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PubMed2006

The genetics of human longevity.

Aging is due to a complex interaction of genetic, epigenetic, and environmental factors, but a strong genetic component appears to have an impact on survival to extreme ages. In order to identify "longevity genes" in humans, different strategies are now available. In our laboratory, we performed association studies on a variety of "candidate" polymorphisms in Italian centenarians. Many genes/polymorphisms gave negative results, while others showed a positive association with human longevity and a sometimes-positive association with unsuccessful aging (myocardial infarction, Alzheimer's disease, and type 2 diabetes). Results regarding genes involved in inflammation (IL-1 cluster, IL-6, IL-10, TNF-alpha, TGF-beta, TLR-4, PPARgamma), insulin/IGF-1 signaling pathway and lipid metabolism (apolipoproteins, CETP, PON1), and oxidative stress (p53, p66(shc)) will be described. In addition, a strong role of the interaction between nuclear and mitochondrial genomes (mtDNA haplogroups and the C150T mutation) emerged from our findings. Thus, the genetics of human longevity appears to be quite peculiar in a context where antagonistic pleiotropy can play a major role and genes can have a different biological role at different ages.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Heat-shock protein 70 genes and human longevity: a view from Denmark.

We have studied the association of three single nucleotide polymorphisms (SNPs) present in the three HSP70 (heat-shock protein) genes on 6p21 with human longevity. The availability of biological samples from various population cohorts in Denmark has given us the opportunity to try novel methods of gene association with human longevity. A significant association of one haplotype with male longevity was observed. Furthermore, a significant difference in the survival of the carriers of the different genotypes in females was observed. We also found an age-dependant decline in the ability of peripheral blood mononuclear cells to respond to heat stress in terms of Hsp70 induction.

Adult↗
PubMed2004

Resting metabolic rate and respiratory quotient in human longevity.

Significant changes in body composition, body fat distribution, and resting metabolic rate (RMR) occur with aging. Interestingly, studies on human longevity pointed out that long-lived subjects are less prone to the anthropometrics and metabolic derangement normally observed in the elderly. Indeed, the relationship between energy expenditure and longevity has been poorly investigated. Thus, energy expenditure parameters of 28 long-lived subjects were assessed and compared with those of 26 adults and 27 younger elderly. All subjects enrolled were female. In the whole population, RMR was negatively correlated with age (P < 0.05), waist to hip ratio (WHR) (P < 0.001), fat mass (P < 0.001), and percent body fat (P < 0.03); respiratory quotient (Rq) displayed an age-related decrease (P < 0.001) and was negatively correlated with WHR (P < 0.001) and fat-free mass (FFM) (P < 0.006). In multivariate analysis, both RMR and Rq had FFM, WHR, but not body mass index as significant and independent determinants. Splitting the whole study group into subgroups according to age, long-lived subjects had oxygen volume, carbon dioxide volume, and Rq significantly higher than aged subjects but lower than adult subjects. In addition, long-lived subjects had total volume of expired air and RMR greater than aged subjects but not different from ones found in adults. In long-lived subjects, Rq was negatively correlated with percent body fat (P < 0.02), plasma glucose (P < 0.05), free fatty acid (P < 0.05), and WHR (P < 0.05), whereas RMR was negatively correlated with WHR (P < 0.05). No significant associations of RMR and Rq with FFM were found. In conclusion, our data demonstrate that human longevity seems protected toward an age-related decline. It is likely that the lack of the anthropometrics derangement may preserve long-lived subjects from the age-related decrease in energy metabolism.

Adult↗
PubMed2006

A genotype of exceptional longevity is associated with preservation of cognitive function.

