test, at the concentrations tested, although a secondary analysis suggested that GTE might diminish the risk of midlife deaths in females only. PMID:22451473

  7. Life-Span Extension by Axenic Dietary Restriction Is Independent of the Mitochondrial Unfolded Protein Response and Mitohormesis in Caenorhabditis elegans.

    PubMed

    Cai, Huaihan; Rasulova, Madina; Vandemeulebroucke, Lieselot; Meagher, Lea; Vlaeminck, Caroline; Dhondt, Ineke; Braeckman, Bart P

    2017-03-17

    In Caenorhabditis elegans, a broad range of dietary restriction regimens extend life span to different degrees by separate or partially overlapping molecular pathways. One of these regimens, axenic dietary restriction, doubles the worm's life span but currently, almost nothing is known about the underlying molecular mechanism. Previous studies suggest that mitochondrial stress responses such as the mitochondrial unfolded protein response (UPRmt) or mitohormesis may play a vital role in axenic dietary restriction-induced longevity. Here, we provide solid evidence that axenic dietary restriction treatment specifically induces an UPRmt response in C elegans but this induction is not required for axenic dietary restriction-mediated longevity. We also show that reactive oxygen species-mediated mitohormesis is not involved in this phenotype. Hence, changes in mitochondrial physiology and induction of a mitochondrial stress response are not necessarily causal to large increases in life span.

  8. [Observations on oviposition, hatching and the life span of Triatoma matogrossensis Leite & Barbosa, 1953 (Hemiptera, Reduviidae) as a function of their feeding on pigeons and rabbits].

    PubMed

    Marassá, A M; Veiga-Barreiros, R M; Moraes, R H; de Andrade, R M; Castillo, A; Corrêa, F M

    1998-01-01

    A laboratory study was carried out concerning the influence of two kinds of blood-meal on egg laying, egg hatching and life span of Triatoma matogrossensis. 68 couples in 4 different groups with 20, 12, 20 and 16 individuals of each sex per group were formed. Maintained under laboratory conditions groups A1 and A2 were fed on pigeons and groups C1 and C2 were fed on rabbits. In relation to egg laying the best results were found in group A1. No differences on egg hatching were found between the groups fed on rabbits and those fed on pigeons. Concerning the life span, no differences between males and females in the 4 groups were observed but group A1 presented the longest life span and group C2 the shortest.

  9. Diet-derived advanced glycation end products or lipofuscin disrupts proteostasis and reduces life span in Drosophila melanogaster.

    PubMed

    Tsakiri, Eleni N; Iliaki, Kalliopi K; Höhn, Annika; Grimm, Stefanie; Papassideri, Issidora S; Grune, Tilman; Trougakos, Ioannis P

    2013-12-01

    Advanced glycation end product (AGE)-modified proteins are formed by the nonenzymatic glycation of free amino groups of proteins and, along with lipofuscin (a highly oxidized aggregate of covalently cross-linked proteins, sugars, and lipids), have been found to accumulate during aging and in several age-related diseases. As the in vivo effects of diet-derived AGEs or lipofuscin remain elusive, we sought to study the impact of oral administration of glucose-, fructose-, or ribose-modified albumin or of artificial lipofuscin in a genetically tractable model organism. We report herein that continuous feeding of young Drosophila flies with culture medium enriched in AGEs or in lipofuscin resulted in reduced locomotor performance and in accelerated rates of AGE-modified proteins and carbonylated proteins accumulation in the somatic tissues and hemolymph of flies, as well as in a significant reduction of flies health span and life span. These phenotypic effects were accompanied by reduced proteasome peptidase activities in both the hemolymph and the somatic tissues of flies and higher levels of oxidative stress; furthermore, oral administration of AGEs or lipofuscin in flies triggered an upregulation of the lysosomal cathepsin B, L activities. Finally, RNAi-mediated cathepsin D knockdown reduced flies longevity and significantly augmented the deleterious effects of AGEs and lipofuscin, indicating that lysosomal cathepsins reduce the toxicity of diet-derived AGEs or lipofuscin. Our in vivo studies demonstrate that chronic ingestion of AGEs or lipofuscin disrupts proteostasis and accelerates the functional decline that occurs with normal aging.

  10. Histone H1 Is Dispensable for Methylation-Associated Gene Silencing in Ascobolus immersus and Essential for Long Life Span

    PubMed Central

    Barra, Jose L.; Rhounim, Laïla; Rossignol, Jean-Luc; Faugeron, Godeleine

    2000-01-01

    A gene encoding a protein that shows sequence similarity with the histone H1 family only was cloned in Ascobolus immersus. The deduced peptide sequence presents the characteristic three-domain structure of metazoan linker histones, with a central globular region, an N-terminal tail, and a long positively charged C-terminal tail. By constructing an artificial duplication of this gene, named H1, it was possible to methylate and silence it by the MIP (methylation induced premeiotically) process. This resulted in the complete loss of the Ascobolus H1 histone. Mutant strains lacking H1 displayed normal methylation-associated gene silencing, underwent MIP, and showed the same methylation-associated chromatin modifications as did wild-type strains. However, they displayed an increased accessibility of micrococcal nuclease to chromatin, whether DNA was methylated or not, and exhibited a hypermethylation of the methylated genome compartment. These features are taken to imply that Ascobolus H1 histone is a ubiquitous component of chromatin which plays no role in methylation-associated gene silencing. Mutant strains lacking histone H1 reproduced normally through sexual crosses and displayed normal early vegetative growth. However, between 6 and 13 days after germination, they abruptly and consistently stopped growing, indicating that Ascobolus H1 histone is necessary for long life span. This constitutes the first observation of a physiologically important phenotype associated with the loss of H1. PMID:10594009

  11. The Concept of Homology as a Basis for Evaluating Developmental Mechanisms: Exploring Selective Attention Across the Life-Span

    PubMed Central

    Lickliter, Robert; Bahrick, Lorraine

    2014-01-01

    Research with human infants as well as non-human animal embryos and infants has consistently demonstrated the benefits of intersensory redundancy for perceptual learning and memory for redundantly specified information during early development. Studies of infant affect discrimination, face discrimination, numerical discrimination, sequence detection, abstract rule learning, and word comprehension and segmentation have all shown that intersensory redundancy promotes earlier detection of these properties when compared to unimodal exposure to the same properties. Here we explore the idea that such intersensory facilitation is evident across the life-span and that this continuity is an example of a developmental behavioral homology. We present evidence that intersensory facilitation is most apparent during early phases of learning for a variety of tasks, regardless of developmental level, including domains that are novel or tasks that require discrimination of fine detail or speeded responses. Under these conditions, infants, children, and adults all show intersensory facilitation, suggesting a developmental homology. We discuss the challenge and propose strategies for establishing appropriate guidelines for identifying developmental behavioral homologies. We conclude that evaluating the extent to which continuities observed across development are homologous can contribute to a better understanding of the processes of development. PMID:22711341

  12. Older adults prescribed methadone: a review of the literature across the life span from opiate initiation to methadone maintenance treatment.

    PubMed

    Doukas, Nick

    2014-01-01

    Professionals currently working with methadone patients are facing challenges with the rise of polydrug use, HIV and Hepatitis epidemics, and treating a large volume of individuals who are older than ever before, presenting for the first time in their 50's, 60's and 70's. There have been two literature reviews conducted on this older population, but they can only provide a snap-shot view on the later stage of life of this unique group. A longitudinal literature review of the long-term opiate abuser who has transitioned into opiate replacement therapy will provide depth and illustrate the complexity of interrelated factors that have been affected throughout their life span. This paper reviews the literature conducted on opiate addicts from their earlier stages of substance use to older adulthood where many have chosen to enter into a methadone maintenance program. The paper will also take a biopsychosocial approach when reviewing the literature because of how these three domains are deeply affected and interrelated with this population.

  13. Spermatozoid life-span of two brown seaweeds, Saccharina japonica and Undaria pinnatifida, as measured by fertilization efficiency

    NASA Astrophysics Data System (ADS)

    Li, Jing; Pang, Shaojun; Liu, Feng; Shan, Tifeng; Gao, Suqin

    2013-07-01

    During sexual reproduction of seaweeds, spermatozoid (sperm) discharge is triggered by chemical messengers (pheromones) released by the female gametes. The chemotactic ability of the sperm ensures fertilization success. Using unialgal male and female gametophyte material under designated standard gametogenesis testing (SGT) conditions, the potential life-span of the sperm of two seaweeds, Saccharina japonica and Undaria pinnatifida, was assessed by their ability to fertilize eggs. Results show that within 20-30 min after being discharged, sperm of both species could complete fertilization without an apparent decline in fertilization rate. Although fertilization rate 60-120 min after sperm discharge dropped significantly in both species, some sperm were viable enough to fertilize the eggs. In S. japonica, at 12°C, some sperm were able to fertilize eggs up to 12 h after discharge. In both species, egg discharge rates (EDR) in the male and female mixed positive controls were significantly higher than those of all the sperm-testing groups. Doubling the seeded male gametophytes of S. japonica in the SGT tests significantly increased the EDR, further confirming the effect of the presence of the male on the female in terms of facilitating egg discharge from oogonia.

  14. The SNF1 Kinase Ubiquitin-associated Domain Restrains Its Activation, Activity, and the Yeast Life Span.

    PubMed

    Jiao, Rubin; Postnikoff, Spike; Harkness, Troy A; Arnason, Terra G

    2015-06-19

    The enzyme family of heterotrimeric AMP-dependent protein kinases is activated upon low energy states, conferring a switch toward energy-conserving metabolic pathways through immediate kinase actions on enzyme targets and delayed alterations in gene expression through its nuclear relocalization. This family is evolutionarily conserved, including the presence of a ubiquitin-associated (UBA) motif in most catalytic subunits. The potential for the UBA domain to promote protein associations or direct subcellular location, as seen in other UBA-containing proteins, led us to query whether the UBA domain within the yeast AMP-dependent protein kinase ortholog, SNF1 kinase, was important in these aspects of its regulation. Here, we demonstrate that conserved UBA motif mutations significantly alter SNF1 kinase activation and biological activity, including enhanced allosteric subunit associations and increased oxidative stress resistance and life span. Significantly, the enhanced UBA-dependent longevity and oxidative stress response are at least partially dependent on the Fkh1 and Fkh2 stress response transcription factors, which in turn are shown to influence Snf1 gene expression.

  15. Sodium Intake of Special Populations in the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) Study

    PubMed Central

    Cotugna, Nancy; Fanelli-Kuczmarksi, Marie; Clymer, Julie; Hotchkiss, Lawrence; Zonderman, Alan B.; Evans, Michele K.

    2013-01-01

    Objective The sodium intake of participants of the Healthy Aging in Neighborhoods of Diversity across the Life Span study who were in three of the special population groups identified by the Dietary Guidelines for Americans, 2010 (those with hypertension, African Americans, and those ≥51 years) was analyzed to determine if they met sodium recommendations. Methods The sample included 2152 African American and White subjects, aged 30-64 years. Major dietary sources of sodium for each group were determined from two 24-hour dietary recalls, and dietary intakes were compared with sodium recommendations. Dietary potassium was also evaluated. Results The intakes of the groups studied exceeded 1500 mg sodium while their potassium intakes were lower than the Adequate Intake of 4700 mg. The major contributors of sodium included “cold cuts, sausage, and franks,” “protein foods”, and yeast breads. Conclusions Excessive sodium intake characterized the diet of an urban, socioeconomically diverse population who are hypertensive or at risk for having hypertension. These findings have implications for health professionals and the food industry. PMID:23769900

  16. Age differences in the monitoring of learning: cross-sectional evidence of spared resolution across the adult life span.

    PubMed

    Hertzog, Christopher; Sinclair, Starlette M; Dunlosky, John

    2010-07-01

    Researchers of metacognitive development in adulthood have exclusively used extreme-age-groups designs. We used a full cross-sectional sample (N = 285, age range: 18-80) to evaluate how associative relatedness and encoding strategies influence judgments of learning (JOLs) in adulthood. Participants studied related and unrelated word pairs and made JOLs. After a cued-recall test, retrospective item strategy reports were collected. Results revealed developmental patterns not available from previous studies (e.g., a linear age-related increase in aggregate JOL resolution across the life span). They also demonstrated the value of investigating multiple cues' influences on JOLs. Multilevel regression models showed that both relatedness and effective strategy use positively and independently influenced JOLs. Furthermore, effective strategy use was responsible for higher resolution of JOLs for unrelated items (relative to related items). The effects of relatedness and strategy use with JOLs did not interact with age. The monitoring of learning is spared by adult development despite age differences in learning itself.

  17. Ecl1 is a zinc-binding protein involved in the zinc-limitation-dependent extension of chronological life span in fission yeast.

    PubMed

    Shimasaki, Takafumi; Ohtsuka, Hokuto; Naito, Chikako; Azuma, Kenko; Tenno, Takeshi; Hiroaki, Hidekazu; Murakami, Hiroshi; Aiba, Hirofumi

    2017-04-01

    Overexpression of Ecl1-family genes (ecl1 (+), ecl2 (+), and ecl3 (+)) results in the extension of the chronological life span in Schizosaccharomyces pombe. However, the mechanism for this extension has not been defined clearly. Ecl1-family proteins consist of approximately 80 amino acids, and four cysteine residues are conserved in their N-terminal domains. This study focused on the Ecl1 protein, mutating its cysteine residues sequentially to confirm their importance. As a result, all mutated Ecl1 proteins nearly lost the function to extend the chronological life span, suggesting that these four cysteine residues are essential for the Ecl1 protein. Utilizing ICP-AES (inductively coupled plasma atomic emission spectroscopy) analysis, we found that wild-type Ecl1 proteins contain zinc, while cysteine-mutated Ecl1 proteins do not. We also analyzed the effect of environmental zinc on the chronological life span. We found that zinc limitation extends the chronological life span, and this extension depends on the Ecl1-family proteins.

  18. Life-Span Data on Continuous-Naming Speeds of Numbers, Letters, Colors, and Pictured Objects, and Word-Reading Speed.

    ERIC Educational Resources Information Center

    van den Bos, Kees P.; Zijlstra, Bonne J. H.; lutje Spelberg, Henk C.

    2002-01-01

    Addresses life-span developmental relations between naming and reading speed. Finds word-reading speed and naming speeds of colors and pictures increased into mature adulthood, but for letter and number naming, asymptotes were reached at around 16 years of age. Supports the theory that describes reading recognition development as a domain-specific…

  19. Improvement/Maintenance and Reorientation as Central Features of Coping with Major Life Change and Loss: Contributions of Three Life-Span Theories

    ERIC Educational Resources Information Center

    Boerner, Kathrin; Jopp, Daniela

    2007-01-01

    This article focuses on the common and unique contributions of three major life-span theories in addressing improvement/maintenance and reorientation, which represent central processes of coping with major life change and loss. For this purpose, we review and compare the dual-process model of assimilative and accommodative coping, the model of…

  20. Life-Span and Life-Space Literacy: Research and Policy in National and International Perspective. Occasional Paper OP92-1.

    ERIC Educational Resources Information Center

    Wagner, Daniel A.

    A more literate society cannot be created in the United States or elsewhere without a more comprehensive conceptual framework. This framework attempts explicitly to link children's acquisition of literacy with that of adults and assumes there is no single normative theory to literacy development. In a life-span and life-space approach, literacy…

  1. Stem Cell Transplant Patients and Fungal Infections

    MedlinePlus

    ... Foodborne, Waterborne, and Environmental Diseases Mycotic Diseases Branch Stem Cell Transplant Patients and Fungal Infections Recommend on Facebook ... Mold . Top of Page Preventing fungal infections in stem cell transplant patients Fungi are difficult to avoid because ...

  2. Evaluation of platelet thromboxane radioimmunoassay method to measure platelet life-span: Comparison with /sup 111/indium-platelet method

    SciTech Connect

    Vallabhajosula, S.; Machac, J.; Badimon, L.; Lipszyc, H.; Goldsmith, S.J.; Fuster, V.

    1985-05-01

    The platelet activation during radiolabeling in vitro with Cr-51 and In-111 may affect the platelet life-span (PLS) in vivo. A new RIA method to measure PLS is being evaluated. Aspirin inhibits platelet thromboxane (TxA/sub 2/) by acetylating cyclooxygenase. The time required for the TxA/sub 2/ levels to return towards control values depends on the rate of new platelets entering circulation and is a measure of PLS. A single dose of aspirin (150mg) was given to 5 normal human subjects. Blood samples were collected for 2 days before aspirin and daily for 10 days. TxA/sub 2/ production in response to endogenous thrombin was studied by allowing 1 ml blood sample to clot at 37/sup 0/C for 90 min. Serum TxB/sub 2/ (stable breakdown product of Tx-A/sub 2/) levels determined by RIA technique. The plot of TxB/sub 2/ levels (% control) against time showed a gradual increase. The PLS calculated by linear regression analysis assuming a 2-day lag period before cyclooxygenase recovery is 9.7 +- 2.37. In the same 5 subjects, platelets from a 50ml blood sample were labeled with /sup 111/In-tropolone in 2 ml autologous plasma. Starting at 1 hr after injection of labeled platelets, 10 blood samples were obtained over a 8 day period. The PLS calculated based on a linear regression analysis is 10.2 +. 1.4. The PLS measured from the rate of platelet disappearance from circulation and the rate of platelet regeneration into circulation are quite comparable in normal subjects. TxA/sub 2/ regeneration RIA may provide a method to measure PLS without administering radioactivity to patient.

  3. Parental Educational Attainment and Adult Offspring Personality: An Intergenerational Life Span Approach to the Origin of Adult Personality Traits.

    PubMed

    Sutin, Angelina R; Luchetti, Martina; Stephan, Yannick; Robins, Richard W; Terracciano, Antonio

    2017-03-13

    Why do some individuals have more self-control or are more vulnerable to stress than others? Where do these basic personality traits come from? Although a fundamental question in personality, more is known about how traits are related to important life outcomes than their developmental origins. The present research took an intergenerational life span approach to address whether a significant aspect of the childhood environment-parental educational attainment-was associated with offspring personality traits in adulthood. We tested the association between parents' educational levels and adult offspring personality traits in 7 samples (overall age range 14-95) and meta-analytically combined the results (total N > 60,000). Parents with more years of education had children who were more open, extraverted, and emotionally stable as adults. These associations were small but consistent, of similar modest magnitude to the association between life events and change in personality in adulthood, and were also supported by longitudinal analyses. Contrary to expectations, parental educational attainment was unrelated to offspring Conscientiousness, except for a surprisingly negative association in the younger cohorts. The results were similar in a subsample of participants who were adopted, which suggested that environmental mechanisms were as relevant as shared genetic variants. Participant levels of education were associated with greater conscientiousness, emotional stability, extraversion, and openness and partially mediated the relation between parent education and personality. Child IQ and family income were also partial mediators. The results of this research suggest that parental educational attainment is 1 intergenerational factor associated with offspring personality development in adulthood. (PsycINFO Database Record

  4. Integration-independent Transgenic Huntington Disease Fragment Mouse Models Reveal Distinct Phenotypes and Life Span in Vivo.

    PubMed

    O'Brien, Robert; DeGiacomo, Francesco; Holcomb, Jennifer; Bonner, Akilah; Ring, Karen L; Zhang, Ningzhe; Zafar, Khan; Weiss, Andreas; Lager, Brenda; Schilling, Birgit; Gibson, Bradford W; Chen, Sylvia; Kwak, Seung; Ellerby, Lisa M

    2015-07-31

    The cascade of events that lead to cognitive decline, motor deficits, and psychiatric symptoms in patients with Huntington disease (HD) is triggered by a polyglutamine expansion in the N-terminal region of the huntingtin (HTT) protein. A significant mechanism in HD is the generation of mutant HTT fragments, which are generally more toxic than the full-length HTT. The protein fragments observed in human HD tissue and mouse models of HD are formed by proteolysis or aberrant splicing of HTT. To systematically investigate the relative contribution of the various HTT protein proteolysis events observed in vivo, we generated transgenic mouse models of HD representing five distinct proteolysis fragments ending at amino acids 171, 463, 536, 552, and 586 with a polyglutamine length of 148. All lines contain a single integration at the ROSA26 locus, with expression of the fragments driven by the chicken β-actin promoter at nearly identical levels. The transgenic mice N171-Q148 and N552-Q148 display significantly accelerated phenotypes and a shortened life span when compared with N463-Q148, N536-Q148, and N586-Q148 transgenic mice. We hypothesized that the accelerated phenotype was due to altered HTT protein interactions/complexes that accumulate with age. We found evidence for altered HTT complexes in caspase-2 fragment transgenic mice (N552-Q148) and a stronger interaction with the endogenous HTT protein. These findings correlate with an altered HTT molecular complex and distinct proteins in the HTT interactome set identified by mass spectrometry. In particular, we identified HSP90AA1 (HSP86) as a potential modulator of the distinct neurotoxicity of the caspase-2 fragment mice (N552-Q148) when compared with the caspase-6 transgenic mice (N586-Q148).

  5. Integration-independent Transgenic Huntington Disease Fragment Mouse Models Reveal Distinct Phenotypes and Life Span in Vivo*

    PubMed Central

    O'Brien, Robert; DeGiacomo, Francesco; Holcomb, Jennifer; Bonner, Akilah; Ring, Karen L.; Zhang, Ningzhe; Zafar, Khan; Weiss, Andreas; Lager, Brenda; Schilling, Birgit; Gibson, Bradford W.; Chen, Sylvia; Kwak, Seung; Ellerby, Lisa M.

    2015-01-01

    The cascade of events that lead to cognitive decline, motor deficits, and psychiatric symptoms in patients with Huntington disease (HD) is triggered by a polyglutamine expansion in the N-terminal region of the huntingtin (HTT) protein. A significant mechanism in HD is the generation of mutant HTT fragments, which are generally more toxic than the full-length HTT. The protein fragments observed in human HD tissue and mouse models of HD are formed by proteolysis or aberrant splicing of HTT. To systematically investigate the relative contribution of the various HTT protein proteolysis events observed in vivo, we generated transgenic mouse models of HD representing five distinct proteolysis fragments ending at amino acids 171, 463, 536, 552, and 586 with a polyglutamine length of 148. All lines contain a single integration at the ROSA26 locus, with expression of the fragments driven by the chicken β-actin promoter at nearly identical levels. The transgenic mice N171-Q148 and N552-Q148 display significantly accelerated phenotypes and a shortened life span when compared with N463-Q148, N536-Q148, and N586-Q148 transgenic mice. We hypothesized that the accelerated phenotype was due to altered HTT protein interactions/complexes that accumulate with age. We found evidence for altered HTT complexes in caspase-2 fragment transgenic mice (N552-Q148) and a stronger interaction with the endogenous HTT protein. These findings correlate with an altered HTT molecular complex and distinct proteins in the HTT interactome set identified by mass spectrometry. In particular, we identified HSP90AA1 (HSP86) as a potential modulator of the distinct neurotoxicity of the caspase-2 fragment mice (N552-Q148) when compared with the caspase-6 transgenic mice (N586-Q148). PMID:26025364

  6. Body size, growth and life span: implications for the polewards range shift of Octopus tetricus in south-eastern Australia.

    PubMed

    Ramos, Jorge E; Pecl, Gretta T; Moltschaniwskyj, Natalie A; Strugnell, Jan M; León, Rafael I; Semmens, Jayson M

    2014-01-01

    Understanding the response of any species to climate change can be challenging. However, in short-lived species the faster turnover of generations may facilitate the examination of responses associated with longer-term environmental change. Octopus tetricus, a commercially important species, has undergone a recent polewards range shift in the coastal waters of south-eastern Australia, thought to be associated with the southerly extension of the warm East Australian Current. At the cooler temperatures of a polewards distribution limit, growth of a species could be slower, potentially leading to a bigger body size and resulting in a slower population turnover, affecting population viability at the extreme of the distribution. Growth rates, body size, and life span of O. tetricus were examined at the leading edge of a polewards range shift in Tasmanian waters (40°S and 147°E) throughout 2011. Octopus tetricus had a relatively small body size and short lifespan of approximately 11 months that, despite cooler temperatures, would allow a high rate of population turnover and may facilitate the population increase necessary for successful establishment in the new extended area of the range. Temperature, food availability and gender appear to influence growth rate. Individuals that hatched during cooler and more productive conditions, but grew during warming conditions, exhibited faster growth rates and reached smaller body sizes than individuals that hatched into warmer waters but grew during cooling conditions. This study suggests that fast growth, small body size and associated rapid population turnover may facilitate the range shift of O. tetricus into Tasmanian waters.

  7. Parvovirus infection-induced cell death and cell cycle arrest

    PubMed Central

    Chen, Aaron Yun; Qiu, Jianming

    2011-01-01

    The cytopathic effects induced during parvovirus infection have been widely documented. Parvovirus infection-induced cell death is often directly associated with disease outcomes (e.g., anemia resulting from loss of erythroid progenitors during parvovirus B19 infection). Apoptosis is the major form of cell death induced by parvovirus infection. However, nonapoptotic cell death, namely necrosis, has also been reported during infection of the minute virus of mice, parvovirus H-1 and bovine parvovirus. Recent studies have revealed multiple mechanisms underlying the cell death during parvovirus infection. These mechanisms vary in different parvoviruses, although the large nonstructural protein (NS)1 and the small NS proteins (e.g., the 11 kDa of parvovirus B19), as well as replication of the viral genome, are responsible for causing infection-induced cell death. Cell cycle arrest is also common, and contributes to the cytopathic effects induced during parvovirus infection. While viral NS proteins have been indicated to induce cell cycle arrest, increasing evidence suggests that a cellular DNA damage response triggered by an invading single-stranded parvoviral genome is the major inducer of cell cycle arrest in parvovirus-infected cells. Apparently, in response to infection, cell death and cell cycle arrest of parvovirus-infected cells are beneficial to the viral cell lifecycle (e.g., viral DNA replication and virus egress). In this article, we will discuss recent advances in the understanding of the mechanisms underlying parvovirus infection-induced cell death and cell cycle arrest. PMID:21331319

  8. Differential longitudinal changes in cortical thickness, surface area and volume across the adult life span: regions of accelerating and decelerating change.

    PubMed

    Storsve, Andreas B; Fjell, Anders M; Tamnes, Christian K; Westlye, Lars T; Overbye, Knut; Aasland, Hilde W; Walhovd, Kristine B

    2014-06-18

    Human cortical thickness and surface area are genetically independent, emerge through different neurobiological events during development, and are sensitive to different clinical conditions. However, the relationship between changes in the two over time is unknown. Additionally, longitudinal studies have almost invariably been restricted to older adults, precluding the delineation of adult life span trajectories of change in cortical structure. In this longitudinal study, we investigated changes in cortical thickness, surface area, and volume after an average interval of 3.6 years in 207 well screened healthy adults aged 23-87 years. We hypothesized that the relationships among metrics are dynamic across the life span, that the primary contributor to cortical volume reductions in aging is cortical thinning, and that magnitude of change varies with age and region. Changes over time were seen in cortical area (mean annual percentage change [APC], -0.19), thickness (APC, -0.35), and volume (APC, -0.51) in most regions. Volume changes were primarily explained by changes in thickness rather than area. A negative relationship between change in thickness and surface area was found across several regions, where more thinning was associated with less decrease in area, and vice versa. Accelerating changes with increasing age was seen in temporal and occipital cortices. In contrast, decelerating changes were seen in prefrontal and anterior cingulate cortices. In conclusion, a dynamic relationship between cortical thickness and surface area changes exists throughout the adult life span. The mixture of accelerating and decelerating changes further demonstrates the importance of studying these metrics across the entire adult life span.

  9. Precision-cut intestinal slices as a culture system to analyze the infection of differentiated intestinal epithelial cells by avian influenza viruses.

    PubMed

    Punyadarsaniya, Darsaniya; Winter, Christine; Mork, Ann-Kathrin; Amiri, Mahdi; Naim, Hassan Y; Rautenschlein, Silke; Herrler, Georg

    2015-02-01

    Many viruses infect and replicate in their host via the intestinal tract, e.g. many picornaviruses, several coronaviruses and avian influenza viruses of waterfowl. To analyze infection of enterocytes is a challenging task as culture systems for differentiated intestinal epithelial cells are not readily available and often have a life span that is too short for infection studies. Precision-cut intestinal slices (PCIS) from chicken embryos were prepared and shown that the epithelial cells lining the lumen of the intestine are viable for up to 4 days. Using lectin staining, it was demonstrated that α2,3-linked sialic acids, the preferred receptor determinants of avian influenza viruses, are present on the apical side of the epithelial cells. Furthermore, the epithelial cells (at the tips) of the villi were shown to be susceptible to infection by an avian influenza virus of the H9N2 subtype. This culture system will be useful to analyze virus infection of intestinal epithelial cells and it should be applicable also to the intestine of other species.

  10. Effects of exogenous antioxidants on the levels of endogenous antioxidants, lipid-soluble fluorescent material and life span in the housefly, Musca domestica.

