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PubMedDate not supplied

Factors contributing to the plasticity of the extended longevity phenotypes of Drosophila.

A number of laboratories have constructed independently derived long-lived strains of Drosophila, each of which have similar but not identical patterns of variability in their adult longevity. Given the observed plasticity of longevity within each of these strains, it would be useful to review the operational and environmental factors that give rise to this phenotypic plasticity and ascertain whether they are common or strain specific. Our review of the more extensively analyzed strains suggests that the allelic composition of the initial genomes and the selection/transgene strategy employed yield extended longevity strains with superficially similar phenotypes but which are probably each the result of different proximal genetic mechanisms. This then offers a plausible explanation for the differential effects of various environmental factors on each strain's particular pattern of phenotypic plasticity. It also illustrates that the species has the potential to employ any one of a number of different proximal mechanisms, each of which give rise to a similar longevity phenotype.

Animals↗
PubMed2004

Regulation of C. elegans longevity by specific gustatory and olfactory neurons.

The life span of C. elegans is extended by mutations that inhibit the function of sensory neurons. In this study, we show that specific subsets of sensory neurons influence longevity. We find that certain gustatory neurons inhibit longevity, whereas others promote longevity, most likely by influencing insulin/IGF-1 signaling. Olfactory neurons also influence life span, and they act in a distinct pathway that involves the reproductive system. In addition, we find that a putative chemosensory G protein-coupled receptor that is expressed in some of these sensory neurons inhibits longevity. Together our findings imply that the life span of C. elegans is regulated by environmental cues and that these cues are perceived and integrated in a complex and sophisticated fashion by specific chemosensory neurons.

Animals↗
PubMed2002

Genomic plasticity, energy allocations, and the extended longevity phenotypes of Drosophila.

The antagonistic pleiotropy theory of the evolution of aging is shown to be too simple to fully apply to the situation in which Drosophila are selected directly for delayed female fecundity and indirectly for extended longevity. We re-evaluated our own previously reported selection experiments using previously unreported data, as well as new data from the literature. The facts that led to this re-evaluation were: (1) the recognition that there are at least three different extended longevity phenotypes; (2) the existence of metabolic and mitochondrial differences between normal- and long-lived organisms; and most importantly; (3) the observation that animals selected for extended longevity are both more fecund and longer-lived than their progenitor control animals. This latter observation appears to contradict the theory. A revised interpretation of the events underlying the selection process indicates that there is a two-step change in energy allocations leading to a complex phenotype. Initial selection first allows the up-regulation of the antioxidant defense system genes and a shift to the use of the pentose shunt. This is later followed by alterations in mitochondrial fatty acid composition and other changes necessary to reduce the leakage of H(2)O(2) from the mitochondria into the cytosol. The recaptured energy available from the latter step is diverted from somatic maintenance back into reproduction, resulting in animals that are both long-lived and fecund. Literature review suggests the involvement of mitochondrial and antioxidant changes are likely universal in the Type 1 extended longevity phenotype.

Aging↗
PubMed1992

Intrapair differences of physical aging and longevity in identical twins.

The genetic and environmental contributions to physical aging (hair graying, balding, presbyopia) and longevity (age at death) were examined by within-pair comparison in monozygotic (MZ) and dizygotic (DZ) twins in later adulthood. Physical aging was investigated on 135 pairs of adult twins aged over 50. Hair graying and hair loss (baldness) showed significantly higher rates of concordance in the MZ twins than in the DZ twins. The intrapair difference of the degree of hair graying was negligible in 79%, slight in 15% and striking in 5% among the MZ pairs; while negligible in 40%, slight in 50% and striking in 10% among the DZ pairs. The intrapair difference of the degree of hair loss was negligible in 92%, slight in 8% (and striking in none) among the MZ pairs; while negligible in 69%, slight in 25% and striking in 6% among the DZ pairs. The age at onset of presbyopia showed a slightly higher rate of concordance in the MZ than in the DZ pairs. Longevity (age at death) was surveyed on 184 pairs of twins who died at over 40 years of age. The intrapair difference of longevity was 6.65 +/- 5.6 years (maximum 18.0; minimum 0.04) in the MZ pairs, and 8.66 +/- 7.2 years (maximum 18.6; minimum 2.9) in the DZ pairs. The MZ pairs showed a slightly smaller within-pair difference of longevity than the DZ pairs.

