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PubMed1977

Body weight change over the life span and longevity for C57BL/6J mice and mutations which differ in maximal body weight.

Body weights were obtained monthly for mutant groups with the C57BL/6J genetic background which differ in body weight (bg, c,J Ay, ob), and for a control group (C57BL/6J) (n = 16, N = 80). The mean longevity was significantly lower for all mutant groups compared with the mean longevity of the control group. Although obese mice (ob) had a shorter life span than other mutant groups, mice which also attained a very high body weight (yellow, Ay) did not differ significantly in longevity from thin mutant mice. Moreover, peak body weight was positively correlated with longevity for all mouse groups. All mouse groups showed a terminal decline in body weight except the albino group which gained weight throughout life. In general, long-lived mice obtained a greater terminal weight loss than short-lived mice within groups. The major finding of this study was that within each group there was a negative relationship obtained between growth rate and longevity.

Aging↗
PubMed1994

Age estimation and longevity in reptiles.

After a brief recall of the classical meaning of the concept of longevity, the first part of this chapter describes and summarises the main current technique for the estimation of age in reptiles. Among them, sclerochronology is primarily taken into account. The cautious analysis of seasonal growth cycles recorded in hard tissues, although not as rigorous as the mark-release-recapture method of animals in their natural conditions, now appears as a rapid and reliable chronological tool already successfully used in individuals of many reptile species. Sclerochronology is especially efficient for the comparison of several populations, and it is the only method for fossils. The second part presents a synthetic review of known longevities and records in the different groups of reptiles. A short discussion about the significance of longevity shows that for reptiles, because of their thermic metabolism (ectothermy), the physiological longevity must be strongly distinguished from the chronological longevity, especially for a comparison with that known for birds and most mammals.

Aging↗
PubMed1995

Selection for increased longevity in Drosophila melanogaster: a reply to Lints.

An important tool in the genetic analysis of longevity and aging in Drosophila melanogaster is the use of strains selected directly for late-age reproduction and indirectly for extended longevity. Following some initial failures to select for extended longevity, there are now a number of laboratories which have successfully selected for long life, using the techniques of late-age reproduction as well as selection for stress resistance. Baret and Lints [Gerontology 1993;39:252-259] have recently cast doubt on the reality of a number of these selected strains, including our own, suggesting that the difference in longevity between the long-lived and normal-lived strains disappears when the data are examined as a function of the number of days after the beginning of the selection experiment instead of as a function of the number of generations. With regard to our selected lines, they based their analysis on a subset of the published data dealing with these strains, and which covered 21 generations, or 40 months, of selection. We now present data for over 70 generations, or 155 months, of selection and maintenance. The Baret-Lints hypothesis makes two strong predictions, namely that (1) the longevity difference between the several strains should disappear when the data are replotted according to their fashion, and (2) there should be no other significant biological difference between the strains. Our data falsifies both of these predictions. The Baret-Lints hypothesis is flawed and should be disregarded.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

Polymorphic variants of insulin-like growth factor I (IGF-I) receptor and phosphoinositide 3-kinase genes affect IGF-I plasma levels and human longevity: cues for an evolutionarily conserved mechanism of life span control.

Current literature indicates that abrogation of the IGF-I response pathway affects longevity in Caenorhabditis elegans, and that the down-regulation of IGF-I gene expression is associated with an extension of the life span in mice. In this paper we tested the hypothesis that polymorphic variants of IGF-I response pathway genes, namely IGF-IR (IGF-I receptor; G/A, codon 1013), PI3KCB (phosphoinositol 3-kinase; T/C, -359 bp; A/G, -303 bp), IRS-1 (insulin receptor substrate-1; G/A, codon 972), and FOXO1A (T/C, +97347 bp), play a role in systemic IGF-I regulation and human longevity. The major finding of this investigation was that subjects carrying at least an A allele at IGF-IR have low levels of free plasma IGF-I and are more represented among long-lived people. Moreover, genotype combinations at IGF-IR and PI3KCB genes affect free IGF-I plasma levels and longevity. These findings represent the first indication that free IGF-I plasma levels and human longevity are coregulated by an overlapping set of genes, contributing to the hypothesis that the impact of the IGF-I/insulin pathway on longevity is a property that has been evolutionarily conserved throughout the animal kingdom.

Adolescent↗
PubMed2006

Lipoprotein genotype and conserved pathway for exceptional longevity in humans.

