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At least 325 records · Page 18Linked to original sources
PubMed2004

The role of ubiquinone in Caenorhabditis elegans longevity.

Aging is an irreversible physiological process that affects all living organisms. Different mutations in the insulin signaling pathway and caloric restriction have been shown to retard aging in Caenorhabditis elegans. In addition, mutations or RNAi silencing of components of the respiratory chain results in the modification of adult life span. Another class of genes that affect life span in C. elegans is the clock (clk) genes. Particularly interesting is clk-1, which encodes an enzyme required for ubiquinone (coenzyme Q, CoQ) biosynthesis. Down-regulation by RNAi silencing of the genes required for ubiquinone biosynthesis also extends life span in C. elegans, and CoQ supplied in the diet also affects nematode longevity in both clk-1 and wild-type strains. Although there are many aspects that can be considered in aging, we focus this review on the role of CoQ in the longevity of C. elegans. We will review the current information about the biosynthesis of CoQ and its dietary supplementation related to the extension of life span. We will also analyze the function of CoQ in the electron transport chain and reactive oxygen species production in the context of aging. We hypothesize that the role of CoQ on longevity of C. elegans supports the oxidative damage theory of aging.

Animals↗
PubMed2005

Common promoter polymorphisms of inflammation and thrombosis genes and longevity in older adults: the cardiovascular health study.

Inflammatory response genes may influence life span or quality at advanced ages. Using data from the population-based cardiovascular health study (CHS) cohort, we examined the associations between promoter polymorphisms of several inflammation and thrombosis genes with longevity. We ascertained genotypes for interleukin (IL)-6 -174 G/C, beta-fibrinogen -455 G/A, plasminogen activator inhibitor (PAI)-1 -675 4G/5G, and thrombin-activatable fibrinolysis inhibitor (TAFI) -438 G/A in 2224 men and women > or = 65 years old at baseline. During 10 years of follow-up, men with the TAFI -438 A/A genotype had decreased mortality due to all causes, and lived, on average, 0.9 more years of life, or 1.1 more years of healthy life, than men with the -438 G allele. The effects of TAFI -438 G/A in women were smaller and not statistically significant. PAI-1 4G/4G genotype appeared to be associated with lower non-cardiovascular mortality in men, but with greater cardiovascular mortality in women. In exploratory analyses, we observed a possible interaction among anti-inflammatory drugs, interleukin-6 -174 C/C genotype, and longevity. These findings suggest that modulators of fibrinolytic activity may have a generalized influence on aging, and merit further investigation in studies of genetic determinants of human longevity.

Aged↗
PubMed2004

Longevity of cryogenically stored seeds.

Though cryogenic storage is presumed to provide nearly infinite longevity to cells, the actual shelf life achieved under ultra-cold temperatures has not been addressed theoretically or empirically. Here, we report measurable changes in germination of dried seeds stored under liquid nitrogen conditions for >10 years. There was considerable variability in the extent of deterioration among species and accessions within a species. Aging time courses for lettuce seeds stored at temperatures between 50 and -196 degrees C were fit to a form of the Avrami equation to determine rate coefficients and predict half-life of accessions. A reduction in the temperature dependency on aging rate, determined as a break in the Arrhenius plot, occurred at about -15 degrees C, and this resulted in faster deterioration than anticipated from extrapolation of kinetics measured at higher temperatures. The break in Arrhenius behavior occurred at temperatures in between the glass transition temperature (28 degrees C) and the Kauzmann temperature (-42 degrees C) and also coincided with a major triacylglycerol phase change (-40 to -7 degrees C). In spite of the faster than anticipated deterioration, cryogenic storage clearly prolonged shelf life of lettuce seeds with half-lives projected as approximately 500 and approximately 3400 years for fresh lettuce seeds stored in the vapor and liquid phases of liquid nitrogen, respectively. The benefit of low temperature storage (-18 or -135 degrees C) on seed longevity was progressively lost if seeds were first stored at 5 degrees C. Collectively, these results demonstrate that lowering storage temperature progressively increases longevity of seeds. However, cryogenic temperatures were not sufficient to stop deterioration, especially if initial stages of aging were allowed to progress at higher storage temperatures. This work contributes to reliable assessments of the potential benefit and cost of different genebanking strategies.

Cryopreservation↗
PubMed2004

Variation in the SHC1 gene and longevity in humans.

