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Senescence
Kinds of Senescence Terms modified by Senescence Selected AbstractsOXIDIZED LOW-DENSITY LIPOPROTEIN INDUCES ENDOTHELIAL PROGENITOR CELL SENESCENCE, LEADING TO CELLULAR DYSFUNCTIONCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2004Toshio Imanishi SUMMARY 1.,Recent studies have revealed an association between coronary risk factors and both the number and function of bone marrow-derived endothelial progenitor cells (EPC). We investigated the effect of oxidized low-density lipoprotein (ox-LDL) on the senescence of EPC, leading to cellular dysfunction. 2.,Endothelial progenitor cells were isolated from human peripheral blood and characterized. The exposure of cultured EPC to ox-LDL (10 µg/mL) significantly accelerated the rate of senescence compared with control during 20 days in culture as determined by acidic ,-galactosidase staining. Oxidized LDL-induced EPC senescence was significantly inhibited by pretreatment with either lectin-like ox-LDL receptor-1 (LOX-1) antibody (Ab) or atorvastatin (P < 0.01). 3.,Because cellular senescence is critically influenced by telomerase, which elongates telomeres, we measured telomerase activity using a polymerase chain reaction,ELISA-based assay. Oxidized LDL significantly diminished telomerase activity to approximately 50%, an effect that was significantly abolished by pretreatment with either LOX-1 Ab or atorvastatin (P < 0.01). 4.,We examined whether ox-LDL-induced EPC senescence translates into EPC dysfunction. An MTS assay disclosed an inhibitory effect of ox-LDL on EPC proliferation. In a Matrigel assay, EPC treated with ox-LDL were less likely to participate in network fomation compared with controls. 5.,In conclusions, ox-LDL accelerates the onset of EPC senescence, which may be related to telomerase inactivation. Oxidized LDL-induced EPC senescence leads to the impairment of proliferative capacity and network formation. [source] Senescence of immune defence in Bombus workersECOLOGICAL ENTOMOLOGY, Issue 2 2002Claudie Doums Abstract 1. Senescence in workers of social insects is a particularly intriguing life-history trait as the future fitness of workers relies primarily on age-dependent survival rate. The pattern of senescence of immune defence traits was investigated under laboratory conditions in workers of two bumble bees: Bombus terrestris and B. lucorum. 2. In both species, there was a significant decrease with age in the ability to encapsulate a foreign object (a global measure of the efficiency of immune systems). This pattern of senescence was observed in all colonies in B. terrestris (seven) and B. lucorum (eight) assayed, even though, for the latter, there was some heterogeneity among colonies. 3. In B. terrestris, two other measures of immune defence were taken: the relative percentage of fat body in the abdomen and the concentration of haemocytes (the immune defence cells). The quantity of fat body increased only slightly with age and there was no effect for the concentration of haemocytes. Interestingly, the concentration of haemocytes decreased strongly after an encapsulation response, regardless of the age of workers. 4. The importance of the senescence pattern observed for the immune defence traits is discussed in the context of the social biology of workers. [source] CALORIE RESTRICTION AND AGING: A LIFE-HISTORY ANALYSISEVOLUTION, Issue 3 2000Daryl P. Shanley Abstract., The disposable soma theory suggests that aging occurs because natural selection favors a strategy in which fewer resources are invested in somatic maintenance than are necessary for indefinite survival. However, laboratory rodents on calorie-restricted diets have extended life spans and retarded aging. One hypothesis is that this is an adaptive response involving a shift of resources during short periods of famine away from reproduction and toward increased somatic maintenance. The potential benefit is that the animal gains an increased chance of survival with a reduced intrinsic rate of senescence, thereby permitting reproductive value to be preserved for when the famine is over. We describe a mathematical life-history model of dynamic resource allocation that tests this idea. Senescence is modeled as a change in state that depends on the resources allocated to maintenance. Individuals are assumed to allocate the available resources to maximize the total number of descendants. The model shows that the evolutionary hypothesis is plausible and identifies two factors, both likely to exist, that favor this conclusion. These factors are that survival of juveniles is reduced during periods of famine and that the organism needs to pay an energetic "overhead" before any litter of offspring can be produced. If neither of these conditions holds, there is no evolutionary advantage to be gained from switching extra resources to maintenance. The model provides a basis to evaluate whether the life-extending effects of calorie-restriction might apply in other species, including humans. [source] Reactive Oxygen Species as Mediators of Cellular SenescenceIUBMB LIFE, Issue 4-5 2005Renata Colavitti Abstract Aging has often been viewed as a random process arising from the accumulation of both genetic and epigenetic changes. Increasingly, the notion that aging is a stochastic process is being supplanted by the concept that maximum lifespan of an organism is tightly regulated. This knowledge has led to a growing overlap between classical signal transduction paradigms and the biology of aging. We review certain specific examples where these seemingly disparate disciplines intersect. In particular, we review the concept that intracellular reactive oxygen species function as signalling molecules and that oxidants play a central role as mediators of cellular senescence. IUBMB Life, 57: 277-281, 2005 [source] Fat tissue, aging, and cellular senescenceAGING CELL, Issue 5 2010Tamara Tchkonia Summary Fat tissue, frequently the largest organ in humans, is at the nexus of mechanisms involved in longevity and age-related metabolic dysfunction. Fat distribution and function change dramatically throughout life. Obesity