Alteration of single genes involved in nutrient and lipoprotein metabolism increases longevity in several animal models. Because exceptional longevity in humans is familial, it is likely that polymorphisms in genes favorably influence certain phenotypes and increase the likelihood of exceptional longevity. A group of Ashkenazi Jewish centenarians (n = 213), their offspring (n = 216), and an age-matched Ashkenazi control group (n = 258) were genotyped for 66 polymorphisms in 36 candidate genes related to cardiovascular disease (CVD). These genes were tested for association with serum lipoprotein levels and particle sizes, apolipoprotein A1, B, and C-3 levels and with outcomes of hypertension, insulin resistance, and mortality. The prevalence of homozygosity for the -641C allele in the APOC3 promoter (rs2542052) was higher in centenarians (25%) and their offspring (20%) than in controls (10%) (p = 0.0001 and p = 0.001, respectively). This genotype was associated with significantly lower serum levels of APOC3 and a favorable pattern of lipoprotein levels and sizes. We found a lower prevalence of hypertension and greater insulin sensitivity in the -641C homozygotes, suggesting a protective effect against CVD and the metabolic syndrome. Finally, in a prospectively studied cohort, a significant survival advantage was demonstrated in those with the favorable -641C homozygote (p < 0.0001). Homozygosity for the APOC3 -641C allele is associated with a favorable lipoprotein profile, cardiovascular health, insulin sensitivity, and longevity. Because modulation of lipoproteins is also seen in genetically altered longevity models, it may be a common pathway influencing lifespan from nematodes to humans.

Aged↗
PubMed1996

Personality, longevity, and successful aging among Tokyo metropolitan centenarians.

The purpose of our study was to examine two hypotheses: 1) that androgyny and Type B behavior are related to longevity; and 2) that personality characteristics associated with longevity may also be related to successful aging. Participants were eighty-two centenarians (37 men and 45 women) who were compared with 605 elderly in their sixties, seventies, and eighties. Both groups were living in the Tokyo metropolitan area. We used the Bem Sex Role Inventory and Bortner Pattern A Behavior Scales to measure personality, and the Rosenberg Self-Esteem Scale and Cattell Anxiety Scale to measure successful aging. We found that androgyny was not more prominent among centenarians than masculinity, femininity, or undifferentiated. In fact, more femininity was observed. Additionally, we found that more women were classified as feminine than were men. The results indicated more Type B's among centenarians than among those in their sixties and more women than men showed Type B behavior. Our hypothesis that Type B behavior is related to longevity was supported. We observed lower self-esteem for femininity than for either the masculinity or androgyny. We also observed that anxiety was lower for femininity than masculinity but higher than androgyny among women. Type B women showed lower self-esteem than Type A women. Type B men showed lower anxiety than Type A men. We conclude that femininity is related to longevity and that androgyny may be related to successful aging. Further, we suggest that Type B behavior is associated with longevity, but its relationship to successful aging differs between men and women.

Aged↗
PubMed2004

Prediction of longevity breeding values for US Holstein sires using survival analysis methodology.

Breeding values of Holstein sires for daughter longevity in each of 9 geographical regions of the United States were predicted using a Weibull proportional hazards model. Longevity (also commonly referred to as herd life or length of productive life) was defined as the number of days from first calving until culling or censoring. Records from 2,322,389 Holstein cows with first calving from 1990 to 2000 were used. In addition to the sire's additive genetic merit, our failure time model included time-dependent effects of herd-year-season of calving, parity-stage of lactation, and within-herd-year quintiles for mature equivalent fat plus protein yield, as well as the time-independent effect of age at first calving. Sire variances and parameters of the Weibull distribution were estimated separately for each region. The relative risk of culling for daughters of each individual sire was expressed relative to that of daughters of an average sire (within a specific region). Predicted breeding values for functional longevity, expressed as relative risk ratios, ranged from 0.7 to 1.3. Sizable differences were observed between geographical regions in sire rankings, as well as estimated sire variances and gamma parameters (of the distribution of herd-year-season effects), suggesting that a single national ranking may not be appropriate for every region. Two random samples of herds were selected from the full national data set; these contained 375,086 records and 256,751 records, respectively. Predicted transmitting abilities (PTA) of sires for daughter longevity were calculated using the Weibull proportional hazards (sire) model described previously but without the correction for milk production. These were compared with predictions from a linear (animal) model, as currently used for routine genetic evaluation of length of productive life in the United States. Logistic regression of daughters' stayability to 36, 48, 60, 72, or 84 mo of life (among animals that had opportunity to stay that long) on sires' PTA indicated that the proportional hazards model yielded more accurate predictions of daughter longevity than the linear animal model, even though the latter relied on denser pedigree information.

