SEARCH · Search PubMed

Results for “longevity”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources

PubMed2006

Mitochondrial DNA involvement in human longevity.

The main message of this review can be summarized as follows: aging and longevity, as complex traits having a significant genetic component, likely depend on a number of nuclear gene variants interacting with mtDNA variability both inherited and somatic. We reviewed the data available in the literature with particular attention to human longevity, and argued that what we hypothesize for aging and longevity could have a more general relevance and be extended to other age-related complex traits such as Alzheimer's and Parkinson's diseases. The genetics which emerges for complex traits, including aging and longevity, is thus even more complicated than previously thought, as epistatic interactions between nuclear gene polymorphisms and mtDNA variability (both somatic and inherited) as well as between mtDNA somatic mutations (tissue specific) and mtDNA inherited variants (haplogroups and sub-haplogroups) must be considered as additional players capable of explaining a part of the aging and longevity phenotype. To test this hypothesis is one of the main challenge in the genetics of aging and longevity in the next future.

Cell Nucleus↗

PubMed2004

Identification of a geographic area characterized by extreme longevity in the Sardinia island: the AKEA study.

High prevalence and low female/male ratio for validated centenarians are observed in Sardinia and these findings appear to be thus far unique to this island. Moreover a specific region on the island is characterized by exceptional male longevity. We calculated the extreme longevity index (ELI), defined as the percentage of persons born in Sardinia between 1880 and 1900, who became centenarians. A gaussian smoothing method was used in order to identify the so-called 'Blue Zone', where longevity is concentrated in the central-eastern part of the island and covers all the mountainous areas of central Sardinia. The estimated life expectancy in the 'Blue Zone' is longer than in the remaining territory of the island especially for men and the male to female ratio among centenarians born in this area is 1.35 compared to 2.43 in the rest of Sardinia. The specific mechanism by which persons living in this territory were more likely to reach extreme longevity remains unknown but it is interesting to note that most of the 'longevity hot spots' identified in various regions of the world over the years have been located in mountainous geographical areas even if none of these longevity regions have been fully validated. An alternative and interesting hypothesis is that the high rate of inbreeding determined by frequent marriages between consanguineous individuals and low immigration rates have progressively decreased the variability of the genetic pool and facilitated the emergence of genetic characteristics that protect individuals from diseases that are major causes of mortality particularly in older individuals. Given the exceptionally high prevalence of male centenarians in the 'Blue Zone', it is reasonable to assume that either the environmental characteristics or the genetic factors, or both, exert their favorable effect more strongly in men than in women. Thus, the mechanism involved may be modulated by the hormonal milieu, or may be associated with genes located in the sex chromosomes.

Aged↗

PubMed2004

Dietary glycerol and adult access to water: effects on fecundity and longevity in the almond moth.

The quality of food eaten by larval insects will affect traits such as gamete production, fat reserves, muscle bulk and body size in the adult. Moreover, larvae also depend on high moisture content in the diet for survival. The almond moth (Ephestia cautella) (W.) (Lepidoptera; Pyralidae) does not feed as an adult although it continues to drink water. We tested the idea that an almond moth could compensate for a low-water diet as a larva by increasing its water intake as an adult. We reared larvae on two different food sources with different moisture regimes; standard laboratory diet with glycerol (relatively wet) and standard diet without glycerol (relatively dry). Half the adult moths from each treatment were given water to drink before their first and only mating. Our results show that wet larval diets (i.e. containing glycerol) significantly decreased fecundity (total number of eggs laid and the proportion of hatched larvae), whilst it significantly increased male and female longevity. The interaction effect of water access for adult males and females was significant, independent of the glycerol in the larval diet. Longevity in females that were not presented with water as adults was slightly higher if mated with a male that had had access to water, suggesting a mating donation of water. However, females that received water as adults showed a decreased longevity if mated with a male who had also had access to water as an adult, indicating a negative effect of water if received by both males and females. In addition, when the larval diet included glycerol, increased number of eggs laid decreased female longevity, whilst an absence of glycerol in the larval diet resulted in low female longevity that was unlinked with fecundity. Glycerol is used in many artificial insect diets and the fact that it shows a strong effect on key life-history traits (reproductive output and longevity in this species), merits careful re-examination of its effects on these important traits in other laboratory models. We also discuss the possibility that larval diet can affect female reproductive decisions.