Mice in which the p66(SHC) specific region of the SHC gene is deleted live 30% longer without apparent disease. These mice have lower levels of oxidative stress and apoptosis, both of which have been linked to old age survival in man. This makes SHC1 an important candidate gene for longevity in humans. We found no variations in the p66 specific region of the SHC1 gene in 30 young and 30 extreme long-lived subjects. Thus in man, no common sequence variations occur in p66 specific region of the SHC1 gene. In two independent cohorts of respectively 730 and 563 subjects aged 85 and over, we tested the only known non-synonymous polymorphism, Met(410)Val, for association with longevity using a prospective follow-up design. In the first cohort, we found increasing valine allele frequency in three strata of increasing age at death (2.8-5.2%). Moreover, compared to Met/Met carriers, mortality rate was a factor of 0.71 (95% CI 0.45-1.13) reduced for Met/Val carriers in the combined cohorts, with similar risk estimates in both cohorts. Low valine allele frequency resulted, however, in low power to detect statistical significance. These data suggest that an association between the Met(410)Val polymorphism and longevity in humans may exist.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Interleukin 6-174 G/C promoter gene polymorphism in centenarians: no evidence of association with human longevity or interaction with apolipoprotein E alleles.

The C allele at position -174 in the promoter of the interleukin 6 (IL-6) gene has been associated with reduced gene expression and reduced plasma levels of IL-6. Given that IL-6 tracks with functional disability and age-related diseases, there may be attrition or reduction in the frequency of the homozygous subjects, who produce higher IL-6 serum levels, in older survivors in a population. In fact, a marked reduction of the IL-6*G/*G genotype was recently demonstrated in male though not female Italian centenarians compared with younger age groups. First aim of the present study was to investigate whether there was evidence of an association among IL-6 -174 G/C promoter polymorphism and extreme longevity in a population of 81 centenarians compared with a control group of 122 middle-aged healthy subjects (mean age: 51+/-18 SD; range: 19-73 years), from Apulia (Southern Italy). Secondly, we also tested possible interaction of apolipoprotein E (APOE) alleles with the IL-6 -174 G/C promoter polymorphism in view of our recent findings for reduced APOE epsilon4 allele in centenarians. No differences have been found in the IL-6 -174 G/C promoter allele and genotype frequencies between centenarians and controls nor was there any observed interaction with APOE alleles that are also reputed to be linked to longevity. Regional genetic differences in conjunction with differing environmental factors may explain in part previous results suggesting a role of this polymorphism in longevity.

Adult↗
PubMedDate not supplied

p53: guardian AND suppressor of longevity?

The p53 tumor suppressor gene enhances longevity by inhibiting cancer development. However, Van Heemst et al. in this issue show that polymorphisms in the p53 gene may affect longevity in unexpected ways. A meta-analysis indicates that individuals homozygous for the p53 codon 72 Pro allele instead of the more prevalent Arg allele have a modest increase in cancer incidence. This difference in cancer suspectibility is consistent with molecular studies showing that the p53 Pro polymorphic variant is a less robust anti-proliferative molecule than its Arg counterpart. The most surprising result was obtained in a prospective study of individuals age 85 or older. Despite having a 2.5-fold increased cancer incidence, the p53 codon 72 Pro/Pro individuals exhibited a significant 41% enhanced survival compared to codon 72 Arg/Pro and Arg/Arg individuals. These paradoxical findings suggest that p53 may enhance survival through most of our life span, but may actively suppress longevity during old age. The mechanisms for such duplicity remain unclear, but insights from p53 mutant mouse models may help to sort out the mystery.

Aging↗
PubMed2005

Extended longevity and insulin signaling in adipose tissue.

Caloric restriction and leanness have been shown to increase longevity in organisms ranging from yeast to mammals. Adipose tissue seems to be a pivotal organ in the aging process and in determination of lifespan. We have recently shown that fat-specific disruption of the insulin receptor gene is sufficient to increase lifespan in FIRKO mice, suggesting that reduced adiposity, even in the presence of normal or increased food intake, can extend lifespan. The model also suggests a special role for the insulin-signaling pathway in adipose tissue in the longevity process. Reduced fat mass has an impact on the duration of life in several other model organisms. In Drosophila, a specific reduction in the fat body through overexpression of forkhead type transcription factor (dFOXO) extends lifespan. Furthermore, sirtuin1 (SIRT1), the mammalian ortholog of the life-extending yeast gene silent information regulator 2 (SIR2), was proposed to be involved in the molecular mechanisms linking lifespan to adipose tissue. In the control of human aging and longevity, one of the striking physiological characteristics identified in centenarians is their greatly increased insulin sensitivity even compared with younger individuals. The effect of reduced adipose tissue mass on lifespan could be due to the prevention of obesity-related metabolic disorders including type 2 diabetes and atherosclerosis.

Adipose Tissue↗
PubMed2005

Sirtuin 1 (SIRT1) sequence variation is not associated with exceptional human longevity.