Animals↗
PubMed1999

The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans.

Longevity is regulated by the daf-2 gene network in Caenorhabditis elegans. Mutations in the daf-2 gene, which encodes a member of the insulin receptor family, confer the life extension (Age) phenotype and the constitutive dauer (a growth-arrested larval form specialized for dispersal) formation phenotype. The Age phenotype is mutually potentiated by two life extension mutations in the daf-2 gene and the clk-1 gene, a homologue of yeast CAT5/COQ7 known to regulate ubiquinone biosynthesis. In this study, we demonstrated that the daf-2 mutation also conferred an oxidative stress resistance (Oxr) phenotype, which was also enhanced by the clk-1 mutation. Similar to the Age phenotype, the Oxr phenotype was regulated by the genetic pathway of insulin-like signaling from daf-2 to the daf-16 gene, a homologue of the HNF-3/forkhead transcription factor. These findings led us to examine whether the insulin-like signaling pathway regulates the gene expression of antioxidant defense enzymes. We found that the mRNA level of the sod-3 gene, which encodes Mn-superoxide dismutase (SOD), was much higher in daf-2 mutants than in the wild type. Moreover, the increased sod-3 gene expression phenotype is regulated by the insulin-like signaling pathway. Although the clk-1 mutant itself did not display Oxr and the increased sod-3 expression phenotypes, the clk-1 mutation enhanced them in the daf-2 mutant, suggesting that clk-1 is involved in longevity in two ways: clk-1 composes the original clk-1 longevity program and the daf-2 longevity program. These observations suggest that the daf-2 gene network controls longevity by regulating the Mn-SOD-associated antioxidant defense system. This system appears to play a role in efficient life maintenance at the dauer stage.

Animals↗
PubMed2003

[How long can a life be? Longevity not a matter for health care alone; today a host of companies would lure us with remedies said to postpone aging].

Studies of changes in longevity address two main questions. Firstly, why does life expectancy vary in different parts of the western world? Secondly, what are the prospects of human longevity: a life span of no more than 85-90 years on average, or the possibility of reaching much higher ages? The study of longevity and its relation to changes in social circumstances, health care and the number of available general practitioners might be of importance for health care planning. Sweden has a special responsibility to use its unique system of health statistics for such studies. The increase in longevity has inspired many scientists to try to commercialize the results of their studies in various models, and to sell products that are supposed to prolong life. "Science of longevity medicine" is a concept from which serious researchers want to distance themselves.

Aged↗
PubMed2004

The influence of temperature and feeding on development, adult longevity and larviposition of Parasarcophaga hirtipes Wiedemann (Diptera: Sarcophagidae).

Number of sarcophagid flies was collected from the area of Dokki, Giza and kept in laboratory under normal weather conditions. Adult development, longevity and reproduction of Parasarcophaga hirtipes were studied in relation to variations of temperature and relative humidity during the period from January to May 2002. The mean longevity of adults of both sexes decreased with increase of temperature and decrease of relative humidity. The mean larval duration periods also significantly decreased with increased temperature but the mean pupae duration for both sexes did not change significantly during the experiment. The total development time from larvae to adults of both sexes decreased with increase of temperature. The mean longevity of adults female and male was affected by the presence of both sexes together every day rather than their presence together for only 3 days period to allow for one mating to occur. The effects of meat, liver and fish as food constituent on developmental period, longevity and larviposition of the fly were investigated under variation of relative humidity and temperature. The mean longevity of adult of both sexes was increased on feeding on meat. The change was not affected when fed on liver and fish. The mean development period of larvae and pupae and the total development period of both sexes not significantly increased with liver feeding.

Animals↗
PubMed2006

The effect of simulated censored data on estimates of heritability of longevity in the Thoroughbred racing industry.

We examined the impact of censored data on estimates of heritability of longevity. Longevity, defined as the length of productive racing life of an individual, is influenced by many factors. A simulated data set, modelled on the Irish Thoroughbred industry, was used to estimate heritabilities of longevity. Several scenarios representing various levels of censoring of performance data were created. The heritability of longevity was estimated for each scenario and compared to the estimated heritability of 0.120 for the complete data set. It was found that the estimates of heritability (0.107, 0.106, 0.082) were biased downwards with (10, 20, and 25%, respectively) censoring of data from poor-performing animals. We found that for a complete reporting it is necessary to reduce bias in the estimation of heritability of longevity.

Algorithms↗
PubMed2006

Multitrait evolution in lines of Drosophila melanogaster selected for increased starvation resistance: the role of metabolic rate and implications for the evolution of longevity.