Aged↗
PubMed2001

Effects of mild heat shocks at young age on aging and longevity in Drosophila melanogaster.

Young adult flies were submitted to heat shocks (37 degrees C) of various durations (5, 10, 20, 40 or 60 min daily) for 1, 2 or 3 weeks. A slight longevity increase, in both sexes, was only observed with the lowest heat shock. Longer shocks had neutral or negative effects. Flies submitted to the procedure providing a longevity increase did not show a delayed behavioral aging but survived longer at 37 degrees C than control flies. This higher thermotolerance was not associated with an increased hsp70 induction. The results are discussed in connection with hormesis and previous results showing that hypergravity, an other mild stress, increases longevity and delays behavioral aging: different mild stresses may have contrasting effects on aging and longevity.

Aging↗
PubMed2000

The effects of gamma rays on longevity.

A number of animal model studies have assessed the capacity of long-term whole body gamma rays to affect life span. The initial goal of such studies was to establish the equivalent of a no observed adverse effects level (NOAEL) that would provide a toxicological foundation for deriving an acceptable worker exposure standard. In the course of initial studies to establish such a 'tolerance threshold', data emerged suggesting that low dose rates/cumulative doses enhanced longevity in mice and guinea pigs of both sexes. Extensive large scale follow-up investigations with other mouse strains and rats revealed what appear to be inter-strain/species differences in response with some models providing strong evidence for a low dose increase in longevity. The subsequent positive studies in mouse models were generally well designed, well conducted and used extensive numbers of mice. In all experiments that displayed enhanced longevity the average life span was enhanced by 10-30% but not the maximum life span potential. The underlying mechanisms affecting the apparent enhancement in longevity are believed to result from the stimulation of hematopoietic and immune systems following an initial low level chronic injury to the bone marrow.

Animals↗
PubMed1993

Does childhood personality predict longevity?

Key models relating personality and health predict that personality in childhood is indicative of later health and longevity. Longevity predictions are tested using data derived from the 7-decade longitudinal study initiated by L. M. Terman 1921 (L. M. Terman & M. H. Oden, 1947). Variables representing major dimensions of personality are used in statistical survival analyses of longevity in 1,178 males and females. Conscientiousness in childhood was clearly related to survival in middle to old age. This finding (a) establishes that childhood personality is related to survival decades into the future, (b) confirms the validity of the conscientiousness dimension in conceptualizing personality, and (c) points to likely and unlikely pathways linking personality to health. Contrary to expectation, cheerfulness (optimism and sense of humor) was inversely related to longevity, suggesting a possible need for reconceptualization of its health relevance.

Adaptation, Psychological↗
PubMedDate not supplied

Human longevity at the cost of reproductive success.

The disposable soma theory on the evolution of ageing states that longevity requires investments in somatic maintenance that reduce the resources available for reproduction. Experiments in Drosophila melanogaster indicate that trade-offs of this kind exist in non-human species. We have determined the interrelationship between longevity and reproductive success in Homo sapiens using a historical data set from the British aristocracy. The number of progeny was small when women died at an early age, increased with the age of death, reaching a plateau through the sixth, seventh and eighth decades of life, but decreased again in women who died at an age of 80 years or over. Age at first childbirth was lowest in women who died early and highest for women who died at the oldest ages. When account was taken only of women who had reached menopause, who were aged 60 years and over, female longevity was negatively correlated with number of progeny and positively correlated with age at first childbirth. The findings show that human life histories involve a trade-off between longevity and reproduction.