OBJECTIVE: To test whether cholesterol ester transfer protein (CETP) genotype (VV homozygosity for I405V) is associated with preservation of cognitive function in addition to its association with exceptional longevity. METHODS: We studied Ashkenazi Jews with exceptional longevity (n = 158; age 99.2 +/- 0.3 years) for the associations of CETP VV genotype and lipoprotein phenotype, using the Mini-Mental State Examination (MMSE). To confirm the role of CETP in a younger cohort, we studied subjects from the Einstein Aging Study (EAS) for associations between CETP VV and cognitive impairment. RESULTS: Subjects with MMSE > 25 were twice as likely to have the CETP VV genotype (29% vs 14%, p = 0.02), and those with the VV genotype were more likely (61% vs 30%, p = 0.02) to have MMSE > 25. Subjects with the VV genotype had lower levels of CETP (1.73 +/- 0.11 vs 2.12 +/- 0.10 mug/mL, p = 0.01), higher high-density lipoprotein (HDL) levels (p = 0.02), and larger lipoprotein particles (p = 0.03). In the EAS cohort, an approximately fivefold increase in the VV genotype (21% vs 4%, p = 0.02), higher HDL levels, and larger lipoprotein particle sizes were associated with less dementia and improved memory. CONCLUSIONS: Using two independent cohorts, we implicate the longevity CETP gene as a modulator of age-related cognitive function. A specific CETP genotype is associated with lower CETP levels and a favorable lipoprotein profile. It has not been determined whether modulation of this gene prevents age-related decline or AD.

Age Distribution↗
PubMed2004

Saccharomyces cerevisiae SSD1-V confers longevity by a Sir2p-independent mechanism.

The SSD1 gene of Saccharomyces cerevisiae is a polymorphic locus that affects diverse cellular processes including cell integrity, cell cycle progression, and growth at high temperature. We show here that the SSD1-V allele is necessary for cells to achieve extremely long life span. Furthermore, addition of SSD1-V to cells can increase longevity independently of SIR2, although SIR2 is necessary for SSD1-V cells to attain maximal life span. Past studies of yeast aging have been performed in short-lived ssd1-d strain backgrounds. We propose that SSD1-V defines a previously undescribed pathway affecting cellular longevity and suggest that future studies on longevity-promoting genes should be carried out in long-lived SSD1-V strains.

Alleles↗
PubMed2001

Male genotype affects female longevity in Drosophila melanogaster.

Several recent studies suggest that interactions with conspecific males can reduce the longevity of female Drosophila melanogaster or support the idea that male and female fitness components are involved in antagonistic interactions. Here we report that males from third-chromosome isogenic lines demonstrated significant genetic variation in male reproductive performance and in the longevity of their mates. Increased male performance was marginally significantly associated with one measure of increased female survival rate. However, there was no indication of tradeoffs or negative correlations between male reproductive success and female survival. We discuss alternative hypotheses for the cause of the induced variation in female longevity.

Animals↗
PubMedDate not supplied

Influence of photoperiod on Orius thyestes Herring (Hemiptera: Anthocoridae) reproduction and longevity.

Several species of Orius Wolff are used in biological control of thrips in protected cultivations in temperate regions, but some of them show reproductive diapause, compromising the efficiency of these agents of biological control. There are no reports on the biology of the neotropical species Orius thyestes Herring under different environmental conditions. The purpose of this work was to investigate the influence of photoperiod on reproduction and longevity of this predator. Nymphs were kept in petri dishes in climatic chambers at 28+/-1 degree C, 70+/-10% RH and under the photoperiods of 12L:12D, 11L:13D, 10 L:14D e 09L:15D. The mating adults were kept in petri dishes with Bidens pilosa L. Asteraceae inflorescences as oviposition substracts and eggs of Anagasta kuehniella (Zeller) (Lepidoptera: Pyralidae) as food. The pre-oviposition and oviposition periods, fecundity and longevity were evaluated and O. thyestes did not show reprodutive diapause in all photoperiod conditions established. The mean number of eggs obtained per female decreased with the reduction of the photophase, with a difference (P < 0.05) between the values obtained in 12h and 9h of photophase. Longevity of females and males under 9h photophase was shorter (P < 0.05) than in all other photoperiods tested. The knowledge of the biology of the natural enemy under different conditions allows to optimise the mass rearing and to predict the performance of the predator in different photoperiods which may occur along the year and in greenhouses.

Animals↗
PubMed2002

Longevity and reproductive success of Aethina tumida (Coleoptera: Nitidulidae) fed different natural diets.