Starvation resistance is a trait often associated with longevity. Animals with increased longevity frequently show elevated starvation resistance and vice versa. Consequently, both life-history traits are thought to share genetic and physiological mechanisms, such as increased fat content and lowered metabolic rate. Here, we present results from 20 generations of selection on Drosophila melanogaster for increased starvation resistance at the time of adult eclosion. We observe that starvation resistance can be the result of more than one mechanism, all associated with an increase in fat resources. In general, metabolic rate is lowered under starved conditions relative to fed conditions. Metabolic rate in the starvation resistant lines is generally higher than in control lines under starved conditions. Starvation resistant flies are able to sustain a higher metabolic rate for a longer period of time when food is unavailable. This implies depletion of the increased fat reserves. However, longevity was not consistently affected by selection for increased starvation resistance. Similarly, paraquat resistance differed between selection lines and did not associate with starvation resistance, but rather with longevity. The results are discussed in relation to previous reported results on starvation resistance and its relation with mechanisms of aging and longevity.

Animals↗
PubMed2006

[Comparative study of APOB gene 3'VNTR polymorphisms between natural longevity and controls in Uighur nationality].

OBJECTIVE: To investigate the association of polymorphisms in the apolipoprotein B gene (APOB) 3'variable number of tandem repeat with natural longevity in the Xinjiang Uighur nationality people. METHODS: Totally 191 healthy individuals over 90 years and 53 individuals aged 65-70 years were recruited among Xinjiang Uighur population, the nationality, gender and living area were matched. Genotyping was performed using polymerase chain reaction-sequence specific primer(PCR-SSP) and PCR-sequencing. RESULTS: Fourteen alleles were found in the Xinjiang Uighur nationality population. The frequency of HVE36 and HVE42 in the natural longevity group were significantly higher than that in the control group (both P<0.05) and HVE44, HVE46, HVE48 and HVE58 were only found in the natural longevity group. However, the frequency of HVE26, HVE30 and HVE34 were markedly lower in the natural longevity group compared to the control group. Logistic regression analyses revealed that allele L and the genotypes LL were positively associated with age, whereas the allele S and genotype SS were negatively associated with age (both P<0.05). Each allele consists of 15 bp tandem repeats with rich-AT by PCR-sequencing. CONCLUSION: These results indicate that the S allele, and SS genotype are frail factors in China Uighur natural longevity people, whereas allele L and genotypes LL are protective factors.

Aged↗
PubMed1979

[Theories of longevity (author's transl)].

Any modern theory of longevity has to take into account the multifactorial combined effect of biological-medical, social and psychological factors and of factors pertaining to molecular biology, each with their different weighting. For this reason research into greater-than-average life expectancy and longevity is only possible on an interdisciplinary basis. Many theories of longevity despite convincing arguments also have their weak points. Critical analysis of the theories available to date reveals that longevity rests on an optimal combination of two major factors: 1. on a genetic predisposition in people with longevity in the family--this is the case in most instances. 2. on additional exogenous factors of a social, psychological, ecological and medical kind.

Aged↗
PubMedDate not supplied

[Lipoproteins, apolipoproteins and blood plasma lipids in senility and longevity in men and women from Georgia and Kirghizia].

In men with increase of age from senile to longevity content of total cholesterol was practically unaltered (182 and 184 mg/100 ml), concentration of cholesterol in LPHD was increased from 52 mg up to 58.3 mg/100 ml simultaneously with unaltered content of LPLD cholesterol (102 mg/100 ml) and of LPVLD cholesterol (27.1 and 27 mg/100 ml). Triglycerides decreased from 136 mg down to 101 mg/100 ml. In women content of total blood cholesterol was about 218 mg/100 ml in senile age and 204 mg/100 ml in longevity and concentration of LPHD cholesterol--61 mg and 64.6 mg/100 ml, respectively. Contrary to men, in women a distinct decrease in content of LPLD cholesterol (from 127 mg to 110 mg/100 ml) as well as of triglycerides (from 154 to 145 mg/100 ml) were found on transition from senile age to longevity. Concentration of the apolipoproteins studied was unaltered in men on transition from senile age to longevity and in women concentration of apolipoprotein A-I decreased from 143 mg to 130 mg/100 ml and of apo-E from 11.1 mg to 9.2 mg/100 ml. The decrease in LPLD cholesterol content and increase of LPHD cholesterol, simultaneously with relatively low content of total blood cholesterol, appear to be considered among the reasons responsible for longevity and lesser risk of heart ischemic disease.