Adult↗
PubMed1986

A density threshold for the expression of longevity in Drosophila melanogaster.

Long- and short-lived strains, selected for longevity for up to 27 generations, were raised under two treatments of developmental density. Selected stocks, controls and F1 crosses between them are respectively long-lived, short-lived and intermediate, when raised at a high and uncontrolled developmental density. But when development takes place at a low density, longevity is sharply reduced, showing the existence of a developmental-density threshold for the expression of long life in selected strains and crosses. Selection for longevity is shown to have had effects in males comparable with those in females in the long-lived stock and in reciprocal F1 crosses with the short-lived control. No age-specific effects on longevity were found in progeny from young, middle-aged and old adults.

Animals↗
PubMed1991

On the developmental theory of ageing. I. starvation resistance and longevity in Drosophila melanogaster in relation to pre-adult breeding conditions.

The developmental theory of ageing predicts a positive correlation between developmental time and adult longevity. Experiments that vary larval density and food level have been carried out to test this prediction. The results show differences in viability, developmental time, starvation resistance and adult longevity. It is concluded that pre-adult developmental time is not a causal factor for the determination of adult longevity in Drosophila melanogaster. The observed variation in adult longevity is discussed in relation to viability selection and changed adult physiology.

Aging↗
PubMed2003

Dopa decarboxylase (Ddc) affects variation in Drosophila longevity.

Mutational analyses in model organisms have shown that genes affecting metabolism and stress resistance regulate life span, but the genes responsible for variation in longevity in natural populations are largely unidentified. Previously, we mapped quantitative trait loci (QTLs) affecting variation in longevity between two Drosophila melanogaster strains. Here, we show that the longevity QTL in the 36E;38B cytogenetic interval on chromosome 2 contains multiple closely linked QTLs, including the Dopa decarboxylase (Ddc) locus. Complementation tests to mutations show that Ddc is a positional candidate gene for life span in these strains. Linkage disequilibrium (LD) mapping in a sample of 173 alleles from a single population shows that three common molecular polymorphisms in Ddc account for 15.5% of the genetic contribution to variance in life span from chromosome 2. The polymorphisms are in strong LD, and the effects of the haplotypes on longevity suggest that the polymorphisms are maintained by balancing selection. DDC catalyzes the final step in the synthesis of the neurotransmitters, dopamine and serotonin. Thus, these data implicate variation in the synthesis of bioamines as a factor contributing to natural variation in individual life span.

Animals↗
PubMed2026

Genetic trade-offs in fertility and longevity explain the maintenance of disease-associated alleles in humans.

Genetic variants that increase the risk for complex diseases persist in human populations, despite adverse effects on health and longevity. Life-history theory predicts that such alleles can be maintained by trade-offs arising from pleiotropy, yet direct genomic evidence has been limited. We asked whether disease-associated variants persist because they enhance reproduction, despite costs to health and lifespan. By analysing genome-wide data across 62 diseases, longevity and fertility, we show that disease-risk alleles are, on average, associated with reduced longevity and increased fertility. Moreover, the subset of alleles that increase both fertility and disease risk appear to have been favoured by natural selection over the past 50,000 years. Using Mendelian randomization, we detect a causal effect of genetic liability to disease on longevity, but no robust evidence for a causal effect on fertility; importantly, these estimates remain stable after adjusting for socioeconomic factors. At the individual level, we compared offspring numbers between affected and unaffected individuals with high polygenic disease risk. For most diseases, affected individuals had more children than unaffected ones. But for early-onset diseases, the pattern reverses, indicating reproductive costs of early morbidity. Together, these results support antagonistic pleiotropy and help explain the persistence of disease-risk alleles in human populations.

Humans↗
PubMed2005

A combination of three common inherited mitochondrial DNA polymorphisms promotes longevity in Finnish and Japanese subjects.