The longevity and reproductive success of newly emerged, unfed adult Aethina tumida Murray assigned different diets (control = unfed; honey-pollen; honey; pollen; empty brood comb; bee brood; fresh Kei apples; and rotten Kei apples) were determined. Longevity in honey-fed small hive beetle adults (average maximum: 167 d) was significantly higher than on other diets. Small hive beetles fed empty brood comb lived significantly longer (average maximum: 49.8 d) than unfed beetles (average maximum: 9.6 d). Small hive beetle offspring were produced on honey-pollen, pollen, bee brood, fresh Kei apples, and rotten Kei apples but not on honey alone, empty brood comb, or in control treatments. The highest reproductive success occurred in pollen fed adults (1773.8 +/- 294.4 larvae per three mating pairs of adults). The data also show that A. tumida can reproduce on fruits alone, indicating that they are facultative parasites. The pupation success and sex ratio of small hive beetle offspring were also analyzed. Larvae fed pollen, honey-pollen, or brood had significantly higher pupation success rates of 0.64, 0.73, and 0.65 respectively than on the other diets. Sex ratios of emerging adults fed diets of pollen or brood as larvae were significantly skewed toward females. Because small hive beetle longevity and overall reproductive success was highest on foodstuffs located in honey bee colonies, A. tumida are efficient at causing large-scale damage to colonies of honey bees resulting in economic injury for the beekeeper. Practical considerations for the control of A. tumida are briefly discussed.

Animals↗
PubMed1994

Is breast-feeding in infancy associated with adult longevity?

OBJECTIVES: The purpose of the study was to determine whether breast-feeding is associated with increased longevity or cause-specific survival. METHODS: Teachers throughout California identified intellectually gifted children as part of a prospective study begun in the 1920s by Lewis Terman. Information on breast-feeding was available on 1170 subjects, who have been followed for more than 65 years. RESULTS: Survival analysis (Cox proportional hazards model) indicated that breast-feeding was associated with increased longevity, even after adjustment for age at baseline, birthweight, infant health, and childhood socioeconomic status, but only among men, and the association was not significant (P = .15). Neither cardiovascular disease nor cancer survival was significantly associated with duration of breast-feeding for either sex. Survival from deaths due to injuries was positively associated with breast-feeding after adjustment (P = .03) and demonstrated a clear gradient with duration, but only among men. CONCLUSIONS: Overall, the present study does not provide strong evidence that breast-feeding is associated with adult longevity. The reduced risk of death from injury may reflect chance, in that the association was significant only for men, or it may reflect psychosocial correlates of breast-feeding practices.

Aged↗
PubMed2001

Comparison of F1 Bos indicus x Hereford cows in central Texas: II. Udder, mouth, longevity, and lifetime productivity.

Postpartum udder characteristics, aged mouth condition scores, and cow survival, longevity, and productivity were evaluated for 15 yr on F1 cows in central Texas (temperate winters and subtropical summers). The cows (n = 116) were progeny of Angus, Gray Brahman, Gir, Indu-Brazil, Nellore, and Red Brahman sires and Hereford dams. Crossbred cows sired by Nellore had smaller (P < 0.05) postpartum teat length than cows of all other crossbred groups and smaller (P < 0.10) postpartum teat diameter than Indu-Brazil and Red Brahman crossbreds. The Nellore crossbred cows had larger (P < 0.10) postpartum udder support scores (more well-supported udders) than Gir, Indu-Brazil, and Red Brahman crossbreds. As 14-yr-old cows, Angus crossbreds had lower (P < 0.05) mouth scores (indicative of one or more missing incisors) than Bos indicus crossbreds. Under actual and artificial (records were removed) culling procedures, Nellore crossbreds had the highest cow survival to age 14 and the highest longevity. Indu-Brazil crossbreds tended to be the lowest for both survival and longevity. Curves were fitted by nonlinear regression procedures to the adjusted frequencies of cows remaining at each age; scale and shape parameters were estimated and compared for the different breed groups. Breed group cow survival rates, calf crop weaned, and calf weaning weights were used 1) to construct population projection and production matrices for each breed group and 2) to generate breed group vectors containing projected age distributions and production information. Cows sired by Nellore and Gir were projected to require the fewest purebred cows to generate replacement heifers and to have the most calves and the largest total calf weight sold per year.