is associated with accelerated onset of diseases common in old age, while fat ablation and certain mutations affecting fat increase life span. Fat cells turn over throughout the life span. Fat cell progenitors, preadipocytes, are abundant, closely related to macrophages, and dysdifferentiate in old age, switching into a pro-inflammatory, tissue-remodeling, senescent-like state. Other mesenchymal progenitors also can acquire a pro-inflammatory, adipocyte-like phenotype with aging. We propose a hypothetical model in which cellular stress and preadipocyte overutilization with aging induce cellular senescence, leading to impaired adipogenesis, failure to sequester lipotoxic fatty acids, inflammatory cytokine and chemokine generation, and innate and adaptive immune response activation. These pro-inflammatory processes may amplify each other and have systemic consequences. This model is consistent with recent concepts about cellular senescence as a stress-responsive, adaptive phenotype that develops through multiple stages, including major metabolic and secretory readjustments, which can spread from cell to cell and can occur at any point during life. Senescence could be an alternative cell fate that develops in response to injury or metabolic dysfunction and might occur in nondividing as well as dividing cells. Consistent with this, a senescent-like state can develop in preadipocytes and fat cells from young obese individuals. Senescent, pro-inflammatory cells in fat could have profound clinical consequences because of the large size of the fat organ and its central metabolic role. [source] Selection and Use of Postharvest Technologies as a Component of the Food ChainJOURNAL OF FOOD SCIENCE, Issue 2 2004MALCOLM C. BOURNE ABSTRACT: Postharvest technologies refer to the stabilization and storage of unprocessed or minimally processed foods from the time of harvest until final preparation for human consumption. There is a special emphasis on seasonal crops, and simple, labor-intensive, capital-sparing technologies suitable for developing countries where food spoilage rates are high and malnutrition is prevalent. The first step is to determine the major spoilage vectors for each type of food and then identify a technology that will control that vector. For cereal grains the major spoilage vectors are mold, insects, rodents, and other vertebrate pests. Mold is controlled by prompt and adequate drying to a water activity below 0.7. Insects are controlled by good housekeeping, and use of insecticides and fumigants. Rodents are controlled by baits, traps, fumigants, and rodent-proof storage structures. For fruits, vegetables, roots, and tubers the main spoilage vectors are bruising, rotting, senescence, and wilting. Bruising is avoided by careful handling and use of shock-resistant packaging. Rotting is controlled by good housekeeping, gentle handling to avoid breaking the skin, cool storage, and use of preservatives. Senescence is retarded by cold storage or controlled-atmosphere storage. Wilting is controlled by high humidity and cold storage. Growth of microbes is the major spoilage of fish and other foods of animal origin. This is controlled by refrigerated or frozen storage, drying, freezing, or canning. Most spoilage vectors accelerate as the temperature and humidity increase; this makes it more difficult to control spoilage in tropical than in temperate regions. [source] PPF1 May Suppress Plant Senescence via Activating TFL1 in Transgenic Arabidopsis PlantsJOURNAL OF INTEGRATIVE PLANT BIOLOGY, Issue 4 2008Da-Yong Wang Abstract Senescence, a sequence of biochemical and physiological events, constitutes the final stage of development in higher plants and is modulated by a variety of environmental factors and internal factors. PPF1 possesses an important biological function in plant development by controlling the Ca2+ storage capacity within chloroplasts. Here we show that the expression of PPF1 might play a pivotal role in negatively regulating plant senescence as revealed by the regulation of overexpression and suppression of PPF1 on plant development. Moreover, TFL1, a key regulator in the floral repression pathway, was screened out as one of the downstream targets for PPF1 in the senescence-signaling pathway. Investigation of the senescence-related phenotypes in PPF1(,) tfl1-1 and PPF1(+) tfl1-1 double mutants confirmed and further highlighted the relation of PPF1 with TFL1 in transgenic plants. The activation of TFL1 expression by PPF1 defines an important pathway possibly essential for the negative regulation of plant senescence in transgenic Arabidopsis. [source] Endopeptidase Isoenzyme Characteristics in Cucumis sativus Leaves During Dark-induced SenescenceJOURNAL OF INTEGRATIVE PLANT BIOLOGY, Issue 4 2007Peng Zhang Abstract The changes and characteristics of endopeptidase (EP) isoenzymes in cucumber (Cucumis sativus L.) leaves during dark-induced senescence were investigated by activity staining after gradient-polyacrylamide gel electrophoresis (G-PAGE) containing co-polymerized gelatin as substrate. The results showed that both the chlorophyll and the protein contents of leaves were decreased, and the protein degradation was correlated with the increase of proteolytic activity during the course of leaf senescence. Meanwhile, nine cucumber endopeptidases isoenzymes (CEP) with 140, 120, 106, 94, 76, 55, 46, 39 and 35 kDa molecular weights were detected. Four of these, CEP2, 3, 4 and CEP9 appeared all the time, but the changes of the activity were different during incubation. Another four CEPs (CEP5, 6, 7 and CEP8) whose activities increased with dark-induced time were only detected in senescent leaves. Furthermore, the biochemical properties of these nine CEP were also characterized. All the CEPs had high activities from 35 °C to 45 °C, and the optimum temperature was found to be 40 °C. However, the activities of CEPs were not detected below 25 °C or over 60 °C. The activity bands appeared at a wide range of pH from 5.0 to 9.0, but the optimum pH was found at 7.0. No CEPs were detected at pH 4 or pH 10. By inhibition analysis we concluded that CEP2, 3, 4 and CEP9 were serine