Mitochondrial DNA (mtDNA) coding region polymorphisms, as well as the 150T polymorphism in the noncoding region, have been associated with longevity. We have studied here the association of 150T with longevity further and assessed differences in this association between various mtDNA haplogroups. We analysed a sample of 321 very old subjects and 489 middle-aged controls from Finland and Japan. 150T was more frequent among the very old than among the controls in both the Finnish and Japanese subjects. Interestingly, the association was not similar in all haplogroups, and a stratified analysis revealed that two additional common polymorphisms, 489C and 10398G, modified the association between 150T and longevity. These findings suggest that longevity is partly determined by epistatic interactions involving these three mtDNA loci.

Aged↗
PubMed2002

Gender-specific association between -1082 IL-10 promoter polymorphism and longevity.

Ageing is characterized by a pro-inflammatory status, which could contribute to the onset of major age-related diseases. Thus, genetic variations in pro- or anti-inflammatory cytokines might influence successful ageing and longevity. IL-10 is an appropriate candidate because it exerts powerful inhibitory effects on pro-inflammatory function. IL-10 production is controlled by several polymorphic elements in the 5' flanking region of IL-10 gene on 1q32 locus, involving alleles at two microsatellite regions and several polymorphisms in promoter region. We analysed in 190 Italian centenarians (>99 years old, 159 women and 31 men) and in 260 <60 years old control subjects (99 women and 161 men), matched for geographical distribution, genotype frequencies for -1082G-->A, -819C-->T and -592C-->A IL-10 proximal promoter gene biallelic polymorphisms by sequence specific probes. -1082G homozygous genotype was increased in centenarian men (P < 0.025) but not in centenarian women. No difference was found between centenarians and control subjects regarding the other two polymorphisms. The presence of -1082GG genotype, suggested to be associated with high IL-10 production, significantly increases the possibility to reach the extreme limit of human lifespan in men. Together with previous data on other polymorphic loci (Tyrosine Hydroxylase, mitochondrial DNA, IL-6, haemochromatosis, IFN-gamma), this finding points out that that gender is a major variable in the genetics of longevity, suggesting that men and women follow different strategies to reach longevity. Concerning the biological significance of this association, we have not searched for functional proves that IL-10 is involved. Thus, we should conclude that our data only suggest that a marker on 1q32 genomic region may be involved in successful ageing in man. However, recent data on IL-6 and IFN-gamma genes suggest that longevity is negatively associated with genotypes coding for a pro-inflammatory profile. Thus, it is intriguing that the possession of -1082G genotype, suggested to be associated with IL-10 high production, is significantly increased in centenarians.

Aged↗
PubMed2002

Extended leaf longevity in the ore4-1 mutant of Arabidopsis with a reduced expression of a plastid ribosomal protein gene.

The longevity of plant leaf organs is genetically determined. However, the molecular mechanisms underlying the control of longevity are still largely unknown. Here, we describe a T-DNA-insertional mutation of Arabidopsis thaliana that confers extended leaf longevity. The mutation, termed ore4-1, delays a broad spectrum of age-dependent leaf senescence, but has little effect on leaf senescence artificially induced by darkness, abscisic acid (ABA), methyl jasmonate (MeJA), or ethylene. The T-DNA was inserted within the promoter region of the plastid ribosomal small subunit protein 17 (PRPS17) gene, and this insertion dramatically reduced PRPS17 mRNA expression. In the ore4-1 mutant, the leaf growth rate is decreased, while the maturation timing is similar to that of wild-type. In addition, the activity of the photosystem I (PSI) is significantly reduced in the ore4-1 mutant, as compared to wild-type. Thus, the ore4-1 mutation results in a deficiency in various chloroplast functions, including photosynthesis, which may decrease leaf growth. Our results suggest a possible link between reduced metabolism and extended longevity of the leaf organs in the ore4-1 mutation.