Age Factors↗
PubMed2004

Suppressor analysis points to the subtle role of the LAG1 ceramide synthase gene in determining yeast longevity.

Individual yeast cells display a finite replicative capacity. LAG1 was identified as a gene that is differentially expressed during the yeast replicative life span and was shown to play a role in determining yeast longevity. This gene is not essential, but simultaneous deletion of LAG1 and its close homologue LAC1 is lethal. Lag1p and Lac1p have been found to be an essential component of ceramide synthase. In this study, multicopy suppressors of the lethality of a lag1delta lac1delta double mutant were isolated to help clarify the role of LAG1 in yeast longevity. The two multicopy suppressors YBR183w (YPC1) and YPL087w (YDC1) encode ceramidases unrelated to Lag1p and Lac1p, which were previously found to support the reverse reaction of ceramide synthesis. Multiple copies of YPC1 were much more efficient than YDC1 in rescuing cell growth. They were also much more effective in rescuing the life span of a lag1delta lac1delta double mutant, sustaining a life span approaching that obtained by the restoration of LAG1 expression. Neither deletion of LAC1 nor overexpression of YPC1 had a detectable effect on wild-type life span. However, the overexpression of LAG1 had a bimodal effect on longevity, with moderate expression resulting in increased longevity and with higher expression curtailing life span. These results suggest that subtle changes in ceramide/sphingolipid metabolism are important in determining yeast longevity. They also indicate that Lag1p plays a special role in this relationship. Homologues of Lag1p have been identified in higher eukaryotes, including human, raising the possibility that ceramide and other sphingolipid metabolites play a wider role in biological aging.

Aging↗
PubMed1999

Comparison of longevity, pacing, and sensing characteristics of steroid-eluting epicardial versus conventional endocardial pacing leads in children.

OBJECTIVE: Because of either cardiac anatomy or small size, pacing in children often occurs by means of epicardial leads. The disadvantage of epicardial leads is the shorter longevity of these leads compared with endocardial leads. During short-term follow-up, improved stimulation thresholds were found for the newer steroid-eluting epicardial leads. The longevity of these leads may be better than that of conventional epicardial leads. An improved longevity of epicardial leads may influence the choice to either epicardial or endocardial pacing in children. METHODS: We studied the longevity and the pacing and sensing characteristics of 33 steroid-eluting epicardial pacing leads (group I, 15 atrial, 18 ventricular) implanted between November 1991 and October 1996 in 20 children with a mean age of 7.6 +/- 6.5 years (mean +/- SD), and 29 endocardial pacing leads (group II, 15 atrial, 14 ventricular) implanted during the same period in 21 children with a mean age of 11.7 +/- 4.7 years. RESULTS: The mean follow-up in group I was 2.9 +/- 1.6 years and in group II 3.1 +/- 1.7 years (P =.61). The 2-year survival of the leads in group I was 91% +/- 5% and in group II 86% +/- 7% (P =.97). Lead failure occurred in both groups in 4 leads (P =.85). Chronic stimulation and sensing thresholds were similar. CONCLUSIONS: Steroid-eluting epicardial leads have the same longevity as the conventional endocardial leads. Pacing and sensing thresholds were similar and did not change during follow-up. Therefore steroid-eluting epicardial pacing leads are a good alternative for endocardial leads in small children and in children with congenital heart disease.

Cardiac Pacing, Artificial↗
PubMed2001

Challenges with studies investigating longevity of dental restorations--a critique of a systematic review.

OBJECTIVES: A systematic review is a method of evaluating the published and unpublished literature relating to a specific area or topic. The objectives of this paper are to identify and discuss problems encountered in synthesising the available literature; and to make recommendations for the future conduct and reporting of clinical trials that aim to determine the longevity of dental restorations. DATA SOURCES: Studies were identified by a wide search of published and unpublished material in any language using a large number of general and specialist data bases, hand searching of key dental journals and searching of abstracts from conference proceedings. STUDY SELECTION: Pre-defined inclusion criteria based on objective outcome measures of restoration longevity and study designs were applied to determine study selection. CONCLUSIONS: A review of the longevity of dental restorations completed recently encountered substantial problems in designing an appropriate protocol to address this issue. The review found that many of the factors reported previously as affecting restoration longevity could not be confirmed using the agreed systematic review protocol that incorporated an objective study design. Further, the multiplicity of study designs, and reporting methods found in the literature made meta-analyses impossible. A proforma is proposed in order to aid the design of future research into the longevity of restorations.

Dental Materials↗