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At least 613 records · Page 34Linked to original sources
PubMed1999

Longevity, genes, and aging: a view provided by a genetic model system.

The genetic analysis of aging in the yeast Saccharomyces cerevisiae has revealed the importance of metabolic capacity, resistance to stress, integrity of gene regulation, and genetic stability for longevity. A balance between these life maintenance processes is sustained by the RAS2 gene, which channels cellular resources among them. This gene cooperates with mitochondria and PHB1 in metabolic adjustments important for longevity. It also modulates stress responses. Transcriptional silencing of heterochromatic regions of the genome is lost during aging, suggesting that gene dysregulation accompanies the aging process. There is evidence that this age change plays a causal role. Aging possesses features of a nonlinear process, and it is likely that application of nonlinear system methodology to aging will be productive.

Aging↗
PubMed1999

Extended longevity lines of Drosophila melanogaster: abundance of yolk protein gene mRNA in fat body and ovary.

Lines of Drosophila melanogaster selected for late-life female reproduction typically exhibit correlated responses of reduced early fecundity and increased longevity. This relationship suggests a tradeoff between reproductive effort and somatic maintenance, which in turn, underlies some evolutionary theories of senescence. The mechanistic basis of the apparent tradeoff between increased longevity and reduced early-age fecundity has remained obscure. The present manuscript addresses the issues of whether the reduced early-age fecundity in selected lines corresponds to reduced yolk-protein mRNA production, and whether long-lived flies exhibit somatic maintenance in terms of relatively reduced yolk-protein mRNA production in the fat body. Yolk protein is one of the most abundant proteins used for female reproduction. By comparing a set of lines selected for late life reproduction with the corresponding control lines, we show that that yolk-protein gene mRNA relative abundance during the first four days posteclosion did not correspond to reduced early-life fecundity in the selected lines. In D. melanogaster, yolk protein is produced in the fat body and ovarian follicle cells. On the fourth day posteclosion, relatively more yolk-protein gene mRNA was present in the fat body. On day 1 posteclosion, supplemental yeast did not alter relative yolk-protein gene mRNA abundance. However, on day 4 posteclosion, supplemental yeast stimulated yolk-protein gene mRNA production in the fat body, which suggests an underlying mechanism for the nutrition-based phenotypic plasticity of fecundity previously documented in these lines. On medium without supplemental yeast, the relatively low abundance of fat body yolk-protein gene mRNA in the selected lines on day 4 posteclosion corresponds to a prediction derived from the disposable soma theory.

Aging↗
PubMed2003

Nicotinamide adenine dinucleotide, a metabolic regulator of transcription, longevity and disease.

Nicotinamide adenine dinucleotide (NAD) is a ubiquitous biological molecule that participates in many metabolic reactions. Recent studies show that NAD also plays important roles in transcriptional regulation, longevity, calorie-restriction-mediated life-span extension and age-associated diseases. It has been shown that NAD affects longevity and transcriptional silencing through the regulation of the Sir2p family, which are NAD-dependent deacetylases. Many human diseases are associated with changes in NAD level and/or the NAD : NADH ratio, raising the possibility that the Sir2p family might play a role in these diseases.

Aging↗
PubMed2002

Prolonged longevity in naked mole-rats: age-related changes in metabolism, body composition and gastrointestinal function.