Aging↗
PubMed2002

Life history, ecology and longevity in bats.

The evolutionary theory of aging predicts that life span should decrease in response to the amount of mortality caused by extrinsic sources. Using this prediction, we selected six life history and ecological factors to use in a comparative analysis of longevity among 64 bat species. On average, the maximum recorded life span of a bat is 3.5 times greater than a non-flying placental mammal of similar size. Records of individuals surviving more than 30 years in the wild now exist for five species. Univariate and multivariate analyses of species data, as well as of phylogenetically independent contrasts obtained using a supertree of Chiroptera, reveal that bat life span significantly increases with hibernation, body mass and occasional cave use, but decreases with reproductive rate and is not influenced by diet, colony size or the source of the record. These results are largely consistent with extrinsic mortality risk acting as a determinant of bat longevity. Nevertheless, the strong association between life span and both reproductive rate and hibernation also suggests that bat longevity is strongly influenced by seasonal allocation of non-renewable resources to reproduction. We speculate that hibernation may provide a natural example of caloric restriction, which is known to increase longevity in other mammals.

Animals↗
PubMed2003

Testing an 'aging gene' in long-lived drosophila strains: increased longevity depends on sex and genetic background.

Molecular advances of the past decade have led to the discovery of a myriad of 'aging genes' (methuselah, Indy, InR, Chico, superoxide dismutase) that extend Drosophila lifespan by up to 85%. Despite this life extension, these mutants are no longer lived than at least some recently wild-caught strains. Typically, long-lived mutants are identified in relatively short-lived genetic backgrounds, and their effects are rarely tested in genetic backgrounds other than the one in which they were isolated or derived. However, the mutant's high-longevity phenotype may be dependent on interactions with alleles that are common in short-lived laboratory strains. Here we set out to determine whether one particular mutant could extend lifespan in long-lived genetic backgrounds in the fruit fly, Drosophila melanogaster. We measured longevity and resistance to thermal stress in flies that were transgenically altered to overexpress human superoxide dismutase (SOD) in the motorneurones in each of 10 genotypes. Each genotype carried the genetic background from a different naturally long-lived wild-caught Drosophila strain. While SOD increased lifespan on average, the effect was genotype- and sex-specific. Our results indicate that naturally segregating genes interact epistatically with the aging gene superoxide dismutase to modify its ability to extend longevity. This study points to the need to identify mutants that increase longevity not only in the lab strain of origin but also in naturally long-lived genetic backgrounds.

Aging↗
PubMed2005

No association between microsomal triglyceride transfer protein (MTP) haplotype and longevity in humans.

Human longevity is a multifactorial condition with a significant genetic contribution. A recent association study in two independent samples of long-lived U.S. Caucasians [long-lived individuals (LLI)] identified a SNP haplotype of the microsomal triglyceride transfer protein (MTP, 4q25) that was underrepresented among LLI when compared with younger controls. This suggested that variation in the MTP gene might modify human longevity. Because of its function in lipid metabolism, the MTP gene product could plausibly play a pivotal role in the physiology of aging. However, the association observed in the U.S. samples could not be replicated by the same authors in a larger French LLI sample. We have therefore investigated the MTP "risk" haplotype in our own collection of 1,589 German nonagenarians, centenarians, and appropriately matched controls. No statistically significant differences were observed between LLI and controls at the allele, genotype, or haplotype level. This indicates that a noteworthy influence of the respective MTP haplotype on human longevity in the German population is unlikely. Furthermore, in comparison with all other U.S. and European samples analyzed, the MTP "risk" haplotype was found to be overrepresented only in the U.S. controls. This implies that the putative association is more likely to reflect recent changes in the genetic structure of the U.S. Caucasian population as a whole, rather than genetic effects upon survival to old age. In our view, the original study therefore highlights potential problems that arise when the case-control design is used as a means to map longevity genes in humans.

Aged↗