endopeptidases and CEP6 was a kind of cysteine protease. It is suggested that serine endopeptidases might play a major role in cucumber leaf senescence, and for the first time, six senescence-related endopeptidases (CEP1, 5, 6, 7, 8 and 9) were found in cucumber leaves. [source] Differential and Age-Dependent Effects of Maternal Deprivation on the Hypothalamic-Pituitary-Adrenal Axis of Brown Norway Rats from Youth to SenescenceJOURNAL OF NEUROENDOCRINOLOGY, Issue 7 2001J. O. Workel Abstract In this study, the hypothesis was tested that infants deprived from maternal care show persistent changes in hypothalamic-pituitary-adrenal activity. For this purpose, we studied the effect of maternal deprivation in one cohort of the healthy ageing Brown Norway rat strain showing still more than 80% survival rate at 32 months of age. Three-day-old male Brown Norway rats were either maternally deprived for 24 h or remained with the dam. In 3, 12 and 30,32 months (young, adult, senescent) deprived rats and their nondeprived littermates (controls), we determined basal resting and stress-induced plasma adrenocorticotropic hormone (ACTH) and corticosterone as well as corticotropin releasing hormone (CRH) mRNA expression in the paraventricular nucleus (PVN) of the hypothalamus. Mineralocorticoid (MR) and glucocorticoid receptors (GR) in hippocampus and PVN were also assessed using in vitro cytosol binding and in situ hybridization. The effect of ageing per se showed that in the control nondeprived Brown Norway rats, basal corticosterone and ACTH concentrations did not change during life. However, with age, the corticosterone response to novelty stress became progressively attenuated, but prolonged, while there was an age-related increase in the ACTH response. CRH mRNA expression in PVN decreased with age. Hippocampal MR binding and MR mRNA expression in the dentate gyrus were reduced at senescence, as were the GR binding capacities in hippocampus and hypothalamus. Maternal deprivation did not affect survival rate, body weight, nor adrenal weight of the ageing Brown Norway rats. Basal corticosterone and ACTH levels were not affected by deprivation, except for a rise in basal corticosterone concentrations at 3 months. At this age, the corticosterone output in response to novelty was attenuated in the deprived rats. In contrast, a striking surge in novelty stress-induced corticosterone output occurred at midlife while, at senescence, the corticosterone and ACTH responses were attenuated again in the deprived animals, particularly after the more severe restraint stressor. CRH mRNA expression was reduced only during adulthood in the deprived animals. After maternal deprivation, the MR mRNA in dentate gyrus showed a transient midlife rise. GR binding in hypothalamus and hippocampus GR binding was reduced in young rats while, in the senescent deprived animals, a reduced GRmRNA expression was observed in PVN and hippocampal CA1. In conclusion, in the Brown Norway rat, ageing causes a progressive decline in corticosterone output after stress, which is paralleled at senescence by decreased MR and GR mRNA expression in hippocampus and hypothalamus. The long-term effects of maternal deprivation become manifest differently at different ages and depend on test conditions. The deprivation effect culminates in a midlife corticosterone surge and results at senescence in a strongly reduced corticosterone output. [source] Mechanical role of the leaf sheath in rattansNEW PHYTOLOGIST, Issue 3 2008S. Isnard Summary ,,Leaf sheaths of rattans are long, tubular and persistent and unlike many self-supporting palms, extend far from the apex of the plant. The mechanical role of the leaf sheath was investigated in eight rattan species of the subfamily Calamoideae. The main objective was to analyse its influence on the mechanical architecture and contribution to the climbing habit. ,,Bending mechanical properties were measured along climbing axes before and after removal of leaf sheaths. Results were related to stem and leaf sheath geometry and mechanical properties. ,,Contribution of the leaf sheath to axial flexural rigidity was high (c. 90%) in the early stages of growth and towards the apex of older climbing axes for all climbing palms tested. Senescence and loss of the leaf sheath strongly influenced axial stiffness. A nonclimbing species, Calamus erectus, showed a different mechanical architecture. ,,Although lacking secondary growth, palms have been able to develop successful climbers with a mechanical architecture broadly analogous to, although developmentally different from, dicotyledonous lianas. The role of the leaf sheath in modulating mechanical properties during ontogeny ought not to be neglected in studies on monocotyledons, as it possibly contributed significantly to the ways in which different growth forms have evolved in the group. [source] Why men have shorter lives than women: Effects of resource availability, infectious disease, and senescenceAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 3 2009A.P. Møller Senescence arises from age-specific deterioration of the soma as a consequence of optimization of life history, and such effects of senescence should appear when comparing species that differ in intensity of sexual selection, as well as when comparing, within a species, the two sexes that often differ in intensity of sexual selection. However, any extrinsic cause of mortality that reduces life expectancy will reduce the possibility of detecting sex-specific differences in senescence. We investigated geographical variation in human sex differences in longevity across 121 countries to test whether differences in sexual competition for limiting resources, reflecting intensity of sexual selection, affected sex differences in longevity. Men on average lived 5 years shorter than women. High rates of childhood morbidity and mortality reduced the sex difference in longevity, while increased overall longevity increased the sex difference in longevity. Increased resource availability estimated from gross domestic product per capita reduced the sex difference in longevity, accounting for 10% of the