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Human Longevity (human + longevity)
Selected AbstractsAssociation of longevity with IL-10 ,1082 G/A and TNF-,,308 G/A polymorphismsINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 4 2010O. F. Khabour Summary Cytokines are crucial for the regulation of inflammation development in humans. Many studies have shown that variations in cytokine genes might play a role in determining human longevity. This study examined the changes in the gene pool relevant to the ,308 G/A polymorphism in the promoter region of the proinflammatory cytokine tumour necrosis factor (TNF)-, gene and the ,1082 G/A polymorphism in the promoter region of anti-inflammatory cytokine interleukin (IL)-10 gene with aging and survival selection occurs in the Jordanian population. IL-10 ,1028 G/A and TNF-,,308 G/A were genotyped in 119 randomly selected elderly subjects (41 women and 78 men) with a mean age of 90.2 years and young control subjects of 118 (46 women and 72 men) with a mean age of 31.9 years. No significant differences were found in the genotype and allele frequencies of TNF-, gene variants between the two groups (P > 0.05) while the IL-10 genotype and allele frequencies were significantly associated with longevity in men (P < 0.05) but not in women (P < 0.05). Thus, IL-10 ,1028 G/A polymorphism seems to play a role in the pathway to longevity in Jordanian men. [source] HRAS1 and LASS1 with APOE are associated with human longevity and healthy agingAGING CELL, Issue 5 2010S. Michal Jazwinski Summary The search for longevity-determining genes in human has largely neglected the operation of genetic interactions. We have identified a novel combination of common variants of three genes that has a marked association with human lifespan and healthy aging. Subjects were recruited and stratified according to their genetically inferred ethnic affiliation to account for population structure. Haplotype analysis was performed in three candidate genes, and the haplotype combinations were tested for association with exceptional longevity. An HRAS1 haplotype enhanced the effect of an APOE haplotype on exceptional survival, and a LASS1 haplotype further augmented its magnitude. These results were replicated in a second population. A profile of healthy aging was developed using a deficit accumulation index, which showed that this combination of gene variants is associated with healthy aging. The variation in LASS1 is functional, causing enhanced expression of the gene, and it contributes to healthy aging and greater survival in the tenth decade of life. Thus, rare gene variants need not be invoked to explain complex traits such as aging; instead rare congruence of common gene variants readily fulfills this role. The interaction between the three genes described here suggests new models for cellular and molecular mechanisms underlying exceptional survival and healthy aging that involve lipotoxicity. [source] Exploring mechanisms of sex differences in longevity: lifetime ovary exposure and exceptional longevity in dogsAGING CELL, Issue 6 2009David J. Waters Summary To move closer to understanding the mechanistic underpinnings of sex differences in human longevity, we studied pet dogs to determine whether lifetime duration of ovary exposure was associated with exceptional longevity. This hypothesis was tested by collecting and analyzing lifetime medical histories, age at death, and cause of death for a cohort of canine ,centenarians', exceptionally long-lived Rottweiler dogs that lived more than 30% longer than average life expectancy for the breed. Sex and lifetime ovary exposure in the oldest-old Rottweilers (age at death, , 13 years) were compared to a cohort of Rottweilers that had usual longevity (age at death, 8.0,10.8 years). Like women, female dogs were more likely than males to achieve exceptional longevity (OR, 95% CI = 2.0, 1.2,3.3; P = 0.006). However, removal of ovaries during the first 4 years of life erased the female survival advantage. In females, a strong positive association between ovaries and longevity persisted in multivariate analysis that considered other factors, such as height, body weight, and mother with exceptional longevity. A beneficial effect of ovaries on longevity in females could not be attributed to resistance against a particular disease or major cause of death. Our results document in dogs a female sex advantage for achieving exceptional longevity and show that lifetime ovary exposure, a factor not previously evaluated in women, is associated with exceptional longevity. This work introduces a conceptual framework for designing additional studies in pet dogs to define the ovary-sensitive biological processes that promote healthy human longevity. [source] Stress-induced responses of human skin fibroblasts in vitro reflect human longevityAGING CELL, Issue 5 2009Pim Dekker Summary Unlike various model organisms, cellular responses to stress have not