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PubMedDate not supplied

Physical activity, physical fitness and longevity.

Numerous studies consistently have shown that higher levels of physical activity are associated with decreased risks of coronary heart disease, cerebrovascular disease, hypertension, non-insulin-dependent diabetes mellitus, colon and, possibly, breast cancer, as well as osteoporosis. The biological processes proposed to explain these inverse associations are highly plausible. If physical activity does reduce the risk of developing these chronic diseases, we also would expect physical activity to delay mortality and enhance longevity. In this article, we review the major epidemiological studies worldwide that have examined the association between physical activity or physical fitness and all-cause mortality. The data from these studies indicate that physical activity is effective in postponing mortality and enhancing longevity. Public health professionals worldwide should emphasize the need to increase activity levels during leisure time, as well as the need to incorporate physical activity into the daily activities of life.

Animals↗
PubMed1998

Effects of caloric restriction or augmentation in adult rats: longevity and lesion biomarkers of aging.

Caloric restriction (CR) initiated in young rodents has been thoroughly documented to enhance longevity, but its efficacy when introduced at older ages has not been well investigated. Cohorts of 18- and 26-month-old male F344 x BN F1 hybrid rats were fed either: 1) NIH-31 meal (C); 2) vitamin and mineral fortified NIH-31 meal (R); or 3) vitamin and mineral fortified NIH-31 meal supplemented with corn oil and sweetened condensed milk (S). The C control rats were fed ad libitum, R rats were restricted to 32% of the caloric intake of the controls, and S rats were allowed to consume not more than 8% more calories than C rats. After 6 weeks, the average weights were significantly different between all diet and age groups. Although calorie manipulation altered body weight, no significant effect of the dietary intervention on longevity was found. The average lesion burden, including tumor burden and prevalence of nearly all commonly occurring lesions, were comparable between the groups. Thus, the manipulation of weight at ages beyond middle age has a much less profound impact than similar interventions during growth and maturation in rats.

Adrenal Gland Neoplasms↗
PubMed2003

Deficiency of choresteryl ester transfer protein and gene polymorphisms of lipoprotein lipase and hepatic lipase are not associated with longevity.

Cholesteryl ester transfer protein (CETP) is one of the key proteins in reverse cholesterol transport (RCT). The role of CETP in atherosclerosis remains controversial. In this study we investigated the associations between polymorphisms of CETP (mutations in intron 14 and exon 15, and Taq1B), hepatic lipase (C-514T), lipoprotein lipase ( PvuII and HindIII), and ATP-binding cassette transporter 1 (R219K) loci and longevity in 256 centenarians and 190 healthy younger controls. Although heterozygous CETP deficiency and the B2 allele of the Taq1B polymorphism was consistently associated with higher HDL-C concentrations both in centenarians and controls, the allelic frequencies of those polymorphisms did not differ between the two groups. The allelic frequencies of other gene polymorphisms in RCT were not different between the two groups. Centenarians with lipoprotein lipase P(-/-) genotype had significantly higher HDL-C concentration than those with P(-/+) or with P(+/+), in contrast, there was no such a relationship among controls. In stepwise multiple regression analysis, serum albumin, CETP deficiency and lipoprotein lipase PvuII genotype were independently associated with HDL-C in centenarians. Sex, CETP deficiency, and the Taq1B genotype were also independently associated with HDL-C; however, lipoprotein lipase PvuII genotype had no significant effect on their HDL-C in controls. In conclusion, we observed that CETP deficiency and other gene polymorphisms in RCT have no impact on longevity for Japanese centenarians.

Adult↗
PubMed2002

Mitochondrial DNA 5178A polymorphism and longevity.

Previous studies have shown that mitochondrial DNA (mtDNA) 5178 adenine/cytosine (5178A) polymorphism, which is one of the haplogroup-specific mutations for mtDNA haplogroup D, was apparently associated with aging and longevity in humans. We genotyped the 5178A in 293 samples representing three age groups (Old, n=95; Young, n=103; and Infant, n=95) from Yunnan Province, China. The distribution frequency of the 5178A in the Old samples (16.84%) is slightly higher than in those of the Young (13.59%) and Infant (15.79%), but the frequency difference between the age groups is far from being statistically significant ( P>0.05). Our results fail to support the suggestion of association between mtDNA 5178A (or haplogroup D) and longevity.

Adult↗
PubMed2006

Genetic influence on human lifespan and longevity.