Analysis of Variance↗

PubMed1998

Longevity of exercising male rats: effect of an antioxidant supplemented diet.

Food restriction increases maximal life span in rodents. Male rats that exercise in voluntary running wheels do not have an increase in maximal longevity despite a relative caloric deficit. In contrast, sedentary rats that are food restricted so as to cause the same caloric deficit have an extension of maximal longevity. It seemed possible that exercise-induced oxidative stress might prevent a maximum life span-extending effect of a caloric deficit to manifest itself. This study was done to determine if antioxidants would allow a maximal longevity-extending effect of exercise to manifest itself in male rats. The antioxidant diet had no effect on longevity of the runners (Antiox., 951 +/- 158 days versus control 937 + 171 days), or of the sedentary controls (875 +/- 127 versus 858 +/- 152 days). As in previous studies, wheel running modestly increased average longevity (approximately 9%), but had no effect on maximal life span. The finding that antioxidants had no effect on longevity of the wheel runners supports the interpretation that the caloric deficit induced by exercise in male rats does not have a life-extending effect that is countered by oxidative tissue damage.

Animals↗

PubMed2000

Double bond content of phospholipids and lipid peroxidation negatively correlate with maximum longevity in the heart of mammals.

Free radical damage is currently considered a main determinant of the rate of aging. Unsaturated fatty acids are the tissue macromolecules most sensitive to oxidative damage. Therefore, the presence of relatively low degrees of fatty acid unsaturation is expected in the tissues of longevous animals. In agreement with this prediction, fatty acid analyses of heart phospholipids in eight mammals ranging in maximum life span (MLSP) from 3.5 to 46 years showed that their total number of double bonds is negatively correlated with MLSP (r = -0.78, P < 0.02). The low double content of longevous mammals was not due to a low polyunsaturated fatty acid content. Instead, it was mainly due to a redistribution between types of polyunsaturated fatty acids from the highly unsaturated docosahexaenoic acid (22:6n-3) to the less unsaturated linoleic acid (18:2n-6) in longevous animals (r = -0.89, P < 0.003 for 22:6n-3 and r = 0.91, P < 0.002 for 18:2n-6 versus MLSP), where n = number of different animals in each species. This redistribution suggests that one of the mechanisms responsible for the low number of fatty acid double bonds is the presence of low desaturase activities in longevous animals, although other causing factors must be involved. In agreement with the low degree of fatty acid unsaturation of longevous mammals, the sensitivity to lipid peroxidation (r = -0.87; P < 0.005) and the in vivo lipid peroxidation (r = -0.86, P < 0.005) in the heart were also negatively correlated with MLSP across species. These results, together with previous ones obtained in rodents, birds, and humans, suggest that the low degree of tissue fatty acid unsaturation of longevous homeothermic animals could have been selected during evolution to protect the tissues against oxidative damage.

Aging↗

PubMed2001

Sex-specific longevity associations defined by Tyrosine Hydroxylase-Insulin-Insulin Growth Factor 2 haplotypes on the 11p15.5 chromosomal region.

By studies in centenarians, it was recently found that an STR marker of the Tyrosine Hydroxylase (TH, 11p15.5) gene is associated with human longevity. The aim of the present study was to continue the exploration of the 11p15.5 chromosomal region in human longevity by analyzing two additional RFLP markers, which lie in the Insulin (INS) and Insulin Growth Factor 2 (IGF2) genes. Both the genes, which are localized downstream TH, are indeed good candidates in longevity, as ascertained on the basis of laboratory studies in experimental models. Neither INS nor IGF2 markers did reveal association with longevity. Nevertheless, linkage disequilibrium analyses showed sex-specific longevity associations defined by both TH-INS and TH-IGF2 haplotypes. On the whole, the results reinforce the involvement of the chromosomal region spanning from TH to IGF2 loci in controlling the longevity phenotype in humans.

Adult↗

PubMed2002

Longevity, mortality and body weight.