been related to human longevity. We investigated cellular responses to stress in skin fibroblasts that were isolated from young and very old subjects, and from offspring of nonagenarian siblings and their partners, representatives of the general population. Fibroblasts were exposed to rotenone and hyperglycemia and assessed for senescence-associated ,-galactosidase (SA-,-gal) activity by flow cytometry. Apoptosis/cell death was measured with the Annexin-V/PI assay and cell-cycle analysis (Sub-G1 content) and growth potential was determined by the colony formation assay. Compared with fibroblasts from young subjects, baseline SA-,-gal activity was higher in fibroblasts from old subjects (P = 0.004) as were stress-induced increases (rotenone: P < 0.001, hyperglycemia: P = 0.027). For measures of apoptosis/cell death, fibroblasts from old subjects showed higher baseline levels (Annexin V+/PI+ cells: P = 0.040, Sub-G1: P = 0.014) and lower stress-induced increases (Sub-G1: P = 0.018) than fibroblasts from young subjects. Numbers and total size of colonies under nonstressed conditions were higher for fibroblasts from young subjects (P = 0.017 and 0.006, respectively). Baseline levels of SA-,-gal activity and apoptosis/cell death were not different between fibroblasts from offspring and partner. Stress-induced increases were lower for SA-,-gal activity (rotenone: P = 0.064, hyperglycemia: P < 0.001) and higher for apoptosis/cell death (Annexin V+/PI, cells: P = 0.041, Annexin V+/PI+ cells: P = 0.008). Numbers and total size of colonies under nonstressed conditions were higher for fibroblasts from offspring (P = 0.001 and 0.024, respectively) whereas rotenone-induced decreases were lower (P = 0.008 and 0.004, respectively). These data provide strong support for the hypothesis that in vitro cellular responses to stress reflect the propensity for human longevity. [source] Increasing longevity through caloric restriction or rapamycin feeding in mammals: common mechanisms for common outcomes?AGING CELL, Issue 5 2009Lynne S. Cox Summary Significant extension of lifespan in important mammalian species is bound to attract the attention not only of the aging research community, but also the media and the wider public. Two recent papers published by Harrison et al. (2009) in Nature and by Colman et al. (2009) in Science report increased longevity of mice fed with rapamycin and of rhesus monkeys undergoing caloric restriction, respectively. These papers have generated considerable debate in the aging community. Here we assess what is new about these findings, how they fit with our knowledge of lifespan extension from other studies and what prospects this new work holds out for improvements in human longevity and human health span. [source] Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevityAGING CELL, Issue 4 2009Ludmila Pawlikowska Summary The insulin/IGF1 signaling pathways affect lifespan in several model organisms, including worms, flies and mice. To investigate whether common genetic variation in this pathway influences lifespan in humans, we genotyped 291 common variants in 30 genes encoding proteins in the insulin/IGF1 signaling pathway in a cohort of elderly Caucasian women selected from the Study of Osteoporotic Fractures (SOF). The cohort included 293 long-lived cases (lifespan , 92 years (y), mean ± standard deviation (SD) = 95.3 ± 2.2y) and 603 average-lifespan controls (lifespan , 79y, mean = 75.7 ± 2.6y). Variants were selected for genotyping using a haplotype-tagging approach. We found a modest excess of variants nominally associated with longevity. Nominally significant variants were then replicated in two additional Caucasian cohorts including both males and females: the Cardiovascular Health Study and Ashkenazi Jewish Centenarians. An intronic single nucleotide polymorphism in AKT1, rs3803304, was significantly associated with lifespan in a meta-analysis across the three cohorts (OR = 0.78 95%CI = 0.68,0.89, adjusted P = 0.043); two intronic single nucleotide polymorphisms in FOXO3A demonstrated a significant lifespan association among women only (rs1935949, OR = 1.35, 95%CI = 1.15,1.57, adjusted P = 0.0093). These results demonstrate that common variants in several genes in the insulin/IGF1 pathway are associated with human lifespan. [source] The Human Ageing Genomic Resources: online databases and tools for biogerontologistsAGING CELL, Issue 1 2009Joćo Pedro De Magalhćes Summary Aging is a complex, challenging phenomenon that requires multiple, interdisciplinary approaches to unravel its puzzles. To assist basic research on aging, we developed the Human Ageing Genomic Resources (HAGR). This work provides an overview of the databases and tools in HAGR and describes how the gerontology research community can employ them. Several recent changes and improvements to HAGR are also presented. The two centrepieces in HAGR are GenAge and AnAge. GenAge is a gene database featuring genes associated