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Cloning and expression of the sponge longevity gene SDLAGL.

Porifera show a characteristic Bauplan in spite of the fact that (almost) all cells are telomerase-positive and presumably provided with an unlimited potency for cell proliferation. One gene, SDLAGL, was identified in the marine sponge Suberites domuncula whose deduced polypeptide showed high sequence similarity to the longevity assurance genes from other Metazoa. While in single cells no transcripts of SDLAGL could be identified, high expression was seen after re-aggregation of single cells and in proliferating cells of primmorphs.

Animals↗

Mammalian longevity under the protection of PARP-1's multi-facets.

Given the presence of continuous endogenous and exogenous sources of stress, mammalian species have evolved complex systems of protection, detoxification and repair, in order to maintain homeostasis during development and until reproductive maturity for the sake of the species. However, since no system is perfect, complete prevention of damage is unlikely to occur. Accumulation of macromolecular damage, including damage to DNA and genomic instability, is considered a driving force for the ageing process and age-related diseases. One of the immediate eukaryotic cellular responses to DNA breakage is the covalent post-translational modification of nuclear proteins with poly(ADP-ribose) from NAD+ as precursor, mostly catalysed by poly(ADP-ribose) polymerase-1 (PARP-1). Poly(ADP-ribosyl)ation is involved in DNA base-excision repair (BER), DNA-damage signalling and regulation of genomic stability. In recent years, many groups have become involved in PARP field, shedding light on new partners for PARP-1, new members of the PARP family and new physiological and pathophysiological properties for the founding member of the poly(ADP-ribose) polymerase super family. The present review focuses on PARP-1 and its role in the maintenance of genome stability and in mammalian longevity.

Aging↗

Replication studies in longevity: puzzling findings in Danish centenarians at the 3'APOB-VNTR locus.

In Danes we replicated the 3'APOB-VNTR gene/longevity association study previously carried out in Italians, by which the Small alleles (less than 35 repeats) had been identified as frailty alleles for longevity. In Danes, neither genotype nor allele frequencies differed between centenarians and 20-64-year-old subjects. However, when Danish and Italian data were compared, a significant difference (p = 0.0004) was found between the frequencies of Small alleles in youths, which disappeared in centenarians (p = 0.290). Furthermore, the demographic-genetic approach revealed in Danes a significant gene-sex interaction relevant to Long alleles (more than 37 repeats). The different findings in Denmark and Italy suggest that gene/longevity associations are population-specific, and heavily affected by the population-specific genetic and environmental history.

Adult↗

Insurance and other socioeconomic determinants of elderly longevity in a Costa Rican panel.

Official figures show that life expectancy in Costa Rica is longer than in the United States (US), in spite of the fact that per capita health expenditure is only one-tenth that of the US. To check whether this is for real and to explore some of its determinants, 900 Costa Ricans aged 60+ were followed from 1984 to 2001. Follow-up household visits were made, deaths were tracked in the national death registry, and survival status in the voting registry was double-checked. In addition, the survivors were contacted in 2002. Two-thirds of the panel had died by December 2001. Kaplan-Meier curves, life tables and Cox regression were used to analyse the panel's survival. Mortality in the panel was slightly higher than the Costa Rican average and similar to that in the US, confirming the exceptional longevity of Costa Ricans. Survival was substantially lower among unmarried men and individuals with limited autonomy at the beginning of the study. The effect of socioeconomic status is weak. Insurance effects seem to be confounded by selection biases.

Aged↗

Effects of diets containing different proportions of macronutrients on longevity of normotensive Wistar rats.

The present investigation examined effects of diets containing different proportions of macronutrients on longevity in two substrains of normotensive Wistar rats--Wistar Kyoto (WKY), the most widely accepted normotensive control for spontaneously hypertensive rats (SHR) and Munich Wistar rats (WAM as designated here). Each substrain was divided into five dietary groups composed of 15 rats each. Compared to a baseline diet composed of near equal calories of sucrose, fat, and protein, the remaining four diets were high sucrose-low protein, high sucrose-low fat, low sucrose-high protein, and low sucrose-high fat. Significantly higher systolic blood pressures were found in the two groups of WKY and WAM ingesting the high sucrose diets compared to the other three groups. The high sucrose groups were also hyperinsulinemic. Although only the group of WKY consuming the high sucrose-low fat diet showed a significantly shortened lifespan, the lifespan of WKY positively correlated with systolic blood pressure when data from all dietary groups were combined. WKY and WAM with an average systolic blood pressure exceeding 150 mm Hg had a significantly shorter lifespan than the rats with lower average blood pressure. Accordingly, elevated systolic blood pressure, especially when the blood pressure exceeds 150 mm Hg, significantly shortens lifespan.

Animal Nutritional Physiological Phenomena↗

Longevity and aging of mice from lines divergently selected for body weight for over 90 generations.