There is an intense search for longevity genes in both animal models and humans. Human family studies have indicated that a modest amount of the overall variation in adult lifespan (approximately 20-30%) is accounted for by genetic factors. But it is not known if genetic factors become increasingly important for survival at the oldest ages. We study the genetic influence on human lifespan and how it varies with age using the almost extinct cohorts of Danish, Finnish and Swedish twins born between 1870 and 1910 comprising 20,502 individuals followed until 2003-2004. We first estimate mean lifespan of twins by lifespan of co-twin and then turn to the relative recurrence risk of surviving to a given age. Mean lifespan for male monozygotic (MZ) twins increases 0.39 [95% CI (0.28, 0.50)] years for every year his co-twin survives past age 60 years. This rate is significantly greater than the rate of 0.21 (0.11, 0.30) for dizygotic (DZ) males. Females and males have similar rates and these are negligible before age 60 for both MZ and DZ pairs. We moreover find that having a co-twin surviving to old ages substantially and significantly increases the chance of reaching the same old age and this chance is higher for MZ than for DZ twins. The relative recurrence risk of reaching age 92 is 4.8 (2.2, 7.5) for MZ males, which is significantly greater than the 1.8 (0.10, 3.4) for DZ males. The patterns for females and males are very similar, but with a shift of the female pattern with age that corresponds to the better female survival. Similar results arise when considering only those Nordic twins that survived past 75 years of age. The present large population based study shows genetic influence on human lifespan. While the estimated overall strength of genetic influence is compatible with previous studies, we find that genetic influences on lifespan are minimal prior to age 60 but increase thereafter. These findings provide a support for the search for genes affecting longevity in humans, especially at advanced ages.

Adolescent↗
PubMed1998

Lack of association between human longevity and genetic polymorphisms in drug-metabolizing enzymes at the NAT2, GSTM1 and CYP2D6 loci.

In the present study, the possible role of genetic polymorphism of three drug-metabolizing enzymes, debrisoquine/sparteine hydroxylase (CYP2D6), glutathione S-transferase mu (GSTM1), and N-acetyltransferase (NAT2), as a putative genetic component of human longevity, was explored. A total of 817 DNA samples from a centenarian and a control (20-70 years) population was subjected to PCR-coupled RFLP methods. Subjects were genotyped for the CYP2D6*3 (A2637 deletion) and CYP2D6*4 (G1934A transition) alleles, for four mutations of NAT2 [namely, NAT2*5A (C481T), NAT2*6A (G590A), NAT2*7A (G857A), and NAT2*14A (G191A)], and for the presence or absence of GSTM1 gene deletion. No significant difference was found at these three loci between centenarian and control subjects with respect to allelic variant frequencies, genotype distributions or predicted phenotypes deduced from genotype combinations. By comparing the distribution of combined genotypes for the polymorphisms tested at the CYP2D6, NAT2, and GSTM1 loci, none of the predicted phenotypes concerning debrisoquine hydroxylase extensive-metabolizer or poor-metabolizer phenotypes, slow or fast N-acetylation capacities, and active or defective glutathione S-transferase, could be correlated with human longevity, alone or in combination.

Adult↗
PubMed2002

Seasonal programming of adult longevity in Ukraine.

Longevity was significantly associated with season of birth in 101,634 individuals who died in Kiev during the period 1990-2000. The relationship between age at death and month of birth showed a very similar pattern for both men and women. Mean values for the age at death were lowest for subjects born in April-July, and highest for individuals born at the beginning and end of the year. Minimum and maximum ages at death, analysed according to month of birth, differed by 2.6 years in men and 2.3 years in women. For all major causes of death causes, the mean age at death for persons born in the fourth quarter was the highest. These results suggest that, in this population, longevity is affected by prenatal or early postnatal seasonal factors. This is consistent with the hypothesis that the rate of ageing may be programmed in response to environmental influences at critical periods of early development.

Adult↗
PubMed2006

Genotype profiles of loci encoding DNA repair enzymes in newborn and elderly populations: no evidence of association with longevity.

The comparison of genotype frequencies between neonates and elderly populations can aid in the identification of loci, and polymorphisms within those loci, that affect longevity. Here we have compared genotype frequencies of seven polymorphisms at four loci involved in DNA repair between a cohort of newborns (n = 290) and a retired population (average age at sampling 70.02 years; n = 430) who have suffered a lifetime of DNA damage from normal, metabolic processes, and on whom selection on DNA repair gene variants may be expected to have acted. No differences in genotype frequencies at the four SNP loci were seen, indicating that there is no evidence of association with longevity in this population. Significant differences in frequency of certain repeat sizes at three microsatellite loci were detected. However, since there is no known functional consequence of these repeat lengths, the action of selection cannot yet be ascribed.