with aging and longevity in model organisms, a curated database of genes potentially associated with human aging, and a list of genes tested for their association with human longevity. A myriad of biological data and information is included for hundreds of genes, making GenAge a reference for research that reflects our current understanding of the genetic basis of aging. GenAge can also serve as a platform for the systems biology of aging, and tools for the visualization of protein,protein interactions are also included. AnAge is a database of aging in animals, featuring over 4000 species, primarily assembled as a resource for comparative and evolutionary studies of aging. Longevity records, developmental and reproductive traits, taxonomic information, basic metabolic characteristics, and key observations related to aging are included in AnAge. Software is also available to aid researchers in the form of Perl modules to automate numerous tasks and as an SPSS script to analyse demographic mortality data. The HAGR are available online at http://genomics.senescence.info. [source] Beyond Material Explanations: Family Solidarity and Mortality, a Small Area-level AnalysisPOPULATION AND DEVELOPMENT REVIEW, Issue 1 2010Jon Anson Social solidarity, being embedded in a network of binding social relationships, tends to extend human longevity. Yet while average incomes in the Western world, and with them, life expectancies, have risen dramatically, the second demographic transition has occasioned a breakdown in traditional family forms. This article considers whether these trends in family life may have slowed the rise in life expectancy. I present a cross-sectional analysis of Israeli statistical areas (SAs), for which I construct indexes of Standard of Living (SOL), Traditional Family Structure (TFS), and Religiosity (R). I show that (1) increases in all three of these indexes are associated with lower levels of mortality, (2) male mortality is more sensitive to differences in SOL and TFS than is female mortality, and (3) net of differences in SOL and TFS, there is no difference in the mortality levels of Arab and Jewish populations. [source] Logistic Regression Models for Polymorphic and Antagonistic Pleiotropic Gene Action on Human Aging and LongevityANNALS OF HUMAN GENETICS, Issue 6 2003Qihua Tan Summary In this paper, we apply logistic regression models to measure genetic association with human survival for highly polymorphic and pleiotropic genes. By modelling genotype frequency as a function of age, we introduce a logistic regression model with polytomous responses to handle the polymorphic situation. Genotype and allele-based parameterization can be used to investigate the modes of gene action and to reduce the number of parameters, so that the power is increased while the amount of multiple testing minimized. A binomial logistic regression model with fractional polynomials is used to capture the age-dependent or antagonistic pleiotropic effects. The models are applied to HFE genotype data to assess the effects on human longevity by different alleles and to detect if an age-dependent effect exists. Application has shown that these methods can serve as useful tools in searching for important gene variations that contribute to human aging and longevity. [source] The skin as a mirror of the ageing process in the human organism , results of the ageing research in the German National Genome Research Network 2EXPERIMENTAL DERMATOLOGY, Issue 8 2006CH. C. Zouboulis Intrinsic human skin ageing is influenced by the individual genetic predisposition and reflects degradation processes of the body. Hormones are decisively involved in intrinsic ageing with reduced secretion of pituitary, adrenal glands, and gonads, which leads to characteristic body and skin phenotypes. A number of advances were recently made in understanding skin ageing mechanisms and major molecular changes, especiallly of the extracellular matrix, were identified. Gene expression patterns compatible with mitotic misregulation and alterations in intracellular transport and metabolism were identified in fibroblasts of ageing humans and humans with progeria. Age-associated changes of extracellular matrix of the skin correlate well with changes been detected in the extracellular matrix of other organs of the human body. Within the National Genome Research Network 2 (NGFN-2) in Germany, the explorative project ,Genetic etiology of human longevity' targets the identification of age-related molecular pathways. For this purpose, skin models of ageing are used. Expression profiling employing cDNA microarrays from known and novel genes and RT-PCR are employed for gene detection and confirmation. Among the potential candidate genes several interesting target genes have been identified. The evaluation of ageing-associated genes in skin models will facilitate the understanding of global molecular ageing mechanisms in the future. [source] | |||||||||||||