variance, while there was no additional effect of income inequality as reflected by the Gini coefficient. In a separate analysis of sex differences in longevity among the states of the US, there was a strong effect of the Gini coefficient on sex difference in longevity, with the negative effect on male longevity being stronger than that on female longevity. In contrast, there was only a marginal effect of average household income. Thus, there was evidence of increased competition for resources contributing to increased sex differences in longevity within a single nation. Am. J. Hum. Biol., 2009. © 2009 Wiley-Liss, Inc. [source] Senescence and hyperspectral reflectance of cotton leaves exposed to ultraviolet-B radiation and carbon dioxidePHYSIOLOGIA PLANTARUM, Issue 2 2004Vijaya Gopal Kakani The objectives of this study were to determine the effects of UV-B radiation and atmospheric carbon dioxide concentrations ([CO2]) on leaf senescence of cotton by measuring leaf photosynthesis and chlorophyll content and to identify changes in leaf hyperspectral reflectance occurring due to senescence and UV-B radiation. Plants were grown in controlled-environment growth chambers at two [CO2] (360 and 720 µmol mol,1) and three levels of UV-B radiation (0, 7.7 and 15.1 kJ m,2 day,1). Photosynthesis, chlorophyll, carotenoids and phenolic compounds along with leaf hyperspectral reflectance were measured on three leaves aged 12, 21 and 30 days in each of the treatments. No interaction was detected between [CO2] and UV-B for any of the measured parameters. Significant interactions were observed between UV-B and leaf age for photosynthesis and stomatal conductance. Elevated [CO2] enhanced leaf photosynthesis by 32%. On exposure to 0, 7.7 and 15.1 kJ of UV-B, the photosynthetic rates of 30-day-old leaves compared with 12-day-old leaves were reduced by 52, 76 and 86%, respectively. Chlorophyll pigments were not affected by leaf age at UV-B radiation of 0 and 7.7 kJ, but UV-B of 15.1 kJ reduced the chlorophylls by 20, 60 and 80% in 12, 21 and 30-day-old leaves, respectively. The hyperspectral reflectance between 726 and 1142 nm showed interaction for UV-B radiation and leaf age. In cotton, leaf photosynthesis can be used as an indicator of leaf senescence, as it is more sensitive than photosynthetic pigments on exposure to UV-B radiation. This study revealed that, cotton leaves senesced early on exposure to UV-B radiation as indicated by leaf photosynthesis, and leaf hyperspectral reflectance can be used to detect changes caused by UV-B and leaf ageing. [source] Senescence and ageing in plants and cyanobacteriaPHYSIOLOGIA PLANTARUM, Issue 1 2003Erwin Beck This article is an introductory synopsis of the papers on senescence and ageing, presented in this issue of Physiologia Plantarum. The major results of the individual articles have been put into contiguity and are briefly reviewed in the light of the literature. Genetically controlled processes and stochastic reactions closely interact in the course of ageing of an individual. This holds for the cells and tissues of green plants as well as for the strongly specialized heterocysts of filamentous cyanobacteria. [source] Antioxidant and Pigment Composition during Autumnal Leaf Senescence in Woody Deciduous Species Differing in their Ecological TraitsPLANT BIOLOGY, Issue 5 2003J. I. García-Plazaola Abstract: Photoprotection mechanisms have been studied during autumnal senescence in sun and shade leaves of woody plants with different ecological characteristics and senescence patterns. Three of them belonging to the same family, Betulaceae: the shade-intolerant and early successional species (Betula alba L.), the shade-tolerant and late successional species (Corylus avellana L.), and an N-fixing tree with low N resorption efficiency (Alnus glutinosa L.). The other two species: a shade-intolerant (Populus tremula L.) and a shade-tolerant (Cornus sanguinea L.), were chosen because of their ability to accumulate anthocyanins during autumnal leaf senescence. The study of plants with different ecological strategies allowed us to establish general trends in photoprotection mechanisms during autumnal senescence, when nutrient remobilisation occurs, but also during whole leaf ontogeny. We have not found a clear relationship between shade tolerance and the level of photoprotection; the main difference between both groups of species being the presence of ,-carotene in shade leaves of shade-tolerant species. Preceding autumn, nitrogen resorption started in mid-summer and occurred in parallel with a slight and continuous ascorbate, chlorophyll and carotenoid degradation. However, the ascorbate pool remained highly reduced and lipid oxidation did not increase at this time. Contrasting with ascorbate, ,-tocopherol accumulated progressively in all species. Only during the last stages of senescence was chlorophyll preferentially degraded with respect to carotenoids, leading to the yellowing of leaves, except in A. glutinosa in which a large retention of chlorophyll and N took place. Senescing leaves were characterised, except in C. sanguinea, by a relative increase in the proportion of de-epoxidised xanthophylls: zeaxanthin, antheraxanthin and lutein. The light-induced accumulation of anthocyanins in C. sanguinea could play an additional protective role, compensating for the low retention of de-epoxidised xanthophylls. These different strategies among deciduous species are consistent with a role for photoprotective compounds in enhancing nitrogen remobilization and storage for the next growing season. [source] The molecular analysis of leaf senescence , a genomics approachPLANT BIOTECHNOLOGY JOURNAL, Issue 1 2003Vicky Buchanan-Wollaston Summary Senescence in green plants is a complex and highly regulated process that occurs as part of plant development or can be prematurely induced by stress. In the last decade, the main focus of research has been on the identification of senescence mutants, as well as on genes that show enhanced expression during senescence. Analysis of these is beginning to expand our understanding of the processes by which senescence functions. Recent rapid