Aged↗
PubMed2006

Genes and longevity: a genetic-demographic approach reveals sex- and age-specific gene effects not shown by the case-control approach (APOE and HSP70.1 loci).

Association analyses between gene variability and human longevity carried out by comparing gene frequencies between population samples of different ages (case/control design) may provide information on genes and pathways playing a role in modulating survival at old ages. However, by dealing with cross-sectional data, the gene-frequency (GF) approach ignores cohort effects in population mortality changes. The genetic-demographic (GD) approach adds demographic information to genetic data and allows the estimation of hazard rates and survival functions for candidate alleles and genotypes. Thus mortality changes in the cohort to which the cross-sectional sample belongs are taken into account. In this work, we applied the GD method to a dataset relevant to two genes, APOE and HSP70.1, previously shown to be related to longevity by the GF method. We show that the GD method reveals sex- and age-specific allelic effects not shown by the GF analysis. In addition, we provide an algorithm for the implementation of a non-parametric GD analysis.

Adolescent↗
PubMed2006

Alpha1-antitrypsin heterozygosity plays a positive role in attainment of longevity.

Genes involved in cardiovascular diseases (CVD) play an opposite role in human longevity. The alpha1-antitrypsin (AAT) is a serine-protease inhibitor required for the prevention of proteolytic tissue damage, by neutrophil elastase. The role of AAT in CVD has not been definitively assessed and its effect on longevity has not yet fully been studied. To clarify these points, we have studied the distribution of AAT allele variants in 3 cohorts: 127 young patients affected by acute myocardial infarction (AMI), 255 young controls and 143 centenarians from Sicily. The Z allele frequency was most frequent in centenarians (13.3%), intermediate in healthy young controls (3.1%) and less frequent in AMI patients (1.2%) (P = 0.0000001). The heterozygous MZ genotype was significantly over represented in centenarians (38/143) and under represented in AMI patients (3/127) with intermediate values in young controls (16/255) (P = 0.0000001). After adjustment for well-recognized AMI risk factors, the MZ genotype still predicted a significant negative risk factor for developing AMI in the Sicilian population. Thus, our data show a positive role of MZ heterozygosity in attainment of successful ageing linked to the positive effects of this genotype versus the cardiovascular ischemic diseases.

Adult↗
PubMed1983

Body size, mortality, and longevity.

The body-size dependent relationships of mortality and longevity are examined for birds and eutherian mammals. Differences between mass exponents for maximum recorded longevity and survival times for fractions of original adult populations confirm the age-dependence of mortality in both classes and a size-dependency of population-age distribution. The potential number of offspring produced by a surviving fraction of a mammalian population appears to be a size-independent ecological constant. Social structure would be more likely in larger animals since greater continuity would be provided when a higher proportion of the population consisted of senior, experienced animals, as described by the ratio of time for survival of 1 in 1000 to maximum potential lifespan: t0.001/tmax = 0.91 m0.32/2.94 m0.20 = 0.31 m0.12, that is, the expected lifespan approaches the maximum as size increases.

Animals↗
PubMed1994

Age-related memory decline and longevity under treatment with selegiline.

The MAO-B inhibitor selegiline is used in the treatment of Parkinson's disease. Further, beneficial effects in Alzheimer's disease have also been described as well as neuroprotective effects, increased longevity and an attenuation of age-related cognitive decline in experiments using rats. Our studies in mice and Syrian hamsters aim at the question whether the effects of selegiline reported in the rat can be generalized to other species. Aged female NMRI-mice (23 mo.) treated with selegiline (0.25 mg/kg, i.p., 3 times a week for 2-3 weeks) showed no treatment effect in the Morris water maze and in passive avoidance learning after 2 and 3 weeks of treatment. However, Syrian hamsters chronically treated with selegiline (0.05 mg/kg/day in the food, starting at 12 months old) showed a 3 month delay in the age-related decline of spontaneous alteration behavior, a measure of longer-term memory, compared to untreated controls. Since treated hamsters also show increased longevity (study still in progress) the data suggest a protective effect of a chronic treatment with selegiline against age-related cognitive and physical decline.