Animals↗
PubMed1988

Productive longevity of first-cross cows produced in a five-breed diallel: I. Reasons for removal.

Data from 498 cows of 15 breed-types produced in a five-breed diallel (reciprocals pooled) including Angus, Brahman, Hereford, Holstein and Jersey were analyzed for differences in productive longevity, mean life span and reasons for removal from the herd over approximately 14 yr. The only culling related to production was of cows that did not give birth to at least one live calf every 24 mo. Otherwise, cows were only removed when they appeared to be incapable of weaning another live calf. The average age at removal, estimated from linear regression, was 3,470 d, with values ranging from 2,174 d (Jersey) to 4,087 d (Angus-Brahman). Longevity of crossbred cows was greater than that of purebred cows (P less than .001). Purebred cows usually had higher initial rates of removal than crossbred cows. Estimates of mean longevity from the nonlinear regression resembled the results of the linear regression analysis; mean life spans ranged from 6.2 yr (Jersey) to 14.6 yr (Angus-Brahman). The major reason for removal of Brahman and Brahman-cross cows was for reproductive reasons. Angus and Angus-cross cows were culled more frequently for structural unsoundness; Hereford cows had a higher incidence of cancer eye, calving difficulty and mammary problems; cows with 100% dairy breeding had exceptionally high susceptibility to diseases and mineral imbalance.

Animals↗
PubMed2000

Relationships between mastitis and functional longevity in Danish Black and White dairy cattle estimated using survival analysis.

The relationship between mastitis and functional longevity was assessed with survival analysis on data of Danish Black and White dairy cows. Different methods of including the effect of mastitis treatment on the culling decision by a farmer in the model were compared. The model in which mastitis treatment was assumed to have an effect on functional longevity until the end of the lactation had the highest likelihood, and the model in which mastitis treatment had an effect for only a short period had the lowest likelihood. A cow with mastitis had 1.69 times greater risk of being culled than did a healthy herdmate with all other effects being the same. A model without mastitis treatment was used to predict transmitting abilities of bulls for risk of being culled, based on longevity records of their daughters, and was expressed in terms of risk of being culled. The correlation between the risk of being culled and the national evaluations of the bulls for mastitis resistance was approximately -0.4, indicating that resistance against mastitis was genetically correlated with a lower risk of being culled and, thus, a longer functional length of productive life.

Animals↗
PubMed2004

Effect of maternal age on milk production traits, fertility, and longevity in cattle.

Longevity is the economically most important functional trait in cattle populations. However, with an increased productive lifespan, the number of offspring born by older dams increases. A higher maternal age might have negative effects on the performance of offspring. The objective of this study was to investigate the effect of maternal age on production (energy-corrected milk yield [ECM]) and functional traits (fertility; somatic cell score, and functional longevity) in Austrian dual-purpose Simmental cows. Age of dam had a significant effect on ECM yield and longevity. The ECM yield of daughters decreased with age of dam. Although the risk of culling slightly increased with age of dam, it was lowest for daughters of oldest dams. Results for fertility were non-significant, and results for somatic cell scores were inconsistent across parities.

Aging↗
PubMed1998

A comparison of breeding value predictors for longevity using a linear model and survival analysis.

A comparison was made among breeding values of sires for longevity that were obtained by different methods: phenotypic averages of daughters using only uncensored records, BLUP using only uncensored records, survival analysis using only uncensored records, and survival analysis using both censored and uncensored records. Two data files were used: one contained data from small herds, and the other contained data from large herds. The results from both data files were similar. Different methods of predicting breeding values resulted in different rankings of sires. The results obtained using phenotypic averages were weakly correlated (< or = 0.46) with those results obtained using the other methods of prediction. The REML BLUP had strong correlations (< or = -0.91) with the survival analysis predictor if the same data were used, and correlations weakened (< or = -0.60) when censored records were included in the survival analysis. The correlations are negative because the linear method analyzed longevity, and survival analysis measured the risk of being culled, which has an antagonistic relationship with longevity. The results from REML BLUP and survival analysis methods differed mainly because of the different data that were used (uncensored only versus both censored and uncensored).