advances in genomics resources, especially for the model plant species Arabidopsis, are providing scientists with a dazzling array of tools for the identification and functional analysis of the genes and pathways involved in senescence. In this review, we present the current understanding of the mechanisms by which plants control senescence and the processes that are involved. [source] The different fates of mitochondria and chloroplasts during dark-induced senescence in Arabidopsis leavesPLANT CELL & ENVIRONMENT, Issue 12 2007OLIVIER KEECH ABSTRACT Senescence is an active process allowing the reallocation of valuable nutrients from the senescing organ towards storage and/or growing tissues. Using Arabidopsis thaliana leaves from both whole darkened plants (DPs) and individually darkened leaves (IDLs), we investigated the fate of mitochondria and chloroplasts during dark-induced leaf senescence. Combining in vivo visualization of fates of the two organelles by three-dimensional reconstructions of abaxial parts of leaves with functional measurements of photosynthesis and respiration, we showed that the two experimental systems displayed major differences during 6 d of dark treatment. In whole DPs, organelles were largely retained in both epidermal and mesophyll cells. However, while the photosynthetic capacity was maintained, the capacity of mitochondrial respiration decreased. In contrast, IDLs showed a rapid decline in photosynthetic capacity while maintaining a high capacity for mitochondrial respiration throughout the treatment. In addition, we noticed an unequal degradation of organelles in the different cell types of the senescing leaf. From these data, we suggest that metabolism in leaves of the whole DPs enters a ,stand-by mode' to preserve the photosynthetic machinery for as long as possible. However, in IDLs, mitochondria actively provide energy and carbon skeletons for the degradation of cell constituents, facilitating the retrieval of nutrients. Finally, the heterogeneity of the degradation processes involved during senescence is discussed with regard to the fate of mitochondria and chloroplasts in the different cell types. [source] Senescence and serration: a new twist to an old taleTHE JOURNAL OF PATHOLOGY, Issue 2 2006P Minoo Abstract Interest in the role of oncogene-induced senescence in tumorigenesis is mounting. Raf-associated senescence in cutaneous nevi has been advanced as an example of this process occurring in the context of a human tumour. In this model, conversion from a senescent nevus to a malignant melanoma is accompanied by loss of expression of p16. Serrated polyps of the colorectum may provide a further example of oncogene-induced senescence. BRAF and KRAS mutation may initiate different pathways of senescence-associated serrated neoplasia in the colorectum, the former linked to CpG island methylator phenotype (CIMP)-high (CIMP1) and microsatellite instability (MSI)-high status and the latter with CIMP-low (CIMP2) and MSI-low status. The role of methylation in both Raf- and Ras-associated pathways is to drive tumorigenesis by silencing pro-apoptotic and cell cycle inhibitory genes. Both pathways are associated with mutation of Ras-induced senescence 1 (RIS1), but the biological role of RIS1 requires further elucidation. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Effects of Donor Age and Cell Senescence on Kidney Allograft SurvivalAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2009A. Melk The biological processes responsible for somatic cell senescence contribute to organ aging and progression of chronic diseases, and this may contribute to kidney transplant outcomes. We examined the effect of pre-existing donor aging on the performance of kidney transplants, comparing mouse kidney isografts and allografts from old versus young donors. Before transplantation, old kidneys were histologically normal, but displayed an increased expression of senescence marker p16INK4a. Old allografts at day 7 showed a more rapid emergence of epithelial changes and a further increase in the expression of p16INK4a. Similar but much milder changes occurred in old isografts. These changes were absent in young allografts at day 7, but emerged by day 21. The expression of p16INK4a remained low in young kidney allografts at day 7, but increased with severe rejection at day 21. Isografts from young donors showed no epithelial changes and no increase in p16INK4a. The measurements of the alloimmune response,infiltrate, cytology, expression of perforin, granzyme B, IFN-, and MHC,were not increased in old allografts. Thus, old donor kidneys display abnormal parenchymal susceptibility to transplant stresses and enhanced induction of senescence marker p16INK4a, but were not more immunogenic. These data are compatible with a key role of somatic cell senescence mechanisms in kidney transplant outcomes by contributing to donor aging, being accelerated by transplant stresses, and imposing limits on the capacity of the tissue to proliferate. [source] Airway Epithelial Cell Senescence in the Lung AllograftAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2008S. M. Parker Chronic lung allograft dysfunction, manifesting as bronchiolitis obliterans syndrome (BOS), is characterized by airway epithelial injury, impaired epithelial regeneration and subsequent airway remodeling. Increased cellular senescence has been reported in renal and liver allografts affected by chronic allograft dysfunction but the significance of cellular senescence in the airway epithelium of the transplanted lung is unknown. Thirty-four lung transplant recipients, 20 with stable graft function and 14 with BOS, underwent transbronchial lung biopsy and histochemical studies for senescence markers in small airways. Compared to nontransplant control lung tissue (n = 9), lung allografts demonstrate significantly increased airway epithelial staining for senescence-associated beta galactosidase (SA ,-gal) (p = 0.0215), p16ink4a (p = 0.0002) and p21waf1/cip (p = 0.0138) but there was no difference in expression of these markers between stable and BOS affected recipients (p > 0.05). This preliminary