Aging↗
PubMed1979

Longevity benefits and costs of reducing various risks.

"Increased longevity is one alternative to lives saved as a measure of benefits derived from large-scale risk-reduction programs that demand resources of the total population. This measure, for several categories of risk, is presented in the context of the risks prevalent to society. Some estimates of the theoretical benefits due to the successful reduction of risks imposed by industry are provided. Cost-effectiveness values and these measures of program impact on longevity are graphically presented for several mortality-reducing programs."

Demography↗
PubMedDate not supplied

Selection at implantation and longevity. A tentative theory.

Women enjoy a superior longevity, possibly at the price of a heavy loss of female conceptuses at an early stage of gestation. An immunological mechanism is proposed. A theory of selection at implantation is developed and generalized which leads to a new approach of longevity.

Blastocyst↗
PubMed1979

Spontaneous mutations balance reproductive selective advantage and genetically determine longevity.

The theory is presented that the genetic potential for longevity of a given species in a protected environment is determined by the rate of predation in the wild and by the frequency of spontaneous mutations. A common genetically determined lifespan representative of rare, long-lived individuals in the wild results from the slight selective advantage conferred by genotypes which do not cause early death. The selective advantage of reproductive rare survivors is limited by the rate of spontaneous mutations from a common potential longevity to those which limit lifespan to shorter times. The equilibrium frequency of life-limiting genes increases exponentially with increasing age when the rate of mutations is uniform for different degrees of life-shortening.

Aging↗
PubMed1984

Genetic study of high longevity index populations.

Five-year multidisciplinary study of longevity in the Georgian SSR made it possible to select two populations (Abkhazian and Imeretian), in which indices of longevity were much higher, than the average level for the rural population of the whole region. The distribution of polymorphic systems of red cell enzymes (adenilate kinase, esterase D, phosphoglucomutase I, acid phosphatase, 6-phosphogluconate dehydrogenase, glyoxalase I, lactate dehydrogenase, adenosine deaminase, glutamate pyruvate transaminase, phosphoglycolate phosphatase, phosphohexose isomerase) and serum proteins (haptoglobin, Gc-component and transferrin) was studied for genetic analysis of these populations. The results indicate that for all the studied loci the observed genotypic frequencies in both populations are distributed according to Hardy-Weinberg equilibrium. The genetic comparison of the studied populations with some other neighbouring populations did not reveal any genetic peculiarities and the both populations concord with the scheme of anthropological types of Hither Asia. The study of age-related changes of gene frequencies and heterozygosity showed some age-related fluctuations of genetic indices in all age groups, but the heterogeneous nature of these deviations indicate that they may be the result of random genetic processes.

Adolescent↗
PubMedDate not supplied

Dominance and complementation relationships of conidial longevity mutants of Neurospora crassa.

Previously we reported the occurrence of 16 linked conidial longevity determinant genes in Neurospora. Mutations of those genes are characterized by a reduction of longevity, a pleiotropic morphological defect, and deficiency of five antioxygenic enzymes. On the basis of the linkage and biochemical data, it was proposed that the genes are spatially and functionally redundant. The results of the present investigation support the hypothesis of functional redundancy. All of the mutants examined were dominant to wild type and failed to complement in heterokaryons. These results are discussed in terms of two molecular models of gene function.

Chromosome Mapping↗
PubMed1986

Stagewise decline in the activity of brain protein synthesis factors and relationship between this decline and longevity in two rodent species.

The activities of brain initiation factor 2 and brain elongation factor 1, which function as rate-limiting in total protein synthesis, and estimations of brain weight were followed during postnatal life in the rat and the mouse. Both activities decreased in parallel while cumulative brain weight increased. Three exponential components were required for the mathematical expression of each of the three processes in semilogarithmic plots against time. The acceleration curves for the activities and tissue weight demonstrated a mirror image symmetry. Within the general pattern of diminution with age, the negative acceleration of the activities and the positive acceleration of the brain weight displayed repeated bursts. The activities of both factors could also be arranged into several regression lines in log/log plots against time. Significantly, in these plots, the regression line calculated for the whole set of data for each factor activity showed that the value of the ratio of the slopes (mouse to rat) was inversely related to the square root of the ratio of species longevity and was in agreement with the power law relating life spans of cells to species longevity (Röhme, Proc. Natl. Acad. Sci. U.S.A., 78 (1981) 5009).

Animals↗