Aging is characterized by declines in all physiological processes and concomitant changes in body composition. Age-related changes in metabolism, body composition and gastrointestinal function were investigated in naked mole-rats (Heterocephalus glaber), rodents that exhibit extended longevity. Maximum lifespan of these 40 g rodents (>27 year) is approximately 9 times greater than predicted allometrically. We investigated changes in basal metabolic rate (BMR), body composition and intestinal glucose transport in 1, 5, 10 and 20-year-old male individuals. Body composition was measured using dual X-ray absorptiometry and activity of sodium glucose co-transporters (SGLT1) determined using everted gut sleeves. One-year-olds had lower body mass than other age cohorts, as they had not attained full adult form. Among the 5, 10, and 20-year-olds, no age-related changes in body mass, BMR, percentage body fat, fat-free mass or bone mineral density were found. SGLT1 activity declined moderately (<20%) from 5 to 20 years and was similar at 10-20 years, whereas age-related declines are 40-60% in mice. Although mole-rats have low metabolic rates, their prolonged longevity results in a lifetime energy expenditure more than 4 times that of mice. Since lifetime energy expenditure is an important index of potential exposure to oxidative damage, naked mole-rats may be valuable for studying mechanisms of aging.

Aging↗
PubMed2006

Longevity and pheromone output in stored-product Bostrichidae.

Information on longevity and on the effect of ageing on pheromone signalling in Bostrichidae infesting stored products is important because pheromones play a crucial role in mediating aggregation by the species in storages. The longevity of starved and unstarved Prostephanus truncatus (Horn) and Rhyzopertha dominica (Fabricius) were determined at 28+/-1 degrees C, 65+/-2% RH and L12:D12 cycle. Additionally, the effects of ageing on rate of pheromone emission were investigated in R. dominica by comparing emission rates of the aggregation pheromones Dominicalure-1 (DL1) and Dominicalure-2 (DL2) released by adult males ranging from 4, 8, 12, 24 and 48 weeks of age. Mean survival time of starved male and female P. truncatus was 8.6+/-0.6 and 9.1+/-0.4 days, respectively. Starved R. dominica males lived for 5.7+/-0.2 days, and females for 4.7+/-0.1 days. However, mean survival times were not significantly different for starved males vs. females of either species. Mean survival time of unstarved male and female P. truncatus was 27.5+/-2.0 and 18.0+/-3.3 weeks, respectively, and for unstarved male and female R. dominica was 26.1+/-2.8 and 16.7+/-2.9 weeks, respectively. Difference in mean survival times of unstarved males vs. females in both P. truncatus and R. dominica were significant. Between species, no significant difference was observed in mean survival time between unstarved males of P. truncatus or R. dominica, nor between females of both species. Rate of pheromone emission in R. dominica was higher when the insects were relatively young (4, 8 and 12 weeks old), but declined by almost 55% in treatments where the insect were at about 24 or 48 weeks old, suggesting that recruitment potential of R. dominica might reduce substantially as the insects age.

Age Factors↗
PubMed2004

A social component in the negative effect of sons on maternal longevity in pre-industrial humans.

Due to their effect on maternal testosterone levels, sons are said to have reduced maternal longevity in pre-industrial humans. This analysis, using information from a Flemish agricultural village in the 18th-20th centuries, confirms the presence of a negative effect of sons on maternal longevity. However, the effect is mainly observed for mothers belonging to the least privileged social group and for sons surviving their fifth birthday. Both findings make the above-mentioned biological explanation relative. However, a plausible alternative, social interpretation is male-dominated intra-household resource competition. It is reasonable to assume that only sons above a certain age are able to claim a serious amount of resources and that competition is strongest within the least privileged social group.

Belgium↗
PubMed1998

The effects of salinity, pH and temperature on the half-life and longevity of Echinostoma caproni miracidia.

Miracidia of Echinostoma caproni were exposed to solutions varying in salinity, pH, and temperature in 1 ml concavity slides. Half-lives of the miracidial populations were determined and longevity curves constructed to find maximum life spans of the miracidia in the different conditions. Control miracidia in aquarium water at pH 7.2 and 22 degrees C. had a half-life of 3.6 h and a maximum life span of 9 h. Miracidia of E. caproni were not very tolerant of saline solutions from 0.1% to 0.4%, the latter being lethal within an hour. A bimodal effect was found with exposure to aquarium water of varying pH, with a peak at pH 5 in acid solutions and pH 9 in alkaline solutions. Miracidia tolerated pH ranges from 3 to 11 exhibiting half-lives of 2.4 h or greater in these solutions. At lower than ambient temperatures, E. caproni miracidia lived longer, the greatest being a half-life of 5.0 h and a maximum life span of 15 h at 5 degrees C. At warmer temperatures, the half-life was reduced until lethality was reached at 40 degrees C. ANCOVA analysis of log transformed longevity curves supported the observation that in pH trials many miracidia survived initially with a major die-off after 3.3 h. The opposite trend of early die-off and gradual mortality of the survivors was supported in the temperature trials.