The purpose of this study was to analyze the relation of total body weight to longevity and mortality. The MEDLINE database was searched for data that allow analysis of the relationship between absolute body weight and longevity or mortality. Additional data were used involving US veterans and baseball players. Trend lines of age at death versus body weight are presented. Findings show absolute body size is negatively related to longevity and life expectancy and positively to mortality. Trend lines show an average age at death versus weight slope of -0.4 years/kg. We also found that gender differences in longevity may be due to differences in body size. Animal research is consistent with the findings presented. Biological mechanisms are also presented to explain why increased body mass may reduce longevity. Life expectancy has increased dramatically through improved public health measures and medical care and reduced malnutrition. However, overnourishment and increased body size have promoted an epidemic of chronic disease and reduced our potential longevity. In addition, both excess lean body mass and fat mass may promote chronic disease.

Animals↗

PubMed2001

Application of the gene search system to screen for longevity genes in Drosophila.

We have developed a strategy using Drosophila as a model system to identify genes that are crucial for extension of longevity. A collection of transgenic lines with a P-element based gene search (GS) vector containing UAS (Upstream Activating Sequence) was screened for longevity in combination with an hsp70 promoter-driven GAL4 transgene. Misexpression of the vector-flanking sequence was induced throughout the adult stage to assess its effects on the aging process rather than development. We showed that the longevity was greatly affected by GS inserts, and it was positively correlated with paraquat resistance. Of 646 GS inserts, we selected 23 inserts with relatively longer longevity for further molecular analysis. All of the misexpressed sequences matched either known genes or ESTs (Expressed Sequence Tags). Among 13 genes whose functions are already known or suggested, six were related to stress resistance or redox balance (DmGST2, hsp26, nla, and Drosophila homologs of mammalian TRX, GILT and POSH), suggesting the importance of stress resistance for the extension of longevity. This is the first demonstration that a systematic gain-of-function screen could efficiently detect longevity genes.

Animals↗

PubMed2002

Longevity genes in the nematode Caenorhabditis elegans also mediate increased resistance to stress and prevent disease.

More than 40 single-gene mutants in Caenorhabditis elegans have been demonstrated to lead to increased lifespan (a rigorous, operational test for being a gerontogene) of 20% or more; these are referred to collectively as 'Age' mutants. Age mutants must change key functions that are rate-limiting determinants of longevity; moreover, important genes can be identified independently of prior hypotheses as to actual mode of gene action in extending longevity and/or 'slowing' of ageing. These Age mutants define as many as nine (possibly) distinct pathways and/or modes of action, as defined by primary phenotype. Each of three well-studied mutants (age-1, clk-1, and spe-26) alters age-specific mortality rates in a fashion unique to itself. In age-1 mutants, the decreases in mortality rates are quite dramatic, with an almost tenfold drop in mortality throughout most of life. All Age mutants (so far without exception) increase the ability of the worm to respond to several (but not all) stresses, including heat, UV, and reactive oxidants. We have used directed strategies as well as random mutagenesis to identify novel genes that increase the worm's ability to resist stress. Two genes (daf-16 and old-1) are epistatic to the long-life phenotype of most mutants and also yield over-expression strains that are stress-resistant and long-lived. We have also used a variety of approaches to determine what transcriptional alterations are associated with increased longevity (and with ageing itself), including whole-genome expression studies using microarrays and GFP reporter constructs. We suggest that the role of the Age genes in both longevity and stress resistance indicates that a major evolutionary determinant of longevity is the ability to respond to stress. In mammals, both dietary restriction and hormesis are phenomena in which the endogenous level of resistance to stress has been upregulated; both of these interventions extend longevity, suggesting possible evolutionary conservation.

Animals↗

PubMed2003

Impact of automatic adjustment of stimulation outputs on pacemaker longevity in a new dual-chamber pacing system.