    PubMed

    Sohal, R S; Allen, R G; Farmer, K J; Newton, R K; Toy, P L

    1985-09-01

    Effects of exogenous antioxidant administration (0.5% and 2% ascorbate, beta-carotene and alpha-tocopherol in sucrose) on life-span, metabolic rate, activities of superoxide dismutase and catalase, levels of glutathione, inorganic peroxides and chloroform-soluble fluorescent material (lipofuscin) were examined in adult male houseflies. Administration of antioxidants at a level of 0.5% did not affect life-span, whereas, 2% ascorbate and alpha-tocopherol decreased average life-span. Metabolic rate of flies was unaffected, except by 2% ascorbate, which caused a decrease. Superoxide dismutase activity was depressed by 2% ascorbate at all ages, and by beta-carotene and alpha-tocopherol in older flies. Catalase activity was unaffected except by alpha-tocopherol at younger ages. Glutathione concentration was decreased by ascorbate and beta-carotene at both concentrations administered. Inorganic peroxides (H2O2) were increased by 2% beta-carotene and alpha-tocopherol. Only high concentrations of ascorbate and beta-carotene decreased the level of soluble fluorescent material. Results suggest that administration of exogenous antioxidants causes a compensatory depression of endogenous defenses.

  11. Acacetin 7-O-α-l-rhamnopyranosyl (1-2) β-D-xylopyranoside Elicits Life-span Extension and Stress Resistance in Caenorhabditis elegans.

    PubMed

    Asthana, Jyotsna; Yadav, Deepti; Pant, Aakanksha; Yadav, A K; Gupta, M M; Pandey, Rakesh

    2016-09-01

    The advancements in the field of gerontology have unraveled the signaling pathways that regulate life span, suggesting that it might be feasible to modulate aging. To this end, we isolated a novel phytomolecule Acacetin 7-O-α-l-rhamnopyranosyl (1-2) β-D-xylopyranoside (ARX) from Premna integrifolia and evaluated its antiaging effects in Caenorhabditis elegans The spectral data analysis revealed the occurrence of a new compound ARX. Out of the three tested pharmacological doses of ARX, viz. 5, 25, and 50 µM, the 25-µM dose was able to extend life span in C. elegans by more than 39%. The present study suggests that ARX affects bacterial metabolism, which in turn leads to dietary restriction (DR)-like effects in the worms. The effect of ARX on worms with mutations (mev-1, eat-2, sir-2.1, skn-1, daf-16, and hsf-1) indicates that ARX-mediated life-span extension involves mechanisms associated with DR and maintenance of cellular redox homeostasis. This study is the first time report on longevity-promoting activity of ARX in C. elegans mediated by stress and DR-regulating genes. This novel phytomolecule can contribute in designing therapeutics for managing aging and age-related diseases.

  12. Multiple Metazoan Life-span Interventions Exhibit a Sex-specific Strehler-Mildvan Inverse Relationship Between Initial Mortality Rate and Age-dependent Mortality Rate Acceleration.

    PubMed

    Shen, Jie; Landis, Gary N; Tower, John

    2017-01-01

    The Gompertz equation describes survival in terms of initial mortality rate (parameter a), indicative of health, and age-dependent acceleration in mortality rate (parameter b), indicative of aging. Gompertz parameters were analyzed for several published studies. In Drosophila females, mating increases egg production and decreases median life span, consistent with a trade-off between reproduction and longevity. Mating increased parameter a, causing decreased median life span, whereas time parameter b was decreased. The inverse correlation between parameters indicates the Strehler-Mildvan (S-M) relationship, where loss of low-vitality individuals yields a cohort with slower age-dependent mortality acceleration. The steroid hormone antagonist mifepristone/RU486 reversed these effects. Mating and mifepristone showed robust S-M relationships across genotypes, and dietary restriction showed robust S-M relationship across diets. Because nutrient optima differed between females and males, the same manipulation caused opposite effects on mortality rates in females versus males across a range of nutrient concentrations. Similarly, p53 mutation in Drosophila and mTOR mutation in mice caused increased median life span associated with opposite direction changes in mortality rate parameters in females versus males. The data demonstrate that dietary and genetic interventions have sex-specific and sometimes sexually opposite effects on mortality rates consistent with sexual antagonistic pleiotropy.

  13. Effects of radiation and lifestyle factors on risks of urothelial carcinoma in the Life Span Study of atomic bomb survivors.

    PubMed

    Grant, E J; Ozasa, K; Preston, D L; Suyama, A; Shimizu, Y; Sakata, R; Sugiyama, H; Pham, T-M; Cologne, J; Yamada, M; De Roos, A J; Kopecky, K J; Porter, M P; Seixas, N; Davis, S

    2012-07-01

    Among the Life Span Study (LSS) of Atomic-bomb survivors, recent estimates showed that unspecified bladder cancer had high radiation sensitivity with a notably high female-to-male excess relative risk (ERR) per radiation dose ratio and were the only sites for which the ERR did not decrease with attained age. These findings, however, did not consider lifestyle factors, which could potentially confound or modify the risk estimates. This study estimated the radiation risks of the most prevalent subtype of urinary tract cancer, urothelial carcinoma, while accounting for smoking, consumption of fruit, vegetables, alcohol and level of education (a surrogate for socioeconomic status). Eligible study subjects included 105,402 (males = 42,890) LSS members who were cancer-free in 1958 and had estimated radiation doses. Members were censored due to loss of follow-up, incident cancer of another type, death, or the end of calendar year 2001. Surveys (by mail or clinical interview) gathered lifestyle data periodically for 1963-1991. There were 63,827 participants in one or more survey. Five hundred seventy-three incident urothelial carcinoma cases occurred, of which 364 occurred after lifestyle information was available. Analyses were performed using Poisson regression methods. The excess relative risk per weighted gray unit (the gamma component plus 10 times the neutron component, Gy(w)) was 1.00 (95% CI: 0.43-1.78) but the risks were not dependent upon age at exposure or attained age. Lifestyle factors other than smoking were not associated with urothelial carcinoma risk. Neither the magnitude of the radiation ERR estimate (1.00 compared to 0.96), nor the female-to-male (F:M) ERR/Gy(w) ratio (3.2 compared to 3.4) were greatly changed after accounting for all lifestyle factors. A multiplicative model of gender-specific radiation and smoking effects was the most revealing though there was no evidence of significant departures from either the additive or multiplicative joint

  14. Dengue Virus Infection Perturbs Lipid Homeostasis in Infected Mosquito Cells

    SciTech Connect

    Perera, Rushika M.; Riley, Catherine; Isaac, Georgis; Hopf- Jannasch, Amber; Moore, Ronald J.; Weitz, Karl K.; Pasa-Tolic, Ljiljana; Metz, Thomas O.; Adamec, Jiri; Kuhn, Richard J.

    2012-03-22

    Dengue virus causes {approx}50-100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide. During its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells. This phenomenon is observed both in human and vector-derived cells. Using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virus infection. Specifically, 15% of the metabolites detected were significantly different between DENV infected and uninfected cells while 85% of the metabolites detected were significantly different in isolated replication complex membranes. Furthermore, we demonstrate that intracellular lipid redistribution induced by the inhibition of fatty acid synthase, the rate-limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is inhibitory to dengue virus replication. Lipids that have the capacity to destabilize and change the curvature of membranes as well as lipids that change the permeability of membranes are enriched in dengue virus infected cells. Several sphingolipids and other bioactive signaling molecules that are involved in controlling membrane fusion, fission, and trafficking as well as molecules that influence cytoskeletal reorganization are also up regulated during dengue infection. These observations shed light on the emerging role of lipids in shaping the membrane and protein environments during viral infections and suggest membrane-organizing principles that may influence virus-induced intracellular membrane architecture.

  15. Cell-to-cell infection by HIV contributes over half of virus infection.

    PubMed

    Iwami, Shingo; Takeuchi, Junko S; Nakaoka, Shinji; Mammano, Fabrizio; Clavel, François; Inaba, Hisashi; Kobayashi, Tomoko; Misawa, Naoko; Aihara, Kazuyuki; Koyanagi, Yoshio; Sato, Kei

    2015-10-06

    Cell-to-cell viral infection, in which viruses spread through contact of infected cell with surrounding uninfected cells, has been considered as a critical mode of virus infection. However, since it is technically difficult to experimentally discriminate the two modes of viral infection, namely cell-free infection and cell-to-cell infection, the quantitative information that underlies cell-to-cell infection has yet to be elucidated, and its impact on virus spread remains unclear. To address this fundamental question in virology, we quantitatively analyzed the dynamics of cell-to-cell and cell-free human immunodeficiency virus type 1 (HIV-1) infections through experimental-mathematical investigation. Our analyses demonstrated that the cell-to-cell infection mode accounts for approximately 60% of viral infection, and this infection mode shortens the generation time of viruses by 0.9 times and increases the viral fitness by 3.9 times. Our results suggest that even a complete block of the cell-free infection would provide only a limited impact on HIV-1 spread.

  16. HCV Infection and B-Cell Lymphomagenesis

    PubMed Central

    Ito, Masahiko; Kusunoki, Hideki; Mochida, Keiko; Yamaguchi, Kazunari; Mizuochi, Toshiaki

    2011-01-01

    Hepatitis C virus (HCV) has been recognized as a major cause of chronic liver diseases worldwide. It has been suggested that HCV infects not only hepatocytes but also mononuclear lymphocytes including B cells that express the CD81 molecule, a putative HCV receptor. HCV infection of B cells is the likely cause of B-cell dysregulation disorders such as mixed cryoglobulinemia, rheumatoid factor production, and B-cell lymphoproliferative disorders that may evolve into non-Hodgkin's lymphoma (NHL). Epidemiological data indicate an association between HCV chronic infection and the occurrence of B-cell NHL, suggesting that chronic HCV infection is associated at least in part with B-cell lymphomagenesis. In this paper, we aim to provide an overview of recent literature, including our own, to elucidate a possible role of HCV chronic infection in B-cell lymphomagenesis. PMID:21789042

  17. Chromatin supraorganization, DNA fragmentation, and cell death in erythrocytes of the rattlesnake, Crotalus durissus terrificus (Serpentes, Viperidae), infected with the protozoan, Hepatozoon spp. (Apicomplexa, Hepatozoidae).

    PubMed

    Miyamoto, Maristela; Mello, Maria Luiza S

    2007-05-01

    Forms of the protozoan of the Hepatozoon genus are detected free in the circulation and also within some of the erythrocytes of infected snakes. In healthy snakes, DNA fragmentation and cell death usually affect a few circulating erythrocytes in agreement with the long life span expected for these cells. In the present study we investigated whether infection by Hepatozoon spp. affected the incidence of DNA fragmentation and cell death in erythrocytes from the rattlesnake, Crotalus durissus terrificus. Methods such as the kinetics of Feulgen-DNA hydrolysis, and the TUNEL and comet assays, previously used for the study of chromatin organization and DNA fragmentation in erythrocytes of healthy snakes, were used. The results indicated that Hepatozoon spp. increased the DNA fragmentation and chromatin condensation typical of cell death in circulating erythrocytes of C. d. terrificus, including cells that do not harbour the parasite. The Hepatozoon infection is thus suggested to accelerate destruction of erythrocytes in the rattlesnake, not only affecting cells harbouring the parasite, but also in those without it.

  18. Infection, stem cells and cancer signals.

    PubMed

    Sell, S

    2011-02-01

    The association of cancer with preceding parasitic infections has been observed for over 200 years. Some such cancers arise from infection of tissue stem cells by viruses with insertion of viral oncogenes into the host DNA (mouse polyoma virus, mouse mammary tumor virus). In other cases the virus does not insert its DNA into the host cells, but rather commandeers the metabolism of the infected cells, so that the cells continue to proliferate and do not differentiate (human papilloma virus and cervical cancer). Cytoplasmic Epstein Barr virus infection is associated with a specific gene translocation (Ig/c-myc) that activates proliferation of affected cells (Burkitt lymphoma). In chronic osteomyelitis an inflammatory reaction to the infection appears to act through production of inflammatory cytokines and oxygen radical formation to induce epithelial cancers. Infection with Helicobacter pylori leads to epigenetic changes in methylation and infection by a parasite. Clonorchis sinensis also acts as a promoter of cancer of the bile ducts of the liver (cholaniocarcinoma). The common thread among these diverse pathways is that the infections act to alter tissue stem cell signaling with continued proliferation of tumor transit amplifying cells.

  19. Infection, Stem Cells and Cancer Signals

    PubMed Central

    Sell, S.

    2013-01-01

    The association of cancer with preceding parasitic infections has been observed for over 200 years. Some such cancers arise from infection of tissue stem cells by viruses with insertion of viral oncogenes into the host DNA (mouse polyoma virus, mouse mammary tumor virus). In other cases the virus does not insert its DNA into the host cells, but rather commandeers the metabolism of the infected cells, so that the cells continue to proliferate and do not differentiate (human papilloma virus and cervical cancer). Cytoplasmic Epstein Barr virus infection is associated with a specific gene translocation (Ig/c-myc) that activates proliferation of affected cells (Burkitt lymphoma). In chronic osteomyelitis an inflammatory reaction to the infection appears to act through production of inflammatory cytokines and oxygen radical formation to induce epithelial cancers. Infection with Helicobacter pylori leads to epigenetic changes in methylation and infection by a parasite. Clonorchis sinensis also acts as a promoter of cancer of the bile ducts of the liver (cholaniocarcinoma). The common thread among these diverse pathways is that the infections act to alter tissue stem cell signaling with continued proliferation of tumor transit amplifying cells. PMID:21044009

  20. Polyphenolic drug composition based on benzenepolycarboxylic acids (BP-C3) increases life span and inhibits spontaneous tumorigenesis in female SHR mice

    PubMed Central

    Anisimov, Vladimir N.; Popovich, Irina G.; Zabezhinski, Mark A.; Yurova, Maria N.; Tyndyk, Margarita L.; Anikin, Ivan V.; Egormin, Peter A.; Baldueva, Irina A.; Fedoros, Elena I.; Pigarev, Sergey E.; Panchenko, Andrey V.

    2016-01-01

    Effects of long-term application of novel polyphenolic composition BP-C3, containing polyphenolic benzenepolycarboxylic acids, vitamins and minerals on some biomarkers of aging, life span and spontaneous tumorigenesis has been studied in female SHR mice. Administration of BP-C3 with drinking water (0.005%) did not exert any toxic effect (did not have effect on general condition of animals, weight dynamics and consumption of food), postponed age-related switch-off of estrous function, caused slight reduction of body temperature. An increased survival was observed in mice treated with BP-C3 (p=0.00164, log rank test). BP-C3 increased mean lifespan – by 8.4%, lifespan of the last 10% of animals – by 12.4%, and life span of tumor-free mice – by 11.6%. A tendency in ability of BP-C3 to inhibit development of spontaneous tumors in mice was detected, though it did not reach the level of statistical significance (p=0.166, log rank test). The number of malignant mammary tumors was 1.5 times less and total number of tumors of various localizations was 1.6 times less in BP-C3 treated animals. Multiple tumors were registered in 8% of mice in the control group and no cases – in BP-C3 treated group. Thus, BP-C3 demonstrated some anti-carcinogenic and a pronounced geroprotective activity. PMID:27574962

  1. Vitamin C modulates the metabolic and cytokine profiles, alleviates hepatic endoplasmic reticulum stress, and increases the life span of Gulo−/− mice

    PubMed Central

    Aumailley, Lucie; Warren, Alessandra; Garand, Chantal; Dubois, Marie Julie; Paquet, Eric R.; Le Couteur, David G.; Marette, André; Cogger, Victoria C.; Lebel, Michel

    2016-01-01

    Suboptimal intake of dietary vitamin C (ascorbate) increases the risk of several chronic diseases but the exact metabolic pathways affected are still unknown. In this study, we examined the metabolic profile of mice lacking the enzyme gulonolactone oxidase (Gulo) required for the biosynthesis of ascorbate. Gulo−/− mice were supplemented with 0%, 0.01%, and 0.4% ascorbate (w/v) in drinking water and serum was collected for metabolite measurements by targeted mass spectrometry. We also quantified 42 serum cytokines and examined the levels of different stress markers in liver. The metabolic profiles of Gulo−/− mice treated with ascorbate were different from untreated Gulo−/− and normal wild type mice. The cytokine profiles of Gulo−/− mice, in return, overlapped the profile of wild type animals upon 0.01% or 0.4% vitamin C supplementation. The life span of Gulo−/− mice increased with the amount of ascorbate in drinking water. It also correlated significantly with the ratios of serum arginine/lysine, tyrosine/phenylalanine, and the ratio of specific species of saturated/unsaturated phosphatidylcholines. Finally, levels of hepatic phosphorylated endoplasmic reticulum associated stress markers IRE1α and eIF2α correlated inversely with serum ascorbate and life span suggesting that vitamin C modulates endoplasmic reticulum stress response and longevity in Gulo−/− mice. PMID:26922388

  2. Antioxidant capacity of "Mexican arnica" Heterotheca inuloides Cass natural products and some derivatives: their anti-inflammatory evaluation and effect on C. elegans life span.

    PubMed

    Rodríguez-Chávez, José Luis; Coballase-Urrutia, Elvia; Nieto-Camacho, Antonio; Delgado-Lamas, Guillermo

    2015-01-01

    It has been suggested that the accumulation of biomolecular damage caused by reactive oxygen species (ROS) contributes to aging. The antioxidant activity is related to the ability of certain compounds to protect against the potentially harmful effect of processes or reactions involving ROS. This ability is associated with the termination of free radical propagation in biological systems. From Heterotheca inuloides various compounds which have shown to possess antioxidant capacity and scavenging ROS. The aim of this study was to determine the antioxidant capacity of additional natural components isolated from H. inuloides and some semisynthetic derivatives, their anti-inflammatory activity and the effect on Caenorhabditis elegans nematode life span. Compounds showed ability to inhibit various biological processes such as lipid peroxidation, scavenge nonbiological important oxidants such as (1)O2, OH(∙), H2O2, and HOCl and scavenge non biological stable free radicals (DPPH). Some cadinane type compounds showed possess antioxidant, ROS scavenging capacity, anti-inflammatory activity, and effect on the C. elegans life span. Flavonoid type compounds increased the life of the nematode and quercetin was identified as the compound with the greatest activity. The modification of chemical structure led to a change in the antioxidant capacity, the anti-inflammatory activity, and the survival of the worm.

  3. Polyphenolic drug composition based on benzenepolycarboxylic acids (BP-C3) increases life span and inhibits spontaneous tumorigenesis in female SHR mice.

    PubMed

    Anisimov, Vladimir N; Popovich, Irina G; Zabezhinski, Mark A; Yurova, Maria N; Tyndyk, Margarita L; Anikin, Ivan V; Egormin, Peter A; Baldueva, Irina A; Fedoros, Elena I; Pigarev, Sergey E; Panchenko, Andrey V

    2016-08-28

    Effects of long-term application of novel polyphenolic composition BP-C3, containing polyphenolic benzenepolycarboxylic acids, vitamins and minerals on some biomarkers of aging, life span and spontaneous tumorigenesis has been studied in female SHR mice. Administration of BP-C3 with drinking water (0.005%) did not exert any toxic effect (did not have effect on general condition of animals, weight dynamics and consumption of food), postponed age-related switch-off of estrous function, caused slight reduction of body temperature. An increased survival was observed in mice treated with BP-C3 (p=0.00164, log rank test). BP-C3 increased mean lifespan - by 8.4%, lifespan of the last 10% of animals - by 12.4%, and life span of tumor-free mice - by 11.6%. A tendency in ability of BP-C3 to inhibit development of spontaneous tumors in mice was detected, though it did not reach the level of statistical significance (p=0.166, log rank test). The number of malignant mammary tumors was 1.5 times less and total number of tumors of various localizations was 1.6 times less in BP-C3 treated animals. Multiple tumors were registered in 8% of mice in the сontrol group and no cases - in BP-C3 treated group. Thus, BP-C3 demonstrated some anti-carcinogenic and a pronounced geroprotective activity.

  4. Expression of an AtNAP gene homolog in senescing morning glory (Ipomoea nil) petals of two cultivars with a different flower life span.

    PubMed

    Shinozaki, Yoshihito; Tanaka, Toshimitsu; Ogiwara, Isao; Kanekatsu, Motoki; van Doorn, Wouter G; Yamada, Tetsuya

    2014-05-01

    AtNAP, a NAC family transcription factor, has been shown to promote leaf senescence in Arabidopsis. We isolated an AtNAP homolog in morning glory (Ipomoea nil), designated InNAP, and investigated its expression during petal senescence. We used two cultivars, one showing a normal short flower life span (cv. Peking Tendan) and another a longer life span (cv. Violet). InNAP was highly expressed in both cultivars. Expression was high before that of the senescence marker gene InSAG12. InNAP and InSAG12 expression was high in cv. Peking Tendan before cv. Violet. The expression of both genes was therefore temporally related to the onset of the visible senescence symptoms. An inhibitor of ethylene action (silver thiosulphate, STS) delayed petal senescence in cv. Peking Tendan but had no effect in cv. Violet. STS treatment had no clear effect on the InNAP expression in petals of both cultivars, suggesting that endogenous ethylene may not be necessary for its induction. These data suggest the hypothesis that InNAP plays a role in petal senescence, independent of the role of endogenous ethylene.

  5. Dmp53, basket and drICE gene knockdown and polyphenol gallic acid increase life span and locomotor activity in a Drosophila Parkinson’s disease model

    PubMed Central

    Ortega-Arellano, Hector Flavio; Jimenez-Del-Rio, Marlene; Velez-Pardo, Carlos

    2013-01-01

    Understanding the mechanism(s) by which dopaminergic (DAergic) neurons are eroded in Parkinson’s disease (PD) is critical for effective therapeutic strategies. By using the binary tyrosine hydroxylase (TH)-Gal4/UAS-X RNAi Drosophila melanogaster system, we report that Dmp53, basket and drICE gene knockdown in dopaminergic neurons prolong life span (p < 0.05; log-rank test) and locomotor activity (p < 0.05; χ2 test) in D. melanogaster lines chronically exposed to (1 mM) paraquat (PQ, oxidative stress (OS) generator) compared to untreated transgenic fly lines. Likewise, knockdown flies displayed higher climbing performance than control flies. Amazingly, gallic acid (GA) significantly protected DAergic neurons, ameliorated life span, and climbing abilities in knockdown fly lines treated with PQ compared to flies treated with PQ only. Therefore, silencing specific gene(s) involved in neuronal death might constitute an excellent tool to study the response of DAergic neurons to OS stimuli. We propose that a therapy with antioxidants and selectively “switching off” death genes in DAergic neurons could provide a means for pre-clinical PD individuals to significantly ameliorate their disease condition. PMID:24385865

  6. Time scale matters: genetic analysis does not support adaptation-by-time as the mechanism for adaptive seasonal declines in kokanee reproductive life span

    PubMed Central

    Morbey, Yolanda E; Jensen, Evelyn L; Russello, Michael A

    2014-01-01

    Seasonal declines of fitness-related traits are often attributed to environmental effects or individual-level decisions about reproductive timing and effort, but genetic variation may also play a role. In populations of Pacific salmon (Oncorhynchus spp.), seasonal declines in reproductive life span have been attributed to adaptation-by-time, in which divergent selection for different traits occurs among reproductively isolated temporal components of a population. We evaluated this hypothesis in kokanee (freshwater obligate Oncorhynchus nerka) by testing for temporal genetic structure in neutral and circadian-linked loci. We detected no genetic differences in presumably neutral loci among kokanee with different arrival and maturation dates within a spawning season. Similarly, we detected no temporal genetic structure in OtsClock1b, Omy1009uw, or OmyFbxw11, candidate loci associated with circadian function. The genetic evidence from this study and others indicates a lack of support for adaptation-by-time as an important evolutionary mechanism underlying seasonal declines in reproductive life span and a need for greater consideration of other mechanisms such as time-dependent, adaptive adjustment of reproductive effort. PMID:25478160

  7. Effects of salinity on egg and fecal pellet production, development and survival, adult sex ratio and total life span in the calanoid copepod, Acartia tonsa: a laboratory study

    NASA Astrophysics Data System (ADS)

    Shayegan, Majid; Esmaeili Fereidouni, Abolghasem; Agh, Naser; Jani Khalili, Khosrow

    2016-07-01

    The effects of salinity on the copepod, Acartia tonsa in terms of daily egg production rate (EPR), hatching success, fecal pellet production rate (FPR), naupliar development time and survival, sex ratio, and total life span were determined in laboratory conditions through three experiments. In experiment 1, EPR, hatching success, and FPR of individual females were monitored at salinities of 13, 20, 35 and 45 during short-periods (seven consecutive days). Results show EPR was affected by salinity with the highest outputs recorded at 20 and 35, respectively, which were considerably higher than those at 13 and 45. Mean FPR was also higher in 35 and 20. In experiment 2, the same parameters were evaluated over total life span of females (long-term study). The best EPR and FPR were observed in 35, which was statistically higher than at 13 and 20. In experiment 3, survival rates of early nauplii until adult stage were lowest at a salinity of 13. The development time increased with increasing of salinity. Female percentage clearly decreased with increasing salinity. Higher female percentages (56.7% and 52.2%, respectively) were significantly observed at two salinities of 13 and 20 compared to that at 35 (25%). Total longevity of females was not affected by salinity increment. Based on our results, for mass culture we recommend that a salinity of 35 be adopted due to higher reproductive performances, better feeding, and faster development of A. tonsa.

  8. Antioxidant Capacity of “Mexican Arnica” Heterotheca inuloides Cass Natural Products and Some Derivatives: Their Anti-Inflammatory Evaluation and Effect on C. elegans Life Span

    PubMed Central

    Rodríguez-Chávez, José Luis; Nieto-Camacho, Antonio; Delgado-Lamas, Guillermo

    2015-01-01

    It has been suggested that the accumulation of biomolecular damage caused by reactive oxygen species (ROS) contributes to aging. The antioxidant activity is related to the ability of certain compounds to protect against the potentially harmful effect of processes or reactions involving ROS. This ability is associated with the termination of free radical propagation in biological systems. From Heterotheca inuloides various compounds which have shown to possess antioxidant capacity and scavenging ROS. The aim of this study was to determine the antioxidant capacity of additional natural components isolated from H. inuloides and some semisynthetic derivatives, their anti-inflammatory activity and the effect on Caenorhabditis elegans nematode life span. Compounds showed ability to inhibit various biological processes such as lipid peroxidation, scavenge nonbiological important oxidants such as 1O2, OH∙, H2O2, and HOCl and scavenge non biological stable free radicals (DPPH). Some cadinane type compounds showed possess antioxidant, ROS scavenging capacity, anti-inflammatory activity, and effect on the C. elegans life span. Flavonoid type compounds increased the life of the nematode and quercetin was identified as the compound with the greatest activity. The modification of chemical structure led to a change in the antioxidant capacity, the anti-inflammatory activity, and the survival of the worm. PMID:25821555

  9. Needle life span, photosynthetic rate and nutrient concentration of Picea glehnii, P. jezoensis and P. abies planted on serpentine soil in northern Japan.

    PubMed

    Kayama, Masazumi; Sasa, Kaichiro; Koike, Takayoshi

    2002-07-01

    We investigated the adaptation of three spruce species (Picea glehnii Masters, P. jezoensis Carr. and P. abies Karst.) to growth in northern Japan on serpentine soils (characterized by high concentrations of heavy metals and Mg, a low Ca/Mg ratio and low fertility) and fertile brown forest soils. Among species, seedling survival on serpentine soil was highest in P. glehnii. Shoot growth of P. glehnii was similar whether grown on serpentine or brown forest soil, whereas shoot growth of the other species was significantly less on serpentine soil than on brown forest soil. On serpentine soil, needle life span of P. glehnii was at least 3 years longer than that of the other two species. Needle area per shoot of P. glehnii was significantly higher on serpentine soil than on brown forest soil up to a shoot age of 8 years. In all three species, light-saturated photosynthetic rate (Pmax) decreased with needle age independently of soil type. However, on serpentine soil, Pmax in P. glehnii was higher, particularly in older needles, than in the other species. Furthermore, on serpentine soil, needle concentrations of nitrogen and phosphorus were higher in P. glehnii than in the other species. We conclude that P. glehnii is better adapted to serpentine soil than P. jezoensis and P. abies at least in part because of its greater needle life span and higher needle nutrient concentrations.