The SIR2/Sirt1 gene has been demonstrated as regulating lifespan in many model organisms, including yeast, Caenorhabditis elegans and rodents. These findings render the human homologue, SIRT1, a very plausible candidate as a modifier of human life expectancy. We therefore sought to investigate whether common allelic variation in the SIRT1 gene was associated with human longevity. Five single nucleotide polymorphisms (SNPs), distributed across the entire gene, including the promoter region, were genotyped in our extensive DNA collections of 1573 long-lived individuals (centenarians and nonagenarians) and matched younger controls. Four of the markers were haplotype-tagging SNPs (htSNPs) that defined five common haplotypes. No evidence for an association was detected between any of the tested SNPs and the longevity phenotype at the allele, genotype or haplotype levels. These findings, based on an htSNP approach, suggest that there is no noteworthy influence of SIRT1 sequence variation on exceptional human longevity in the German population. However, this does not rule out the possibility that allelic variants in direct regulators or downstream substrates of SIRT1 could play critical roles in extending lifespan in humans.

Aged↗
PubMed2006

Genetic control of longevity in C. elegans.

The nematode Caenorhabditis elegans has proven to be a very useful tool for studying the genetics of longevity. Over 70 genes have been found to influence lifespan in this worm. Those related to the Ins/IGF signaling pathway are among the best studied and will be focused on in this review. The master regulator of this pathway, the forkhead transcription factor DAF-16, can activate an enhanced life maintenance program in response to environmental and gonadal inputs. DAF-16 up- and downregulates expression of many genes leading to metabolic alterations and increased stress and microbial resistance. This is generally confirmed by biochemical and physiological data. Longevity mutants are not hypometabolic and probably produce more reactive oxygen species than wild type. However, their high antioxidant capacity may result in lower oxidative damage. Enhanced molecular turnover rates may also play a role in their longevity phenotype.

Animals↗
PubMed2006

The longevity effect of dietary restriction in Caenorhabditis elegans.

The nematode Caenorhabditis elegans has been subjected to DR by food (Escherichia coli) dilution, growth in axenic medium and using animals having defects in feeding behavior or in specific nutrient transporter proteins. There is evidence that DR causes increased resistance against environmental stressors but no decrease of metabolic rate. The insulin/IGF-1 signaling pathway does not mediate the longevity effect of DR in this species, but TOR signaling may be involved. The metabolic stability-longevity theory offers a plausible explanation of the longevity effect of DR but needs experimental validation.

Aging↗
PubMed2006

Family clustering in Sardinian longevity: a genealogical approach.

This paper aims to discuss the validation and family determinants affecting the longevity of Sardinian centenarians, using a genealogical approach. This preliminary study presents the first results of a genealogical tree reconstruction of selected centenarians aged 105 and over, from certain areas. These are mostly situated in the province of Nuoro, an area with the highest rate of centenarians and where the female-to-male sex ratio tends to be male-biased. An accurate centenarian age validation was performed that required a meticulous examination of numerous civil status records and parish registers. An important finding was that longevity occurs among the ascendants of a particular branch of the family. The data used are still provisional but, should it apply to other validated cases, it would provide empirical evidence of a genetic component in longevity. A more thorough examination of the data available may yield deeper insights into the role played by endogamy and consanguinity.

Aged, 80 and over↗
PubMed2006

Nampt/PBEF/Visfatin: a regulator of mammalian health and longevity?

Eukaryotes have evolved elaborate mechanisms to survive periods of adversity. By manipulating genes that control these mechanisms, researchers have found they can generate more stress resistant, longer-lived organisms. One of these is the PNC1 gene of Saccharomyces cerevisiae, a master "longevity regulatory gene" that translates a variety of environmental stresses into lifespan extension by activating the sirtuin family of longevity deacetylases. Master longevity genes such as PNC1 are highly adaptive because they allow organisms to respond in a concerted way to adversity and to rapidly evolve life strategies to compensate for a changing environment. Hence, they should be well conserved. We propose that there is a functional equivalent of PNC1 in mammals called Nampt (a.k.a. PBEF/Visfatin), a stress-responsive gene that would coordinately regulate metabolism, cell defenses, and resistance to diseases of aging.

Aging↗
PubMed2006

Whole genome RNAi screens for increased longevity: important new insights but not the whole story.

This article discusses the pros and cons of using RNAi screening to identify longevity genes in Caenorhabditis elegans. The discussion will focus on the results of two large-scale longevity RNAi screens that were recently published. The two screens revealed largely non-overlapping sets of candidate longevity genes. The possible reasons for such differences and their implications will be discussed.

Aging↗
PubMed2004

Reduced free-radical production and extreme longevity in the little brown bat (Myotis lucifugus) versus two non-flying mammals.