cross-sectional study demonstrates that cellular senescence occurs with increased frequency in the airway epithelium of the lung allograft but does not establish any association between airway epithelial senescence and BOS. A prospective longitudinal study is required to better address any potential causal association between airway epithelial senescence in stable allograft recipients and the subsequent development of BOS. [source] Impairment of endothelial cell differentiation from bone marrow,derived mesenchymal stem cells: New insight into the pathogenesis of systemic sclerosisARTHRITIS & RHEUMATISM, Issue 6 2007P. Cipriani Objective Systemic sclerosis (SSc) is a disorder characterized by vascular damage and fibrosis of the skin and internal organs. Despite marked tissue hypoxia, there is no evidence of compensatory angiogenesis. The ability of mesenchymal stem cells (MSCs) to differentiate into endothelial cells was recently demonstrated. The aim of this study was to determine whether impaired differentiation of MSCs into endothelial cells in SSc might contribute to disease pathogenesis by decreasing endothelial repair. Methods MSCs obtained from 7 SSc patients and 15 healthy controls were characterized. The number of colony-forming unit,fibroblastoid colonies was determined. After culture in endothelial-specific medium, the endothelial-like MSC (EL-MSC) phenotype was assessed according to the surface expression of vascular endothelial growth factor receptors (VEGFRs). Senescence, chemoinvasion, and capillary morphogenesis studies were also performed. Results MSCs from SSc patients displayed the same phenotype and clonogenic activity as those from controls. In SSc MSCs, a decreased percentage of VEGFR-2+, CXCR4+, VEGFR-2+/CXCR4+ cells and early senescence was detected. After culturing, SSc EL-MSCs showed increased expression of VEGFR-1, VEGFR-2, and CXCR4, did not express CD31 or annexin V, and showed significantly decreased migration after specific stimuli. Moreover, the addition of VEGF and stromal cell,derived factor 1 to cultured SSc EL-MSCs increased their angiogenic potential less than that in controls. Conclusion Our data strongly suggest that endothelial repair may be affected in SSc. The possibility that endothelial progenitor cells could be used to increase vessel growth in chronic ischemic tissues may open up new avenues in the treatment of vascular damage caused by SSc. [source] Omega-3 polyunsaturated fatty acids ameliorate the severity of ileitis in the senescence accelerated mice (SAM)P1/Yit mice modelCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2009H. Matsunaga Summary Clinical studies using omega-3 polyunsaturated fatty acids (,3-PUFA) to Crohn's disease (CD) are conflicting. Beneficial effects of dietary ,3-PUFA intake in various experimental inflammatory bowel disease (IBD) models have been reported. However, animal models of large intestinal inflammation have been used in all previous studies, and the effect of ,3 fat in an animal model of small intestinal inflammation has not been reported. We hypothesized that the effects of ,3 fat are different between large and small intestine. The aim of this study was to determine whether the direct effect of ,3 fat is beneficial for small intestinal inflammation. Senescence accelerated mice (SAM)P1/Yit mice showed remarkable inflammation of the terminal ileum spontaneously. The numbers of F4/80-positive monocyte,macrophage cells as well as ,7-integrin-positive lymphocytes in the intestinal mucosa were increased significantly compared with those in the control mice (AKR-J mice). The area of mucosal addressin cell adhesion molecule-1 (MAdCAM-1)-positive vessels was also increased. The degree of expression levels of monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6 and interferon (IFN)-, mRNA were increased significantly compared with those in the control mice. The feeding of two different kinds of ,3 fat (fish-oil-rich and perilla-oil-rich diets) for 16 weeks to SAMP1/Yit mice ameliorated inflammation of the terminal ileum significantly. In both the ,3-fat-rich diet groups, enhanced infiltration of F4/80-positive monocytes/macrophages in intestinal mucosa of SAMP1/Yit mice cells and the increased levels of MCP-1, IL-6 and IFN-, mRNA expression were ameliorated significantly compared with those in the control diet group. The results suggest that ,3 fat is beneficial for small intestinal inflammation by inhibition of monocyte recruitment to inflamed intestinal mucosa. [source] How best to halt and/or revert UV-induced skin ageing: strategies, facts and fictionEXPERIMENTAL DERMATOLOGY, Issue 3 2008Lübeck Ralf Paus Besides obvious market pressures, increasing insight into the mechanistic overlap between UV-induced skin cancer and UV-induced skin ageing has contributed to this development. Also, as strategies that work to antagonize intrinsic skin ageing/senescence may also be exploited against photoageing (and vice versa!), it has become an important skin research challenge to dissect both the differences and the overlap mechanisms between these interwined, yet distinct phenomena. Finally, the current surge in putative ,antiageing' products, devices, and strategies , too many of which boldly promise to fight and/or repair the perils that come along with a lifetime spent in the sun in the absence of convincing evidence of efficacy , makes it particularly pertinent to critically review the available evidence to support often made antiageing claims. The current CONTROVERSIES feature, therefore, aimed to provide both guidance through, and critical voices in, the antiageing circus. Here, a panel of experts defines relevant key problems, points the uninaugurated to intriguing aspects of photoageing that one may not have considered before, highlights promising strategies for how best to halt and/or revert it, and spiritedly debates some controversially discussed approaches. [source] Origin and evolution of the protein-repairing enzymes methionine sulphoxide reductasesBIOLOGICAL REVIEWS, Issue 3 2008Xing-Hai Zhang Abstract The majority of extant life forms thrive in an O2 -rich environment, which unavoidably induces