  10. Intestinal immune cells in Strongyloides stercoralis infection.

    PubMed Central

    Trajman, A; MacDonald, T T; Elia, C C

    1997-01-01

    BACKGROUND: Strongyloides stercoralis can cause a wide spectrum of disease in man, ranging from a chronic asymptomatic infection to a hyperinfective, often fatal syndrome. In rodents, spontaneous expulsion of Strongyloides spp occurs after experimental infection. Mast cells, goblet cells, and eosinophils have been identified as possible effectors of this expulsion. AIMS: To investigate intestinal histopathology and mucosal immunity in immunocompetent patients with chronic S stercoralis infection. METHODS: Jejunal biopsies were performed in 19 immunocompetent patients with a positive stool examination for S stercoralis and few or no symptoms, and in seven healthy controls. Specimens were processed for histopathological analysis and stained by the immunoperoxidase technique, using the following monoclonal antibodies: CD2, CD3, CD4, CD8, anti-T cell receptor (TcR) gamma/delta, RFD1 and RFD7 (two different macrophage markers), Ki67+ (proliferating) cells, antihuman leucocyte antigen (HLA)-DR, and anticollagen IV. In addition, CD25+ cells, mast cells, IgE expressing cells, calprotectin containing cells, and neutrophil elastase positive cells were stained by the alkaline phosphatase method. RESULTS: Jejunal morphology and the numbers of different T cell subsets, mast cells, IgE expressing cells, eosinophils, and goblet cells were unaffected by S stercoralis infection. Conversely, the numbers of mature macrophages and dividing enterocytes in the crypts were reduced significantly. Crypt enterocytes did not express HLA-DR in both groups. The expression of HLA-DR by villus enterocytes was also comparable in patients and controls. There were no activated (CD25+) cells in the mucosa of either patients or controls. CONCLUSIONS: Compared with seven healthy uninfected volunteers, a group of 19 Brazilians with clinically mild strongyloides infection showed no abnormality of mucosal structure and no increase in non-specific inflammatory cells. Likewise, there was no increase in

  11. Fungal Cell Gigantism during Mammalian Infection

    PubMed Central

    Zaragoza, Oscar; García-Rodas, Rocío; Nosanchuk, Joshua D.; Cuenca-Estrella, Manuel; Rodríguez-Tudela, Juan Luis; Casadevall, Arturo

    2010-01-01

    The interaction between fungal pathogens with the host frequently results in morphological changes, such as hyphae formation. The encapsulated pathogenic fungus Cryptococcus neoformans is not considered a dimorphic fungus, and is predominantly found in host tissues as round yeast cells. However, there is a specific morphological change associated with cryptococcal infection that involves an increase in capsule volume. We now report another morphological change whereby gigantic cells are formed in tissue. The paper reports the phenotypic characterization of giant cells isolated from infected mice and the cellular changes associated with giant cell formation. C. neoformans infection in mice resulted in the appearance of giant cells with cell bodies up to 30 µm in diameter and capsules resistant to stripping with γ-radiation and organic solvents. The proportion of giant cells ranged from 10 to 80% of the total lung fungal burden, depending on infection time, individual mice, and correlated with the type of immune response. When placed on agar, giant cells budded to produce small daughter cells that traversed the capsule of the mother cell at the speed of 20–50 m/h. Giant cells with dimensions that approximated those in vivo were observed in vitro after prolonged culture in minimal media, and were the oldest in the culture, suggesting that giant cell formation is an aging-dependent phenomenon. Giant cells recovered from mice displayed polyploidy, suggesting a mechanism by which gigantism results from cell cycle progression without cell fission. Giant cell formation was dependent on cAMP, but not on Ras1. Real-time imaging showed that giant cells were engaged, but not engulfed by phagocytic cells. We describe a remarkable new strategy for C. neoformans to evade the immune response by enlarging cell size, and suggest that gigantism results from replication without fission, a phenomenon that may also occur with other fungal pathogens. PMID:20585557

  12. Fungal cell gigantism during mammalian infection.

    PubMed

    Zaragoza, Oscar; García-Rodas, Rocío; Nosanchuk, Joshua D; Cuenca-Estrella, Manuel; Rodríguez-Tudela, Juan Luis; Casadevall, Arturo

    2010-06-17

    The interaction between fungal pathogens with the host frequently results in morphological changes, such as hyphae formation. The encapsulated pathogenic fungus Cryptococcus neoformans is not considered a dimorphic fungus, and is predominantly found in host tissues as round yeast cells. However, there is a specific morphological change associated with cryptococcal infection that involves an increase in capsule volume. We now report another morphological change whereby gigantic cells are formed in tissue. The paper reports the phenotypic characterization of giant cells isolated from infected mice and the cellular changes associated with giant cell formation. C. neoformans infection in mice resulted in the appearance of giant cells with cell bodies up to 30 microm in diameter and capsules resistant to stripping with gamma-radiation and organic solvents. The proportion of giant cells ranged from 10 to 80% of the total lung fungal burden, depending on infection time, individual mice, and correlated with the type of immune response. When placed on agar, giant cells budded to produce small daughter cells that traversed the capsule of the mother cell at the speed of 20-50 m/h. Giant cells with dimensions that approximated those in vivo were observed in vitro after prolonged culture in minimal media, and were the oldest in the culture, suggesting that giant cell formation is an aging-dependent phenomenon. Giant cells recovered from mice displayed polyploidy, suggesting a mechanism by which gigantism results from cell cycle progression without cell fission. Giant cell formation was dependent on cAMP, but not on Ras1. Real-time imaging showed that giant cells were engaged, but not engulfed by phagocytic cells. We describe a remarkable new strategy for C. neoformans to evade the immune response by enlarging cell size, and suggest that gigantism results from replication without fission, a phenomenon that may also occur with other fungal pathogens.

  13. Plasmacytoid dendritic cells sense hepatitis C virus-infected cells, produce interferon, and inhibit infection.

    PubMed

    Takahashi, Ken; Asabe, Shinichi; Wieland, Stefan; Garaigorta, Urtzi; Gastaminza, Pablo; Isogawa, Masanori; Chisari, Francis V

    2010-04-20

    Hepatitis C virus (HCV), a member of the Flaviviridae family, is a single-stranded positive-sense RNA virus that infects >170 million people worldwide and causes acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Despite its ability to block the innate host response in infected hepatocyte cell lines in vitro, HCV induces a strong type 1 interferon (IFN) response in the infected liver. The source of IFN in vivo and how it is induced are currently undefined. Here we report that HCV-infected cells trigger a robust IFN response in plasmacytoid dendritic cells (pDCs) by a mechanism that requires active viral replication, direct cell-cell contact, and Toll-like receptor 7 signaling, and we show that the activated pDC supernatant inhibits HCV infection in an IFN receptor-dependent manner. Importantly, the same events are triggered by HCV subgenomic replicon cells but not by free virus particles, suggesting the existence of a novel cell-cell RNA transfer process whereby HCV-infected cells can activate pDCs to produce IFN without infecting them. These results may explain how HCV induces IFN production in the liver, and they reveal a heretofore unsuspected aspect of the innate host response to viruses that can subvert the classical sensing machinery in the cells they infect, and do not infect or directly activate pDCs.

  14. Global self-esteem across the life span: a cross-sectional comparison between representative and self-selected internet samples.

    PubMed

    Pullmann, Helle; Allik, Jüri; Realo, Anu

    2009-01-01

    The cross-sectional trajectory of global self-esteem across the life span was examined administering the Rosenberg and Single-Item Self-Esteem scales to Estonians (N = 29,463) who were either randomly selected from the National Census to represent the population or self-recruited through the Internet. The results (a) challenge the recent conclusion of a universal age trajectory of self-esteem, (b) demonstrate that self-recruited Internet data collection method is biased compared to random sampling, and (c) present that different self-esteem items have dissimilar trajectories. A variance component analysis confirmed that age differences in self-esteem are relatively small compared to interindividual differences and measurement error.

  15. The effects of lifelong ubiquinone Q10 supplementation on the Q9 and Q10 tissue concentrations and life span of male rats and mice.

    PubMed

    Lönnrot, K; Holm, P; Lagerstedt, A; Huhtala, H; Alho, H

    1998-04-01

    The effect of lifelong oral supplementation with ubiquinone Q10 (10 mg/kg/day) was examined in Sprague-Dawley rats and C57/B17 mice. There were no significant differences in survival or life-span found in either rats or mice. Histopathologic examination of different rat tissues showed no differences between the groups. In Q10 supplemented rats, plasma and liver Q10 levels were 2.6 to 8.4 times higher at all age points than in control rats. Interestingly, in supplemented rats the Q9 levels also were significantly higher (p<0.05) in plasma and liver at ages 18 and 24 months. Neither Q9 nor Q10 levels were affected by supplementation in kidney, heart, or brain tissues. In spite of the significant changes in plasma and liver ubiquinone concentrations, lifelong Q10 supplementation did not prolong or shorten the lifespan of either rats or mice.

  16. Continuity of genetic and environmental influences on cognition across the life span: a meta-analysis of longitudinal twin and adoption studies.

    PubMed

    Tucker-Drob, Elliot M; Briley, Daniel A

    2014-07-01

    The longitudinal rank-order stability of cognitive ability increases dramatically over the life span. Theoretical perspectives differ in their emphasis on genetic mechanisms in explaining the longitudinal stability of cognition and how stability changes with development. However, the patterns of stability of genetic and environmental influences on cognition over the life span remain poorly understood. We searched for longitudinal studies of cognition that reported raw genetically informative longitudinal correlations or parameter estimates from longitudinal behavior genetic models. We identified 150 combinations of time points and measures from 15 independent longitudinal samples. In total, longitudinal data came from 4,548 monozygotic twin pairs raised together, 7,777 dizygotic twin pairs raised together, 34 monozygotic twin pairs raised apart, 78 dizygotic twin pairs raised apart, 141 adoptive sibling pairs, and 143 nonadoptive sibling pairs, ranging in age from infancy through late adulthood. At all ages, cross-time genetic correlations and shared environmental correlations were substantially larger than cross-time nonshared environmental correlations. Cross-time correlations for genetic and shared environmental components were, respectively, low and moderate during early childhood, increased sharply over child development, and remained high from adolescence through late adulthood. Cross-time correlations for nonshared environmental components were low across childhood and gradually increased to moderate magnitudes in adulthood. Increasing phenotypic stability over child development was almost entirely mediated by genetic factors. Time-based decay of genetic and shared environmental stability was more pronounced earlier in child development. Results are interpreted in reference to theories of gene-environment correlation and interaction.

  17. Dual expression of hTERT and VEGF prolongs life span and enhances angiogenic ability of aged BMSCs

    SciTech Connect

    Tang, Hao; Xiang, Yongsheng; Jiang, Xiaodan; Ke, Yiquan; Xiao, Zongyu; Guo, Yang; Wang, Qiujing; Du, Mouxuan; Qin, Linsha; Zou, Yuxi; Cai, Yingqian; Chen, Zhenzhou; Xu, Ruxiang

    2013-11-01

    Highlights: •Expression of hTERT and VEGF changed the lifespan and morphology of hBMSCs. •The expression of VEGF and hTRET promoted angiogenesis in vitro and in vivo. •The expression of VEGF and hTRET in hBMSCs had few effects on tumorigenicity. -- Abstract: Previous studies have confirmed the therapeutic effects of bone marrow stromal cells (BMSCs) transplantation on cerebral ischemia. However, the proliferative, differentiative, and homing capacity of BMSC from the elderly are significantly reduced, especially after several passages expansion in vitro. In this study, by introducing lentivirus-mediated hTERT and VEGF genes to modify human BMSCs from aged donors, we observed extended lifespan, promoted angiogenic capacity while less enhanced tumorigenicity of the genetically engineering BMSCs. These results therefore suggest that the modification of aged BMSCs by dual expression of hTERT and VEGF may be used for autologous cell replacement for ischemic cerebrovascular disease in elderly patients.

  18. Life-spanning murine gene expression profiles in relation to chronological and pathological aging in multiple organs

    PubMed Central

    Kuiper, Raoul V; van der Hoeven, Tessa V; Wackers, P.F.K.; Robinson, Joke; van der Horst, Gijsbertus TJ; Dollé, Martijn ET; Vijg, Jan; Breit, Timo M; Hoeijmakers, Jan HJ; van Steeg, Harry

    2013-01-01

    Summary Aging and age-related pathology is a result of a still incompletely-understood intricate web of molecular and cellular processes. We present a C57BL/6J female mice in vivo aging study of five organs (liver, kidney, spleen, lung and brain), in which we compare genome-wide gene expression profiles during chronological aging with pathological changes throughout the entire murine lifespan (13, 26, 52, 78, 104 and 130 weeks). Relating gene expression changes to chronological aging revealed many differentially expressed genes (DEGs) and altered gene-sets (AGSs) were found in most organs, indicative of intra-organ generic aging processes. However, only ≤ 1% of these DEGs are found in all organs. For each organ, at least one of 18 tested pathological parameters showed a good age-predictive value, albeit with much inter- and intra-individual (organ) variation. Relating gene expression changes to pathology-related aging revealed correlated genes and gene-sets, which made it possible to characterize the difference between biological and chronological aging. In liver, kidney and brain, a limited number of overlapping pathology-related AGSs were found. Immune responses appeared to be common, yet the changes were specific in most organs. Furthermore, changes were observed in energy homeostasis, reactive oxygen species, cell cycle, cell motility and DNA damage. Comparison of chronological and pathology-related AGSs revealed substantial overlap and interesting differences. For example, the presence of immune processes in liver pathology-related AGSs which were not detected in chronological aging. The many cellular processes that are only found employing aging–related pathology could provide important new insights into the progress of aging. PMID:23795901

  19. Platon G. Kostyuk (August 20, 1924-May 10, 2010): A unique survey of a life spanning turbulent times.

    PubMed

    Bregestovski, Piotr

    2012-01-01

    On May 10th 2010 Platon Grigorevitch Kostyuk sadly left us at the age of 85. He was a talented scientist, a brilliant experimenter, an outstanding organizer of science and an excellent teacher. Platon Kostyuk was born in 1924 in Kiev, Ukraine. He obtained a double education: a graduate of the Kiev University Department of Biology in 1946 and the Kiev Medical Institute in 1949, he became a pioneer in neuroscience, the first in the Soviet Union to use microelectrodes for intracellular recording of electrical signals in neurons. Despite the difficulties for international travel for those living behind the Iron Curtain, he was able to present his work at the International Congress of Physiology in Buenos Aires in 1959 and here met Prof. John Eccles who invited him to work at the University of Canberra in Australia in 1960–1961. This was the start of an outstanding international career, complementing his creative achievements in the Soviet Union. In 1966 P.G. Kostyuk became director of the Bogomoletz Institute of Physiology in Kiev, which he headed for nearly 45 years. Under his direction this Institute became a leading centre for neuroscience, renowned not only in the Soviet Union but also internationally. New directions of research were developed in cell physiology, molecular biophysics and neurophysiology. Several important discoveries were made including the development of a method for intracellular perfusion, evidence for a calcium-dependent conductance in nerve cells and the discovery of new types of ion channels. Elected to the Ukraine Academy of Science in 1969 and Grand Academician of the Soviet Academy of Science in 1974, Kostyuk has also been honoured by many international societies. He is the author of more than 650 articles, 17 monographs and 7 discoveries and was the creator and editor of two scientific journals: "Neurophysiology" and "Neuroscience". The outstanding career and multifaceted activities of Academician Platon Kostyuk form a pyramid of

  20. Prolactin independent rescue of mouse corpus luteum life span: identification of prolactin and luteinizing hormone target genes

    PubMed Central

    Bachelot, Anne; Beaufaron, Julie; Servel, Nathalie; Kedzia, Cécile; Monget, Philippe; Kelly, Paul A.; Gibori, Geula; Binart, Nadine

    2009-01-01

    The corpus luteum (CL) plays a central role in the maintenance of pregnancy in rodents, mainly by secreting progesterone. Female mice lacking prolactin (PRL) receptor (R) are sterile due to a failure of embryo implantation, which is a consequence of decreased luteinizing hormone (LH) receptor expression in the CL and inadequate levels of progesterone. We attempted to treat PRLR−/− females with human chorionic gonadotropin (hCG) and showed a de novo expression of LHR mRNA in the corpora lutea. Binding analysis confirmed that the LHR in hCG-treated PRLR−/− animals was functional. This was accompanied with increased expression of steroidogenic enzymes involved in progesterone synthesis. Despite these effects, no embryo implantation was observed because of high expression of 20α-hydroxysteroid dehydrogenase. To better appreciate the molecular mechanisms underlying maintenance of the CL, a series of mRNA expression-profiling experiments was performed on isolated corpora lutea of PRLR−/− and hCG-treated PRLR−/− mice. This approach revealed several novel candidate genes with potentially pivotal roles in ovarian function, among them, p27, VE-cadherin, Pten, and sFRP-4, a member of the Wnt/frizzled family. This study showed the differential role of PRL and LH in CL function and identified new targets of these hormones in luteal cells. PMID:19531635

  1. Infective substructures of measles virus from acutely and persistently infected cells.

    PubMed Central

    Rozenblatt, S; Koch, T; Pinhasi, O; Bratosin, S

    1979-01-01

    Ribonucleoprotein from cells acutely or persistently infected with measles virus were shown to be infectious by the calcium phosphate technique. Very little or no infectivity was obtained when calcium phosphate precipitation was omitted. Electron microscopy showed that the majority of ribonucleoprotein structures isolated from acutely infected cells were folded, whereas those from persistently infected cells were linear in appearance. Images PMID:120450

  2. Life span in online communities.

    PubMed

    Grabowski, A; Kosiński, R A

    2010-12-01

    Recently online communities have attracted great interest and have become an important medium of information exchange between users. The aim of this work is to introduce a simple model of the evolution of online communities. This model describes (a) the time evolution of users' activity in a web service, e.g., the time evolution of the number of online friends or written posts, (b) the time evolution of the degree distribution of a social network, and (c) the time evolution of the number of active users of a web service. In the second part of the paper we investigate the influence of the users' lifespan (i.e., the total time in which they are active in an online community) on the process of rumor propagation in evolving social networks. Viral marketing is an important application of such method of information propagation.

  3. Life span in online communities

    NASA Astrophysics Data System (ADS)

    Grabowski, A.; Kosiński, R. A.

    2010-12-01

    Recently online communities have attracted great interest and have become an important medium of information exchange between users. The aim of this work is to introduce a simple model of the evolution of online communities. This model describes (a) the time evolution of users’ activity in a web service, e.g., the time evolution of the number of online friends or written posts, (b) the time evolution of the degree distribution of a social network, and (c) the time evolution of the number of active users of a web service. In the second part of the paper we investigate the influence of the users’ lifespan (i.e., the total time in which they are active in an online community) on the process of rumor propagation in evolving social networks. Viral marketing is an important application of such method of information propagation.

  4. Families as Life Span Experts

    ERIC Educational Resources Information Center

    Brendtro, Larry K.; Mitchell, Martin L.

    2011-01-01

    Professionals dealing with challenging behavior frequently operate detached from the other relationships in the child's life. This narrow approach has been called the unilateral strategy based on the belief that the child's outside world can be ignored and behavior can be changed by administering specific corrective interventions. In contrast,…

  5. Life span of the biosphere

    NASA Astrophysics Data System (ADS)

    Lovelock, J. E.; Whitfield, M.

    1982-04-01

    Since main sequence stars appear to increase their burning rate as they age, the sun may be thought to have increased its output by 30% since the earth's origin 4.5 billion years ago. Due to the requirement for some means of planetary thermostasis in the maintenance of an equable climate since life began, possible links are considered between the biological, Gaia hypothesis of Lovelock and Margulis (1974) for climate control, and Walker et al's (in press) model of automatic thermostasis, in which the abundance of such atmospheric greenhouse gases as CO2 adjusts to resist the warming tendency of the increased solar flux. It is concluded that, since atmospheric CO2 is now close to its partial pressure lower limit, the biosphere will on a geological time-scale be soon exposed, without protection, to the predicted solar luminosity increases.

  6. Prospects for life span extension.

    PubMed

    Sierra, Felipe; Hadley, Evan; Suzman, Richard; Hodes, Richard

    2009-01-01

    Life expectancy has increased dramatically in the United States and in much of the world in recent years and decades. The factors underlying this increase are incompletely understood and are undoubtedly complex. A question that drives current research is whether life expectancy can be further extended using current knowledge of modifiable risk factors. A still more challenging research focus is on the possibility that life expectancy might be further increased through knowledge gained from studies of the basic biology of aging and its genetic and environmental modifiers.

  7. Changes in gas exchange characteristics during the life span of giant sequoia: implications for response to current and future concentrations of atmospheric ozone.

    PubMed

    Grulke, N. E.; Miller, P. R.

    1994-01-01

    Native stands of giant sequoia (Sequoiadendron giganteum Bucholz) are being exposed to relatively high concentrations of atmospheric ozone produced in urban and agricultural areas upwind. The expected change in environmental conditions over the next 100 years is likely to be unprecedented in the life span (about 2,500 years) of giant sequoia. We determined changes in physiological responses of three age classes of giant sequoia (current-year, 12-, and 125-year-old) to differing concentrations of ozone, and assessed age-related differences in sensitivity to pollutants by examining physiological changes (gas exchange, water use efficiency) across the life span of giant sequoia (current-year, 2-, 5-, 20-, 125-, and > 2,000-year-old trees). The CO(2) exchange rate (CER) was greater in current-year (12.1 micro mol CO(2) m(-2) s(-1)) and 2-year-old seedlings (4.8 micro mol CO(2) m(-2) s(-1)) than in all older trees (3.0 micro mol CO(2) m(-2) s(-1), averaged across the four older age classes). Dark respiration was highest for current-year seedlings (-6.5 +/- 0.7 micro mol CO(2) m(-2) s(-1)) and was increased twofold in symptomatic individuals exposed to elevated ozone concentrations. Stomatal conductance (g(s)) was greater in current-year (355 mmol H(2)O m(-2) s(-1)) and 2-year-old seedlings (200 mmol H(2)O m(-2) s(-1)) than in all older trees (50 mmol H(2)O m(-2) s(-1)), indicating that the ozone concentration in substomatal cavities is higher in young seedlings than in trees. Significant changes in water use efficiency, as indicated by C(i)/C(a), occurred in trees between ages 5 and 20 years. We conclude that giant sequoias seedlings are sensitive to atmospheric ozone until they are about 5 years old. Low conductance, high water use efficiency, and compact mesophyll all contribute to a natural ozone tolerance, or defense, or both, in foliage of older trees.

  8. Alteration of cell cycle progression by Sindbis virus infection

    SciTech Connect

    Yi, Ruirong; Saito, Kengo; Isegawa, Naohisa; Shirasawa, Hiroshi

    2015-07-10

    We examined the impact of Sindbis virus (SINV) infection on cell cycle progression in a cancer cell line, HeLa, and a non-cancerous cell line, Vero. Cell cycle analyses showed that SINV infection is able to alter the cell cycle progression in both HeLa and Vero cells, but differently, especially during the early stage of infection. SINV infection affected the expression of several cell cycle regulators (CDK4, CDK6, cyclin E, p21, cyclin A and cyclin B) in HeLa cells and caused HeLa cells to accumulate in S phase during the early stage of infection. Monitoring SINV replication in HeLa and Vero cells expressing cell cycle indicators revealed that SINV which infected HeLa cells during G{sub 1} phase preferred to proliferate during S/G{sub 2} phase, and the average time interval for viral replication was significantly shorter in both HeLa and Vero cells infected during G{sub 1} phase than in cells infected during S/G{sub 2} phase. - Highlights: • SINV infection was able to alter the cell cycle progression of infected cancer cells. • SINV infection can affect the expression of cell cycle regulators. • SINV infection exhibited a preference for the timing of viral replication among the cell cycle phases.

  9. Glycosaminoglycan receptors facilitate infection of mammalian cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A growing list of viruses has been reported to use more than one receptor for binding and internalization during infection of the host cell. Sialic acid residues or glycosaminoglycans, such as heparin sulfate, frequently function in this scenario, as a first contact, charge based, low affinity bindi...

  10. How Stable Is the Personal Past? Stability of Most Important Autobiographical Memories and Life Narratives Across Eight Years in a Life Span Sample.

    PubMed

    Köber, Christin; Habermas, Tilmann

    2017-03-23

    Considering life stories as the most individual layer of personality (McAdams, 2013) implies that life stories, similar to personality traits, exhibit some stability throughout life. Although stability of personality traits has been extensively investigated, only little is known about the stability of life stories. We therefore tested the influence of age, of the proportion of normative age-graded life events, and of global text coherence on the stability of the most important memories and of brief entire life narratives as 2 representations of the life story. We also explored whether normative age-graded life events form more stable parts of life narratives. In a longitudinal life span study covering up to 3 measurements across 8 years and 6 age groups (N = 164) the stability of important memories and of entire life narratives was measured as the percentage of events and narrative segments which were repeated in later tellings. Stability increased between ages 8 and 24, leveling off in middle adulthood. Beyond age, stability of life narratives was also predicted by proportion of normative age-graded life events and by causal-motivational text coherence in younger participants. Memories of normative developmental and social transitional life events were more stable than other memories. Stability of segments of life narratives exceeded the stability of single most important memories. Findings are discussed in terms of cognitive, personality, and narrative psychology and point to research questions in each of these fields. (PsycINFO Database Record

  11. Rho kinase inhibitor Y-27632 prolongs the life span of adult human keratinocytes, enhances skin equivalent development, and facilitates lentiviral transduction.

    PubMed

    van den Bogaard, Ellen H; Rodijk-Olthuis, Diana; Jansen, Patrick A M; van Vlijmen-Willems, Ivonne M J J; van Erp, Piet E; Joosten, Irma; Zeeuwen, Patrick L J M; Schalkwijk, Joost

    2012-09-01

    The use of tissue-engineered human skin equivalents (HSE) for fundamental research and industrial application requires the expansion of keratinocytes from a limited number of skin biopsies donated by adult healthy volunteers or patients. A pharmacological inhibitor of Rho-associated protein kinases, Y-27632, was recently reported to immortalize neonatal human foreskin keratinocytes. Here, we investigated the potential use of Y-27632 to expand human adult keratinocytes and evaluated its effects on HSE development and in vitro gene delivery assays. Y-27632 was found to significantly increase the life span of human adult keratinocytes (up to five to eight passages). The epidermal morphology of HSEs generated from high-passage, Y-27632-treated keratinocytes resembled the native epidermis and was improved by supplementing Y-27632 during the submerged phase of HSE development. In addition, Y-27632-treated keratinocytes responded normally to inflammatory stimuli, and could be used to generate HSEs with a psoriatic phenotype, upon stimulation with relevant cytokines. Furthermore, Y-27632 significantly enhanced both lentiviral transduction efficiency of primary adult keratinocytes and epidermal morphology of HSEs generated thereof. Our study indicates that Y-27632 is a potentially powerful tool that is used for a variety of applications of adult human keratinocytes.

  12. A unifying perspective on personality pathology across the life span: Developmental considerations for the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders

    PubMed Central

    TACKETT, JENNIFER L.; BALSIS, STEVE; OLTMANNS, THOMAS F.; KRUEGER, ROBERT F.

    2010-01-01

    Proposed changes in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) include replacing current personality disorder (PD) categories on Axis II with a taxonomy of dimensional maladaptive personality traits. Most of the work on dimensional models of personality pathology, and on personality disorders per se, has been conducted on young and middle-aged adult populations. Numerous questions remain regarding the applicability and limitations of applying various PD models to early and later life. In the present paper, we provide an overview of such dimensional models and review current proposals for conceptualizing PDs in DSM-V. Next, we extensively review existing evidence on the development, measurement, and manifestation of personality pathology in early and later life focusing on those issues deemed most relevant for informing DSM-V. Finally, we present overall conclusions regarding the need to incorporate developmental issues in conceptualizing PDs in DSM-V and highlight the advantages of a dimensional model in unifying PD perspectives across the life span. PMID:19583880

  13. Assessing Planning Ability Across the Adult Life Span: Population-Representative and Age-Adjusted Reliability Estimates for the Tower of London (TOL-F).

    PubMed

    Kaller, Christoph P; Debelak, Rudolf; Köstering, Lena; Egle, Johanna; Rahm, Benjamin; Wild, Philipp S; Blettner, Maria; Beutel, Manfred E; Unterrainer, Josef M

    2016-03-01

    Planning ahead the consequences of future actions is a prototypical executive function. In clinical and experimental neuropsychology, disc-transfer tasks like the Tower of London (TOL) are commonly used for the assessment of planning ability. Previous psychometric evaluations have, however, yielded a poor reliability of measuring planning performance with the TOL. Based on theory-grounded task analyses and a systematic problem selection, the computerized TOL-Freiburg version (TOL-F) was developed to improve the task's psychometric properties for diagnostic applications. Here, we report reliability estimates for the TOL-F from two large samples collected in Mainz, Germany (n = 3,770; 40-80 years) and in Vienna, Austria (n = 830; 16-84 years). Results show that planning accuracy on the TOL-F possesses an adequate internal consistency and split-half reliability (>0.7) that are stable across the adult life span while the TOL-F covers a broad range of graded difficulty even in healthy adults, making it suitable for both research and clinical application.

  14. A unifying perspective on personality pathology across the life span: developmental considerations for the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders.

    PubMed

    Tackett, Jennifer L; Balsis, Steve; Oltmanns, Thomas F; Krueger, Robert F

    2009-01-01

    Proposed changes in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) include replacing current personality disorder (PD) categories on Axis II with a taxonomy of dimensional maladaptive personality traits. Most of the work on dimensional models of personality pathology, and on personality disorders per se, has been conducted on young and middle-aged adult populations. Numerous questions remain regarding the applicability and limitations of applying various PD models to early and later life. In the present paper, we provide an overview of such dimensional models and review current proposals for conceptualizing PDs in DSM-V. Next, we extensively review existing evidence on the development, measurement, and manifestation of personality pathology in early and later life focusing on those issues deemed most relevant for informing DSM-V. Finally, we present overall conclusions regarding the need to incorporate developmental issues in conceptualizing PDs in DSM-V and highlight the advantages of a dimensional model in unifying PD perspectives across the life span.

  15. Increased production of mitochondrial reactive oxygen species and reduced adult life span in an insecticide-resistant strain of Anopheles gambiae.

    PubMed

    Otali, D; Novak, R J; Wan, W; Bu, S; Moellering, D R; De Luca, M

    2014-06-01

    Control of the malaria vector An. gambiae is still largely obtained through chemical intervention using pyrethroids, such as permethrin. However, strains of An. gambiae that are resistant to the toxic effects of pyrethroids have become widespread in several endemic areas over the last decade. The objective of this study was to assess differences in five life-history traits (larval developmental time and the body weight, fecundity, hatch rate, and longevity of adult females) and energy metabolism between a strain of An. gambiae that is resistant to permethrin (RSP), due to knockdown resistance and enhanced metabolic detoxification, and a permethrin susceptible strain reared under laboratory conditions. We also quantified the expression levels of five antioxidant enzyme genes: GSTe3, CAT, GPXH1, SOD1, and SOD2. We found that the RSP strain had a longer developmental time than the susceptible strain. Additionally, RSP adult females had higher wet body weight and increased water and glycogen levels. Compared to permethrin susceptible females, RSP females displayed reduced metabolic rate and mitochondrial coupling efficiency and higher mitochondrial ROS production. Furthermore, despite higher levels of GSTe3 and CAT transcripts, RSP females had a shorter adult life span than susceptible females. Collectively, these results suggest that permethrin resistance alleles might affect energy metabolism, oxidative stress, and adult survival of An. gambiae. However, because the strains used in this study differ in their genetic backgrounds, the results need to be interpreted with caution and replicated in other strains to have significant implications for malaria transmission and vector control.