Animals↗
PubMed1998

Male reproductive strategy and decreased longevity.

An explanation of the inter-gender difference in longevity consistent with the 'disposable soma' theory of ageing is proposed. It is based on the concept of r-K selection as applied to the inter-gender situation. The concept predicts that the gender with a higher potential reproductive rate (males) should invest relatively less in somatic maintenance, which in its turn should result in a lower longevity according to the 'disposable soma' theory of ageing. In females, which are interpreted as K-selected organisms, the reproductive strategy strongly depends on steady, secure constitution designed for oocyte/embryo bearing and is therefore closely related to somatic maintenance, whereas in (r-selected) males it has a greater behavioural component--risky, variable, with a greater potential productive success at the expense of somatic maintenance. The higher metabolic and growth rates, a higher premature mortality and a longer period of sexual competence of males also find explanation as a complex of r-selected traits.

Aging↗
PubMed2001

Mitochondrial involvement in brain function and dysfunction: relevance to aging, neurodegenerative disorders and longevity.

It is becoming increasingly evident that the mitochondrial genome may play a key role in neurodegenerative diseases. Mitochondrial dysfunction is characteristic of several neurodegenerative disorders, and evidence for mitochondria being a site of damage in neurodegenerative disorders is partially based on decreases in respiratory chain complex activities in Parkinson's disease, Alzheimer's disease, and Huntington's disease. Such defects in respiratory complex activities, possibly associated with oxidant/antioxidant balance perturbation, are thought to underlie defects in energy metabolism and induce cellular degeneration. Efficient functioning of maintenance and repair process seems to be crucial for both survival and physical quality of life. This is accomplished by a complex network of the so-called longevity assurance processes, which are composed of genes termed vitagenes. A promising approach for the identification of critical gerontogenic processes is represented by the hormesis-like positive effect of stress. In the present review, we discuss the role of energy thresholds in brain mitochondria and their implications in neurodegeneration. We then review the evidence for the role of oxidative stress in modulating the effects of mitochondrial DNA mutations on brain age-related disorders and also discuss new approaches for investigating the mechanisms of lifetime survival and longevity.

Aging↗
PubMed2000

Heritability of life span in mice and its implication for direct and indirect selection for longevity.

We found high narrow-sense heritability of life span based on the regression of offspring on average parental (midparent) life spans. In two mouse populations prepared using the 4-way-cross design, mean +/- SE heritabilities were 62 +/- 11% (P < 0.001) and 44 +/- 15% (P < 0.01). To reflect inherited rates of aging, rather than resistance to early disease, data from the first 25% to die were deleted, so that only about 40% of families were used for offspring-midparent regressions. Heritabilities still remained high, 38% and 55%, for the same two populations, respectively. Populations studied in two other experiments did not show nearly as high heritabilities; in one case probably due to environmental stress, and in the other probably because the strains used did not have sufficient additive variance in genes regulating longevity. Significant heritabilities occurred only when a wild derived inbred strain was included in the 4-way cross. The age when a female ceased to reproduce appeared to be related to the life spans of her offspring, but only weakly, not approaching significance for any individual experiment. The age when a female became infertile was related to her life span, but the relationship disappeared when short-lived mice were excluded from the analysis. Our findings indicate that, in sufficiently diverse mouse populations, selection for increased longevity should be possible and that the direct selection for parental life span will be a more efficient strategy than selection for female reproductive life span.