INTRODUCTION: Automatic capture verification using the Autocapture (AC) feature enabled by paced evoked response detection and delivery of high energy back-up pulses intends to increase patient safety. Furthermore, adjustment of stimulation outputs can save energy and potentially improve pacemaker (PM) longevity. The purpose of this study was to evaluate the theoretical longevity of a new dual chamber PM with the integrated AC feature (Affinity DR, St. Jude Medical) in comparison to the longevity of a previous model from the same manufacturer without AC (Trilogy DR). METHOD: Affinity PMs were implanted in 16 patients and connected to a compatible lead with low polarization properties. AC was activated when the evoked response was significantly higher than the polarization voltage. Theoretical PM longevity was calculated with and without AC during follow-up. The measured and calculated values were compared to measurements in 19 patients, who consecutively received Trilogy-PMs during the same time period. RESULTS: In only one patient the evoked response was not adequate, and as a result, AC was not programmed. The calculated longevity of the Affinity-PMs 79 +/- 28 days after implantation was significantly higher in comparison to the Trilogy-PMs (Affinity-PMs: 8.9 +/- 1.2 years without and 9.5 +/- 1.1 years with AC; Trilogy-PMs: 6.5 +/- 0.8 years) (p < 0.005). CONCLUSION: The AC feature is an optional algorithm that can be activated in most patients and it significantly prolongs predicted battery longevity due to automatic adjustment of stimulation outputs.

Adult↗

PubMed2000

The effect of longevity on spending for acute and long-term care.

BACKGROUND: The proportion of the population made up of elderly persons in the United States is projected to increase from 13 percent of the population in 2000 to 20 percent by 2030. The implications for health care expenditures may be profound, because elderly persons use health care services at a greater rate than younger persons. We estimated total expenditures for acute and long-term care from the age of 65 years until death and in the last two years of life. METHODS: We combined data from Medicare, the National Mortality Followback Survey, and the National Medical Expenditure Survey to estimate total national expenditures for health care according to the age at death. We also simulated expenditures with the use of projected demographic characteristics of two cohorts: people turning 65 in 2000 and those turning 65 in 2015. RESULTS: Total expenditures (in 1996 dollars) from the age of 65 years until death increase substantially with longevity, from $31,181 for persons who die at the age of 65 years to more than $200,000 for those who die at the age of 90, in part because of steep increases in nursing home expenditures for very old persons. Spending in the last two years of life also increases with longevity, but a reduction in Medicare expenditures ($37,000 for persons who die at the age of 75 years and $21,000 for those who die at the age of 95) moderates the effect of the increase in nursing home expenditures ($6,000 for those who die at the age of 75 years and $32,000 for those who die at the age of 95). Health care spending for women is consistently higher than that for men, after adjustment for the increased longevity of women. Simulations show that increased longevity after the age of 65 years has a relatively small effect on the anticipated increase in spending, especially for services covered by Medicare, from 2000 to 2015. The effects of the larger number of people born in 1950 than in 1935 and the larger number of people surviving to the age of 65 years are much more important. CONCLUSIONS: In the United States, the effect of longevity on expenditures for acute care differs from its effect on expenditures for long-term care. Acute care expenditures, principally for hospital care and physicians' services, increase at a reduced rate as the age at death increases, whereas expenditures for long-term care increase at an accelerated rate. Increases in longevity after the age of 65 years may result in greater spending for long-term care, but the increase in the number of elderly persons has a more important effect on total spending.

Aged↗

PubMed1983

Physiological assays for biological age in mice: relationship of collagen, renal function, and longevity.

Tests of physiological changes with age are illustrated by collagen denaturation times of tail tendon fibers, and urine concentrating abilities; the tests are evaluated using the following four criteria: change with age, repeatability, relationship to other assays, and relationship to longevity. These tests usually showed highly significant changes with age when mice of different ages were compared for nine mouse genotypes, however neither appeared to be related to subsequent longevities of individual mice. When average values for eleven mouse genotypes were compared, the mean longevities of the genotypes were not significantly correlated with their mean collagen denaturation times or mean renal concentrating abilities, testes at two different ages. The relationships between all three factors--collagen denaturation times, urine concentrating abilities, and longevities--were tested in the same individuals for mice of six different genotypes at 600-700 days of age. Only one marginally significant correlation appeared out of 21 tested; this probably occurred by chance. We conclude that tail tendon collagen denaturation times and urine concentrating abilities change with age independently of each other; furthermore, these changes are unrelated to subsequent longevities, at least when linear relationships are tested. These data suggest that aging is timed by more than one mechanism and demonstrate that strong correlations with chronological age do not necessarily indicate that independent tests will be correlated with longevity or with each other.