  16. Zika virus infection of Hofbauer cells.

    PubMed

    Simoni, Michael K; Jurado, Kellie Ann; Abrahams, Vikki M; Fikrig, Erol; Guller, Seth

    2017-02-01

    Recent studies have linked antenatal infection with Zika virus (ZIKV) with major adverse fetal and neonatal outcomes, including microcephaly. There is a growing consensus for the existence of a congenital Zika syndrome (CZS). Previous studies have indicated that non-placental macrophages play a key role in the replication of dengue virus (DENV), a closely related flavivirus. As the placenta provides the conduit for vertical transmission of certain viruses, and placental Hofbauer cells (HBCs) are fetal-placental macrophages located adjacent to fetal capillaries, it is not surprising that several recent studies have examined infection of HBCs by ZIKV. In this review, we describe congenital abnormalities associated with ZIKV infection, the role of HBCs in the placental response to infection, and evidence for the susceptibility of HBCs to ZIKV infection. We conclude that HBCs may contribute to the spread of ZIKV in placenta and promote vertical transmission of ZIKV, ultimately compromising fetal and neonatal development and function. Current evidence strongly suggests that further studies are warranted to dissect the specific molecular mechanism through which ZIKV infects HBCs and its potential impact on the development of CZS.

  17. Origin of the transmitted virus in HIV infection: infected cells versus cell-free virus.

    PubMed

    Sagar, Manish

    2014-12-15

    All human immunodeficiency virus type 1 (HIV-1)-infected inocula, such as genital secretions, breast milk, and blood, contain both cell-free virus and infected cells. The relative contributions of cell-free and/or cell-associated virus in establishing an infection in a naive host during the different modes of HIV-1 acquisition remains unclear. Studies aim to elucidate the source of the acquired virus because strategies to prevent acquisition may have differential efficacy against the different modes of transmission. In this review, I will detail some of the challenges in identifying the source of the transmitted virus, genotypic and phenotypic differences among cell-free compared with cell-associated HIV-1, and implications on the efficacy for prevention strategies.

  18. [Parallelism and paradoxes on viability and the life span of two loss-of-function mutations: heat shock protein transcriptional regulator hsf(1) and l(2)gl tumor suppressor in D. melanogaster].

    PubMed

    Vaĭsman, N Ia; Evgen'ev, M B; Golubovskiĭ, M D

    2012-01-01

    In this study we analyzed how a dosage decrease in mono- and diheterozygotes on both lethal alleles of the lgl-gene and hsfheat shock regulator influences viability and life span at optimal and high temperature 29 degrees C conditions. We found that hsf(1) (1 dosage of active hsf-factor) heterozygote animals had significantly increased viability (up to 30-39%) in case of its development from egg to imago under the stress of 29 degrees C. However, this stress-protective effect of a decreased dosage of HSF1 was suppressed in diheterozygotes, while the dosage of tumor suppressor lgl was simultaneously decreased. Under stress temperature conditions, a decrease in dosage of one of the alleles also increased the average life span and delayed aging, especially in the case of maternal inheritance of each of the loss-of-function mutations. In diheterozygotes the average life span had intermediate meanings. However, in diheterozygote males under stress conditions the positive longevity effect of hsf was suppressed in the presence of the lgl-mutation. Paradoxically, that decrease of expression of each of the studied vital genes provided a positive effect on both viability and life span under stress conditions. However, a simultaneous dosage decrease of two loss-of-function alleles in diheterozygotes resulted in disbalanced effects on the organism level. The received data indicate interaction between HSF1 and LGL gene products during ontogenesis and stress-defending processes.

  19. The control processes and subjective well-being of Chinese teachers: evidence of convergence with and divergence from the key propositions of the motivational theory of life-span development.

    PubMed

    Wong, Wan-Chi; Li, Yin; Sun, Xiaoyan; Xu, Huanu

    2014-01-01

    An analytical review of the motivational theory of life-span development reveals that this theory has undergone a series of elegant theoretical integrations. Its claim to universality nonetheless brings forth unresolved controversies. With the purpose of scrutinizing the key propositions of this theory, an empirical study was designed to examine the control processes and subjective well-being of Chinese teachers (N = 637). The OPS-Scales (Optimization in Primary and Secondary Control Scales) for the Domain of Teaching were constructed to assess patterns of control processes. Three facets of subjective well-being were investigated with the Positive and Negative Affect Schedule, the Life Satisfaction Scale, and the Subjective Vitality Scale. The results revealed certain aspects of alignment with and certain divergences from the key propositions of the motivational theory of life-span development. Neither "primacy of primary control" nor "primacy of secondary control" was clearly supported. Notably, using different criteria for subjective well-being yielded different subtypes of primary and secondary control as predictors. The hypothesized life-span trajectories of primary and secondary control received limited support. To advance the theory in this area, we recommend incorporating Lakatos' ideas about sophisticated falsification by specifying the hard core of the motivational theory of life-span development and articulating new auxiliary hypotheses.

  20. The control processes and subjective well-being of Chinese teachers: evidence of convergence with and divergence from the key propositions of the motivational theory of life-span development

    PubMed Central

    Wong, Wan-chi; Li, Yin; Sun, Xiaoyan; Xu, Huanu

    2014-01-01

    An analytical review of the motivational theory of life-span development reveals that this theory has undergone a series of elegant theoretical integrations. Its claim to universality nonetheless brings forth unresolved controversies. With the purpose of scrutinizing the key propositions of this theory, an empirical study was designed to examine the control processes and subjective well-being of Chinese teachers (N = 637). The OPS-Scales (Optimization in Primary and Secondary Control Scales) for the Domain of Teaching were constructed to assess patterns of control processes. Three facets of subjective well-being were investigated with the Positive and Negative Affect Schedule, the Life Satisfaction Scale, and the Subjective Vitality Scale. The results revealed certain aspects of alignment with and certain divergences from the key propositions of the motivational theory of life-span development. Neither “primacy of primary control” nor “primacy of secondary control” was clearly supported. Notably, using different criteria for subjective well-being yielded different subtypes of primary and secondary control as predictors. The hypothesized life-span trajectories of primary and secondary control received limited support. To advance the theory in this area, we recommend incorporating Lakatos' ideas about sophisticated falsification by specifying the hard core of the motivational theory of life-span development and articulating new auxiliary hypotheses. PMID:24904483

  1. Bacterial foodborne infections after hematopoietic cell transplantation.

    PubMed

    Boyle, Nicole M; Podczervinski, Sara; Jordan, Kim; Stednick, Zach; Butler-Wu, Susan; McMillen, Kerry; Pergam, Steven A

    2014-11-01

    Diarrhea, abdominal pain, and fever are common among patients undergoing hematopoietic cell transplantation (HCT), but such symptoms are also typical with foodborne infections. The burden of disease caused by foodborne infections in patients undergoing HCT is unknown. We sought to describe bacterial foodborne infection incidence after transplantation within a single-center population of HCT recipients. All HCT recipients who underwent transplantation from 2001 through 2011 at the Fred Hutchinson Cancer Research Center in Seattle, Washington were followed for 1 year after transplantation. Data were collected retrospectively using center databases, which include information from transplantation, on-site examinations, outside records, and collected laboratory data. Patients were considered to have a bacterial foodborne infection if Campylobacter jejuni/coli, Listeria monocytogenes, E. coli O157:H7, Salmonella species, Shigella species, Vibrio species, or Yersinia species were isolated in culture within 1 year after transplantation. Nonfoodborne infections with these agents and patients with pre-existing bacterial foodborne infection (within 30 days of transplantation) were excluded from analyses. A total of 12 of 4069 (.3%) patients developed a bacterial foodborne infection within 1 year after transplantation. Patients with infections had a median age at transplantation of 50.5 years (interquartile range [IQR], 35 to 57), and the majority were adults ≥18 years of age (9 of 12 [75%]), male gender (8 of 12 [67%]) and had allogeneic transplantation (8 of 12 [67%]). Infectious episodes occurred at an incidence rate of 1.0 per 100,000 patient-days (95% confidence interval, .5 to 1.7) and at a median of 50.5 days after transplantation (IQR, 26 to 58.5). The most frequent pathogen detected was C. jejuni/coli (5 of 12 [42%]) followed by Yersinia (3 of 12 [25%]), although Salmonella (2 of 12 [17%]) and Listeria (2 of 12 [17%]) showed equal frequencies; no cases of Shigella

  2. Virus-induced aggregates in infected cells.

    PubMed

    Moshe, Adi; Gorovits, Rena

    2012-10-17

    During infection, many viruses induce cellular remodeling, resulting in the formation of insoluble aggregates/inclusions, usually containing viral structural proteins. Identification of aggregates has become a useful diagnostic tool for certain viral infections. There is wide variety of viral aggregates, which differ by their location, size, content and putative function. The role of aggregation in the context of a specific virus is often poorly understood, especially in the case of plant viruses. The aggregates are utilized by viruses to house a large complex of proteins of both viral and host origin to promote virus replication, translation, intra- and intercellular transportation. Aggregated structures may protect viral functional complexes from the cellular degradation machinery. Alternatively, the activation of host defense mechanisms may involve sequestration of virus components in aggregates, followed by their neutralization as toxic for the host cell. The diversity of virus-induced aggregates in mammalian and plant cells is the subject of this review.

  3. Measurement invariance of big-five factors over the life span: ESEM tests of gender, age, plasticity, maturity, and la dolce vita effects.

    PubMed

    Marsh, Herbert W; Nagengast, Benjamin; Morin, Alexandre J S

    2013-06-01

    This substantive-methodological synergy applies evolving approaches to factor analysis to substantively important developmental issues of how five-factor-approach (FFA) personality measures vary with gender, age, and their interaction. Confirmatory factor analyses (CFAs) conducted at the item level often do not support a priori FFA structures, due in part to the overly restrictive assumptions of CFA models. Here we demonstrate that exploratory structural equation modeling (ESEM), an integration of CFA and exploratory factor analysis, overcomes these problems with the 15-item Big Five Inventory administered as part of the nationally representative British Household Panel Study (N = 14,021; age: 15-99 years, Mage = 47.1). ESEM fitted the data substantially better and resulted in much more differentiated (less correlated) factors than did CFA. Methodologically, we extended ESEM (introducing ESEM-within-CFA models and a hybrid of multiple groups and multiple indicators multiple causes models), evaluating full measurement invariance and latent mean differences over age, gender, and their interaction. Substantively the results showed that women had higher latent scores for all Big Five factors except for Openness and that these gender differences were consistent over the entire life span. Substantial nonlinear age effects led to the rejection of the plaster hypothesis and the maturity principle but did support a newly proposed la dolce vita effect in old age. In later years, individuals become happier (more agreeable and less neurotic), more self-content and self-centered (less extroverted and open), more laid back and satisfied with what they have (less conscientious, open, outgoing and extroverted), and less preoccupied with productivity.

  4. Recruitment and Retention Strategies for Minority or Poor Clinical Research Participants: Lessons From the Healthy Aging in Neighborhoods of Diversity Across the Life Span Study

    PubMed Central

    Ejiogu, Ngozi; Norbeck, Jennifer H.; Mason, Marc A.; Cromwell, Bridget C.; Zonderman, Alan B.; Evans, Michele K.

    2011-01-01

    Purpose of the study: Investigating health disparities requires studies designed to recruit and retain racially and socioeconomically diverse cohorts. It is critical to address the barriers that disproportionately affect participation in clinical research by minorities and the socioeconomically disadvantaged. This study sought to identify and rectify these barriers to recruit and retain a biracial (African American and non-Hispanic White) and socioeconomically diverse cohort for a longitudinal study. Design and Method: The Healthy Aging in Neighborhoods of Diversity across the Life Span study is a 20-year longitudinal examination of how race and socioeconomic status influence the development of age-related health disparities. One goal was to create a multifactorial recruitment and retention strategy. The recruitment paradigm targeted known barriers and identified those unique to the study's urban environment. The retention paradigm mirrored the recruitment plan but was based on specifically developed approaches. Results: This cohort recruitment required attention to developing community partnerships, designing the research study to meet the study hypotheses and to provide benefit to participants, providing a safe community-based site for the research and creating didactics to develop staff cultural proficiency. These efforts facilitated study implementation and enhanced recruitment resulting in accrual of a biracial and socioeconomically diverse cohort of 3,722 participants. Implications: Recruiting and retaining minority or poor research participants is challenging but possible. The essential facets include clear communication of the research hypothesis, focus on providing a direct benefit for participants, and selection of a hypothesis that is directly relevant to the community studied PMID:21565817

  5. Differential effects of IGF-1 deficiency during the life span on structural and biomechanical properties in the tibia of aged mice.

    PubMed

    Ashpole, Nicole M; Herron, Jacquelyn C; Estep, Patrick N; Logan, Sreemathi; Hodges, Erik L; Yabluchanskiy, Andriy; Humphrey, Mary Beth; Sonntag, William E

    2016-04-01

    Advanced aging is associated with the loss of structural and biomechanical properties in bones, which increases the risk for bone fracture. Aging is also associated with reductions in circulating levels of the anabolic signaling hormone, insulin-like growth factor (IGF)-1. While the role of IGF-1 in bone development has been well characterized, the impact of the age-related loss of IGF-1 on bone aging remains controversial. Here, we describe the effects of reducing IGF-1 at multiple time points in the mouse life span--early in postnatal development, early adulthood, or late adulthood on tibia bone aging in both male and female igf (f/f) mice. Bone structure was analyzed at 27 months of age using microCT. We find that age-related reductions in cortical bone fraction, cortical thickness, and tissue mineral density were more pronounced when IGF-1 was reduced early in life and not in late adulthood. Three-point bone bending assays revealed that IGF-1 deficiency early in life resulted in reduced maximum force, maximum bending moment, and bone stiffness in aged males and females. The effects of IGF-1 on bone aging are microenvironment specific, as early-life loss of IGF-1 resulted in decreased cortical bone structure and strength along the diaphysis while significantly increasing trabecular bone fraction and trabecular number at the proximal metaphysis. The increases in trabecular bone were limited to males, as early-life loss of IGF-1 did not alter bone fraction or number in females. Together, our data suggest that the age-related loss of IGF-1 influences tibia bone aging in a sex-specific, microenvironment-specific, and time-dependent manner.

  6. Character strengths and well-being across the life span: data from a representative sample of German-speaking adults living in Switzerland

    PubMed Central

    Martínez-Martí, María L.; Ruch, Willibald

    2014-01-01

    Character strengths are positive, morally valued traits of personality. This study aims at assessing the relationship between character strengths and subjective well-being (i.e., life satisfaction, positive and negative affect) in a representative sample of German-speaking adults living in Switzerland (N = 945). We further test whether this relationship is consistent at different stages in life. Results showed that hope, zest, love, social intelligence and perseverance yielded the highest positive correlations with life satisfaction. Hope, zest, humor, gratitude and love presented the highest positive correlations with positive affect. Hope, humor, zest, honesty, and open-mindedness had the highest negative correlations with negative affect. When examining the relationship between strengths and well-being across age groups, in general, hope, zest and humor consistently yielded the highest correlations with well-being. Additionally, in the 27–36 years group, strengths that promote commitment and affiliation (i.e., kindness and honesty) were among the first five positions in the ranking of the relationship between strengths and well-being. In the 37–46 years group, in addition to hope, zest and humor, strengths that promote the maintenance of areas such as family and work (i.e., love, leadership) were among the first five positions in the ranking. Finally, in the 47–57 years group, in addition to hope, zest and humor, strengths that facilitate integration and a vital involvement with the environment (i.e., gratitude, love of learning) were among the first five positions in the ranking. This study partially supports previous findings with less representative samples on the association between character strengths and well-being, and sheds light on the relative importance of some strengths over others for well-being across the life span. PMID:25408678

  7. Character strengths and well-being across the life span: data from a representative sample of German-speaking adults living in Switzerland.

    PubMed

    Martínez-Martí, María L; Ruch, Willibald

    2014-01-01

    Character strengths are positive, morally valued traits of personality. This study aims at assessing the relationship between character strengths and subjective well-being (i.e., life satisfaction, positive and negative affect) in a representative sample of German-speaking adults living in Switzerland (N = 945). We further test whether this relationship is consistent at different stages in life. Results showed that hope, zest, love, social intelligence and perseverance yielded the highest positive correlations with life satisfaction. Hope, zest, humor, gratitude and love presented the highest positive correlations with positive affect. Hope, humor, zest, honesty, and open-mindedness had the highest negative correlations with negative affect. When examining the relationship between strengths and well-being across age groups, in general, hope, zest and humor consistently yielded the highest correlations with well-being. Additionally, in the 27-36 years group, strengths that promote commitment and affiliation (i.e., kindness and honesty) were among the first five positions in the ranking of the relationship between strengths and well-being. In the 37-46 years group, in addition to hope, zest and humor, strengths that promote the maintenance of areas such as family and work (i.e., love, leadership) were among the first five positions in the ranking. Finally, in the 47-57 years group, in addition to hope, zest and humor, strengths that facilitate integration and a vital involvement with the environment (i.e., gratitude, love of learning) were among the first five positions in the ranking. This study partially supports previous findings with less representative samples on the association between character strengths and well-being, and sheds light on the relative importance of some strengths over others for well-being across the life span.

  8. Parasitic Infections in Hematopoietic Stem Cell Transplantation

    PubMed Central

    Jarque, Isidro; Salavert, Miguel; Pemán, Javier

    2016-01-01

    Parasitic infections are rarely documented in hematopoietic stem cell transplant recipients. However they may be responsible for fatal complications that are only diagnosed at autopsy. Increased awareness of the possibility of parasitic diseases both in autologous and allogeneic stem cell transplant patients is relevant not only for implementing preventive measures but also for performing an early diagnosis and starting appropriate therapy for these unrecognized but fatal infectious complications in hematopoietic transplant recipients. In this review, we will focus on parasitic diseases occurring in this population especially those with major clinical relevance including toxoplasmosis, American trypanosomiasis, leishmaniasis, malaria, and strongyloidiasis, among others, highlighting the diagnosis and management in hematopoietic transplant recipients. PMID:27413527

  9. Hospital infection control in hematopoietic stem cell transplant recipients.

    PubMed Central

    Dykewicz, C. A.

    2001-01-01

    Guidelines for Preventing Opportunistic Infections Among Hematopoietic Stem Cell Transplant Recipients contains a section on hospital infection control including evidence-based recommendations regarding ventilation, construction, equipment, plants, play areas and toys, health-care workers, visitors, patient skin and oral care, catheter-related infections, drug-resistant organisms, and specific nosocomial infections. These guidelines are intended to reduce the number and severity of hospital infections in hematopoietic stem cell transplant recipients. PMID:11294720

  10. CD8+ T Cells in Leishmania Infections: Friends or Foes?

    PubMed Central

    Stäger, Simona; Rafati, Sima

    2012-01-01

    Host protection against several intracellular pathogens requires the induction of CD8+ T cell responses. CD8+ T cells are potent effector cells that can produce high amounts of pro-inflammatory cytokines and kill infected target cells efficiently. However, a protective role for CD8+ T cells during Leishmania infections is still controversial and largely depends on the infection model. In this review, we discuss the role of CD8+ T cells during various types of Leishmania infections, following vaccination, and as potential immunotherapeutic targets. PMID:22566891

  11. Interferon Response in Hepatitis C Virus (HCV) Infection: Lessons from Cell Culture Systems of HCV Infection.

    PubMed

    Sung, Pil Soo; Shin, Eui-Cheol; Yoon, Seung Kew

    2015-10-07

    Hepatitis C virus (HCV) is a positive-stranded RNA virus that infects approximately 130-170 million people worldwide. In 2005, the first HCV infection system in cell culture was established using clone JFH-1, which was isolated from a Japanese patient with fulminant HCV infection. JFH-1 replicates efficiently in hepatoma cells and infectious virion particles are released into the culture supernatant. The development of cell culture-derived HCV (HCVcc) systems has allowed us to understand how hosts respond to HCV infection and how HCV evades host responses. Although the mechanisms underlying the different outcomes of HCV infection are not fully understood, innate immune responses seem to have a critical impact on the outcome of HCV infection, as demonstrated by the prognostic value of IFN-λ gene polymorphisms among patients with chronic HCV infection. Herein, we review recent research on interferon response in HCV infection, particularly studies using HCVcc infection systems.

  12. Dichotomy between T Cell and B Cell Tolerance to Neonatal Retroviral Infection Permits T Cell Therapy

    PubMed Central

    Mavrommatis, Bettina; Baudino, Lucie; Levy, Prisca; Merkenschlager, Julia; Eksmond, Urszula; Donnarumma, Tiziano; Young, George; Stoye, Jonathan

    2016-01-01

    Elucidation of the immune requirements for control or elimination of retroviral infection remains an important aim. We studied the induction of adaptive immunity to neonatal infection with a murine retrovirus, under conditions leading to immunological tolerance. We found that the absence of either maternal or offspring adaptive immunity permitted efficient vertical transmission of the retrovirus. Maternal immunodeficiency allowed the retrovirus to induce central Th cell tolerance in the infected offspring. In turn, this compromised the offspring’s ability to mount a protective Th cell–dependent B cell response. However, in contrast to T cells, offspring B cells were not centrally tolerized and retained their ability to respond to the infection when provided with T cell help. Thus, escape of retrovirus-specific B cells from deletional tolerance offers the opportunity to induce protective retroviral immunity by restoration of retrovirus-specific T cell help, suggesting similar T cell immunotherapies for persistent viral infections. PMID:27647833

  13. Modeling malaria infected cells in microcirculation

    NASA Astrophysics Data System (ADS)

    Raffiee, Amir Hossein; Dabiri, Sadegh; Motavalizadeh Ardekani, Arezoo

    2016-11-01

    Plasmodim (P.) falciparum is one of the deadliest types of malaria species that invades healthy red blood cells (RBC) in human blood flow. This parasite develops through 48-hour intra-RBC process leading to significant morphological and mechanical (e.g., stiffening) changes in RBC membrane. These changes have remarkable effects on blood circulation such as increase in flow resistance and obstruction in microcirculation. In this work a computational framework is developed to model RBC suspension in blood flow using front-tracking technique. The present study focuses on blood flow behavior under normal and infected circumstances and predicts changes in blood rheology for different levels of parasitemia and hematocrit. This model allows better understanding of blood flow circulation up to a single cell level and provides us with realistic and deep insight into hematologic diseases such as malaria.

  14. Human immunodeficiency virus can productively infect cultured human glial cells.

    PubMed

    Cheng-Mayer, C; Rutka, J T; Rosenblum, M L; McHugh, T; Stites, D P; Levy, J A

    1987-05-01

    Six isolates of the human immunodeficiency virus (HIV) showed differences in their ability to productively infect glioma-derived cell lines and early-passage human brain cell cultures. Susceptibility to HIV infection correlated well with the expression of the astrocyte marker glial fibrillary acidic protein. The CD4 molecule was expressed on some, but not all, of the brain-derived cells; however, no correlation was observed between CD4 protein expression and susceptibility to virus infection. The results show that HIV can productively infect human brain cells, particularly those of glial origin, and suggest that these cell types in the brain can harbor the virus.

  15. Hepatitis C Virus Infection of Cultured Human Hepatoma Cells Causes Apoptosis and Pyroptosis in Both Infected and Bystander Cells

    PubMed Central

    Kofahi, H. M.; Taylor, N. G. A.; Hirasawa, K.; Grant, M. D.; Russell, R. S.

    2016-01-01

    Individuals infected with hepatitis C virus (HCV) are at high risk of developing progressive liver disease, including cirrhosis and hepatocellular carcinoma (HCC). How HCV infection causes liver destruction has been of significant interest for many years, and apoptosis has been proposed as one operative mechanism. In this study, we employed a tissue culture-adapted strain of HCV (JFH1T) to test effects of HCV infection on induction of programmed cell death (PCD) in Huh-7.5 cells. We found that HCV infection reduced the proliferation rate and induced caspase-3-mediated apoptosis in the infected cell population. However, in addition to apoptosis, we also observed infected cells undergoing caspase-1-mediated pyroptosis, which was induced by NLRP3 inflammasome activation. By co-culturing HCV-infected Huh-7.5 cells with an HCV-non-permissive cell line, we also demonstrated induction of both apoptosis and pyroptosis in uninfected cells. Bystander apoptosis, but not bystander pyroptosis, required cell-cell contact between infected and bystander cells. In summary, these findings provide new information on mechanisms of cell death in response to HCV infection. The observation that both apoptosis and pyroptosis can be induced in bystander cells extends our understanding of HCV-induced pathogenesis in the liver. PMID:27974850

  16. Combination of Antiretroviral Drugs and Radioimmunotherapy Specifically Kills Infected Cells from HIV-Infected Individuals.

    PubMed

    Tsukrov, Dina; McFarren, Alicia; Morgenstern, Alfred; Bruchertseifer, Frank; Dolce, Eugene; Gorny, Miroslaw K; Zolla-Pazner, Susan; Berman, Joan W; Schoenbaum, Ellie; Zingman, Barry S; Casadevall, Arturo; Dadachova, Ekaterina

    2016-01-01

    Eliminating virally infected cells is an essential component of any HIV eradication strategy. Radioimmunotherapy (RIT), a clinically established method for killing cells using radiolabeled antibodies, was recently applied to target HIV-1 gp41 antigen expressed on the surface of infected cells. Since gp41 expression by infected cells is likely downregulated in patients on antiretroviral therapy (ART), we evaluated the ability of RIT to kill ART-treated infected cells using both in vitro models and lymphocytes isolated from HIV-infected subjects. Human peripheral blood mononuclear cells (PBMCs) were infected with HIV and cultured in the presence of two clinically relevant ART combinations. Scatchard analysis of the 2556 human monoclonal antibody to HIV gp41 binding to the infected and ART-treated cells demonstrated sufficient residual expression of gp41 on the cell surface to warrant subsequent RIT. This is the first time the quantification of gp41 post-ART is being reported. Cells were then treated with Bismuth-213-labeled 2556 antibody. Cell survival was quantified by Trypan blue and residual viremia by p24 ELISA. Cell surface gp41 expression was assessed by Scatchard analysis. The experiments were repeated using PBMCs isolated from blood specimens obtained from 15 HIV-infected individuals: 10 on ART and 5 ART-naïve. We found that (213)Bi-2556 killed ART-treated infected PBMCs and reduced viral production to undetectable levels. ART and RIT co-treatment was more effective at reducing viral load in vitro than either therapy alone, indicating that gp41 expression under ART was sufficient to allow (213)Bi-2556 to deliver cytocidal doses of radiation to infected cells. This study provides proof of concept that (213)Bi-2556 may represent an innovative and effective targeting method for killing HIV-infected cells treated with ART and supports continued development of (213)Bi-2556 for co-administration with ART toward an HIV eradication strategy.

  17. Combination of Antiretroviral Drugs and Radioimmunotherapy Specifically Kills Infected Cells from HIV-Infected Individuals

    PubMed Central

    Tsukrov, Dina; McFarren, Alicia; Morgenstern, Alfred; Bruchertseifer, Frank; Dolce, Eugene; Gorny, Miroslaw K.; Zolla-Pazner, Susan; Berman, Joan W.; Schoenbaum, Ellie; Zingman, Barry S.; Casadevall, Arturo; Dadachova, Ekaterina

    2016-01-01

    Eliminating virally infected cells is an essential component of any HIV eradication strategy. Radioimmunotherapy (RIT), a clinically established method for killing cells using radiolabeled antibodies, was recently applied to target HIV-1 gp41 antigen expressed on the surface of infected cells. Since gp41 expression by infected cells is likely downregulated in patients on antiretroviral therapy (ART), we evaluated the ability of RIT to kill ART-treated infected cells using both in vitro models and lymphocytes isolated from HIV-infected subjects. Human peripheral blood mononuclear cells (PBMCs) were infected with HIV and cultured in the presence of two clinically relevant ART combinations. Scatchard analysis of the 2556 human monoclonal antibody to HIV gp41 binding to the infected and ART-treated cells demonstrated sufficient residual expression of gp41 on the cell surface to warrant subsequent RIT. This is the first time the quantification of gp41 post-ART is being reported. Cells were then treated with Bismuth-213-labeled 2556 antibody. Cell survival was quantified by Trypan blue and residual viremia by p24 ELISA. Cell surface gp41 expression was assessed by Scatchard analysis. The experiments were repeated using PBMCs isolated from blood specimens obtained from 15 HIV-infected individuals: 10 on ART and 5 ART-naïve. We found that 213Bi-2556 killed ART-treated infected PBMCs and reduced viral production to undetectable levels. ART and RIT co-treatment was more effective at reducing viral load in vitro than either therapy alone, indicating that gp41 expression under ART was sufficient to allow 213Bi-2556 to deliver cytocidal doses of radiation to infected cells. This study provides proof of concept that 213Bi-2556 may represent an innovative and effective targeting method for killing HIV-infected cells treated with ART and supports continued development of 213Bi-2556 for co-administration with ART toward an HIV eradication strategy. PMID:27725930

  18. Establishment of Human Papillomavirus Infection Requires Cell Cycle Progression

    PubMed Central

    Pyeon, Dohun; Pearce, Shane M.; Lank, Simon M.; Ahlquist, Paul; Lambert, Paul F.