the production of reactive oxygen species (ROS) during cellular activities. ROS readily oxidize methionine (Met) residues in proteins/peptides to form methionine sulphoxide [Met(O)] that can lead to impaired protein function. Two methionine sulphoxide reductases, MsrA and MsrB, catalyse the reduction of the S and R epimers, respectively, of Met(O) in proteins to Met. The Msr system has two known functions in protecting cells against oxidative damage. The first is to repair proteins that have lost activity due to Met oxidation and the second is to function as part of a scavenger system to remove ROS through the reversible oxidation/reduction of Met residues in proteins. Bacterial, plant and animal cells lacking MsrA are known to be more sensitive to oxidative stress. The Msr system is considered an important cellular defence mechanism to protect against oxidative stress and may be involved in ageing/senescence. MsrA is present in all known eukaryotes and eubacteria and a majority of archaea, reflecting its essential role in cellular life. MsrB is found in all eukaryotes and the majority of eubacteria and archaea but is absent in some eubacteria and archaea, which may imply a less important role of MsrB compared to MsrA. MsrA and MsrB share no sequence or structure homology, and therefore probably emerged as a result of independent evolutionary events. The fact that some archaea lack msr genes raises the question of how these archaea cope with oxidative damage to proteins and consequently of the significance of msr evolution in oxic eukaryotes dealing with oxidative stress. Our best hypothesis is that the presence of ROS-destroying enzymes such as peroxiredoxins and a lower dissolved O2 concentration in those msr -lacking organisms grown at high temperatures might account for the successful survival of these organisms under oxidative stress. [source] Regulation of skeletal muscle mitochondrial function: genes to proteinsACTA PHYSIOLOGICA, Issue 4 2010I. R. Lanza Abstract The impact of ageing on mitochondrial function and the deterministic role of mitochondria on senescence continue to be topics of vigorous debate. Many studies report that skeletal muscle mitochondrial content and function are reduced with ageing and metabolic diseases associated with insulin resistance. However, an accumulating body of literature suggests that physical inactivity typical of ageing may be a more important determinant of mitochondrial function than chronological age, per se. Reports of age-related declines in mitochondrial function have spawned a vast body of literature devoted to understanding the underlying mechanisms. These mechanisms include decreased abundance of mtDNA, reduced mRNA levels, as well as decreased synthesis and expression of mitochondrial proteins, ultimately resulting in decreased function of the whole organelle. Effective therapies to prevent, reverse or delay the onset of the aforementioned mitochondrial changes, regardless of their inevitability or precise underlying causes, require an intimate understanding of the processes that regulate mitochondrial biogenesis, which necessitates the coordinated regulation of nuclear and mitochondrial genomes. Herein we review the current thinking on regulation of mitochondrial biogenesis by transcription factors and transcriptional co-activators and the role of hormones and exercise in initiating this process. We review how exercise may help preserve mitochondrial content and functionality across the lifespan, and how physical inactivity is emerging as a major determinant of many age-associated changes at the level of the mitochondrion. We also review evidence that some mitochondrial changes with ageing are independent of exercise or physical activity and appear to be inevitable consequences of old age. [source] Reactive oxygen and nitrogen species in normal physiological processesACTA PHYSIOLOGICA, Issue 1 2010J. Pourova Abstract Reactive oxygen species (ROS) and reactive nitrogen species have generally been considered as being highly reactive and cytotoxic molecules. Besides their noxious effects, ROS participate in physiological processes in a carefully regulated manner. By way of example, microbicidal ROS are produced in professional phagocytes, ROS function as short-lived messengers having a role in signal transduction and, among other processes, participate in the synthesis of the iodothyronine hormones, reproduction, apoptosis and necrosis. Because of their ability to mediate a crosstalk between key molecules, their role might be dual (at least in some cases). The levels of ROS increase from a certain age, being associated with various diseases typical of senescence. The aim of this review is to summarize the recent findings on the physiological role of ROS. Other issues addressed are an increase in ROS levels during ageing, and the possibility of the physiological nature of this process. [source] Supplemental feeding reduces natural selection in juvenile red deerECOGRAPHY, Issue 3 2002Karoline T. Schmidt In red deer, variation in winter and spring weather conditions encountered by the mothers during pregnancy and during the first year of life are a main determinant for individual life-history as well as population dynamics. We tested the hypothesis that supplementary feeding which provides constant food supply throughout winter removes the selective pressure of winter harshness on nutrition-mediated phenotypic traits. We analysed cohort variation in body weight in calves in October, before their first winter, and in yearlings in June, after their first winter, in a food-supplemented population in the Eastern Austrian Alps. Over eleven years, cohort body weight varied between years in calves and yearlings. Contrary to studies on non-supplemented red deer populations we found neither short- nor long-term effects of winter weather on body weight. In calves, autumn body weight was negatively related to April,May and June temperatures, suggesting that cool weather during the main growth period retarded plant senescence and thereby prolonged the period of high protein content of summer forage. In yearlings, variation in June body weight, shortly after the end of the feeding period, was lower after a wet April,May, suggesting a negative effect of a prolonged period of supplemental feeding. For both calves and yearlings intra-cohort variation in body weight was higher, inter-cohort variation was lower as compared to non-supplemented red deer, suggesting that in their first year of life supplemented red deer are under reduced natural selection pressure. [source] Senescence of immune defence in Bombus workersECOLOGICAL ENTOMOLOGY, Issue 2 2002Claudie Doums Abstract 1. Senescence in workers of social insects is a particularly intriguing life-history trait as the future fitness of workers relies primarily on age-dependent survival rate. The pattern of senescence of immune defence traits was investigated under laboratory conditions in workers of two bumble bees: Bombus terrestris and B. lucorum. 