Aging↗

PubMed2003

Regulation of longevity in Caenorhabditis elegans by heat shock factor and molecular chaperones.

The correlation between longevity and stress resistance observed in long-lived mutant animals suggests that the ability to sense and respond to environmental challenges could be important for the regulation of life span. We therefore examined the role of heat shock factor (HSF-1), a master transcriptional regulator of stress-inducible gene expression and protein folding homeostasis, in the regulation of longevity. Down-regulation of hsf-1 by RNA interference suppressed longevity of mutants in an insulin-like signaling (ILS) pathway that functions in the nervous system of Caenorhabditis elegans to influence aging. hsf-1 was also required for temperature-induced dauer larvae formation in an ILS mutant. Using tissue-specific expression of wild-type or dominant negative HSF-1, we demonstrated that HSF-1 acts in multiple tissues to regulate longevity. Down-regulation of individual molecular chaperones, transcriptional targets of HSF-1, also decreased longevity of long-lived mutant but not wild-type animals. However, suppression by individual chaperones was to a lesser extent, suggesting an important role for networks of chaperones. The interaction of ILS with HSF-1 could represent an important molecular strategy to couple the regulation of longevity with an ancient genetic switch that governs the ability of cells to sense and respond to stress.

Animals↗

PubMed2002

Angiotensin-converting enzyme gene and longevity in the Xin Jiang Uighur autonomous region of China: an association study.

BACKGROUND: Longevity can be regarded as a multifactorial trait that results from an interaction between environmental factors and sets of epistatic alleles that have pleiotropic age-dependent effects. The Hotan district in the Xin Jiang Uighur Autonomous region of China is relatively isolated and is well known for an ethnic group that displays marked longevity. METHODS: We performed a correlation study between the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and longevity by comparing distributions of the polymorphism between three different ethnic groups in this region. We obtained data from 424 subjects comprising 227 Uighur individuals, 108 Kazakh individuals, and 89 Han individuals. All subjects in the latter two groups ranged in age from 65 to 70 years, whereas the Uighur subjects actually comprised two different age groups: those ranging in age from 59 to 70 years (Uighur older group in Hotan [UOH]) and those ranging in age from 90 to 113 years (Uighur longevity group in Hotan [ULH]). Genomic DNA was extracted from peripheral white blood cells. Polymerase chain reaction was performed to amplify the I/D polymorphic region of the ACE gene. RESULTS: Frequencies of the insertion (I) and deletion (D) alleles were 0.596 (243/408) and 0.404 (165/408) in the Uighur group, 0.606 (130/216) and 0.394 (85/216) in the Kazakh group, and 0.657 (117/178) and 0.343 (61/178) in the Han group. The overall distributions of alleles in these three groups did not differ significantly (chi(2) = 4.6, p =.33). Within the Uighur group, frequency of the D allele was significantly higher in the ULH group (0.448) than in the UOH group (0.355) (p <.04). CONCLUSIONS: This association reflects a genetic influence on differential survival and may point to pleiotropic age-dependent effects on longevity. Our data may help elucidate the relationship between natural longevity and race difference among individuals in the Xin Jiang Uighur Autonomous region of China.

Aged↗

PubMed1989

Is greater female longevity a general finding among animals?

(A) There are data showing beyond question a gender gap, with women living longer than men, especially in economically developed societies. There is greater male vulnerability to the major causes of human death. (B) In lower animals there are data suggesting a female survival advantage to adult life in many species, but the observations do not consider longevity or survival to an advanced age. (C) In laboratory rodents kept under controlled conditions the relationship of sex to longevity is variable, with males sometimes showing greater longevity than females and with life span being dependent on factors like breeding and diet. (D) Similar genetic and hormonal processes operate in humans and in non-human mammals including the genetic mechanism of sex determination, the hormonal consequences of sex determination, and the effects of hormones on processes which affect longevity such as cholesterol levels and immune functions. (E) Causes of death in humans and animals are different, and it seems unlikely, therefore, that the same mechanisms could be determinants of longevity in all mammalian species. (F) Human male and female longevity continue to change, and it is likely that the gender gap will narrow, with societal and medical changes in post-industrial societies reducing the male disadvantages in behaviour and in the handling of cholesterol. (G) It remains an important question whether part of the gender gap seen in humans is based on other differences in the basic biology of males and females.