    2009-01-01

    Human papillomaviruses (HPVs) are DNA viruses associated with major human cancers. As such there is a strong interest in developing new means, such as vaccines and microbicides, to prevent HPV infections. Developing the latter requires a better understanding of the infectious life cycle of HPVs. The HPV infectious life cycle is closely linked to the differentiation state of the stratified epithelium it infects, with progeny virus only made in the terminally differentiating suprabasal compartment. It has long been recognized that HPV must first establish its infection within the basal layer of stratified epithelium, but why this is the case has not been understood. In part this restriction might reflect specificity of expression of entry receptors. However, this hypothesis could not fully explain the differentiation restriction of HPV infection, since many cell types can be infected with HPVs in monolayer cell culture. Here, we used chemical biology approaches to reveal that cell cycle progression through mitosis is critical for HPV infection. Using infectious HPV16 particles containing the intact viral genome, G1-synchronized human keratinocytes as hosts, and early viral gene expression as a readout for infection, we learned that the recipient cell must enter M phase (mitosis) for HPV infection to take place. Late M phase inhibitors had no effect on infection, whereas G1, S, G2, and early M phase cell cycle inhibitors efficiently prevented infection. We conclude that host cells need to pass through early prophase for successful onset of transcription of the HPV encapsidated genes. These findings provide one reason why HPVs initially establish infections in the basal compartment of stratified epithelia. Only this compartment of the epithelium contains cells progressing through the cell cycle, and therefore it is only in these cells that HPVs can establish their infection. By defining a major condition for cell susceptibility to HPV infection, these results also have

  19. Listeria monocytogenes infection differentially affects expression of ligands for NK cells and NK cell responses, depending on the cell type infected.

    PubMed

    Shegarfi, Hamid; Rolstad, Bent; Kane, Kevin P; Nestvold, Janne

    2016-04-22

    The pivotal role of NK cells in viral infection is extensively studied, whereas the role of NK cells in bacterial infection has been poorly investigated. Here, we have examined how Listeria monocytogenes (LM) affects expression of ligands for NK cell receptors and subsequent NK cell responses, depending on the type of cell infected. LM infected rat cell lines derived from different tissues were coincubated with splenic NK cells, and NK cell proliferation and IFN-γ production were measured. In addition, expression of ligands for the NK cell receptors Ly49 and NK cell receptor protein 1 (NKR-P1), MHC class I and C-type lectin-related molecules, respectively, was assessed. Infected pleural R2 cells, but not epithelium-derived colon carcinoma cell line CC531 cells, induced proliferation of NK cells. Reporter cells expressing the inhibitory NKR-P1G receptor or the activating NKR-P1F receptor were less stimulated under incubation with infected CC531 cells versus uninfected CC531 controls, suggesting that the ligand(s) in question were down-regulated by infection. Conversely, LM infection of R2 cells did not affect reporter cell stimulation compared with uninfected R2 controls. We characterized a rat monocyte cell line, termed RmW cells. In contrast to LM infected R2 cells that up-regulate MHC class I molecules, RmW cells displayed unchanged MHC class I expression following infection. In line with MHC class I expression, more NK cells produced a higher amount of IFN-γ against infected R2 cells compared with RmW cells. Together, L. monocytogenes infection may variously regulate cellular ligands for NK cells, depending on the cell type infected, affecting the outcome of NK cell responses.

  20. Regulatory T Cells in Hepatitis B and C Virus Infections

    PubMed Central

    2016-01-01

    Hepatitis B virus (HBV) and hepatitis C virus (HCV) are hepatotropic viruses that establish chronic persistent infection by effectively escaping the host immune response and can cause immune-mediated liver injury. It has recently become apparent that regulatory T (Treg) cells, specifically CD4+CD25+Foxp3+ Treg cells, modulate viral diseases by suppressing antiviral immune responses and regulating inflammatory host injury. The roles of Treg cells in HBV and HCV infections range from suppressing antiviral T cell responses to protecting the liver from immune-mediated damage. This review describes Treg cells and subpopulations and focuses on the roles of these cells in HBV and HCV infections. PMID:28035208

  1. Are Basophils and Mast Cells Masters in HIV Infection?

    PubMed

    Marone, Gianni; Varricchi, Gilda; Loffredo, Stefania; Galdiero, Maria Rosaria; Rivellese, Felice; de Paulis, Amato

    2016-01-01

    The World Health Organization AIDS epidemic update estimates that more than 37 million people are living with HIV infection. Despite the unprecedented success of antiretroviral treatments, significant challenges remain in the fight against HIV. In particular, how uninfected cells capture HIV and transmit virions to target cells remains an unanswered question. Tissue mast cells and peripheral blood basophils can be exposed to virions or HIV products during infection. Several HIV proteins (i.e., envelope glycoproteins gp120 and gp41, Tat, and Nef) can interact with distinct surface receptors expressed by human basophils and mast cells and modulate their functional responses at different levels. Additionally, several groups have provided evidence that human mast cells can be infected in vitro, as well as in vivo, by certain strains of HIV. Recently, it has been demonstrated that basophils purified from healthy donors and intestinal mast cells can efficiently capture HIV on their cell surface and, cocultured with CD4+ T cells, they can transfer the virus to the cocultured cells leading to infection. Direct contact between human basophils or intestinal mast cells and CD4+ T cells can mediate viral trans-infection of T cells through the formation of viral synapses. Thus, basophils and mast cells can provide a cellular basis for capturing and then spreading viruses throughout the body. Collectively, these findings suggest that human basophils and mast cells play a complex and possibly distinct role in HIV infection, warranting further investigations.

  2. Natural killer cells in hepatitis B virus infection.

    PubMed

    Wu, Shao-fei; Wang, Wen-jing; Gao, Yue-qiu

    2015-01-01

    Natural killer cells are a unique type of lymphocytes with cytotoxic capacity, and play important roles against tumors and infections. Recently, natural killer cells have been increasingly valued in their effects in hepatitis B virus infection. Since hepatitis B virus is not cytopathic, the subsequent antiviral immune responses of the host are responsible for sustaining the liver injury, which may result in cirrhosis and even hepatocellular carcinoma. Many studies have confirmed that natural killer cells participate in anti-hepatitis B virus responses both in the early phase after infection and in the chronic phase via cytolysis, degranulation, and cytokine secretion. However, natural killer cells play dichotomic roles: they exert antiviral and immunoregulatory functions whilst contribute to the pathogenesis of liver injury. Here, we review the roles of natural killer cells in hepatitis B virus infection, introducing novel therapeutic strategies for controlling hepatitis B virus infection via the modulation of natural killer cells.

  3. TIM3 Mediates T Cell Exhaustion during Mycobacterium tuberculosis Infection.

    PubMed

    Jayaraman, Pushpa; Jacques, Miye K; Zhu, Chen; Steblenko, Katherine M; Stowell, Britni L; Madi, Asaf; Anderson, Ana C; Kuchroo, Vijay K; Behar, Samuel M

    2016-03-01

    While T cell immunity initially limits Mycobacterium tuberculosis infection, why T cell immunity fails to sterilize the infection and allows recrudescence is not clear. One hypothesis is that T cell exhaustion impairs immunity and is detrimental to the outcome of M. tuberculosis infection. Here we provide functional evidence for the development T cell exhaustion during chronic TB. Second, we evaluate the role of the inhibitory receptor T cell immunoglobulin and mucin domain-containing-3 (TIM3) during chronic M. tuberculosis infection. We find that TIM3 expressing T cells accumulate during chronic infection, co-express other inhibitory receptors including PD1, produce less IL-2 and TNF but more IL-10, and are functionally exhausted. Finally, we show that TIM3 blockade restores T cell function and improves bacterial control, particularly in chronically infected susceptible mice. These data show that T cell immunity is suboptimal during chronic M. tuberculosis infection due to T cell exhaustion. Moreover, in chronically infected mice, treatment with anti-TIM3 mAb is an effective therapeutic strategy against tuberculosis.

  4. Macrophage infection via selective capture of HIV-1-infected CD4+ T cells.

    PubMed

    Baxter, Amy E; Russell, Rebecca A; Duncan, Christopher J A; Moore, Michael D; Willberg, Christian B; Pablos, Jose L; Finzi, Andrés; Kaufmann, Daniel E; Ochsenbauer, Christina; Kappes, John C; Groot, Fedde; Sattentau, Quentin J

    2014-12-10

    Macrophages contribute to HIV-1 pathogenesis by forming a viral reservoir and mediating neurological disorders. Cell-free HIV-1 infection of macrophages is inefficient, in part due to low plasma membrane expression of viral entry receptors. We find that macrophages selectively capture and engulf HIV-1-infected CD4+ T cells leading to efficient macrophage infection. Infected T cells, both healthy and dead or dying, were taken up through viral envelope glycoprotein-receptor-independent interactions, implying a mechanism distinct from conventional virological synapse formation. Macrophages infected by this cell-to-cell route were highly permissive for both CCR5-using macrophage-tropic and otherwise weakly macrophage-tropic transmitted/founder viruses but restrictive for nonmacrophage-tropic CXCR4-using virus. These results have implications for establishment of the macrophage reservoir and HIV-1 dissemination in vivo.

  5. Stem-Cell-Based Gene Therapy for HIV Infection

    PubMed Central

    Zhen, Anjie; Kitchen, Scott

    2013-01-01

    Despite the enormous success of combined anti-retroviral therapy, HIV infection is still a lifelong disease and continues to spread rapidly worldwide. There is a pressing need to develop a treatment that will cure HIV infection. Recent progress in stem cell manipulation and advancements in humanized mouse models have allowed rapid developments of gene therapy for HIV treatment. In this review, we will discuss two aspects of HIV gene therapy using human hematopoietic stem cells. The first is to generate immune systems resistant to HIV infection while the second strategy involves enhancing anti-HIV immunity to eliminate HIV infected cells. PMID:24368413

  6. Stem-cell-based gene therapy for HIV infection.

    PubMed

    Zhen, Anjie; Kitchen, Scott

    2013-12-24

    Despite the enormous success of combined anti-retroviral therapy, HIV infection is still a lifelong disease and continues to spread rapidly worldwide. There is a pressing need to develop a treatment that will cure HIV infection. Recent progress in stem cell manipulation and advancements in humanized mouse models have allowed rapid developments of gene therapy for HIV treatment. In this review, we will discuss two aspects of HIV gene therapy using human hematopoietic stem cells. The first is to generate immune systems resistant to HIV infection while the second strategy involves enhancing anti-HIV immunity to eliminate HIV infected cells.

  7. HIV Cell-to-Cell Spread Results in Earlier Onset of Viral Gene Expression by Multiple Infections per Cell

    PubMed Central

    Boullé, Mikaël; Müller, Thorsten G.; Dähling, Sabrina; Jackson, Laurelle; Mahamed, Deeqa; Oom, Lance; Lustig, Gila

    2016-01-01

    Cell-to-cell spread of HIV, a directed mode of viral transmission, has been observed to be more rapid than cell-free infection. However, a mechanism for earlier onset of viral gene expression in cell-to-cell spread was previously uncharacterized. Here we used time-lapse microscopy combined with automated image analysis to quantify the timing of the onset of HIV gene expression in a fluorescent reporter cell line, as well as single cell staining for infection over time in primary cells. We compared cell-to-cell spread of HIV to cell-free infection, and limited both types of transmission to a two-hour window to minimize differences due to virus transit time to the cell. The mean time to detectable onset of viral gene expression in cell-to-cell spread was accelerated by 19% in the reporter cell line and by 35% in peripheral blood mononuclear cells relative to cell-free HIV infection. Neither factors secreted by infected cells, nor contact with infected cells in the absence of transmission, detectably changed onset. We recapitulated the earlier onset by infecting with multiple cell-free viruses per cell. Surprisingly, the acceleration in onset of viral gene expression was not explained by cooperativity between infecting virions. Instead, more rapid onset was consistent with a model where the fastest expressing virus out of the infecting virus pool sets the time for infection independently of the other co-infecting viruses. PMID:27812216

  8. Cytotoxic cells induced after Chlamydia psittaci infection in mice

    SciTech Connect

    Lammert, J.K.

    1982-03-01

    The ability of spleen cells from Chlamydia psittaci-infected mice to lyse C. psittaci-infected and uninfected target cell monolayers was studied. The cytotoxicity assay used was a terminal label method in which the number of adherent target cells surviving the interaction with effector cells was determined by measuring the uptake of (3H)uridine by such cells. It was observed that in the first few days postinfection (3 to 5), spleens contained cells that lysed infected and uninfected targets with equal efficiency. Subsequently, infected targets were killed primarily. The activity of effector spleen cells for infected targets continued, although at a reduced level, beyond 21 days postinfection. Intact effector cells were required since a disruption by sonication resulted in a loss of cytotoxicity. The enhanced killing observed with infected targets was also observed when target cells were sensitized with heat- or UV-inactivated C. psittaci. This study suggests that the induction of cytotoxic cells after C. psittaci infection may contribute to the ability of the host to control multiplication of the microorganism.

  9. Extracellular vesicles from infected cells: potential for direct pathogenesis

    PubMed Central

    Schwab, Angela; Meyering, Shabana S.; Lepene, Ben; Iordanskiy, Sergey; van Hoek, Monique L.; Hakami, Ramin M.; Kashanchi, Fatah

    2015-01-01

    Infections that result in natural or manmade spread of lethal biological agents are a concern and require national and focused preparedness. In this manuscript, as part of an early diagnostics and pathogen treatment strategy, we have focused on extracellular vesicles (EVs) that arise following infections. Although the field of biodefense does not currently have a rich resource in EVs literature, none the less, similar pathogens belonging to the more classical emerging and non-emerging diseases have been studied in their EV/exosomal contents and function. These exosomes are formed in late endosomes and released from the cell membrane in almost every cell type in vivo. These vesicles contain proteins, RNA, and lipids from the cells they originate from and function in development, signal transduction, cell survival, and transfer of infectious material. The current review focuses on how different forms of infection exploit the exosomal pathway and how exosomes can be exploited artificially to treat infection and disease and potentially also be used as a source of vaccine. Virally-infected cells can secrete viral as well as cellular proteins and RNA in exosomes, allowing viruses to cause latent infection and spread of miRNA to nearby cells prior to a subsequent infection. In addition to virally-infected host cells, bacteria, protozoa, and fungi can all release small vesicles that contain pathogen-associated molecular patterns, regulating the neighboring uninfected cells. Examples of exosomes from both virally and bacterially infected cells point toward a re-programming network of pathways in the recipient cells. Finally, many of these exosomes contain cytokines and miRNAs that in turn can effect gene expression in the recipient cells through the classical toll-like receptor and NFκB pathway. Therefore, although exosomes do not replicate as an independent entity, they however facilitate movement of infectious material through tissues and may be the cause of many

  10. Predominant Infection of CD150+ Lymphocytes and Dendritic Cells during Measles Virus Infection of Macaques

    PubMed Central

    de Swart, Rik L; Yanagi, Yusuke; van Amerongen, Geert; McQuaid, Stephen; Yüksel, Selma; Geijtenbeek, Teunis B. H; Duprex, W. Paul; Osterhaus, Albert D. M. E

    2007-01-01

    Measles virus (MV) is hypothesized to enter the host by infecting epithelial cells of the respiratory tract, followed by viremia mediated by infected monocytes. However, neither of these cell types express signaling lymphocyte activation molecule (CD150), which has been identified as the receptor for wild-type MV. We have infected rhesus and cynomolgus macaques with a recombinant MV strain expressing enhanced green fluorescent protein (EGFP); thus bringing together the optimal animal model for measles and a virus that can be detected with unprecedented sensitivity. Blood samples and broncho-alveolar lavages were collected every 3 d, and necropsies were performed upon euthanasia 9 or 15 d after infection. EGFP production by MV-infected cells was visualized macroscopically, in both living and sacrificed animals, and microscopically by confocal microscopy and FACS analysis. At the peak of viremia, EGFP fluorescence was detected in skin, respiratory and digestive tract, but most intensely in all lymphoid tissues. B- and T-lymphocytes expressing CD150 were the major target cells for MV infection. Highest percentages (up to 30%) of infected lymphocytes were detected in lymphoid tissues, and the virus preferentially targeted cells with a memory phenotype. Unexpectedly, circulating monocytes did not sustain productive MV infection. In peripheral tissues, large numbers of MV-infected CD11c+ MHC class-II+ myeloid dendritic cells were detected in conjunction with infected T-lymphocytes, suggesting transmission of MV between these cell types. Fluorescent imaging of MV infection in non-human primates demonstrated a crucial role for lymphocytes and dendritic cells in the pathogenesis of measles and measles-associated immunosuppression. PMID:18020706

  11. The cell biology of Cryptosporidium infection

    PubMed Central

    O’Hara, Steven P.; Chen, Xian-Ming

    2011-01-01

    Cryptosporidiosis remains a significant cause of enteric disease worldwide. Basic investigations of host: pathogen interactions have revealed the intricate processes mediating infection. The following summarizes the interactions that mediate infection and the host responses that both permit and ultimately clear the infection. PMID:21458585

  12. The cell biology of cryptosporidium infection.

    PubMed

    O'Hara, Steven P; Chen, Xian-Ming

    2011-08-01

    Cryptosporidiosis remains a significant cause of enteric disease worldwide. Basic investigations of host: pathogen interactions have revealed the intricate processes mediating infection. The following summarizes the interactions that mediate infection and the host responses that both permit and ultimately clear the infection.

  13. Suppression of HIV-1 Infectivity by Human Glioma Cells.

    PubMed

    Hoque, Sheikh Ariful; Tanaka, Atsushi; Islam, Salequl; Ahsan, Gias Uddin; Jinno-Oue, Atsushi; Hoshino, Hiroo

    2016-05-01

    HIV-1 infection to the central nervous system (CNS) is very common in AIDS patients. The predominant cell types infected in the brain are monocytes and macrophages, which are surrounded by several HIV-1-resistant cell types, such as astrocytes, oligodendrocytes, neurons, and microvascular cells. The effect of these HIV-1-resistant cells on HIV-1 infection is largely unknown. In this study, we examined the stability of HIV-1 cultured with several human glioblastoma cell lines, for example, NP-2, U87MG, T98G, and A172, to determine whether these HIV-1-resistant brain cells could enhance or suppress HIV-1 infection and thus modulate HIV-1 infection in the CNS. The HIV-1 titer was determined using the MAGIC-5A indicator cell line as well as naturally occurring CD4(+) T cells. We found that the stability of HIV-1 incubated with NP-2 or U87MG cells at 37°C was significantly shorter (half-life, 2.5-4 h) compared to that of HIV-1 incubated with T98G or A172 cells or in culture medium without cells (half-life, 8-18 h). The spent culture media (SCM) of NP-2 and U87MG cells had the ability to suppress both R5- and X4-HIV-1 infection by inhibiting HIV-1 attachment to target cells. This inhibitory effect was eliminated by the treatment of the SCM with chondroitinase ABC but not heparinase, suggesting that the inhibitory factor(s) secreted by NP-2 and U87MG cells was chiefly mediated by chondroitin sulfate (CS) or CS-like moiety. Thus, this study reveals that some but not all glioma cells secrete inhibitory molecules to HIV-1 infection that may contribute in lowering HIV-1 infection in the CNS in vivo.

  14. MAIT cells are activated during human viral infections.

    PubMed

    van Wilgenburg, Bonnie; Scherwitzl, Iris; Hutchinson, Edward C; Leng, Tianqi; Kurioka, Ayako; Kulicke, Corinna; de Lara, Catherine; Cole, Suzanne; Vasanawathana, Sirijitt; Limpitikul, Wannee; Malasit, Prida; Young, Duncan; Denney, Laura; Moore, Michael D; Fabris, Paolo; Giordani, Maria Teresa; Oo, Ye Htun; Laidlaw, Stephen M; Dustin, Lynn B; Ho, Ling-Pei; Thompson, Fiona M; Ramamurthy, Narayan; Mongkolsapaya, Juthathip; Willberg, Christian B; Screaton, Gavin R; Klenerman, Paul

    2016-06-23

    Mucosal-associated invariant T (MAIT) cells are abundant in humans and recognize bacterial ligands. Here, we demonstrate that MAIT cells are also activated during human viral infections in vivo. MAIT cells activation was observed during infection with dengue virus, hepatitis C virus and influenza virus. This activation-driving cytokine release and Granzyme B upregulation-is TCR-independent but dependent on IL-18 in synergy with IL-12, IL-15 and/or interferon-α/β. IL-18 levels and MAIT cell activation correlate with disease severity in acute dengue infection. Furthermore, HCV treatment with interferon-α leads to specific MAIT cell activation in vivo in parallel with an enhanced therapeutic response. Moreover, TCR-independent activation of MAIT cells leads to a reduction of HCV replication in vitro mediated by IFN-γ. Together these data demonstrate MAIT cells are activated following viral infections, and suggest a potential role in both host defence and immunopathology.

  15. CD8 T cells and Mycobacterium tuberculosis infection.

    PubMed

    Lin, Philana Ling; Flynn, JoAnne L

    2015-05-01

    Tuberculosis is primarily a respiratory disease that is caused by Mycobacterium tuberculosis. M. tuberculosis can persist and replicate in macrophages in vivo, usually in organized cellular structures called granulomas. There is substantial evidence for the importance of CD4 T cells in control of tuberculosis, but the evidence for a requirement for CD8 T cells in this infection has not been proven in humans. However, animal model data support a non-redundant role for CD8 T cells in control of M. tuberculosis infection. In humans, infection with this pathogen leads to generation of specific CD8 T cell responses. These responses include classical (MHC Class I restricted) and non-classical CD8 T cells. Here, we discuss the potential roles of CD8 T cells in defense against tuberculosis, and our current understanding of the wide range of CD8 T cell types seen in M. tuberculosis infection.

  16. HIV–1 Infects Multipotent Progenitor Cells Causing Cell Death and Establishing Latent Cellular Reservoirs

    PubMed Central

    Carter, Christoph C.; Onafuwa–Nuga, Adewunmi; McNamara, Lucy A.; Riddell, James; Bixby, Dale; Savona, Michael R.; Collins, Kathleen L.

    2010-01-01

    HIV causes a chronic infection characterized by depletion of CD4+ T lymphocytes and development of opportunistic infections. Despite drugs that inhibit viral spread, HIV has been difficult to cure because of uncharacterized reservoirs of infected cells that are resistant to highly active antiretroviral therapy and the immune response. Here we used CD34+ cells from infected people as well as in vitro studies of wild type HIV to demonstrate infection and killing of CD34+ multipotent hematopoietic progenitor cells (HPCs). In some HPCs, we detected latent infection that stably persisted in cell culture until viral gene expression was activated by differentiation factors. A novel reporter HIV that directly detects latently infected cells in vitro confirmed the presence of distinct populations of active and latently infected HPCs. These findings have important implications for understanding HIV bone marrow pathology and the mechanisms by which HIV causes persistent infection. PMID:20208541

  17. Human lymphokine-activated killer cells are cytotoxic against cells infected with Toxoplasma gondii

    PubMed Central

    1992-01-01

    Experiments were conducted to determine whether human lymphokine- activated killer (LAK) cells are cytotoxic against cells infected with Toxoplasma gondii. Nylon wool nonadherent (NWNA) peripheral blood lymphocytes, as well as purified natural killer cell (NK) (CD3- CD16+ CD56+) and T (CD3+ CD16- CD56-) cells obtained from five healthy T. gondii seronegative volunteers exhibited minimal cytotoxic activity against T. gondii-infected cells. When standard LAK (S-LAK) cell preparations were induced by incubation of NWNA cells with recombinant interleukin 2, induction of remarkable cytotoxic activity against T. gondii-infected cells. When standard in LAK cell preparations from each of the volunteers. The phenotype of the LAK precursor and effector cells varied depending on the target cell used. Whereas the precursor and the effector cells of most of the LAK activity against K562 and Daudi cells were cells with NK phenotype, when T. gondii-infected cells were used as targets, both cells with NK and T cell phenotypes were precursors and effectors of the lysis. When cytotoxic activity of S-LAK cells was compared with the activity of adherent LAK (A-LAK) cells, A- LAK cells displayed higher cytotoxic activity against T. gondii- infected cells, as well as against K562 and Daudi cells. Cold target inhibition experiments suggested that there is a subset of LAK effector cells capable of lysing both T. gondii-infected cells and Daudi cells, whereas other subsets preferentially or exclusively lyse one of these target cells. PMID:1460415

  18. Kaleidoscope of autoimmune diseases in HIV infection.

    PubMed

    Roszkiewicz, Justyna; Smolewska, Elzbieta

    2016-11-01

    Within the last 30 years, the human immunodeficiency virus (HIV) infection has changed its status from inevitably fatal to chronic disorder with limited impact on life span. However, this breakthrough was mainly the effect of introduction of the aggressive antiviral treatment, which has led to the clinically significant increase in CD4+ cell count, resulting in fewer cases of the acquired immunodeficiency syndrome (AIDS) and improved management of opportunistic infections occurring in the course of the disease. The occurrence of a particular autoimmune disease depends on degree of immunosuppression of the HIV-positive patient. In 2002, four stages of autoimmunity were proposed in patients infected by HIV, based on the absolute CD4+ cell count, feature of AIDS as well as on the presence of autoimmune diseases. Spectrum of autoimmune diseases associated with HIV infection seems to be unexpectedly wide, involving several organs, such as lungs (sarcoidosis), thyroid gland (Graves' disease), liver (autoimmune hepatitis), connective tissue (systemic lupus erythematosus, rheumatoid arthritis, polyarteritis nodosa and other types of vasculitis, antiphospholipid syndrome) or hematopoietic system (autoimmune cytopenias). This paper contains the state of art on possible coincidences between HIV infection and a differential types of autoimmune diseases, including the potential mechanisms of this phenomenon. As the clinical manifestations of autoimmunization often mimic those inscribed in the course of HIV infection, health care providers should be aware of this rare but potentially deadly association and actively seek for its symptoms in their patients.

  19. Human NK Cell Diversity in Viral Infection: Ramifications of Ramification

    PubMed Central

    Strauss-Albee, Dara M.; Blish, Catherine A.

    2016-01-01

    Natural killer (NK) cells are a unique lymphocyte lineage with remarkable agility in the rapid destruction of virus-infected cells. They are also the most poorly understood class of lymphocyte. A spectrum of activating and inhibitory receptors at the NK cell surface leads to an unusual and difficult-to-study mechanism of cellular recognition, as well as a very high capacity for diversity at the single-cell level. Here, we review the evidence for the role of NK cells in the earliest stage of human viral infection, and in its prevention. We argue that single-cell diversity is a logical evolutionary adaptation for their position in the immune response and contributes to their ability to kill virus-infected cells. Finally, we look to the future, where emerging single-cell technologies will enable a new generation of rigorous and clinically relevant studies on NK cells accounting for all of their unique and diverse characteristics. PMID:26973646

  20. Late steps of parvoviral infection induce changes in cell morphology.

    PubMed

    Pakkanen, Kirsi; Nykky, Jonna; Vuento, Matti

    2008-11-01

    Previously, virus-induced non-filopodial extensions have not been encountered in connection with viral infections. Here, we report emergence of long extensions protruding from Norden laboratory feline kidney (NLFK) and A72 (canine fibroma) cells infected with canine parvovirus for 72 h. These extensions significantly differ in length and number from those appearing in control cells. The most striking feature in the extensions is the length, reaching up to 130 microm, almost twice the average length of a healthy NLFK cell. In A72 cells, the extensions were even longer, up to 200 microm. The results presented here also suggest that the events leading to the growth of these extensions start earlier in infection and abnormal extension growth is detectable already at 24-h post-infection (p.i.). These extensions may have a vital role in the cell-to-cell transmission of the virus.

  1. Growth in Agarose of Human Cells Infected with Cytomegalovirus

    PubMed Central

    Lang, David J.; Montagnier, Luc; Latarjet, Raymond

    1974-01-01

    After infection by human cytomegalovirus (CMV), human diploid fibroblasts could grow in agarose medium for several generations. Clones of infected cells grew for weeks, although in every case they ultimately underwent lysis owing to the cytopathic effect of the virus. Virus was inoculated at high dilution and after UV irradiation in an effort to derive cells infected with noninfectious defective particles still capable of inducing cell stimulation. Dilute or irradiated virus occasionally yielded large colonies of replicating cells, although permanent transformation was not observed. One clone derived from UV-CMV-infected cells was passaged four times before undergoing lysis. During these passages the cells exhibited alterations in morphology and orientation. Images PMID:4367907

  2. Early events associated with infection of Epstein-Barr virus infection of primary B-cells.

    PubMed

    Halder, Sabyasachi; Murakami, Masanao; Verma, Subhash C; Kumar, Pankaj; Yi, Fuming; Robertson, Erle S

    2009-09-28

    Epstein Barr virus (EBV) is closely associated with the development of a vast number of human cancers. To develop a system for monitoring early cellular and viral events associated with EBV infection a self-recombining BAC containing 172-kb of the Epstein Barr virus genome BAC-EBV designated as MD1 BAC (Chen et al., 2005, J.Virology) was used to introduce an expression cassette of green fluorescent protein (GFP) by homologous recombination, and the resultant BAC clone, BAC-GFP-EBV was transfected into the HEK 293T epithelial cell line. The resulting recombinant GFP EBV was induced to produce progeny virus by chemical inducer from the stable HEK 293T BAC GFP EBV cell line and the virus was used to immortalize human primary B-cell as monitored by green fluorescence and outgrowth of the primary B cells. The infection, B-cell activation and cell proliferation due to GFP EBV was monitored by the expression of the B-cell surface antigens CD5, CD10, CD19, CD23, CD39, CD40 , CD44 and the intercellular proliferation marker Ki-67 using Flow cytometry. The results show a dramatic increase in Ki-67 which continues to increase by 6-7 days post-infection. Likewise, CD40 signals showed a gradual increase, whereas CD23 signals were increased by 6-12 hours, maximally by 3 days and then decreased. Monitoring the viral gene expression pattern showed an early burst of lytic gene expression. This up-regulation of lytic gene expression prior to latent genes during early infection strongly suggests that EBV infects primary B-cell with an initial burst of lytic gene expression and the resulting progeny virus is competent for infecting new primary B-cells. This process may be critical for establishment of latency prior to cellular transformation. The newly infected primary B-cells can be further analyzed for investigating B cell activation due to EBV infection.

