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PubMed2002

Association between the MHC class I gene HFE polymorphisms and longevity: a study in Sicilian population.

Classes I and II human leukocyte antigens (HLA) genes encode highly polymorphic heterodimeric glycoproteins involved in the control of immune responses. The HLA class I gene HFE seemingly no longer participates in immunity because it has lost its ability to bind peptides and it has acquired the ability to form complex with the receptor for iron-binding transferrin by regulating iron uptake by intestinal cells. Thus, it indirectly regulates immune responses too, because iron availability plays a role in specific and non-specific immune responses. The distribution of HFE polymorphisms in Sicilian centenarians and nonagenarians was studied to evaluate if HFE alleles might be represented differently in people selected for longevity. DNA samples were obtained from 106 young controls (age range from 22 to 55 years; 40 men and 66 women) and 35 elderly subjects (age range from 91 to 105 years; seven men and 28 women). Samples were typed for C282Y, H63D and S65C alleles using polymerase chain reaction and sequence specific primers. Among the young individuals, none was heterozygous for the C282Y or for S65C mutation. Twenty-six were heterozygous for H63D mutation. Among the elderly subjects, 11 were heterozygous for the C282Y mutation or for H63D mutation. None was heterozygous for the S65C mutation. No compound heterozygous individuals (C282Y/H63D) were found. A highly significant difference was observed in frequencies of C282Y alleles between the young and the elderly subjects on the whole. By analysing polymorphisms according to gender, heterozygous subjects for C282Y were found both in old men and in old women, but by comparing the allele frequencies to those of young people significance was attained only in women. Concerning H63D polymorphisms, no significant differences were observed, between old and young people, both in men and in women. Possession of C282Y allele, known to be associated with an increase of iron uptake, significantly increases women possibility to reach longevity. Thus, present data adds another piece of evidence to the complex puzzle of genetic and environmental factors involved in control of lifespan expectancy in humans.

Adult↗

PubMed2005

The human tumour suppressor PTEN regulates longevity and dauer formation in Caenorhabditis elegans.

The PTEN tumour suppressor is a phosphatase that dephosphorylates phosphatidylinositol 3, 4, 5 triphosphate (PIP3) and protein substrates. PTEN function is modulated by its carboxy-terminal region, which contains several clustered phosphorylation sites and a PDZ-binding motif (PDZbm). Although PTEN growth suppression effect is well demonstrated, its additional biological roles are less well understood. DAF-18, a Caenorhabditis elegans homologue PTEN, is a component of the insulin/IGF-I signalling pathway that controls entry to the dauer larval stage and adult longevity. To further explore the role of PTEN in the insulin signalling cascade and its possible involvement in the mechanisms of ageing, we undertook a study of PTEN function in C. elegans. We now report that human PTEN can substitute for DAF-18 and restores the dauer and longevity phenotypes in worms devoid of DAF-18. Furthermore, we provide genetic and biochemical evidence that dauer and lifespan control depends on PTEN-mediated regulation of PIP3 levels. Finally, we established that phosphorylation sites in the C-terminus of PTEN and its PDZbm are necessary for PTEN control of the insulin/IGF-I pathway. These results demonstrate that PTEN negatively regulates the insulin/IGF pathway in a whole organism and raise the hypothesis that PTEN may be involved in mammalian ageing.

Aging↗

PubMed1999

The evolutionary genetics of ageing and longevity.

Evolutionary theories of ageing are based on the observation that the efficacy of natural selection decreases with age. This is because, even without ageing, individuals will die of environmental causes, such as predation, disease and accidents. Ageing is thought to have evolved as the result of optimising fitness early in life. A second process, namely the progressive accumulation of mutations with effects late in life, will reinforce this result. Longevity of a species is therefore determined by the amount of environmental mortality caused by the ecology of a species. The experimental data concerning the relative roles of both processes are reviewed here. Recent discoveries of the levelling of mortality curves, and of age specific mutations in mutation accumulation lines of Drosophila melanogaster, require adjustments to the original models of the evolution of ageing and species longevity. These adjustments do not invalidate the underlying rationale of evolutionary theories of ageing. With current developments in QTL mapping and genetic association studies, the unravelling of the ageing process has the potential to progress rapidly.