2. In both species, there was a significant decrease with age in the ability to encapsulate a foreign object (a global measure of the efficiency of immune systems). This pattern of senescence was observed in all colonies in B. terrestris (seven) and B. lucorum (eight) assayed, even though, for the latter, there was some heterogeneity among colonies. 3. In B. terrestris, two other measures of immune defence were taken: the relative percentage of fat body in the abdomen and the concentration of haemocytes (the immune defence cells). The quantity of fat body increased only slightly with age and there was no effect for the concentration of haemocytes. Interestingly, the concentration of haemocytes decreased strongly after an encapsulation response, regardless of the age of workers. 4. The importance of the senescence pattern observed for the immune defence traits is discussed in the context of the social biology of workers. [source] Lifespan is unrelated to investment in reproduction in populations of mammals and birds in captivityECOLOGY LETTERS, Issue 10 2007Robert E. Ricklefs Abstract We examined the relationship between number of offspring produced to a certain age and subsequent longevity in captive zoo populations of 18 species of mammal and 12 species of bird. The age cut-offs in each analysis were set to include 50%, 75% and 90% of the offspring produced in each of the population samples. Only one of 68 regressions was significant, and its slope was positive. In addition, we examined the relationship between age at first reproduction up to a certain age and longevity after that age, generally 5 years (3,8), among 17 species of mammal and 12 species of bird. Only one of these regressions had a significantly positive slope, indicating that early reproduction rarely reduces lifespan. Overall, we found no evidence that producing offspring in a zoo environment influences the age at death. Thus, although trade-offs might apply in natural populations under resource limitation, neither pregnancy, growth of the foetus and lactation in mammals, nor egg production in birds, reduces lifespan in the absence of such stress. If genetically based or other intrinsic antagonistic pleiotropy underlies the evolution of senescence, it was not evident in our analyses. [source] The senescence of Daphnia from risky and safe habitatsECOLOGY LETTERS, Issue 2 2001Dudycha Evaluating life history in an ecological context is critical for understanding the diversity of life histories found in nature. Lifespan and senescence differ greatly among taxa, but their ecological context is not well known. Life history theory proposes that senescence is ultimately caused by a reduction of the effectiveness of natural selection as organisms age. A key prediction is that different levels of extrinsic mortality risk lead to the evolution of different senescence patterns. I quantified both mortality risk and investment in late-life fitness of Daphnia pulex-pulicaria, a common freshwater zooplankter. I found that Daphnia from high-risk pond habitats invest relatively little in late-life fitness, whereas those from low-risk lake habitats invest relatively more in late-life fitness. This suggests that ecological approaches can be useful for understanding senescence variation. [source] Maternal size and age affect offspring sex ratio in the solitary egg parasitoid Anaphes nitensENTOMOLOGIA EXPERIMENTALIS ET APPLICATA, Issue 1 2007Serena Santolamazza-Carbone Abstract In this study, the effects of maternal age, diet, and size on offspring sex ratio were investigated for the solitary egg parasitoid, Anaphes nitens Girault (Hymenoptera: Mymaridae), both outdoors, during the winter, and inside a climatic chamber under favourable constant conditions. During the winter of 2005,2006, each of seven groups containing 40 1-day-old females was mated and randomly distributed among two treatments: (treatment 1) a droplet of undiluted honey ad libitum + one fresh egg capsule of the snout beetle Gonipterus scutellatus Gyllenhal (Coleoptera: Curculionidae) as host; (treatment 2) drops of water + one fresh egg capsule of G. scutellatus. We recorded the lifetime fecundity, the daily sex allocation, and the lifetime offspring sex ratio to study the existence of a relationship with maternal characteristics. Moreover, we assessed the effect of location (outdoors vs. indoors) and group (groups are representative of early, mid, and late winter) on sex ratio. The most important factor that biased the sex ratio was maternal body size: larger females of both treatments produced more female offspring. As females of A. nitens could gain more advantage than males from body size, larger mothers have a higher fitness return if they produce more daughters. The effect of the treatment was significant: starved females produced more females. Location and group were not significant. Fecundity and sex ratio were age dependent. Old mothers that received honey (treatment 1) had fewer offspring and a more male-biased offspring sex ratio, probably due to reproductive senescence and sperm depletion. Starved females (treatment 2) experienced reproductive decline earlier, perhaps because they invested more energy in maintenance rather than in reproduction. [source] | |||||||||||||||||||||||||||||||||||||||||||