  3. Carbocisteine inhibits rhinovirus infection in human tracheal epithelial cells.

    PubMed

    Yasuda, H; Yamaya, M; Sasaki, T; Inoue, D; Nakayama, K; Yamada, M; Asada, M; Yoshida, M; Suzuki, T; Nishimura, H; Sasaki, H

    2006-07-01

    The aim of the study was to examine the effects of a mucolytic drug, carbocisteine, on rhinovirus (RV) infection in the airways. Human tracheal epithelial cells were infected with a major-group RV, RV14. RV14 infection increased virus titres and the cytokine content of supernatants. Carbocisteine reduced supernatant virus titres, the amount of RV14 RNA in cells, cell susceptibility to RV infection and supernatant cytokine concentrations, including interleukin (IL)-6 and IL-8, after RV14 infection. Carbocisteine reduced the expression of mRNA encoding intercellular adhesion molecule (ICAM)-1, the receptor for the major group of RVs. It also reduced the supernatant concentration of a soluble form of ICAM-1, the number and fluorescence intensity of acidic endosomes in the cells before RV infection, and nuclear factor-kappaB activation by RV14. Carbocisteine also reduced the supernatant virus titres of the minor group RV, RV2, although carbocisteine did not reduce the expression of mRNA encoding a low density lipoprotein receptor, the receptor for RV2. These results suggest that carbocisteine inhibits rhinovirus 2 infection by blocking rhinovirus RNA entry into the endosomes, and inhibits rhinovirus 14 infection by the same mechanism as well as by reducing intercellular adhesion molecule-1 levels. Carbocisteine may modulate airway inflammation by reducing the production of cytokines in rhinovirus infection.

  4. In vivo infection of IgG-containing cells by Jembrana disease virus during acute infection

    SciTech Connect

    Desport, Moira; Tenaya, I.W. Masa; McLachlan, Alexander; McNab, Tegan J.; Rachmat, Judhi; Hartaningsih, Nining; Wilcox, Graham E.

    2009-10-25

    Jembrana disease virus (JDV) is an unusual bovine lentivirus which causes a non-follicular proliferation of lymphocytes, a transient immunosuppression and a delayed humoral response in infected Bali cattle in Indonesia. A double-immunofluorescent labeling method was developed to identify the subset of mononuclear cells in which the viral capsid protein could be detected. Viral antigen was present in pleomorphic centroblast-like cells which were identified as IgG-containing cells, including plasma cells, in lymphoid tissues. There was no evidence of infection of CD3{sup +} T-cells or MAC387{sup +} monocytes in tissues but large vacuolated cells with a macrophage-like morphology in the lung were found to contain viral antigen although they could not be shown conclusively to be infected. The tropism of JDV for mature IgG-containing cells may be relevant to understanding the pathogenesis of Jembrana disease, the delayed antibody responses and the genetic composition of this atypical lentivirus.

  5. Cytomegalovirus-Infected Cells Resist T Cell Mediated Killing in an HLA-Recognition Independent Manner.

    PubMed

    Proff, Julia; Walterskirchen, Christian; Brey, Charlotte; Geyeregger, Rene; Full, Florian; Ensser, Armin; Lehner, Manfred; Holter, Wolfgang

    2016-01-01

    In order to explore the potential of HLA-independent T cell therapy for human cytomegalovirus (HCMV) infections, we developed a chimeric antigen receptor (CAR) directed against the HCMV encoded glycoprotein B (gB), which is expressed at high levels on the surface of infected cells. T cells engineered with this anti-gB CAR recognized HCMV-infected cells and released cytokines and cytotoxic granules. Unexpectedly, and in contrast to analogous approaches for HIV, Hepatitis B or Hepatitis C virus, we found that HCMV-infected cells were resistant to killing by the CAR-modified T cells. In order to elucidate whether this phenomenon was restricted to the use of CARs, we extended our experiments to T cell receptor (TCR)-mediated recognition of infected cells. To this end we infected fibroblasts with HCMV-strains deficient in viral inhibitors of antigenic peptide presentation and targeted these HLA-class I expressing peptide-loaded infected cells with peptide-specific cytotoxic T cells (CTLs). Despite strong degranulation and cytokine production by the T cells, we again found significant inhibition of lysis of HCMV-infected cells. Impairment of cell lysis became detectable 1 day after HCMV infection and gradually increased during the following 3 days. We thus postulate that viral anti-apoptotic factors, known to inhibit suicide of infected host cells, have evolved additional functions to directly abrogate T cell cytotoxicity. In line with this hypothesis, CAR-T cell cytotoxicity was strongly inhibited in non-infected fibroblasts by expression of the HCMV-protein UL37x1, and even more so by additional expression of UL36. Our data extend the current knowledge on Betaherpesviral evasion from T cell immunity and show for the first time that, beyond impaired antigen presentation, infected cells are efficiently protected by direct blockade of cytotoxic effector functions through viral proteins.

  6. Hematopoietic Stem and Immune Cells in Chronic HIV Infection

    PubMed Central

    Zhang, Jielin; Crumpacker, Clyde

    2015-01-01

    Hematopoietic stem cell (HSC) belongs to multipotent adult somatic stem cells. A single HSC can reconstitute the entire blood system via self-renewal, differentiation into all lineages of blood cells, and replenishment of cells lost due to attrition or disease in a person's lifetime. Although all blood and immune cells derive from HSC, immune cells, specifically immune memory cells, have the properties of HSC on self-renewal and differentiation into lineage effector cells responding to the invading pathogens. Moreover, the interplay between immune memory cell and viral pathogen determines the course of a viral infection. Here, we state our point of view on the role of blood stem and progenitor cell in chronic HIV infection, with a focus on memory CD4 T-cell in the context of HIV/AIDS eradication and cure. PMID:26300920

  7. Dendritic Cells and HIV-1 Trans-Infection

    PubMed Central

    McDonald, David

    2010-01-01

    Dendritic cells initiate and sustain immune responses by migrating to sites of pathogenic insult, transporting antigens to lymphoid tissues and signaling immune specific activation of T cells through the formation of the immunological synapse. Dendritic cells can also transfer intact, infectious HIV-1 to CD4 T cells through an analogous structure, the infectious synapse. This replication independent mode of HIV-1 transmission, known as trans-infection, greatly increases T cell infection in vitro and is thought to contribute to viral dissemination in vivo. This review outlines the recent data defining the mechanisms of trans-infection and provides a context for the potential contribution of trans-infection in HIV-1 disease. PMID:21994702

  8. Splenic Damage during SIV Infection: Role of T-Cell Depletion and Macrophage Polarization and Infection.

    PubMed

    Williams, Dionna W; Engle, Elizabeth L; Shirk, Erin N; Queen, Suzanne E; Gama, Lucio; Mankowski, Joseph L; Zink, M Christine; Clements, Janice E

    2016-08-01

    The effects of HIV infection on spleen and its cellular subsets have not been fully characterized, particularly for macrophages in which diverse populations exist. We used an accelerated SIV-infected macaque model to examine longitudinal effects on T-cell and macrophage populations and their susceptibilities to infection. Substantial lymphoid depletion occurred, characterized by follicular burn out and a loss of CD3 T lymphocytes, which was associated with cellular activation and transient dysregulations in CD4/CD8 ratios and memory effector populations. In contrast, the loss of CD68 and CD163(+)CD68(+) macrophages and increase in CD163 cells was irreversible, which began during acute infection and persisted until terminal disease. Mac387 macrophages and monocytes were transiently recruited into spleen, but were not sufficient to mitigate the changes in macrophage subsets. Type I interferon, M2 polarizing genes, and chemokine-chemokine receptor signaling were up-regulated in spleen and drove macrophage alterations. SIV-infected T cells were numerous within the white pulp during acute infection, but were rarely observed thereafter. CD68, CD163, and Mac387 macrophages were highly infected, which primarily occurred in the red pulp independent of T cells. Few macrophages underwent apoptosis, indicating that they are a long-lasting target for HIV/SIV. Our results identify macrophages as an important contributor to HIV/SIV infection in spleen and in promoting morphologic changes through the loss of specific macrophage subsets that mediate splenic organization.

  9. The influence of the hot water extract from shiitake medicinal mushroom, Lentinus edodes (higher Basidiomycetes) on the food intake, life span, and age-related locomotor activity of Drosophila melanogaster.

    PubMed

    Matjuskova, Natalya; Azena, Elena; Serstnova, Ksenija; Muiznieks, Indrikis

    2014-01-01

    Shiitake medicinal mushroom, Lentinus edodes, is among the most widely cultivated edible mushrooms in the world and is a well-studied source of nutrients and biologically active compounds. We have studied the influence of the dietary supplement of the polysaccharides containing a hot water extract of the mushroom L. edodes on the fruit fly Drosophila melanogaster in terms of food intake, body weight, life span, and age-related locomotor activity. L. edodes extract, when added to the D. melanogaster feeding substrate at a 0.003-0.030% concentration (calculated for the dry weight of the polysaccharide fraction) did not influence food intake or body weight of the flies. It increased the life span and locomotor activities of male flies but was associated with early mortality and decreased locomotor activity of female flies. We conclude that the observed anti-aging effects of L. edodes extracts in the male D. melanogaster are not the result of dietary restriction. We propose that D. melanogaster is a suitable model organism for researching the molecular basis of the anti-aging effect of the shiitake mushroom extracts and sex linkage of these effects.

  10. Mycobacterium-Infected Dendritic Cells Disseminate Granulomatous Inflammation

    PubMed Central

    Harding, Jeffrey S.; Rayasam, Aditya; Schreiber, Heidi A.; Fabry, Zsuzsanna; Sandor, Matyas

    2015-01-01

    The disappearance and reformation of granulomas during tuberculosis has been described using PET/CT/X-ray in both human clinical settings and animal models, but the mechanisms of granuloma reformation during active disease remains unclear. Granulomas can recruit inflammatory dendritic cells (iDCs) that can regulate local T-cell responses and can carry bacteria into the lymph nodes, which is crucial for generating systemic T-cell responses against mycobacteria. Here, we report that a subset of mycobacterium-infected iDCs are associated with bacteria-specific T-cells in infected tissue, outside the granuloma, and that this results in the formation of new and/or larger multi-focal lesions. Mycobacterium-infected iDCs express less CCR7 and migrate less efficiently compared to the non-infected iDCs, which may support T-cell capture in granulomatous tissue. Capture may reduce antigen availability in the lymph node, thereby decreasing systemic priming, resulting in a possible regulatory loop between systemic T-cell responses and granuloma reformation. T-cell/infected iDCs clusters outside the granuloma can be detected during the acute and chronic phase of BCG and Mtb infection. Our studies suggest a direct role for inflammatory dendritic cells in the dissemination of granulomatous inflammation. PMID:26515292

  11. Mycobacterium-Infected Dendritic Cells Disseminate Granulomatous Inflammation.

    PubMed

    Harding, Jeffrey S; Rayasam, Aditya; Schreiber, Heidi A; Fabry, Zsuzsanna; Sandor, Matyas

    2015-10-30

    The disappearance and reformation of granulomas during tuberculosis has been described using PET/CT/X-ray in both human clinical settings and animal models, but the mechanisms of granuloma reformation during active disease remains unclear. Granulomas can recruit inflammatory dendritic cells (iDCs) that can regulate local T-cell responses and can carry bacteria into the lymph nodes, which is crucial for generating systemic T-cell responses against mycobacteria. Here, we report that a subset of mycobacterium-infected iDCs are associated with bacteria-specific T-cells in infected tissue, outside the granuloma, and that this results in the formation of new and/or larger multi-focal lesions. Mycobacterium-infected iDCs express less CCR7 and migrate less efficiently compared to the non-infected iDCs, which may support T-cell capture in granulomatous tissue. Capture may reduce antigen availability in the lymph node, thereby decreasing systemic priming, resulting in a possible regulatory loop between systemic T-cell responses and granuloma reformation. T-cell/infected iDCs clusters outside the granuloma can be detected during the acute and chronic phase of BCG and Mtb infection. Our studies suggest a direct role for inflammatory dendritic cells in the dissemination of granulomatous inflammation.

  12. Impairment of B-cell functions during HIV-1 infection.

    PubMed

    Amu, Sylvie; Ruffin, Nicolas; Rethi, Bence; Chiodi, Francesca

    2013-09-24

    A variety of B-cell dysfunctions are manifested during HIV-1 infection, as reported early during the HIV-1 epidemic. It is not unusual that the pathogenic mechanisms presented to elucidate impairment of B-cell responses during HIV-1 infection focus on the impact of reduced T-cell numbers and functions, and lack of germinal center formation in lymphoid tissues. To our understanding, however, perturbation of B-cell phenotype and function during HIV-1 infection may begin at several different B-cell developmental stages. These impairments can be mediated by intrinsic B-cell defects as well as by the lack of proper T-cell help. In this review, we will highlight some of the pathways and molecular interactions leading to B-cell impairment prior to germinal center formation and B-cell activation mediated through the B-cell receptor in response to HIV-1 antigens. Recent studies indicate a regulatory role for B cells on T-cell biology and immune responses. We will discuss some of these novel findings and how these regulatory mechanisms could potentially be affected by the intrinsic defects of B cells taking place during HIV-1 infection.

  13. Cell mechanics and immune system link up to fight infections

    NASA Astrophysics Data System (ADS)

    Ekpenyong, Andrew; Man, Si Ming; Tourlomousis, Panagiotis; Achouri, Sarra; Cammarota, Eugenia; Hughes, Katherine; Rizzo, Alessandro; Ng, Gilbert; Guck, Jochen; Bryant, Clare

    2015-03-01

    Infectious diseases, in which pathogens invade and colonize host cells, are responsible for one third of all mortality worldwide. Host cells use special proteins (immunoproteins) and other molecules to fight viral and bacterial invaders. The mechanisms by which immunoproteins enable cells to reduce bacterial loads and survive infections remain unclear. Moreover, during infections, some immunoproteins are known to alter the cytoskeleton, the structure that largely determines cellular mechanical properties. We therefore used an optical stretcher to measure the mechanical properties of primary immune cells (bone marrow derived macrophages) during bacterial infection. We found that macrophages become stiffer upon infection. Remarkably, macrophages lacking the immunoprotein, NLR-C4, lost the stiffening response to infection. This in vitro result correlates with our in vivo data whereby mice lacking NLR-C4 have more lesions and hence increased bacterial distribution and spread. Thus, the immune-protein-dependent increase in cell stiffness in response to bacterial infection (in vitro result) seems to have a functional role in the system level fight against pathogens (in vivo result). We will discuss how this functional link between cell mechanical properties and innate immunity, effected by actin polymerization, reduces the spread of infection.

  14. Dermal mast cell responses in Paragonimus westermani-infected mice.

    PubMed

    Shin, M H

    1997-12-01

    This study was carried out to determine whether dermal mast cell responses to Paragonimus westermani in an abnormal host, the mouse, were dependent on the site of metacercarial inoculation. In mice during subcutaneous infection, the number of dermal mast cells were increased significantly (p < 0.05) at the first week (38.3/mm2) and then persisted at a high level until the sixth week (45.2/mm2) of infection compared with PBS-injected (control) mice (range: 19.4-25.1/mm2). In mice during oral infection, the number of dermal mast cells were increased significantly (p < 0.05) at two weeks (33.5/mm2) after infection and remained at these levels thereafter compared with non-infected (control) mice (range: 17.4-22.3/mm2). In mice both during subcutaneous and oral infection, the recruited dermal mast cells showed extensive degranulation at the second week (68.4% and 60.7%, respectively), reached a peak at the third week (81.4%, and 92.1%, respectively) and then declined slightly thereafter. By contrast, in both control mice, about 10% of dermal mast cells were degranulated. In conclusion, this study suggests that dermal mast cell responses to P. westermani in mice are dependent on cutaneous sensitization by larval excretory-secretory antigens, irrespective of infection route.

  15. Programmed cell death as a defence against infection.

    PubMed

    Jorgensen, Ine; Rayamajhi, Manira; Miao, Edward A

    2017-03-01

    Eukaryotic cells can die from physical trauma, which results in necrosis. Alternatively, they can die through programmed cell death upon the stimulation of specific signalling pathways. In this Review, we discuss the role of different cell death pathways in innate immune defence against bacterial and viral infection: apoptosis, necroptosis, pyroptosis and NETosis. We describe the interactions that interweave different programmed cell death pathways, which create complex signalling networks that cross-guard each other in the evolutionary 'arms race' with pathogens. Finally, we describe how the resulting cell corpses - apoptotic bodies, pore-induced intracellular traps (PITs) and neutrophil extracellular traps (NETs) - promote the clearance of infection.

  16. TIM-1 Promotes Hepatitis C Virus Cell Attachment and Infection.

    PubMed

    Wang, Jing; Qiao, Luhua; Hou, Zhouhua; Luo, Guangxiang

    2017-01-15

    Human TIM and TAM family proteins were recently found to serve as phosphatidylserine (PS) receptors which promote infections by many different viruses, including dengue virus, West Nile virus, Ebola virus, Marburg virus, and Zika virus. In the present study, we provide substantial evidence demonstrating that TIM-1 is important for efficient infection by hepatitis C virus (HCV). The knockdown of TIM-1 expression significantly reduced HCV infection but not HCV RNA replication. Likewise, TIM-1 knockout in Huh-7.5 cells remarkably lowered HCV cell attachment and subsequent HCV infection. More significantly, the impairment of HCV infection in the TIM-1 knockout cells could be restored completely by ectopic expression of TIM-1 but not TIM-3 or TIM-4. Additionally, HCV infection and cell attachment were inhibited by PS but not by phosphatidylcholine (PC), demonstrating that TIM-1-mediated enhancement of HCV infection is PS dependent. The exposure of PS on the HCV envelope was confirmed by immunoprecipitation of HCV particles with a PS-specific monoclonal antibody. Collectively, these findings demonstrate that TIM-1 promotes HCV infection by serving as an attachment receptor for binding to PS exposed on the HCV envelope.

  17. Invariant NKT Cell Response to Dengue Virus Infection in Human

    PubMed Central

    Matangkasombut, Ponpan; Chan-in, Wilawan; Opasawaschai, Anunya; Pongchaikul, Pisut; Tangthawornchaikul, Nattaya; Vasanawathana, Sirijitt; Limpitikul, Wannee; Malasit, Prida; Duangchinda, Thaneeya; Screaton, Gavin; Mongkolsapaya, Juthathip

    2014-01-01

    Background Dengue viral infection is a global health threat without vaccine or specific treatment. The clinical outcome varies from asymptomatic, mild dengue fever (DF) to severe dengue hemorrhagic fever (DHF). While adaptive immune responses were found to be detrimental in the dengue pathogenesis, the roles of earlier innate events remain largely uninvestigated. Invariant natural killer T (iNKT) cells represent innate-like T cells that could dictate subsequent adaptive response but their role in human dengue virus infection is not known. We hypothesized that iNKT cells play a role in human dengue infection. Methods Blood samples from a well-characterized cohort of children with DF, DHF, in comparison to non-dengue febrile illness (OFI) and healthy controls at various time points were studied. iNKT cells activation were analyzed by the expression of CD69 by flow cytometry. Their cytokine production was then analyzed after α-GalCer stimulation. Further, the CD1d expression on monocytes, and CD69 expression on conventional T cells were measured. Results iNKT cells were activated during acute dengue infection. The level of iNKT cell activation associates with the disease severity. Furthermore, these iNKT cells had altered functional response to subsequent ex vivo stimulation with α-GalCer. Moreover, during acute dengue infection, monocytic CD1d expression was also upregulated and conventional T cells also became activated. Conclusion iNKT cells might play an early and critical role in the pathogenesis of severe dengue viral infection in human. Targeting iNKT cells and CD1d serve as a potential therapeutic strategy for severe dengue infection in the future. PMID:24945350

  18. Virus-Infected Human Mast Cells Enhance Natural Killer Cell Functions.

    PubMed

    Portales-Cervantes, Liliana; Haidl, Ian D; Lee, Patrick W; Marshall, Jean S

    2017-01-01

    Mucosal surfaces are protected from infection by both structural and sentinel cells, such as mast cells. The mast cell's role in antiviral responses is poorly understood; however, they selectively recruit natural killer (NK) cells following infection. Here, the ability of virus-infected mast cells to enhance NK cell functions was examined. Cord blood-derived human mast cells infected with reovirus (Reo-CBMC) and subsequent mast cell products were used for the stimulation of human NK cells. NK cells upregulated the CD69 molecule and cytotoxicity-related genes, and demonstrated increased cytotoxic activity in response to Reo-CBMC soluble products. NK cell interferon (IFN)-γ production was also promoted in the presence of interleukin (IL)-18. In vivo, SCID mice injected with Reo-CBMC in a subcutaneous Matrigel model, could recruit and activate murine NK cells, a property not shared by normal human fibroblasts. Soluble products of Reo-CBMC included IL-10, TNF, type I and type III IFNs. Blockade of the type I IFN receptor abrogated NK cell activation. Furthermore, reovirus-infected mast cells expressed multiple IFN-α subtypes not observed in reovirus-infected fibroblasts or epithelial cells. Our data define an important mast cell IFN response, not shared by structural cells, and a subsequent novel mast cell-NK cell immune axis in human antiviral host defense.

  19. T Cell Responses during Influenza Infection: Getting and Keeping Control

    PubMed Central

    Kim, Taeg S.; Sun, Jie; Braciale, Thomas J.

    2011-01-01

    The 2009 influenza pandemic highlights the threat that type A influenza poses to human health. Thus there is an urgency to understand the pathobiology of influenza infection and the contribution of the host immune response to both virus elimination and the development of lung injury. This review focuses on the T cell arm of the adaptive host immune response to influenza and assesses recent developments in our understanding of the induction of primary influenza virus-specific T cell responses by antigen-presenting cells, the interaction of activated effector T cells with antigen-bearing cells in the infected lungs, and the contribution of influenza-specific effector T cells to the development and control of lung injury and inflammation during infection. PMID:21435950

  20. Human Astrocytic Cells Support Persistent Coxsackievirus B3 Infection

    PubMed Central

    Zhang, Xiaowei; Zheng, Zhenhua; Shu, Bo; Liu, Xijuan; Zhang, Zhenfeng; Liu, Yan; Bai, Bingke; Hu, Qinxue

    2013-01-01

    Enteroviruses can frequently target the human central nervous system to induce a variety of neurological diseases. Although enteroviruses are highly cytolytic, emerging evidence has shown that these viruses can establish persistent infections both in vivo and in vitro. Here, we investigated the susceptibility of three human brain cell lines, CCF-STTG1, T98G, and SK-N-SH, to infection with three enterovirus serotypes: coxsackievirus B3 (CVB3), enterovirus 71, and coxsackievirus A9. Persistent infection was observed in CVB3-infected CCF-STTG1 cells, as evidenced by prolonged detection of infectious virions, viral RNA, and viral antigens. Of note, infected CCF-STTG1 cells expressed the nonfunctional canonical viral receptors coxsackievirus-adenovirus receptor and decay-accelerating factor, while removal of cell surface chondroitin sulfate from CCF-STTG1 cells inhibited the replication of CVB3, suggesting that receptor usage was one of the major limiting factors in CVB3 persistence. In addition, CVB3 curtailed the induction of beta interferon in infected CCF-STTG1 cells, which likely contributed to the initiation of persistence. Furthermore, proinflammatory chemokines and cytokines, such as vascular cell adhesion molecule 1, interleukin-8 (IL-8), and IL-6, were upregulated in CVB3-infected CCF-STTG1 cells and human progenitor-derived astrocytes. Our data together demonstrate the potential of CCF-STTG1 cells to be a novel cell model for studying CVB3-central nervous system interactions, providing the basis toward a better understanding of CVB3-induced chronic neuropathogenesis. PMID:24027313

  1. Discriminating dengue-infected hepatic cells (WRL-68) using dielectrophoresis.

    PubMed

    Yafouz, Bashar; Kadri, Nahrizul Adib; Rothan, Hussin A; Yusof, Rohana; Ibrahim, Fatimah

    2016-02-01

    Dielectrophoresis (DEP), the induced movement of dielectric particles placed in a nonuniform electric field, has been used as a potential technique for manipulation and separation of many biological samples without destructive consequences to the cell. Cells of the same genotype in different physiological and pathological states have unique morphological and structural features, therefore, it is possible to differentiate between them using their DEP responses. This paper reports the experimental discrimination of normal and dengue-infected human hepatic fetal epithelial cells (WRL-68 cells) based on their DEP crossover frequency, at which no resultant movement occurs in the cells in response to the DEP force. A microarray dot electrode was used to conduct the DEP experiments. The DEP forces applied to the cells were quantified by analyzing the light intensity shift within the electrode's dot region based on the Cumulative Modal Intensity Shift image analysis technique. The differences in dielectric properties between infected and uninfected cells were exploited by plotting a unique DEP spectrum for each set of cells. We observed that the crossover frequency decreased from 220 kHz for the normal WRL-68 cells to 140 kHz after infection with the dengue virus in a medium conductivity of 100 μS/cm. We conclude that the change in the DEP crossover frequency between dengue-infected cells and their healthy counterparts should allow direct characterization of these cell types by exploiting their electrophysiological properties.

  2. Backward elastic light scattering of malaria infected red blood cells

    NASA Astrophysics Data System (ADS)

    Lee, Seungjun; Lu, Wei

    2011-08-01

    We investigated the backward light scattering pattern of healthy and malaria (Plasmodium falciparum) parasitized red blood cells. The spectrum could clearly distinguish between predominant ring stage infected blood cells and healthy blood cells. Further, we found that infected samples mixed with different stages of P. falciparum showed different signals, suggesting that even variance in parasite stages could also be detected by the spectrum. These results together with the backward scattering technique suggest the potential of non-invasive diagnosis of malaria through light scattering of blood cells near the surface of human body, such as using eyes or skin surface.

  3. 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

  4. In Vitro Brucella suis Infection Prevents the Programmed Cell Death of Human Monocytic Cells

    PubMed Central

    Gross, Antoine; Terraza, Annie; Ouahrani-Bettache, Safia; Liautard, Jean-Pierre; Dornand, Jacques

    2000-01-01

    During the complex interaction between an infectious agent and a host organism, the pathogen can interfere with the host cell's programmed death to its own benefit. Induction or prevention of host cell apoptosis appears to be a critical step for determining the infection outcome. Members of the gram-negative bacterial genus Brucella are intracellular pathogens which preferentially invade monocytic cells and develop within these cells. We investigated the effect of Brucella suis infection on apoptosis of human monocytic phagocytes. The present study provides evidence that Brucella infection inhibited spontaneously occurring apoptosis in human monocytes. Prevention of monocyte apoptosis was not mediated by Brucella lipopolysaccharide and required bacterial survival within infected cells. Both invaded and noninvaded cells were protected, indicating that soluble mediators released during infection were involved in the phenomenon. Analysis of Brucella-infected monocytes revealed specific overexpression of the A1 gene, a member of the bcl-2 family implicated in the survival of hematopoietic cells. Brucella infection also rendered macrophage-like cells resistant to Fas ligand- or gamma interferon-induced apoptosis, suggesting that Brucella infection protected host cells from several cytotoxic processes occurring at different steps of the immune response. The present data clearly show that Brucella suis modulated the monocyte/macrophage's apoptotic response to the advantage of the pathogen, thus preventing host cell elimination. This might represent a strategy for Brucella development in infected hosts. PMID:10603407

  5. Isolation of single Chlamydia-infected cells using laser microdissection.

    PubMed

    Podgorny, Oleg V; Polina, Nadezhda F; Babenko, Vladislav V; Karpova, Irina Y; Kostryukova, Elena S; Govorun, Vadim M; Lazarev, Vassili N

    2015-02-01

    Chlamydia are obligate intracellular parasites of humans and animals that cause a wide range of acute and chronic infections. To elucidate the genetic basis of chlamydial parasitism, several approaches for making genetic modifications to Chlamydia have recently been reported. However, the lack of the available methods for the fast and effective selection of genetically modified bacteria restricts the application of genetic tools. We suggest the use of laser microdissection to isolate of single live Chlamydia-infected cells for the re-cultivation and whole-genome sequencing of single inclusion-derived Chlamydia. To visualise individual infected cells, we made use of the vital labelling of inclusions with the fluorescent Golgi-specific dye BODIPY® FL C5-ceramide. We demonstrated that single Chlamydia-infected cells isolated by laser microdissection and placed onto a host cell monolayer resulted in new cycles of infection. We also demonstrated the successful use of whole-genome sequencing to study the genomic variability of Chlamydia derived from a single inclusion. Our work provides the first evidence of the successful use of laser microdissection for the isolation of single live Chlamydia-infected cells, thus demonstrating that this method can help overcome the barriers to the fast and effective selection of Chlamydia.