Aging↗

PubMed1996

Determinants of longevity: genetic, environmental and medical factors.

This review focuses on the determinants of longevity in the industrialized world, with emphasis on results from recently established data bases. Strong evidence is now available that demonstrates that in developed countries the maximum lifespan as well as the mean lifespan have increased substantially over the past century. There is no evidence of a genetically determined lifespan of around 85 years. On the contrary, the biggest absolute improvement in survival in recent decades has occurred amongst 80+ year-olds. Approximately one-quarter of the variation in lifespan in developed countries can be attributed to genetic factors. The influence of both genetic and environmental factors on longevity can potentially be modified by medical treatment, behavioural changes and environmental improvements.

Aged↗

PubMed1998

A possible association between paternal longevity and major depression among elderly men.

Ancestral longevity is sometimes thought to contribute to psychosocial well-being in late life. The present paper aims to examine if parental longevity is associated with mental health among the elderly. The age at death of the parents was compared between 68 patients with major depression who were aged 65 or over and 40 subjects of the same age range without any history of psychiatric disorder. Cox regression revealed that the fathers of the elderly men with unipolar depression died at a significantly younger age than those of the control group. Several hypotheses are advanced to explain this unexpected and intriguing association.

Age Factors↗

PubMed2000

Evolution, stress, and longevity.

The disposable soma theory suggests that longevity is determined through the setting of longevity assurance mechanisms so as to provide an optimal compromise between investments in somatic maintenance (including stress resistance) and in reproduction. A corollary is that species with low extrinsic mortality are predicted to invest relatively more effort in maintenance, resulting in slower intrinsic ageing, than species with high extrinsic mortality. We tested this prediction in a comparative study of stress resistance in primary skin fibroblasts and confirmed that cells from long-lived species are indeed more resistant to a variant of stressors. A widely studied example of within-species variation in lifespan is the rodent calorie restriction model. Food-restricted animals show elevations in a range of stress response mechanisms, and it has been suggested that this is an outcome of natural selection for life history plasticity. We have developed a theoretical model for dynamic optimisation of the allocation of effort to maintenance and reproduction in response to fluctuations in food availability. The model supports the suggestion that the response to calorie restriction may be an evolutionary adaptation, raising interesting questions about the hierarchy of genetic control of multiple stress response systems. The model identifies ecological factors likely to support such an adaptation that may be relevant in considering the likely relevance of a similar response to calorie restriction in other species. Comparative and theoretical studies support the role of somatic maintenance and stress response systems in controlling the rate of ageing.

Animals↗

PubMed2003

Logistic regression models for polymorphic and antagonistic pleiotropic gene action on human aging and longevity.

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.

Age Factors↗

PubMed1979

Tumour incidence, growth, reproduction and longevity in female C3H mice fed polyunsaturated ruminant-derived foodstuffs.

Earlier studies with the random-bred Quackenbush mouse strain showed that human-type diets based on linoleic acid-enriched foodstuffs derived from ruminants fed protected polyunsaturated oils have no detrimental effects on growth, reproduction or longevity. Tumour incidence and time of onset of tumour development have now been studied in the inbred, tumour-prone mouse strain C3H, in addition to growth, reproduction and longevity. Mice were fed a polyunsaturated human diet, a conventional human diet, or mouse cubes. The results with C3H mice tended to confirm those with Quackenbush strain mice-growth rates and reproductive productivities were very similar in the two groups eating human diets. Mice on the conventional human diet tended to survive better to about 60 weeks of age than mice on the polyunsaturated diet or the cube diet, after which the mortality rates of the mice on the three diets were similar. The degree of unsaturation of the dietary fat had no significant effect on the incidence of tumours. The tumour incidence was about 40% which, taken in conjunction with the average age of onset (about 80 weeks), suggested that the NIV virus rather than the MMTV virus was responsible. It would appear that the high-fat human diets had no effect on the incidence of mammary tumours caused by this virus.

Animal Feed↗

PubMed1984

Carotenoids and retinol: their possible importance in determining longevity of primate species.