Animal Population Groups↗

PubMed2004

Testing the "rate of living" model: further evidence that longevity and metabolic rate are not inversely correlated in Drosophila melanogaster.

In a recent study examining the relationship between longevity and metabolism in a large number of recombinant inbred Drosophila melanogaster lines, we found no indication of the inverse relationship between longevity and metabolic rate that one would expect under the classical "rate of living" model. A potential limitation in generalizing from that study is that it was conducted on experimental material derived from a single set of parental strains originally developed over 20 years ago. To determine whether the observations made with those lines are characteristic of the species, we studied metabolic rates and longevities in a second, independently derived set of recombinant inbred lines. We found no correlation in these lines between metabolic rate and longevity, indicating that the ability to both maintain a normal metabolic rate and have extended longevity may apply to D. melanogaster in general. To determine how closely our measurements reflect metabolic rates of flies maintained under conditions of life span assays, we used long-term, flow-through metabolic rate measurements and closed system respirometry to examine the effects of variables such as time of day, feeding state, fly density, mobility of the flies, and nitrogen knockout on D. melanogaster metabolic rate. We found that CO2 production estimated in individual flies accurately reflects metabolic rates of flies under the conditions used for longevity assays.

Animals↗

PubMed1980

Effects of long-term voluntary wheel exercise on male and female Wistar rats. I. Longevity, body weight, and metabolic rate.

Male and female Wistar rats (n = 140) age 1.5 months were maintained in either wheel-cage units or cage units for their entire life span. Voluntary wheel exercise significantly increased the mean longevity of both male and female rats compared with that of control rats. Between and within groups, growth duration was positively related to longevity, and growth rate was negatively related to longevity. These factors may explain differences in longevity between exercise and control groups and differences in longevity between male and female groups. These factors of growth, here defined in terms of body weight increment, may possibly account for many instances of group differences in longevity.

Aging↗

PubMed2005

Parental longevity and 7-year changes in blood pressures in adult offspring.

In this report, we examined the cross-sectional and the 7-year longitudinal changes in blood pressures in adult offspring according to parental longevity. A population of volunteers free of symptomatic cardiovascular diseases who participated to the Supplementation en Vitamines et en Minéraux Antioxydants (SUVIMAX) Vascular Study (mean age 52.3 years; 48.3% women) were examined at baseline and 7 years later. Paternal (n=994) and maternal (n=896) longevity were analyzed separately. The prevalence of hypertension at baseline in subjects whose father died at <65 years of age, in those whose fathers were alive by age 65 but died by 80 years of age, and in those whose fathers were alive by age 80 was respectively 34.9%, 28.5%, and 20.2% (P<0.001). The means of systolic blood pressure in the 3 groups of paternal longevity were respectively 128.4 (+/-16.0), 125.3 (+/-14.2), and 123.6 (+/-14.4) mm Hg (P<0.001). During the follow-up, the mean systolic blood pressure increases in the 3 groups of paternal longevity were respectively 5.3 (+/-17.0), 4.2 (+/-14.0), and 1.6 (+/-13.2) mm Hg (P<0.001). In subjects without hypertension at baseline, hypertension occurred during the follow-up in 26.6%, 17.7%, and 15.3% (P<0.009), respectively. Multivariate analyses adjusted for baseline or changes in cardiovascular risk factors did not modify these results. In contrast, there was no relationship between maternal longevity and blood pressure measurements in either cross-sectional or longitudinal analyses. This study suggests that paternal premature death was associated with accelerated progression of systolic blood pressure and higher occurrence of hypertension in offspring. These results indicate that there are dynamic and continuous processes linking paternal longevity to blood pressure in adults.

Adult Children↗