  6. Altered distribution of mucosal NK cells during HIV infection

    PubMed Central

    Sips, Magdalena; Sciaranghella, Gaia; Diefenbach, Thomas; Dugast, Anne-Sophie; Berger, Christoph T.; Liu, Qingquan; Kwon, Douglas; Ghebremichael, Musie; Estes, Jacob D.; Carrington, Mary; Martin, Jeffrey N.; Deeks, Steven G.; Hunt, Peter W.; Alter, Galit

    2013-01-01

    The human gut mucosa is a major site of HIV infection and infection-associated pathogenesis. Increasing evidence shows that natural killer (NK) cells play an important role in control of HIV infection but the mechanism(s) by which they mediate antiviral activity in the gut is unclear. Here we show two distinct subsets of NK cells exist in the gut, one localized to intraepithelial spaces (IEL) and the other to the lamina propria (LP). The frequency of both subsets of NK cells was reduced in chronic infection, whereas IEL NK cells remained stable in spontaneous controllers with protective KIR/HLA genotypes. Both IEL and LP NK cells were significantly expanded in immunologic non-responsive (INR) patients, who incompletely recovered CD4+ T cells on HAART. These data suggest that both IEL and LP NK cells may expand in the gut in an effort to compensate for compromised CD4+ T cell recovery, but that only IEL NK cells may be involved in providing durable control of HIV in the gut, PMID:21993602

  7. Porcine Endogenous Retrovirus Infects but Does Not Replicate in Nonhuman Primate Primary Cells and Cell Lines

    PubMed Central

    Ritzhaupt, Armin; van der Laan, Luc J. W.; Salomon, Daniel R.; Wilson, Carolyn A.

    2002-01-01

    Porcine endogenous retroviruses (PERV) can infect human cell lines in vitro; hence, there is a presumed risk of viral exposure to a recipient when pig cells are transplanted into humans (xenotransplantation). Nonhuman primates (NHP) are considered a potential permissive animal model to study the risk of in vivo infection of PERV after xenotransplantation. We set out to determine whether PERV can infect and replicate in NHP primary cells or established cell lines from African green monkey, rhesus macaque, and baboon. We confirm that the NHP cell lines under investigation were infected with PERV as measured by detection of viral DNA and RNA by PCR and reverse transcription (RT)-PCR, respectively, indicating that a functional receptor must be present on the cell surface. However, the load of detectable viral DNA in infected NHP cells declined over time, and the cells never had detectable reverse transcriptase activity. Utilizing quantitative real-time TaqMan PCR we found detectable levels of unintegrated DNA intermediates, but the levels were approximately 100-fold lower compared to HEK 293 cells infected with PERV. Virions released from infected NHP cells could productively infect naïve human cell lines, HEK 293 and HeLa, as shown by RT-PCR and RT assay. However, naïve NHP cells remained negative in RT-PCR and RT assay after exposure to virions from infected NHP cells. Together our data demonstrate that NHP cells are not permissive to productive replication by PERV, presumably due to inefficient cell entry and replication. In light of these observations, the appropriateness of NHP as suitable animal models to study PERV infection in vivo needs to be reevaluated. PMID:12388691

  8. T Cell Responses to Arenavirus Infections.

    DTIC Science & Technology

    1991-11-01

    FIELD GROUP SUB-GROUP T cells; Arenaviruses ; Hemorrhagic fevers, Lassa fever, 06 13 LCMV Lassa fever virus; Synthetic peptides; Vaccine; I Recombinant...virus-specific effector T cells and that some of the T cell determinants they recognize are conserved among O.W. arenaviruses . For example, Jahrling...specific T cells were not represented by these peptides. fl4AM17.817073 (MFBM24) CONCLUSIONS Our knowledge of the immune response to arenaviruses is

  9. Helicobacter Pylory infection in patients with esophageal squamous cell carcinoma

    PubMed Central

    Poyrazoglu, Omer Bilgehan; Dulger, Ahmet Cumhur; Gultepe, Bilge Sumbul

    2017-01-01

    OBJECTIVE: Esophageal squamous cell carcinoma is one of the most common esophageal diseases in the developing world, but the relationship between esophageal squamous cell carcinoma and Helicobacter pylori infection remains a neglected topic. The primary objective of this study was to determine the association between Helicobacter pylori infection and esophageal squamous cell carcinoma. A second purpose was to determine the incidence and factors associated with Helicobacter pylori infection following esophagectomy. METHOD: The microorganism was identified by testing the gastric biopsy materials from 95 esophageal squamous cell carcinoma patients (66 females; 39 were esophagectomized) for urease activity in a medium containing urea and a power of hydrogen detection reagent and comparing the results with those from a healthy population. Differences in patient characteristics were assessed with chi-square tests and t-tests for categorical and continuous factors, respectively. RESULTS: The patients with esophageal squamous cell carcinoma had a significantly lower prevalence of Helicobacter pylori compared with the healthy population (p<0.001). The naive and esophagectomized patients, in contrast, showed no significant differences in Helicobacter pylori infection (p>0.005). Patients with esophageal squamous cell carcinoma showed a significant association between leukocytosis and hypoglobulinemia and the presence of Helicobacter pylori infection (p=0.023 and p=0.045, respectively). CONCLUSION: These results suggest that Helicobacter pylori is not an etiological factor in patients with esophageal squamous cell carcinoma. We found a statistically significant negative correlation between esophageal squamous cell cancer and Helicobacter pylori infection. These findings may guide new strategies for esophageal squamous cell carcinoma therapy. PMID:28355360

  10. Susceptibility of Human Embryonic Stem Cell-Derived Neural Cells to Japanese Encephalitis Virus Infection

    PubMed Central

    Shen, Shih-Cheng; Shen, Ching-I; Lin, Ho; Chen, Chun-Jung; Chang, Chia-Yu; Chen, Sheng-Mei; Lee, Hsiu-Chin; Lai, Ping-Shan; Su, Hong-Lin

    2014-01-01

    Pluripotent human embryonic stem cells (hESCs) can be efficiently directed to become immature neuroepithelial precursor cells (NPCs) and functional mature neural cells, including neurotransmitter-secreting neurons and glial cells. Investigating the susceptibility of these hESCs-derived neural cells to neurotrophic viruses, such as Japanese encephalitis virus (JEV), provides insight into the viral cell tropism in the infected human brain. We demonstrate that hESC-derived NPCs are highly vulnerable to JEV infection at a low multiplicity of infection (MOI). In addition, glial fibrillary acid protein (GFAP)-expressing glial cells are also susceptible to JEV infection. In contrast, only a few mature neurons were infected at MOI 10 or higher on the third day post-infection. In addition, functional neurotransmitter-secreting neurons are also resistant to JEV infection at high MOI. Moreover, we discover that vimentin intermediate filament, reported as a putative neurovirulent JEV receptor, is highly expressed in NPCs and glial cells, but not mature neurons. These results indicate that the expression of vimentin in neural cells correlates to the cell tropism of JEV. Finally, we further demonstrate that membranous vimentin is necessary for the susceptibility of hESC-derived NPCs to JEV infection. PMID:25517725

  11. Imaging CD8+ T cells during diverse viral infections

    PubMed Central

    Hickman, Heather D

    2015-01-01

    CD8+ T cells play a critical role in host defense against pathogens and tumors. Much of our current knowledge of the activation and subsequent effector activities of CD8+ T cells has been gained using ex vivo approaches examining the T cell population en masse for surface phenotype, activation status and the production of effector molecules. Thus, the precise behaviors and diversity of individual CD8+ T cells responding to virus infection in vivo have not been extensively explored, leaving many unanswered questions relevant to the rational design of antiviral vaccines and therapeutics. Recently, intravital multiphoton microscopy (MPM) has been used to image CD8+ T cell priming after infection with disparate viral pathogens ranging from small RNA viruses encoding few proteins to DNA viruses producing hundreds of viral proteins (many immunomodulatory). After priming, effector CD8+ T cells have been visualized in virus-infected tissue, both during primary infection and after transitioning to tissue resident memory cells (TRM). Here, I highlight recent advances in our understanding of antiviral CD8+ T cell responses revealed through intravital MPM. PMID:28243513

  12. Tractable mammalian cell infections with protozoan-primed bacteria.

    PubMed

    Drennan, Samuel L; Lama, Amrita; Doron, Ben; Cambronne, Eric D

    2013-04-02

    Many intracellular bacterial pathogens use freshwater protozoans as a natural reservoir for proliferation in the environment. Legionella pneumophila, the causative agent of Legionnaires' pneumonia, gains a pathogenic advantage over in vitro cultured bacteria when first harvested from protozoan cells prior to infection of mammalian macrophages. This suggests that important virulence factors may not be properly expressed in vitro. We have developed a tractable system for priming L. pneumophila through its natural protozoan host Acanthamoeba castellanii prior to mammalian cell infection. The contribution of any virulence factor can be examined by comparing intracellular growth of a mutant strain to wild-type bacteria after protozoan priming. GFP-expressing wild-type and mutant L. pneumophila strains are used to infect protozoan monolayers in a priming step and allowed to reach late stages of intracellular growth. Fluorescent bacteria are then harvested from these infected cells and normalized by spectrophotometry to generate comparable numbers of bacteria for a subsequent infection into mammalian macrophages. For quantification, live bacteria are monitored after infection using fluorescence microscopy, flow cytometry, and by colony plating. This technique highlights and relies on the contribution of host cell-dependent gene expression by mimicking the environment that would be encountered in a natural acquisition route. This approach can be modified to accommodate any bacterium that uses an intermediary host as a means for gaining a pathogenic advantage.

  13. Proinflammatory Response of Human Trophoblastic Cells to Brucella abortus Infection and upon Interactions with Infected Phagocytes.

    PubMed

    Fernández, Andrea G; Ferrero, Mariana C; Hielpos, M Soledad; Fossati, Carlos A; Baldi, Pablo C

    2016-02-01

    Trophoblasts are targets of infection by Brucella spp. but their role in the pathophysiology of pregnancy complications of brucellosis is unknown. Here we show that Brucella abortus invades and replicates in the human trophoblastic cell line Swan-71 and that the intracellular survival of the bacterium depends on a functional virB operon. The infection elicited significant increments of interleukin 8 (IL8), monocyte chemotactic protein 1 (MCP-1), and IL6 secretion, but levels of IL1beta and tumor necrosis factor-alpha (TNF-alpha) did not vary significantly. Such proinflammatory response was not modified by the absence of the Brucella TIR domain-containing proteins BtpA and BtpB. The stimulation of Swan-71 cells with conditioned medium (CM) from B. abortus-infected human monocytes (THP-1 cells) or macrophages induced a significant increase of IL8, MCP-1 and IL6 as compared to stimulation with CM from non-infected cells. Similar results were obtained when stimulation was performed with CM from infected neutrophils. Neutralization studies showed that IL1beta and/or TNF-alpha mediated the stimulating effects of CM from infected phagocytes. Reciprocally, stimulation of monocytes and neutrophils with CM from Brucella-infected trophoblasts increased IL8 and/or IL6 secretion. These results suggest that human trophoblasts may provide a local inflammatory environment during B. abortus infections either through a direct response to the pathogen or through interactions with monocytes/macrophages or neutrophils, potentially contributing to the pregnancy complications of brucellosis.

  14. Insufficient natural killer cell responses against retroviruses: how to improve NK cell killing of retrovirus-infected cells.

    PubMed

    Littwitz-Salomon, Elisabeth; Dittmer, Ulf; Sutter, Kathrin

    2016-11-08

    Natural killer (NK) cells belong to the innate immune system and protect against cancers and a variety of viruses including retroviruses by killing transformed or infected cells. They express activating and inhibitory receptors on their cell surface and often become activated after recognizing virus-infected cells. They have diverse antiviral effector functions like the release of cytotoxic granules, cytokine production and antibody dependent cellular cytotoxicity. The importance of NK cell activity in retroviral infections became evident due to the discovery of several viral strategies to escape recognition and elimination by NK cells. Mutational sequence polymorphisms as well as modulation of surface receptors and their ligands are mechanisms of the human immunodeficiency virus-1 to evade NK cell-mediated immune pressure. In Friend retrovirus infected mice the virus can manipulate molecular or cellular immune factors that in turn suppress the NK cell response. In this model NK cells lack cytokines for optimal activation and can be functionally suppressed by regulatory T cells. However, these inhibitory pathways can be overcome therapeutically to achieve full activation of NK cell responses and ultimately control dissemination of retroviral infection. One effective approach is to modulate the crosstalk between NK cells and dendritic cells, which produce NK cell-stimulating cytokines like type I interferons (IFN), IL-12, IL-15, and IL-18 upon retrovirus sensing or infection. Therapeutic administration of IFNα directly increases NK cell killing of retrovirus-infected cells. In addition, IL-2/anti-IL-2 complexes that direct IL-2 to NK cells have been shown to significantly improve control of retroviral infection by NK cells in vivo. In this review, we describe novel approaches to improve NK cell effector functions in retroviral infections. Immunotherapies that target NK cells of patients suffering from viral infections might be a promising treatment option for the

  15. A New Mutation of the Atoh1 Gene in Mice with Normal Life Span Allows Analysis of Inner Ear and Cerebellar Phenotype in Aging

    PubMed Central

    Yu, Heping; Zheng, Tihua; Zhang, Zhaoqiang; Li, Sheng Li; Liu, Shuqing; Zheng, Qing Yin

    2013-01-01

    Atoh1 is a transcription factor that regulates neural development in multiple tissues and is conserved among species. Prior mouse models of Atoh1, though effective and important in the evolution of our understanding of the gene, have been limited by perinatal lethality. Here we describe a novel point mutation of Atoh1 (designated Atoh1trhl) underlying a phenotype of trembling gait and hearing loss. Histology revealed inner ear hair cell loss and cerebellar atrophy. Auditory Brainstem Response (ABR) and Distortion Product Otoacoustic Emission (DPOAE) showed functional abnormalities in the ear. Normal lifespan and fecundity of Atoh1trhlmice provide a complementary model to facilitate elucidation of ATOH1 function in hearing,central nervous system and cancer biology. PMID:24265785

  16. Chlamydia pneumoniae respiratory infection after allogeneic stem cell transplantation.

    PubMed

    Geisler, William M; Corey, Lawrence

    2002-03-27

    Chlamydia pneumoniae is a common cause of upper and lower respiratory tract infections in immunocompetent patients; however, its role as a respiratory pathogen in immunocompromised hosts has been infrequently recognized. We describe C. pneumoniae lower respiratory tract infection in a 19-year-old male after allogeneic stem cell transplantation. The patient developed fever on day +14, and a subsequent computed tomography scan of the chest revealed a right lateral pleural-based opacity, which was then resected during thoracoscopy. Diagnosis was made by culture and staining of the resected tissue with C. pneumoniae-specific monoclonal antibodies, and azithromycin was administered. To the best of our knowledge, this is the first report of C. pneumoniae respiratory infection after stem cell or marrow transplantation. C. pneumoniae often coexists with other etiologic agents of pneumonia in immunocompromised patients. Considering the infrequency of infections from this organism in this clinical setting, one must still rule out other more likely respiratory pathogens.

  17. Epithelial cell apoptosis facilitates Entamoeba histolytica infection in the gut.

    PubMed

    Becker, Stephen M; Cho, Kyou-Nam; Guo, Xiaoti; Fendig, Kirsten; Oosman, Mohammed N; Whitehead, Robert; Cohn, Steven M; Houpt, Eric R

    2010-03-01

    Entamoeba histolytica is the protozoan parasite that causes amebic colitis. The parasite triggers apoptosis on contact with host cells; however, the biological significance of this event during intestinal infection is unclear. We examined the role of apoptosis in a mouse model of intestinal amebiasis. Histopathology revealed that abundant epithelial cell apoptosis occurred in the vicinity of amoeba in histological specimens. Epithelial cell apoptosis occurred rapidly on co-culture with amoeba in vitro as measured by annexin positivity, DNA degradation, and mitochondrial dysfunction. Administration of the pan caspase inhibitor ZVAD decreased the rate and severity of amebic infection in CBA mice by all measures (cecal culture positivity, parasite enzyme-linked immunosorbent assay, and histological scores). Similarly, caspase 3 knockout mice on the resistant C57BL/6 background exhibited even lower cecal parasite antigen burden and culture positive rates than wild type mice. The permissive effect of apoptosis on infection could be tracked to the epithelium, in that transgenic mice that overexpressed Bcl-2 in epithelial cells were more resistant to infection as measured by cecal parasite enzyme-linked immunosorbent assay and histological scores. We concluded that epithelial cell apoptosis in the intestine facilitates amebic infection in this mouse model. The parasite's strategy for inducing apoptosis may point to key virulence factors, and therapeutic maneuvers to diminish epithelial apoptosis may be useful in amebic colitis.

  18. 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

  19. Studying NK cell responses to ectromelia virus infections in mice.

    PubMed

    Fang, Min; Sigal, Luis

    2010-01-01

    Here we describe methods for the in vivo study of antiviral NK cell responses using the mouse Orthopoxvirus ectromelia virus as a model, the agent of mousepox. The methods include those specific for the preparation and use of ectromelia virus such as the production of virus stocks in tissue culture and in live mice, the purification of virus stocks, the titration of virus stocks and virus loads in organs, and the infection of mice. The chapter also includes methods for the specific study of NK cell responses in infected mice such as the preparation of organs (lymph nodes, spleen, and liver) for analysis, the study of NK cell responses by flow cytometry, the adoptive transfer of NK cells, the measurement of NK cell cytolytic activity ex vivo and in vivo, and the determination of NK cell proliferation by bromodeoxyuridine loading or by dilution of carboxyfluorescein diacetate succinimidyl ester (CFSE).

  20. Modeling dynamics of HIV infected cells using stochastic cellular automaton

    NASA Astrophysics Data System (ADS)

    Precharattana, Monamorn; Triampo, Wannapong

    2014-08-01

    Ever since HIV was first diagnosed in human, a great number of scientific works have been undertaken to explore the biological mechanisms involved in the infection and progression of the disease. Several cellular automata (CA) models have been introduced to gain insights into the dynamics of the disease progression but none of them has taken into account effects of certain immune cells such as the dendritic cells (DCs) and the CD8+ T lymphocytes (CD8+ T cells). In this work, we present a CA model, which incorporates effects of the HIV specific immune response focusing on the cell-mediated immunities, and investigate the interaction between the host immune response and the HIV infected cells in the lymph nodes. The aim of our work is to propose a model more realistic than the one in Precharattana et al. (2010) [10], by incorporating roles of the DCs, the CD4+ T cells, and the CD8+ T cells into the model so that it would reproduce the HIV infection dynamics during the primary phase of HIV infection.

  1. Inhibition of cytomegalovirus infection and photothermolysis of infected cells using bioconjugated gold nanoparticles

    PubMed Central

    DeRussy, Bernadette M.; Aylward, Madeline A.; Fan, Zhen; Ray, Paresh C.; Tandon, Ritesh

    2014-01-01

    Human cytomegalovirus (CMV) is a herpesvirus that causes major health problems in neonates as well as in immunocompromised individuals1. At present, a vaccine is not available for CMV infection and the available antiviral drugs suffer from toxicity, poor efficacy and resistance12. Here, we chemically conjugated a monoclonal antibody raised against CMV surface glycoprotein (gB) with gold nanoparticles (GNP) and characterized the potential of this gB-GNP conjugate for antiviral activity against CMV. The gB-GNP blocks viral replication, virus-induced cytopathogenic effects and virus spread in cell culture without inducing cytotoxicity. High concentrations of gB-GNP that coat the surface of virus particles block virus entry, whereas lower concentrations block a later stage of virus life cycle. Also, cells treated with gB-GNP gain resistance to CMV infection. In addition, infected cells when bound to gB-GNP can be selectively lysed after exposing them to specific wavelength of laser (nanophotothermolysis). Thus, we have not only designed a potential antiviral strategy that specifically blocks CMV infection at multiple stages of virus life cycle, but we have also characterized a technique that can potentially be useful in eliminating CMV infected cells from donor tissue during transplant or transfusion. PMID:24989498

  2. Myeloid-Derived Suppressor Cells in Bacterial Infections

    PubMed Central

    Ost, Michael; Singh, Anurag; Peschel, Andreas; Mehling, Roman; Rieber, Nikolaus; Hartl, Dominik

    2016-01-01

    Myeloid-derived suppressor cells (MDSCs) comprise monocytic and granulocytic innate immune cells with the capability of suppressing T- and NK-cell responses. While the role of MDSCs has been studied in depth in malignant diseases, the understanding of their regulation and function in infectious disease conditions has just begun to evolve. Here we summarize and discuss the current view how MDSCs participate in bacterial infections and how this knowledge could be exploited for potential future therapeutics. PMID:27066459

  3. Comparison of the effect of semen from HIV-infected and uninfected men on CD4+ T-cell infection

    PubMed Central

    Camus, Céline; Matusali, Giulia; Bourry, Olivier; Mahe, Dominique; Aubry, Florence; Bujan, Louis; Pasquier, Christophe; Massip, Patrice; Ravel, Célia; Zirafi, Onofrio; Munch, Jan; Roan, Nadia R.; Pineau, Charles; Dejucq-Rainsford, Nathalie

    2016-01-01

    Objectives: Semen composition is influenced by HIV-1 infection, yet the impact of semen components on HIV infection of primary target cells has only been studied in samples from HIV-uninfected donors. Design: We compared the effect of seminal plasma (SP) from chronically HIV-infected (SP+) versus uninfected donors (SP–) on HIV-1 infection of peripheral blood mononuclear cells (PBMCs) and CD4+ T cells. Methods: Primary cells were infected with HIV-1 in the presence of SP+ or SP– and analyzed for infection level, metabolic activity, HIV receptor expression, proliferation and activation. SP+ and SP– were compared for infection-enhancing peptides, cytokines and prostaglandin E2 levels. Results: SP– efficiently enhanced HIV-1 R5 infection of CD4+ T cells, whereas SP+ enhancing activity was significantly reduced. RANTES (CCL5) concentrations were elevated in SP+ relative to SP–, whereas the concentrations of infectivity-enhancing peptides [semen-derived enhancer of viral infection (SEVI), SEM1, SEM2] were similar. CCR5 membrane expression levels were reduced on CD4+ T cells shortly postexposure to SP+ compared with SP– and correlated to R5-tropic HIV-1 infection levels, and CCR5 ligands’ concentrations in semen. SP+ and SP– displayed similar enhancing activity on PBMC infection by X4-tropic HIV-1. Addition/depletion of RANTES (regulated on activation, normal T-cell expressed and secreted) from SPs modulated their effect on PBMC infection by R5-tropic HIV-1. Conclusion: Semen from HIV-infected donors exhibits a significantly reduced enhancing potential on CD4+ T-cell infection by R5-tropic HIV-1 when compared with semen from uninfected donors. Our data indicate that elevated seminal concentrations of RANTES in HIV-infected men can influence the ability of semen to enhance infection. PMID:26854806

  4. Natural killer cells in immunodefense against infective agents.

    PubMed

    Zucchini, Nicolas; Crozat, Karine; Baranek, Thomas; Robbins, Scott H; Altfeld, Marcus; Dalod, Marc

    2008-12-01

    Following the discovery of innate immune receptors, the topics of innate immunity and its role in defense against infective agents have recently blossomed into very active research fields, after several decades of neglect. Among innate immune cells, natural killer (NK) cells are endowed with the unique ability to recognize and kill cells infected with a variety of pathogens, irrespective of prior sensitization to these microbes. NK cells have a number of other functions, including cytokine production and immunoregulatory activities. Major advances have recently been made in the understanding of the role of NK cells in the physiopathology of infectious diseases. The cellular and molecular mechanisms regulating the acquisition of effector functions by NK cells and their triggering upon pathogenic encounters are being unraveled. The possibility that the power of NK cells could be harnessed for the design of innovative treatments against infections is a major incentive for biologists to further explore NK cell subset complexity and to identify the ligands that activate NK cell receptors.

  5. Natural killer cells in immunodefense against infective agents

    PubMed Central

    Zucchini, Nicolas; Crozat, Karine; Baranek, Thomas; Robbins, Scott H; Altfeld, Marcus; Dalod, Marc

    2009-01-01

    Following the discovery of innate immune receptors, the topics of innate immunity and its role in defense against infective agents have recently blossomed into very active research fields, after several decades of neglect. Among innate immune cells, natural killer (NK) cells are endowed with the unique ability to recognize and kill cells infected with a variety of pathogens, irrespective of prior sensitization to these microbes. NK cells have a number of other functions, including cytokine production and immunoregulatory activities. Major advances have recently been made in the understanding of the role of NK cells in the physiopathology of infectious diseases. The cellular and molecular mechanisms regulating the acquisition of effector functions by NK cells and their triggering upon pathogenic encounters are being unraveled. The possibility that the power of NK cells could be harnessed for the design of innovative treatments against infections is a major incentive for biologists to further explore NK cell subset complexity and to identify the ligands that activate NK cell receptors. PMID:19053900

  6. Myeloid Cell Arg1 Inhibits Control of Arthritogenic Alphavirus Infection by Suppressing Antiviral T Cells

    PubMed Central

    Burrack, Kristina S.; Tan, Jeslin J. L.; McCarthy, Mary K.; Her, Zhisheng; Berger, Jennifer N.; Ng, Lisa F. P.; Morrison, Thomas E.

    2015-01-01

    Arthritogenic alphaviruses, including Ross River virus (RRV) and chikungunya virus (CHIKV), are responsible for explosive epidemics involving millions of cases. These mosquito-transmitted viruses cause inflammation and injury in skeletal muscle and joint tissues that results in debilitating pain. We previously showed that arginase 1 (Arg1) was highly expressed in myeloid cells in the infected and inflamed musculoskeletal tissues of RRV- and CHIKV-infected mice, and specific deletion of Arg1 from myeloid cells resulted in enhanced viral control. Here, we show that Arg1, along with other genes associated with suppressive myeloid cells, is induced in PBMCs isolated from CHIKV-infected patients during the acute phase as well as the chronic phase, and that high Arg1 expression levels were associated with high viral loads and disease severity. Depletion of both CD4 and CD8 T cells from RRV-infected Arg1-deficient mice restored viral loads to levels detected in T cell-depleted wild-type mice. Moreover, Arg1-expressing myeloid cells inhibited virus-specific T cells in the inflamed and infected musculoskeletal tissues, but not lymphoid tissues, following RRV infection in mice, including suppression of interferon-γ and CD69 expression. Collectively, these data enhance our understanding of the immune response following arthritogenic alphavirus infection and suggest that immunosuppressive myeloid cells may contribute to the duration or severity of these debilitating infections. PMID:26436766

  7. Deep sea minerals prolong life span of streptozotocin-induced diabetic rats by compensatory augmentation of the IGF-I-survival signaling and inhibition of apoptosis.

    PubMed

    Liao, Hung-En; Shibu, Marthandam Asokan; Kuo, Wei-Wen; Pai, Pei-Ying; Ho, Tsung-Jung; Kuo, Chia-Hua; Lin, Jing-Ying; Wen, Su-Ying; Viswanadha, Vijaya Padma; Huang, Chih-Yang

    2016-07-01

    Consumption of deep sea minerals (DSM), such as magnesium, calcium, and potassium, is known to reduce hypercholesterolemia-induced myocardial hypertrophy and cardiac-apoptosis and provide protection against cardiovascular diseases. Heart diseases develop as a lethal complication among diabetic patients usually due to hyperglycemia-induced cardiac-apoptosis that causes severe cardiac-damages, heart failure, and reduced life expectancy. In this study, we investigated the potential of DSM and its related cardio-protection to increase the life expectancy in diabetic rats. In this study, a heart failure rat model was developed by using streptozotocin (65 mg kg(-1) ) IP injection. Different doses of DSM-1× (37 mg kg(-1) day(-1) ), 2× (74 mg kg(-1) day(-1) ) and 3× (111 mg kg(-1) day(-1) ), were administered to the rats through gavages for 4 weeks. The positive effects of DSM on the survival rate of diabetes rats were determined with respect to the corresponding effects of MgSO4 . Further, to understand the mechanism by which DSM enhances the survival of diabetic rats, their potential to regulate cardiac-apoptosis and control cardiac-dysfunction were examined. Echocardiogram, tissue staining, TUNEL assay, and Western blotting assay were used to investigate modulations in the myocardial contractile function and related signaling protein expression. The results showed that DSM regulate apoptosis and complement the cardiomyocyte proliferation by enhancing survival mechanisms. Moreover DSM significantly reduced the mortality rate and enhanced the survival rate of diabetic rats. Experimental results show that DSM administration can be an effective strategy to improve the life expectancy of diabetic subjects by improving cardiac-cell proliferation and by controlling cardiac-apoptosis and associated cardiac-dysfunction. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 769-781, 2016.

  8. Vertebrate Cell Cycle Modulates Infection by Protozoan Parasites

    NASA Astrophysics Data System (ADS)

    Dvorak, James A.; Crane, Mark St. J.