Aging and cancer share a number of characteristics. This has led to the hypothesis that species' differences in longevity may be governed in part by the same mechanisms as those processes governing species' differences in their age-dependent probability of developing cancer. Much evidence has indicated that beta-carotene and retinol may be important natural anticarcinogens. Accordingly, they also may be important antiaging agents. This possibility has been tested by determining if a positive correlation exists between the concentration of carotenoids and retinol in serum and brain tissue with the maximal life-span potential of mammalian species. The results show a significant positive correlation for the carotenoids but not for retinol. These results suggest that the carotenoids may be biologically active as protective agents against cancer and as longevity determinants. Retinol appears to be less important in these functions.

Aging↗

PubMed2001

Comparative development, longevity and population growth of exotic and native parasitoids of lepidopteran cereal stemborers in Kenya.

Studies on the effect of temperature on the development, longevity and population growth of Cotesia flavipes Cameron and Cotesia sesamiae (Cameron) indicated that the development of both Cotesia spp. from oviposition to cocoon formation and adult emergence was inversely related to temperature. The longevity of the parasitoids was also inversely related to temperature. Both parasitoids lived longer when moisture and food (agar + honey/water) were provided. The mean number of females and total adult progeny produced by C. flavipes on two host species were, in most cases, higher than C. sesamiae. The intrinsic rate of natural increase of C. flavipes was higher than that of C. sesamiae.

Animals↗

PubMed2006

Contribution of natural food sources to reproductive behaviour, fecundity and longevity of Ceratitis cosyra, C. fasciventris and C. capitata (Diptera: Tephritidae).

The influence of food sources comprising the natural diet on the reproductive behaviour, fecundity and longevity of three African fruit flies Ceratitis cosyra (Walker), C. fasciventris (Bezzi) and C. capitata (Wiedemann) was investigated. Three natural food sources, varying in protein and sugar content, were evaluated. These included bird droppings (farm chicken), aphid honeydew and guava (Psidium guajava L.) juice. For C. fasciventris and C. capitata, flies fed on a protein-rich diet displayed higher frequency of calling, mating and oviposition than flies fed on a protein-poor diet, whilst for C. cosyra, quality of diet significantly influenced the mating behaviour of the flies, but not the calling and oviposition behaviour. Net fecundity rates were lowest for C. fasciventris and C. capitata when fed only on guava juice (0.1, 2.6 eggs per female, respectively), and higher for those on a diet of honeydew only (9.5, 33.8 eggs per female, respectively) and a combined diet of guava, honeydew and chicken faeces (11.8, 25.8 eggs per female, respectively). For C. cosyra, due to low numbers of eggs collected, no significant differences in fecundity between diets could be detected. All species fed only on a diet of chicken faeces since emergence died within the first three days of adult life without laying eggs, but when carbohydrates were provided by addition of guava juice and honeydew, the longevity of the flies was sustained for more than four weeks after adult emergence. The practical implications of these findings for control purposes are discussed.

Analysis of Variance↗

PubMed2003

On the longevity of Schistosoma curassoni.

It is demonstrated that Schistosoma curassoni, a parasite of sheep, cattle and goats in parts of West Africa, will live for at least 8 years 5 months in a sheep. The sheep was exposed to 500 cercariae of S. curassoni liberated from infected Bulinus wrighti. The sheep died of natural causes, and at post-mortem 28 pairs of adult S. curassoni were removed from the mesenteric and rectal veins. All female worms were gravid, and eggs were hatched from faeces to produce miracidia. The development of immune responses of the host had apparently little or no effect on the viability of the eggs. Histological studies of the liver, small and large intestines revealed mild pathological symptoms. The longevity of S. curassoni is the first record of longevity of schistosomes to be based on worm counts.

Africa, Western↗

PubMed2004

Traditional Mediterranean diet and longevity in the elderly: a review.

OBJECTIVE: To review the evidence that the traditional Mediterranean diet is associated with longevity. SETTING: Elderly persons of both genders in Greece, Spain, Denmark and Australia studied by different groups of investigators. METHODS: Adherence to the principles of the Mediterranean diet was operationalised through a score devised a priori, and study participants were followed up until death or the end of the study. Proportional hazard models were used. RESULTS: Closer adherence to the Mediterranean diet was associated with a significant decrease in general mortality among the elderly persons studied. CONCLUSION: The Mediterranean diet is positively associated with longevity among the elderly. If the assumption holds that there is no interaction between age and diet with respect to general mortality, it can be inferred that the traditional Mediterranean diet represents a healthy nutritional pattern.