Aging↗
PubMed1993

The association between weight loss and increased longevity. A review of the evidence.

Six published observational epidemiologic studies have reported evidence of reduced mortality rates in persons who have lost weight. In two studies, the reported protective effects of weight loss on mortality could not be justified by the data. In two other studies, weight loss was associated with both increased and decreased longevity in different subgroups. Only one study provided information on whether the weight loss was voluntary, but this study found similar effects of weight loss regardless of volition. These studies provided only limited information on the magnitude of weight loss associated with changes in longevity and no information on the types of methods used to achieve weight loss. Because of difficulties in studying long-term health outcomes related to obesity treatment, randomized, controlled trials are unlikely to provide a practical study design for this issue. Properly designed observational studies will probably provide the most useful information on the effects of voluntary weight loss on longevity.

Epidemiologic Methods↗
PubMed2003

Understanding the determinants of exceptional longevity.

Centenarians represent an extreme of life expectancy. They achieve their exceptional longevity in part by lacking genetic variations linked to premature death. Pedigree studies have shown a substantial familial component in the ability to survive to extreme old age, and a recent study demonstrated a locus on chromosome 4 linked to exceptional longevity, indicating the likely existence of at least one longevity-enabling gene in humans. The children of centenarians have markedly reduced relative risks for age-related diseases, particularly heart disease, hypertension, and diabetes, and are a promising model for genetic and phenotypic studies of 1) aging slowly relative to the general population and 2) the delay of and perhaps escape from important age-related diseases. These studies and those of other mammals and lower organisms show great promise for the delineation of important environmental and genetic determinants of aging well.

Animals↗
PubMed1998

The development of resistance to caffeine in Drosophila prosaltans: productivity and longevity after ten generations of treatment.

The productivity of Drosophila prosaltans treated with six concentrations of caffeine (from 50 micrograms/ml to 2,500 micrograms/ml of culture medium) during ten generations (approximately 8 months) decreased in a dosage dependent manner in every generation, but at the end of the treatment the flies in all experiments recovered normal productivity, except for those treated with 2,500 micrograms/ml. Longevity in the tenth generation was significantly reduced in males and females only in the 2,500 micrograms/ml dosage, with males being much more affected than females. In a previous study in which the treatment was done in a single generation, productivity exhibited only a partial recovery when the treatment ceased and longevity was significantly reduced in 1,500 micrograms/ml dosages. The hypothesis of selection occurring in ten generations leading to recovery in productivity and to a reduction in the processes which cause a decrease in longevity is being considered.

Animals↗
PubMed2000

Longevity of breeding sows in relation to leg weakness symptoms at six months of age.

The objective of this study was to evaluate the influence of leg weakness symptoms measured early in life (at 6 months of age) on the longevity of the sows, i.e. the age at culling due to locomotory problems in a Danish pig herd. One hundred and eighty-seven gilts at 6 months of age were selected according to different leg weakness symptoms and were followed until culling and judged for leg weakness once in every gestation using a scale from 1 (normal) to 4 (severe changes). Age at culling, and the main and secondary reasons for culling were recorded. The influence of leg weakness symptoms on longevity was evaluated by survival analysis. Though only 12% of the gilts showed a stiff locomotion half of the sows had suffered from this and nearly one third had been distinctly lame at some time in their life. Buck-kneed forelegs, upright pasterns, legs turned out, standing under position and swaying hindquarters were associated with stiff locomotion or lameness, whereas weak pasterns on hind legs and splayed digits on forelegs were associated with brisk movement (freedom from locomotor problems). The following leg weakness symptoms at the gilt stage were found to have significant negative effects on longevity: buck-kneed forelegs, swaying hindquarters, and standing under position on hind legs.

Animals↗