The extended longevity of bats, despite their high metabolic rate, may provide insight to patterns and mechanisms of aging. Here I test predictions of the free radical or oxidative stress theory of aging as an explanation for differences in lifespan between the little brown bat, Myotis lucifugus (maximum lifespan potential MLSP=34 years), the short-tailed shrew, Blarina brevicauda (MLSP=2 years), and the white-footed mouse, Peromyscus leucopus (MLSP=8 years) by comparing whole-organism oxygen consumption, hydrogen peroxide production, and superoxide dismutase activity in heart, kidney, and brain tissue. Mitochondria from M. lucifugus produced half to one-third the amount of hydrogen peroxide per unit of oxygen consumed compared to mitochondria from B. brevicauda and P. leucopus, respectively. Superoxide dismutase (SOD) activity did not differ among the three species. These results are similar to those found for birds, which like bats have high metabolic rates and extended longevities, and provide support for the free radical theory of aging as an at least partial explanation for the extreme longevity of bats.

Animals↗
PubMed2005

The voyage to healthy longevity: from experimental models to the ultimate goal.

Understanding mechanisms underlying longevity, and endeavor towards the specific goals of alleviating frailty in old age, require a comprehensive approach that considers the various theoretical and experimental approaches, as well as compiling the data on humans. This logistic has underlined the program of the conference, and is reflected in the present special issue. Considerable volume of data now point to distinct genes that are associated with exceptional longevity in humans, as reflected from the articles in this volume. However, this symposium also highlighted non-genetic effects, including physical, mental and social activities, and elucidate the relevant underlying mechanisms. The symposium focused on understanding the basis of human longevity coupled to extended health-span and function into old age.

Aged↗
PubMed2005

Exploring the genetics of longevity in the Old Order Amish.

Lifespan is a complex phenotype determined by the interaction of genetic and environmental factors. This makes the identification of variants in genes that influence longevity challenging. We believe that the Old Order Amish (OOA) of Lancaster, Pennsylvania is an excellent population for studying the genetics of longevity. They are a closed population derived from a limited number of founders. They have large families and maintain extensive genealogic records dating to the 1700 s. They eschew modern technology; their lifestyle is little changed over the last 250 years. Homogeneity of environment and lifestyle factors across time and across the OOA population minimizes the influence that environmental factors have in determining the differences in lifespan between individuals. We hypothesize that this reduction in environmental variability will make it easier to identify the genetic factors that influence lifespan. In this article, we describe our strategy for identifying variants in genes that influence longevity in the Amish and present the results of our studies to date.

Adult↗
PubMed2005

Gene expression patterns associated with queen honey bee longevity.

The oxidative stress theory of aging proposes that accumulation of oxidative damage is the main proximate cause of aging and that lifespan is determined by the rate at which this damage occurs. Two predictions from this theory are that long-lived organisms produce fewer ROS or have increased antioxidant production. Based in these predictions, molecular mechanisms to promote longevity could include either changes in the regulation of mitochondrial genes that affect ROS production or elevated expression of antioxidant genes. We explored these possibilities in the honey bee, a good model for the study of aging because it has a caste system in which the same genome produces both a long-lived queen and a short-lived worker. We measured mRNA levels for genes encoding eight of the most prominent antioxidant enzymes and five mitochondrial proteins involved in respiration. The expression of antioxidant genes generally decreased with age in queens, but not in workers. Expression of most mitochondrial genes, in particular CytC, was higher in young queens, but these genes showed a faster age-related decline relative to workers. One exception to this trend was COX-I in thorax. This resulted in higher COX-I/CytC ratios in old queens compared to old workers, which suggests caste-specific differences in mitochondrial function that might be related to the caste-specific differences in longevity. Queen honey bee longevity appears to have evolved via mechanisms other than increased antioxidant gene expression.

Aging↗
PubMed2006

Behavioral trajectories as predictors in event history analysis: male calling behavior forecasts medfly longevity.

A recent study on wild male Mediterranean fruit flies [Papadopoulos, N.T., Katsoyannos, B.I., Kouloussis, N.A., Carey, J.R., Müller, H.-G., Zhang, Y., 2004. High sexual signalling rates of young individuals predict extended life span in male Mediterranean fruit flies. Oecologia 138, 127-134] provided evidence that intense sexual signalling (calling behavior) is associated with longer life span. We demonstrate here an approach based on functional data analysis methodology for predicting individual remaining longevity and the distribution of remaining lifetime from individual behavioral trajectories. A key methodological concept is the time evolution of mean functions and eigenfunctions. This methodology is applied to the event history of calling behavior of male medflies. The results demonstrate complex relationships between male calling behavior and subsequent longevity that complement previous biodemographic analyses of these data. A high level of recent calling activity is found to be associated with increased remaining lifetime for an individual male fly, while calling activity at early ages plays no role for remaining longevity.

Animals↗