Aged↗

PubMed1990

Endurance capacity and longevity in women.

The aim of our study was to compare the cardiovascular and metabolic adjustments of 8 female and 8 male subjects to similar situations of physical stress, which involved muscle contractions at various intensities, and to link the results with the fact that in Scandinavia, women survive men by an average of 5-10 years. The mean age of subjects was 25 years old, and all were in good health. It was concluded that the cardiovascular and metabolic reactions to comparable regimens of physical stress differ markedly between female and male subjects: The women demonstrated the healthier adjustments, with lesser blood pressure elevation and a higher degree of lipid utilization. Both reactions are linked to protective mechanisms with respect to developing ischemic heart disease. We suggest that these adjustments are linked to longevity in women, and that part of the explanation of the sex differences in physiological adjustments to physical stress and in longevity lies in the fact that women through life are subjected to a higher degree of physical activity.

Adult↗

PubMed2005

The longevity of Baseball Hall of Famers compared to other players.

The authors compared the longevity of all baseball players alive at the time of their induction into the Baseball Hall of Fame with age-matched controls who were likewise alive at the time of the Hall of Famer's induction, and also matched them for career length, player position, and body-mass index, to assess if fame in sports is associated with increased longevity. Median post-induction survival for Hall of Famers was 5 years shorter than for noninducted players (18 vs. 23 years, respectively). In a second analysis, significantly more Hall of Famers died of cardiovascular or stroke causes than other players for whom cause of death was known. Baseball fame may have a hitherto unrecognized price.

Awards and Prizes↗

PubMedDate not supplied

Longevity of major league baseball players.

The purpose of this study was to determine whether major league baseball players live lontger than the general public. Ages of death of major league baseball players who debuted between 1900 and 1950 were obtained, and differences between ages of death and age-adjusted life expectancies were determined by analysis of variance and t-tests, taking into account player position. Correlational analysis also was conducted to determine if career length affected longevity. Baseball players lived an average of four years longer than age-matched controls from the general public. Career length did not affect longevity among players. We concluded that professional athletes, as represented by major league baseball players, have increased life expectancies. This increase cannot be explained by increased fitness associated with working as a professionral athlete, but is likely the result of an initial selection process for becoming a professional athlete.

Aged↗

PubMedDate not supplied

On the relationship between handedness and longevity.

During the past five years, there have been numerous studies of the relationship between handedness and longevity. In this report, I review previous contributions and use methods of survival analysis on a set of 4,448 males to determine the strength of the relationship between handedness and longevity. The results indicate that left-handers have small, yet significant, declines in survival probabilities between the ages of 65 and 85.

Adolescent↗

PubMed1969

Lasting biological effects of early environmental influences. V. Viability, growth, and longevity.

The effects of neonatal influences on the growth and longevity of mice were studied by using animals derived from a highly inbred germfree colony that had been reassociated with a microbial flora free of known pathogens. The size of the animals at weaning time could be conditioned predictably by manipulating the diet of their mothers during gestation and lactation or by shortening or lengthening the period of lactation. A deficient diet during gestation or during lactation decreased the metabolic efficiency of the adult animal, even if it was fed an optimum diet after weaning. The effect was greatest when malnutrition occurred during both pregnancy and lactation. In contrast, an optimum diet during gestation and lactation rendered the animal less susceptible to the depressing effects of nutritional deficiency during adult life. A marked and lasting growth depression could be reproducibly achieved by contaminating newborn mice orally with an unidentified enterovirus. But neonatal infection with enterobacteria or mycobacteria even though severe, did not significantly alter the growth rate. Regardless of its initial cause, the depression of the growth rate during the preweaning period persisted throughout the whole life span of the animals, even when they were placed under optimum sanitary and nutritional conditions after weaning. Agencies (nutritional or infectious) which brought about a depression of whole body weight also affected the absolute and relative sizes of the various organs, especially of the brain. By manipulating neonatal influences, it was possible to produce at will in a given colony of highly inbred mice a family of strikingly different growth curves. This could be done without causing the death of any animal or affecting longevity.

Animals↗