Animals↗
PubMed2002

Lack of hypergravity-associated longevity extension in Drosophila melanogaster flies overexpressing hsp70.

Previous studies have shown that Drosophila melanogaster males live longer if exposed to hypergravity at young age. Similarly, thermotolerance and climbing activity in old age are enhanced and it has been hypothesized that the 70 kDa inducible heat-shock protein (hsp70) may play a role in some of these effects. In this article, longevity, thermotolerance and climbing activity were studied in transgenic flies (OE+ strain) overexpressing hsp70 and in control flies harboring the transfection vector at the same chromosomal location but no extra-copies of the hsp70 gene (OE- strain). No positive effect from exposure to hypergravity at a young age was observed for longevity and climbing activity. Thermotolerance was increased by hypergravity but to the same extent in OE+ and OE- strains. Since no positive effect from hypergravity exposure or similar effects were observed in the two strains, it may be concluded that overexpression of hsp70 does not provide an advantage to flies subjected to a mild stress and that it may not be of any help during aging.

Adaptation, Physiological↗
PubMed2001

A logistic regression model for measuring gene-longevity associations.

The logistic regression model is a popular model for data analysis in epidemiological research. In this paper, we use this model to analyze genetic data collected from gene-longevity association studies. This new approach models the probability of observing one genotype as a function of the age of investigated individuals. Applying the model to genotype data on the TH and 3'ApoB-VNTR loci collected from an Italian centenarian study, we show how it can be used to model the different ways that genes affect survival, including sex- and age-specific influences. We highlight the advantages of this application over other available models. The application of the model to empirical data indicates that it is an efficient and easily applicable approach for determining the influences of genes on human longevity.

Adolescent↗
PubMed1996

Longevity in Caenorhabditis elegans reduced by mating but not gamete production.

Theories of life-history evolution propose that trade-offs occur between fitness components, including longevity and maximal reproduction. In Drosophila, female lifespan is shortened by increased egg production, receipt of male accessory fluid and courting. Male lifespan is also reduced by courting and/or mating. Here we show that in the nematode Caenorhabditis elegans, mating with males reduces the lifespan of hermaphrodites by a mechanism independent of egg production or receipt of sperm. Conversely, males appear unaffected by mating. Thus, in C. elegans there is no apparent trade-off between longevity and increased egg or sperm production, but there is a substantial cost to hermaphrodites associated with copulation.

Animals↗
PubMed1997

The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans.

In mammals, insulin signalling regulates glucose transport together with the expression and activity of various metabolic enzymes. In the nematode Caenorhabditis elegans, a related pathway regulates metabolism, development and longevity. Wild-type animals enter the developmentally arrested dauer stage in response to high levels of a secreted pheromone, accumulating large amounts of fat in their intestines and hypodermis. Mutants in DAF-2 (a homologue of the mammalian insulin receptor) and AGE-1 (a homologue of the catalytic subunit of mammalian phosphatidylinositol 3-OH kinase) arrest development at the dauer stage. Moreover, animals bearing weak or temperature-sensitive mutations in daf-2 and age-1 can develop reproductively, but nevertheless show increased energy storage and longevity. Here we show that null mutations in daf-16 suppress the effects of mutations in daf-2 or age-1; lack of daf-16 bypasses the need for this insulin receptor-like signalling pathway. The principal role of DAF-2/AGE-1 signalling is thus to antagonize DAF-16. daf-16 is widely expressed and encodes three members of the Fork head family of transcription factors. The DAF-2 pathway acts synergistically with the pathway activated by a nematode TGF-beta-type signal, DAF-7, suggesting that DAF-16 cooperates with nematode SMAD proteins in regulating the transcription of key metabolic and developmental control genes. The probable human orthologues of DAF-16, FKHR and AFX, may also act downstream of insulin signalling and cooperate with TGF-beta effectors in mediating metabolic regulation. These genes may be dysregulated in diabetes.