    1981-11-01

    Synchronized HeLa cell populations were exposed to Trypanosoma cruzi or Toxoplasma gondii, obligate intracellular protozoan parasites that cause Chagas' disease and toxoplasmosis, respectively, in humans. The ability of the two parasites to infect HeLa cells increased as the HeLa cells proceeded from the G1 phase to the S phase of their growth cycle and decreased as the cells entered G2-M. Characterization of the S-phase cell surface components responsible for this phenomenon could be beneficial in the development of vaccines against these parasitic diseases.

  9. Cell Surface Nucleolin Facilitates Enterovirus 71 Binding and Infection

    PubMed Central

    Su, Pei-Yi; Wang, Ya-Fang; Huang, Sheng-Wen; Lo, Yu-Chih; Wang, Ya-Hui; Wu, Shang-Rung; Shieh, Dar-Bin; Wang, Jen-Ren; Lai, Ming-Der

    2015-01-01

    ABSTRACT Because the pathogenesis of enterovirus 71 (EV71) remains mostly ambiguous, identifying the factors that mediate viral binding and entry to host cells is indispensable to ultimately uncover the mechanisms that underlie virus infection and pathogenesis. Despite the identification of several receptors/attachment molecules for EV71, the binding, entry, and infection mechanisms of EV71 remain unclear. Herein, we employed glycoproteomic approaches to identify human nucleolin as a novel binding receptor for EV71. Glycoproteins purified by lectin chromatography from the membrane extraction of human cells were treated with sialidase, followed by immunoprecipitation with EV71 particles. Among the 16 proteins identified by tandem mass spectrometry analysis, cell surface nucleolin attracted our attention. We found that EV71 interacted directly with nucleolin via the VP1 capsid protein and that an antinucleolin antibody reduced the binding of EV71 to human cells. In addition, the knockdown of cell surface nucleolin decreased EV71 binding, infection, and production in human cells. Furthermore, the expression of human nucleolin on the cell surface of a mouse cell line increased EV71 binding and conferred EV71 infection and production in the cells. These results strongly indicate that human nucleolin can mediate EV71 binding to and infection of cells. Our findings also demonstrate that the use of glycoproteomic approaches is a reliable methodology to discover novel receptors for pathogens. IMPORTANCE Outbreaks of EV71 have been reported in Asia-Pacific countries and have caused thousands of deaths in young children during the last 2 decades. The discovery of new EV71-interacting molecules to understand the infection mechanism has become an emergent issue. Hence, this study uses glycoproteomic approaches to comprehensively investigate the EV71-interacting glycoproteins. Several EV71-interacting glycoproteins are identified, and the role of cell surface nucleolin in

  10. Viral infection induces cytokine release by beta islet cells.

    PubMed Central

    Cavallo, M G; Baroni, M G; Toto, A; Gearing, A J; Forsey, T; Andreani, D; Thorpe, R; Pozzilli, P

    1992-01-01

    Viral infection has been suggested to play a triggering role in the pancreatic beta cell destruction which occurs in insulin-dependent diabetes (IDDM). However, the underlying mechanism of this phenomenon is unknown. In this study a human insulinoma cell line has been infected with measles, mumps and rubella viruses since a temporal association is reported between the clinical onset of IDDM and diseases caused by these viruses. The infection with measles and mumps viruses induced the release of interleukin-1 (IL-1) and interleukin-6 (IL-6) by the cell line as assessed by a bioassay and up-regulated the expression of human leucocyte antigen (HLA) class I and class II antigens as evaluated by cytofluorimetric analysis. Stimulation with rubella virus induced the release of IL-6 only and had no effect on HLA antigen expression. These data show for the first time that IL-1 and IL-6 secretion by an insulinoma cell line may occur after viral infection and suggest that cytokine release and increased expression of HLA molecules by beta cells may act to induce the immune response towards beta cells in IDDM. PMID:1592439

  11. Exosomes Secreted by Toxoplasma gondii-Infected L6 Cells: Their Effects on Host Cell Proliferation and Cell Cycle Changes.

    PubMed

    Kim, Min Jae; Jung, Bong-Kwang; Cho, Jaeeun; Song, Hyemi; Pyo, Kyung-Ho; Lee, Ji Min; Kim, Min-Kyung; Chai, Jong-Yil

    2016-04-01

    Toxoplasma gondii infection induces alteration of the host cell cycle and cell proliferation. These changes are not only seen in directly invaded host cells but also in neighboring cells. We tried to identify whether this alteration can be mediated by exosomes secreted by T. gondii-infected host cells. L6 cells, a rat myoblast cell line, and RH strain of T. gondii were selected for this study. L6 cells were infected with or without T. gondii to isolate exosomes. The cellular growth patterns were identified by cell counting with trypan blue under confocal microscopy, and cell cycle changes were investigated by flow cytometry. L6 cells infected with T. gondii showed decreased proliferation compared to uninfected L6 cells and revealed a tendency to stay at S or G2/M cell phase. The treatment of exosomes isolated from T. gondii-infected cells showed attenuation of cell proliferation and slight enhancement of S phase in L6 cells. The cell cycle alteration was not as obvious as reduction of the cell proliferation by the exosome treatment. These changes were transient and disappeared at 48 hr after the exosome treatment. Microarray analysis and web-based tools indicated that various exosomal miRNAs were crucial for the regulation of target genes related to cell proliferation. Collectively, our study demonstrated that the exosomes originating from T. gondii could change the host cell proliferation and alter the host cell cycle.

  12. Human papillomavirus capsids preferentially bind and infect tumor cells

    PubMed Central

    Kines, Rhonda C.; Cerio, Rebecca J.; Roberts, Jeffrey N.; Thompson, Cynthia D.; de Los Pinos, Elisabet; Lowy, Douglas R.; Schiller, John T.

    2015-01-01

    We previously determined that human papillomavirus (HPV) virus-like particles (VLPs) and pseudovirions (PsV) did not, respectively, bind to or infect intact epithelium of the cervicovaginal tract. However, they strongly bound heparin sulfate proteoglycans (HSPG) on the basement membrane of disrupted epithelium and infected the keratinocytes that subsequently entered the disrupted site. We here report that HPV capsids (VLP and PsV) have the same restricted tropism for a wide variety of disrupted epithelial and mesothelial tissues, whereas intact tissues remain resistant to binding. However, the HPV capsids directly bind and infect most tumor-derived cell lines in vitro and have analogous tumor-specific properties in vivo, after local or intravenous injection, using orthotopic models for human ovarian and lung cancer, respectively. The pseudovirions also specifically infected implanted primary human ovarian tumors. Heparin and ι-carrageenan blocked binding and infection of all tumor lines tested, implying that tumor cell binding is HSPG-dependent. A survey using a panel of modified heparins indicate that N-sulfation and, to a lesser degree O-6 sulfation of the surface HSPG on the tumors are important for HPV binding. Therefore, it appears that tumor cells consistently evolve HSPG modification patterns that mimic the pattern normally found on the basement membrane but not on the apical surfaces of normal epithelial or mesothelial cells. Consequently, appropriately modified HPV VLPs and/or PsV could be useful reagents to detect and potentially treat a remarkably broad spectrum of cancers. PMID:26317490

  13. The split personality of regulatory T cells in HIV infection.

    PubMed

    Chevalier, Mathieu F; Weiss, Laurence

    2013-01-03

    Natural regulatory T cells (Tregs) participate in responses to various chronic infections including HIV. HIV infection is associated with a progressive CD4 lymphopenia and defective HIV-specific CD8 responses known to play a key role in the control of viral replication. Persistent immune activation is a hallmark of HIV infection and is involved in disease progression independent of viral load. The consequences of Treg expansion, observed in HIV infection, could be either beneficial, by suppressing generalized T-cell activation, or detrimental, by weakening HIV-specific responses and thus contributing to viral persistence. The resulting balance between Tregs contrasting outcomes might have critical implications in pathogenesis. Topics covered in this review include HIV-induced alterations of Tregs, Treg cell dynamics in blood and tissues, Treg-suppressive function, and the relationship between Tregs and immune activation. This review also provides a focus on the role of CD39(+) Tregs and other regulatory cell subsets. All these issues will be explored in different situations including acute and chronic infection, antiretroviral treatment-mediated viral control, and spontaneous viral control. Results must be interpreted with regard to both the Treg definition used in context and to the setting of the disease in an attempt to draw clearer conclusions from the apparently conflicting results.

  14. Subversion of Cell-Autonomous Host Defense by Chlamydia Infection.

    PubMed

    Fischer, Annette; Rudel, Thomas

    2016-05-13

    Obligate intracellular bacteria entirely depend on the metabolites of their host cell for survival and generation of progeny. Due to their lifestyle inside a eukaryotic cell and the lack of any extracellular niche, they have to perfectly adapt to compartmentalized intracellular environment of the host cell and counteract the numerous defense strategies intrinsically present in all eukaryotic cells. This so-called cell-autonomous defense is present in all cell types encountering Chlamydia infection and is in addition closely linked to the cellular innate immune defense of the mammalian host. Cell type and chlamydial species-restricted mechanisms point a long-term evolutionary adaptation that builds the basis of the currently observed host and cell-type tropism among different Chlamydia species. This review will summarize the current knowledge on the strategies pathogenic Chlamydia species have developed to subvert and overcome the multiple mechanisms by which eukaryotic cells defend themselves against intracellular pathogens.

  15. Apoptosis transcriptional mechanism of feline infectious peritonitis virus infected cells.

    PubMed

    Shuid, Ahmad Naqib; Safi, Nikoo; Haghani, Amin; Mehrbod, Parvaneh; Haron, Mohd Syamsul Reza; Tan, Sheau Wei; Omar, Abdul Rahman

    2015-11-01

    Apoptosis has been postulated to play an important role during feline infectious peritonitis virus (FIPV) infection; however, its mechanism is not well characterized. This study is focused on apoptosis and transcriptional profiling of FIPV-infected cells following in vitro infection of CRFK cells with FIPV 79-1146 WSU. Flow cytometry was used to determine mode of cell death in first 42 h post infection (hpi). FIPV infected cells underwent early apoptosis at 9 hpi (p < 0.05) followed by late apoptosis at 12 hpi (p < 0.05) and necrosis from 24 hpi (p < 0.05). Then, next generation sequencing was performed on 9 hpi and control uninfected cells by Illumina analyzer. An aggregate of 4546 genes (2229 down-regulated and 2317 up-regulated) from 17 cellular process, 11 molecular functions and 130 possible biological pathways were affected by FIPV. 131 genes from apoptosis cluster (80 down-regulated and 51 up-regulated) along with increase of apoptosis, p53, p38 MAPK, VEGF and chemokines/cytokines signaling pathways were probably involved in apoptosis process. Six of the de-regulated genes expression (RASSF1, BATF2, MAGEB16, PDCD5, TNFα and TRAF2) and TNFα protein concentration were analyzed by RT-qPCR and ELISA, respectively, at different time-points. Up-regulations of both pro-apoptotic (i.e. PDCD5) and anti-apoptotic (i.e. TRAF2) were detected from first hpi and continuing to deregulate during apoptosis process in the infected cells.

  16. Membrane Vesicles Released by Intestinal Epithelial Cells Infected with Rotavirus Inhibit T-Cell Function

    PubMed Central

    Barreto, Alfonso; Rodríguez, Luz-Stella; Rojas, Olga Lucía; Wolf, Marie; Greenberg, Harry B.; Franco, Manuel A.

    2010-01-01

    Abstract Rotavirus (RV) predominantly replicates in intestinal epithelial cells (IEC), and “danger signals” released by these cells may modulate viral immunity. We have recently shown that human model IEC (Caco-2 cells) infected with rhesus-RV release a non-inflammatory group of immunomodulators that includes heat shock proteins (HSPs) and TGF-β1. Here we show that both proteins are released in part in association with membrane vesicles (MV) obtained from filtrated Caco-2 supernatants concentrated by ultracentrifugation. These MV express markers of exosomes (CD63 and others), but not of the endoplasmic reticulum (ER) or nuclei. Larger quantities of proteins associated with MV were released by RV-infected cells than by non-infected cells. VP6 co-immunoprecipitated with CD63 present in these MV, and VP6 co-localized with CD63 in RV-infected cells, suggesting that this viral protein is associated with the MV, and that this association occurs intracellularly. CD63 present in MV preparations from stool samples from 36 children with gastroenteritis due or not due to RV were analyzed. VP6 co-immunoprecipitated with CD63 in 3/8 stool samples from RV-infected children, suggesting that these MV are released by RV-infected cells in vivo. Moreover, fractions that contained MV from RV-infected cells induced death and inhibited proliferation of CD4+ T cells to a greater extent than fractions from non-infected cells. These effects were in part due to TGF-β, because they were reversed by treatment of the T cells with the TGF-β-receptor inhibitor ALK5i. MV from RV-infected and non-infected cells were heterogeneous, with morphologies and typical flotation densities described for exosomes (between 1.10 and 1.18 g/mL), and denser vesicles (>1.24 g/mL). Both types of MV from RV-infected cells were more efficient at inhibiting T-cell function than were those from non-infected cells. We propose that RV infection of IEC releases MV that modulate viral immunity. PMID:21142445

  17. Human Cytomegalovirus Infection Enhances NK Cell Activity In Vitro

    PubMed Central

    Tschan-Plessl, Astrid; Stern, Martin; Schmied, Laurent; Retière, Christelle; Hirsch, Hans H.; Garzoni, Christian; van Delden, Christian; Boggian, Katia; Mueller, Nicolas J.; Berger, Christoph; Villard, Jean; Manuel, Oriol; Meylan, Pascal; Terszowski, Grzegorz

    2016-01-01

    Background Occurring frequently after solid organ and hematopoietic stem cell transplantation, cytomegalovirus (CMV) replication remains a relevant cause of mortality and morbidity in affected patients. Despite these adverse effects, an increased alloreactivity of natural killer (NK) cells after CMV infection has been assumed, but the underlying physiopathological mechanisms have remained elusive. Methods We used serial analyses of NK cells before and after CMV infection in kidney transplant recipients as an in vivo model for CMV primary infection to explore the imprint of CMV infection using every patient as their own control: We analyzed NK cell phenotype and function in 47 CMV seronegative recipients of CMV seropositive kidney grafts, who developed CMV primary infection posttransplant. Seronegative recipients of seronegative kidney grafts served as controls. Results We observed a significant increase of NKG2C expressing NK cells after CMV infection (mean increase, 17.5%; 95% confidence interval [95% CI], 10.2-24.9, P < 0.001), whereas cluster of differentiation (CD)57 expressing cells decreased (mean decrease, 14.1%; 95% CI, 8.0-20.2; P < 0.001). Analysis of killer immunoglobulin-like receptor (KIR) expression showed an increase of cells expressing KIR2DL1 as their only inhibitory KIR in patients carrying the cognate ligand HLA-C2 (mean increase, 10.0%; 95% CI, 1.7-18.3; P = 0.018). In C2-negative individuals, KIR2DL1 expression decreased (mean decrease, 3.9%; 95% CI, 1.6-6.2; P = 0.001). As for activating KIR, there was no conclusive change pattern. Most importantly, we observed a significantly higher NK cell degranulation and IFNγ production in response to different target cells (target K562, CD107a: mean increase, 9.9%; 95% CI, 4.8-15.0; P < 0.001; IFNγ: mean increase, 6.6%; 95% CI, 1.6-11.1; P < 0.001; target MRC-5, CD107a: mean increase, 6.9%; 95% CI, 0.7-13.1; P = 0.03; IFNγ: mean increase, 4.8%; 95% CI, 1.7-7.8; P = 0.002). Conclusions We report

  18. Respiratory virus infection among hematopoietic cell transplant recipients: evidence for asymptomatic parainfluenza virus infection.

    PubMed

    Peck, Angela J; Englund, Janet A; Kuypers, Jane; Guthrie, Katherine A; Corey, Lawrence; Morrow, Rhoda; Hackman, Robert C; Cent, Anne; Boeckh, Michael

    2007-09-01

    The incidence of respiratory virus infection after hematopoietic cell transplantation (HCT) has probably been underestimated with conventional testing methods in symptomatic patients. This prospective study assessed viral infection episodes by testing weekly respiratory samples collected from HCT recipients, with and without symptoms reported by questionnaire, for 100 days after HCT. Samples were tested by culture and direct fluorescent antibody testing for respiratory syncytial virus (RSV), parainfluenza virus (PIV), and influenza A and B, and by quantitative reverse transcription-polymerase chain reaction for RSV, PIV, influenza A and B, and metapneumovirus (MPV). Of 122 patients, 30 (25%) had 32 infection episodes caused by RSV (5), PIV (17), MPV (6), influenza (3), RSV, or influenza (1). PIV, with a cumulative incidence estimate of 17.9%, was the only virus for which asymptomatic infection was detected. Lower virus copy number in patients with no or one symptom compared with 2 or more symptoms was found for all viruses in all patients (P < .001), with PIV infection having a similar virus-specific comparison (P = .004). Subclinical infection with PIV may help explain why infection-control programs that emphasize symptoms are effective against RSV and influenza but often not against PIV.

  19. Bioactive Molecules Released From Cells Infected with the Human Cytomegalovirus

    PubMed Central

    Luganini, Anna; Terlizzi, Maria E.; Gribaudo, Giorgio

    2016-01-01

    Following primary infection in humans, the human cytomegalovirus (HCMV) persists in a latent state throughout the host’s lifetime despite a strong and efficient immune response. If the host experiences some form of immune dysregulation, such as immunosuppression or immunodeficiency, HCMV reactivates, thereby emerging from latency. Thus, in the absence of effective functional immune responses, as occurs in immunocompromised or immunoimmature individuals, both HCMV primary infections and reactivations from latency can cause significant morbidity and mortality. However, even in immunocompetent hosts, HCMV represents a relevant risk factor for the development of several chronic inflammatory diseases and certain forms of neoplasia. HCMV infection may shift between the lytic and latent state, regulated by a delicate and intricate balance between virus-mediated immunomodulation and host immune defenses. Indeed, HCMV is a master in manipulating innate and adaptive host defense pathways, and a large portion of its genome is devoted to encoding immunomodulatory proteins; such proteins may thus represent important virulence determinants. However, the pathogenesis of HCMV-related diseases is strengthened by the activities of bioactive molecules, of both viral and cellular origin, that are secreted from infected cells and collectively named as the secretome. Here, we review the state of knowledge on the composition and functions of HCMV-derived secretomes. In lytic infections of fibroblasts and different types of endothelial cells, the majority of HCMV-induced secreted proteins act in a paracrine fashion to stimulate the generation of an inflammatory microenvironment around infected cells; this may lead to vascular inflammation and angiogenesis that, in turn, foster HCMV replication and its dissemination through host tissues. Conversely, the HCMV secretome derived from latently infected hematopoietic progenitor cells induces an immunosuppressive extracellular environment that

  20. HIV infection of monocytes-derived dendritic cells inhibits Vγ9Vδ2 T cells functions.

    PubMed

    Sacchi, Alessandra; Rinaldi, Alessandra; Tumino, Nicola; Casetti, Rita; Agrati, Chiara; Turchi, Federica; Bordoni, Veronica; Cimini, Eleonora; Martini, Federico

    2014-01-01

    DCs act as sentinel cells against incoming pathogens and represent the most potent antigen presenting cells, having the unique capability to prime naïve T cells. In addition to their role in induction of adaptive immune responses, DC are also able to activate innate cells as γδ T cells; in particular, a reciprocal crosstalk between DC and γδ T cells was demonstrated. However, whether HIV infection may alter DC-Vγ9Vδ2 T cells cross-talk was not yet described. To clarify this issue, we cultured activated Vγ9Vδ2 T cells with HIV infected monocyte derived DC (MoDC). After 5 days we evaluated MoDC phenotype, and Vγ9Vδ2 T cells activation and proliferation. In our model, Vγ9Vδ2 T cells were not able to proliferate in response to HIV-infected MoDC, although an up-regulation of CD69 was observed. Upon phosphoantigens stimulation, Vγ9Vδ2 T cells proliferation and cytokine production were inhibited when cultured with HIV-infected MoDC in a cell-contact dependent way. Moreover, HIV-infected MoDC are not able to up-regulate CD86 molecules when cultured with activated Vγ9Vδ2 T cells, compared with uninfected MoDC. Further, activated Vγ9Vδ2 T cells are not able to induce HLA DR up-regulation and CCR5 down-regulation on HIV-infected MoDC. These data indicate that HIV-infected DC alter the capacity of Vγ9Vδ2 T cells to respond to their antigens, pointing out a new mechanisms of induction of Vγ9Vδ2 T cells anergy carried out by HIV, that could contribute to immune evasion.

  1. HIV Infection of Monocytes-Derived Dendritic Cells Inhibits Vγ9Vδ2 T Cells Functions

    PubMed Central

    Sacchi, Alessandra; Rinaldi, Alessandra; Tumino, Nicola; Casetti, Rita; Agrati, Chiara; Turchi, Federica; Bordoni, Veronica; Cimini, Eleonora; Martini, Federico

    2014-01-01

    DCs act as sentinel cells against incoming pathogens and represent the most potent antigen presenting cells, having the unique capability to prime naïve T cells. In addition to their role in induction of adaptive immune responses, DC are also able to activate innate cells as γδ T cells; in particular, a reciprocal crosstalk between DC and γδ T cells was demonstrated. However, whether HIV infection may alter DC-Vγ9Vδ2 T cells cross-talk was not yet described. To clarify this issue, we cultured activated Vγ9Vδ2 T cells with HIV infected monocyte derived DC (MoDC). After 5 days we evaluated MoDC phenotype, and Vγ9Vδ2 T cells activation and proliferation. In our model, Vγ9Vδ2 T cells were not able to proliferate in response to HIV-infected MoDC, although an up-regulation of CD69 was observed. Upon phosphoantigens stimulation, Vγ9Vδ2 T cells proliferation and cytokine production were inhibited when cultured with HIV-infected MoDC in a cell-contact dependent way. Moreover, HIV-infected MoDC are not able to up-regulate CD86 molecules when cultured with activated Vγ9Vδ2 T cells, compared with uninfected MoDC. Further, activated Vγ9Vδ2 T cells are not able to induce HLA DR up-regulation and CCR5 down-regulation on HIV-infected MoDC. These data indicate that HIV-infected DC alter the capacity of Vγ9Vδ2 T cells to respond to their antigens, pointing out a new mechanisms of induction of Vγ9Vδ2 T cells anergy carried out by HIV, that could contribute to immune evasion. PMID:25340508

  2. Infection of cells by Sindbis virus at low temperature

    SciTech Connect

    Wang Gongbo; Hernandez, Raquel; Weninger, Keith; Brown, Dennis T. . E-mail: dennis_brown@ncsu.edu

    2007-06-05

    Sindbis virus, which belongs to the family Togaviridae genus Alphavirus infects a variety of vertebrate and invertebrate cells. The initial steps of Sindbis virus infection involve attachment, penetration and uncoating. Two different pathways of infection have been proposed for Alphaviruses. One proposed mechanism involves receptor mediated virion endocytosis followed by membrane fusion triggered by endosome acidification. This virus-host membrane fusion model, well established by influenza virus, has been applied to other unrelated membrane-containing viruses including Alphaviruses. The other mechanism proposes direct penetration of the cell plasma membrane by the virus glycoproteins in the absence of membrane fusion. This alternate model is supported by both ultrastructural [Paredes, A.M., Ferreira, D., Horton, M., Saad, A., Tsuruta, H., Johnston, R., Klimstra, W., Ryman, K., Hernandez, R., Chiu, W., Brown, D.T., 2004. Conformational changes in Sindbis virions resulting from exposure to low pH and interactions with cells suggest that cell penetration may occur at the cell surface in the absence of membrane fusion. Virology 324(2), 373-386] and biochemical [Koschinski, A., Wengler, G., Wengler, G., and Repp, H., 2005. Rare earth ions block the ion pores generated by the class II fusion proteins of alphaviruses and allow analysis of the biological functions of these pores. J. Gen. Virol. 86(Pt. 12), 3311-3320] studies. We have examined the ability of Sindbis virus to infect Baby Hamster Kidney (BHK) cells at temperatures which block endocytosis. We have found that under these conditions Sindbis virus infects cells in a temperature- and time-dependent fashion.

  3. Airway epithelial cell response to human metapneumovirus infection

    SciTech Connect

    Bao, X.; Liu, T.; Spetch, L.; Kolli, D.; Garofalo, R.P.; Casola, A.

    2007-11-10

    Human metapneumovirus (hMPV) is a major cause of lower respiratory tract infections (LRTIs) in infants, elderly and immunocompromised patients. In this study, we show that hMPV can infect in a similar manner epithelial cells representative of different tracts of the airways. hMPV-induced expression of chemokines IL-8 and RANTES in primary small alveolar epithelial cells (SAE) and in a human alveolar type II-like epithelial cell line (A549) was similar, suggesting that A549 cells can be used as a model to study lower airway epithelial cell responses to hMPV infection. A549 secreted a variety of CXC and CC chemokines, cytokines and type I interferons, following hMPV infection. hMPV was also a strong inducer of transcription factors belonging to nuclear factor (NF)-{kappa}B, interferon regulatory factors (IRFs) and signal transducers and activators of transcription (STATs) families, which are known to orchestrate the expression of inflammatory and immunomodulatory mediators.

  4. Hepatitis C virus infection of cholangiocarcinoma cell lines.

    PubMed

    Fletcher, Nicola F; Humphreys, Elizabeth; Jennings, Elliott; Osburn, William; Lissauer, Samantha; Wilson, Garrick K; van IJzendoorn, Sven C D; Baumert, Thomas F; Balfe, Peter; Afford, Simon; McKeating, Jane A

    2015-06-01

    Hepatitis C virus (HCV) infects the liver and hepatocytes are the major cell type supporting viral replication. Hepatocytes and cholangiocytes derive from a common hepatic progenitor cell that proliferates during inflammatory conditions, raising the possibility that cholangiocytes may support HCV replication and contribute to the hepatic reservoir. We screened cholangiocytes along with a panel of cholangiocarcinoma-derived cell lines for their ability to support HCV entry and replication. While primary cholangiocytes were refractory to infection and lacked expression of several entry factors, two cholangiocarcinoma lines, CC-LP-1 and Sk-ChA-1, supported efficient HCV entry; furthermore, Sk-ChA-1 cells supported full virus replication. In vivo cholangiocarcinomas expressed all of the essential HCV entry factors; however, cholangiocytes adjacent to the tumour and in normal tissue showed a similar pattern of receptor expression to ex vivo isolated cholangiocytes, lacking SR-BI expression, explaining their inability to support infection. This study provides the first report that HCV can infect cholangiocarcinoma cells and suggests that these heterogeneous tumours may provide a reservoir for HCV replication in vivo.

  5. IMMORTALIZATION OF HUMAN AND RHESUS MACAQUE PRIMARY ANTIGEN-SPECIFIC T CELLS BY RETROVIRALLY TRANSDUCED TELOMERASE REVERSE TRANSCRIPTASE

    PubMed Central

    Barsov, Eugene V.

    2011-01-01

    Human and rhesus macaque primary antigen-specific T cells derived from infected or immunized individuals or animals are a valuable material with which to study cellular immune responses against pathogens and tumors. Antigen-specific T cells can be expanded in vitro but have a finite proliferative life span. After a limited period in culture, primary T cells undergo replicative senescence and stop dividing. This restricts their applicability to short term experiments and complicates their use in adoptive immunotherapy. The proliferative life span of primary human and rhesus macaque T cells can be considerably extended by ectopically expressed human telomerase reverse transcriptase (TERT). Antigen-specific T cells transduced with TERT-expressing retroviral vectors can proliferate and expand in culture for long periods of time while maintaining their primary T cell characteristics including antigen-specific responses. Thus, TERT-immortalized T cells are an important and valuable resource for studying T cell immune responses and, potentially, for adoptive immunotherapy. PMID:22048804

  6. Protective role of Th17 cells in pulmonary infection.

    PubMed

    Rathore, Jitendra Singh; Wang, Yan

    2016-03-18

    Th17 cells are characterized as preferential producer of interleukins including IL-17A, IL-17F, IL-21 and IL-22. Corresponding receptors of these cytokines are expressed on number of cell types found in the mucosa, including epithelial cells and fibroblasts which constitute the prime targets of the Th17-associated cytokines. Binding of IL-17 family members to their corresponding receptors lead to modulation of antimicrobial functions of target cells including alveolar epithelial cells. Stimulated alveolar epithelial cells produce antimicrobial peptides and are involved in granulepoesis, neutrophil recruitment and tissue repair. Mucosal immunity mediated by Th17 cells is protective against numerous pulmonary pathogens including extracellular bacterial and fungal pathogens. This review focuses on the protective role of Th17 cells during pulmonary infection, highlighting subset differentiation, effector cytokines production, followed by study of the binding of these cytokines to their corresponding receptors, the subsequent signaling pathway they engender and their effector role in host defense.

  7. Effect of the purinergic receptor P2X7 on Chlamydia infection in cervical epithelial cells and vaginally infected mice.

    PubMed

    Darville, Toni; Welter-Stahl, Lynn; Cruz, Cristiane; Sater, Ali Abdul; Andrews, Charles W; Ojcius, David M

    2007-09-15

    Ligation of the purinergic receptor, P2X7R, with its agonist ATP has been previously shown to inhibit intracellular infection by chlamydiae and mycobacteria in macrophages. The effect of P2X7R on chlamydial infection had never been investigated in the preferred target cells of chlamydiae, cervical epithelial cells, nor in vaginally infected mice. In this study, we show that treatment of epithelial cells with P2X7R agonists inhibi