Alternative Splicing↗
PubMed1991

Relationship between genotypes of longevity genes and developmental speed in Drosophila melanogaster.

Hatching time (the period between egg-laying and hatching) and emerging time were surveyed and their relationship with the adult life span was investigated. A relationship between emerging time and adult life span was clearly evident: early emergers were often long-lived. This relation is considered to have a genetic basis because all the larvae in a group were bred in the same culture bottle. Thus, the longevity genes involved also appear to have control over the rate of development. No significant relation was observed between hatching time and adult life span or between hatching time and emerging time. These results suggest that the function of the longevity genes begins at the larval or pupal stage before emergence, and that adult life spans differentiate at this time.

Animals↗
PubMed1995

Inherited stress resistance and longevity: a stress theory of ageing.

Ageing is considered in the context of the abiotic stresses to which free-living organisms are normally exposed. Assuming that the primary target of selection of stress is at the level of energy carriers, trade-offs under the rate-of-living theory of ageing predict increased longevity from selection for stress resistance. Changes in longevity then become incidental to selection for stress resistance. I therefore suggest the reformulation of the rate-of-living theory to become a stress theory of ageing. This directly incorporates the characteristics of habitats in nature. Under this theory, the primary trait inherited is resistance to stress. Consequently, at extreme ages those with inherited resistance to abiotic stress should dominate. Furthermore, the reduction in homeostasis manifested by deteriorating ability to adapt to abiotic stress as ageing proceeds, should be slowest in those surviving longest.

Aging↗
PubMed1994

Genetic associations with human longevity at the APOE and ACE loci.

In an effort to dissect the genetic components of longevity, we have undertaken case-control studies of populations of centenarians (n = 338) and adults aged 20-70 years at several polymorphic candidate gene loci. Here we report results on two genes, chosen for their impact on cardiovascular risk, encoding apolipoprotein E (ApoE), angiotensin-converting enzyme (ACE). We find that the epsilon 4 allele of APOE, which promotes premature atherosclerosis, is significantly less frequent in centenarians than in controls (p < 0.001), while the frequency of the epsilon 2 allele, associated previously with type III and IV hyperlipidemia, is significantly increased (p < 0.01). A variant of ACE which predisposes to coronary heart disease is surprisingly more frequent in centenarians, with a significant increase of the homozygous genotype (p < 0.01). These associations provide examples of genetic influences on differential survival and may point to pleiotropic age-dependent effects on longevity.

Adult↗
PubMed2006

Evidence of genetic enrichment for exceptional survival using a family approach: the Leiden Longevity Study.

We conducted a sib pair study in very old subjects for the purpose of mapping longevity loci. In the present analysis, we explore whether our recruitment strategy has resulted in a population enriched for a heritable component for exceptional longevity. Our study includes families with at least two long-living siblings (men aged 89 years or above; women aged 91 years or above). Data were collected on date of birth and, if applicable, date of death of parents, brothers and sisters, offspring, and spouses of the long-living participants. Standardised mortality ratios (SMRs) compared with the general Dutch population, were calculated. The SMR for all siblings of the long-living participants was 0.66 (95% CI 0.60-0.73). A similar survival benefit was also observed in the parents (SMR=0.76, 95% CI 0.66-0.87) and in the offspring of the long-living subjects (SMR=0.65, 95% CI 0.51-0.80). The SMR of the spouses of the long-living subjects was 0.95 (95% CI 0.82-1.12). The familial clustering of extended survival is unlikely to be caused by ascertainment bias, because in all analyses the long-living participants were excluded. Moreover, it is also unlikely to be caused by environmental factors, because the spouses of the long-living participants had a mortality risk comparable with the general Dutch population, whereas they share the same environment. We conclude that our sample is genetically enriched for extreme survival.

Aged, 80 and over↗