We have analysed the differences between longevity and aging process in two lines of mice selected divergently for body weight. As a result of long-term selection, the mice from two lines varied significantly in body weight during their life span. The differences regarded maturation rate, the length of the life time, reproduction performance, and fertility. Females from the light line (L) were fertile for a longer period of time than those from the heavy line (C), while the process of spermatogenesis disappearance started earlier in the light males than in the heavy ones. There were also differences in the relative weight of adrenal glands and histopathological changes connected with the hyperplasia of their spindle cells. The adrenal glands in females from both lines were heavier than in males. A significantly higher percentage of the cortex cell hyperplasia was observed in adrenals of mice from the C line than the L line. The differences were also scored between mice from the selection lines in relation to the length of their life. On average, the L mice lived 30 days longer than the heavy ones. Body weight loss was observed earlier in the old heavy males than the L ones and this was correlated with the earlier mortality in this group of animals.

Adipose Tissue↗

Heating stress patterns in Caenorhabditis elegans longevity and survivorship.

Survival data from Caenorhabditis elegans strain TJ1060 (spe-9; fer-15) following brief exposure to 35 degrees C have been investigated. Three experiments with 3-day-old worms were conducted with heat duration ranging between 0 and 12 hours. A statistically significant increase in life expectancy was observed in the groups heated for less than 2 hours, as compared to the unheated control groups. In different experiments P-values for the observed life spans under the hypothesis that heating has no influence on longevity were P < 0.004 after 0.5 hour heat, P < 0.012 after 1 hour heat and P < 0.055 after 2 hours of heating. A biphasic survival model with Gamma distributed frailty has been constructed to describe the survival of worms after heating. The increase in the remaining life expectancy is determined by more effective protection by heat-induced substances in the ages yanger than 27 days. The unheated control group demonstrated acquired heterogeneity of frailty with chronological age while the heat-induced substances defend the worms in a universal way and protect against the development of frailty.

Animals↗

Trust, health, and longevity.

Scores on the Rotter Interpersonal Trust Scale were evaluated as predictors of psychological well-being, functional health, and longevity in a sample of 100 men and women who were between 55 and 80 years old at baseline (mean age 66.8). Cross-sectionally, high levels of trust were associated with better self-rated health and more life satisfaction. Follow-up over approximately 8 years found baseline levels of trust to be positively related to subsequent functional health, but not to subsequent life satisfaction. Mortality follow-up after 14 years demonstrated that those with high levels of trust had longer survival (p = .03), a finding that was somewhat weakened by controlling for baseline health ratings. These findings illustrate the health protective effects of high levels of trust and suggest the potential usefulness of the trust concept for understanding successful aging.

Activities of Daily Living↗

The allele (A)(-110) in the promoter region of the HSP70-1 gene is unfavorable to longevity in women.

Heat shock proteins (HSPs) are crucial for maintenance of cell homeostasis and survival both during and after various stresses. The capability to cope with stress is believed to affect the chance of health and survival at organismal level. We have investigated whether the gene pool relevant to the (A/C)(-110) polymorphism in the promoter region of the HSP70-1 gene changes as the population ages and survival selection occurs. A total of 591 southern Italian subjects were enrolled in the study (263 males and 328 females; age range 18-109 years), free of clinically manifest diseases and with normal haemato-chemical parameters. A significant age-related decrease of the frequency of allele (A)(-110) was observed in females. The probability ratio of 0.403 (95% confidence interval [0.163, 0.910]) computed by considering female centenarians as cases and young women (18-49 years old) as controls showed that the (A)(-110) allele is unfavorable to longevity in females.

Adolescent↗

Psychosocial and behavioral predictors of longevity. The aging and death of the "termites".

Impulsive, undercontrolled personalities and major family stresses are known predictors of impaired adjustment, but long-term health effects are unclear. In an archival prospective cohort design, we followed up on L. M. Terman's (Terman & Oden, 1947) sample of gifted children by collecting and coding death certificates for the half of the sample that is now dead. Statistical survival analyses were used to predict longevity and cause of death as a function of parental divorce during childhood, unstable marriage patterns in adulthood, childhood personality, adult adjustment, and possible mediating health behaviors. Psychosocial factors emerged as important risks for premature mortality.

Adolescent↗

Childhood conscientiousness and longevity: health behaviors and cause of death.

Previous research showed that conscientiousness (social dependability) in childhood predicted longevity in an archival prospective cohort study of bright children first studied by Terman in the 1920s (H. S. Friedman et al., 1993). Possible behavioral mechanisms for this robust association are now examined by gathering cause of death information and by considering the possible mediating influences of drinking alcohol, smoking, and overeating. Survival analyses (N = 1,215) suggest that the protective effect of conscientiousness is not primarily due to accident avoidance and cannot be mostly explained by abstinence from unhealthy substance intake. Conscientiousness may have more wide-ranging effects on health-relevant activities.

Adolescent↗

Parental divorce: effects on individual behavior and longevity.

Using an archival prospective design, the authors studied associations among parental divorce occurring during participants' childhood, adult psychosocial mediators, and mortality over the life span of a subgroup of participants (N = 1,261) in the Terman Life Cycle Study (1921-1991). Children from divorced families grew up to show a higher risk of premature mortality across the life span. The higher mortality risk for men was explained, in part, when 3 mediating factors were controlled: Men who had experienced parental divorce were more likely to have their own marriages end in divorce, obtained less education, and engaged in fewer service activities. Women who had experienced parental divorce smoked more and were more likely themselves to divorce, both of which predicted higher mortality risk. The findings extend previous work on the negative sequelae of parental divorce to long-term effects on personality and longevity.

Adolescent↗

Longevity increased by positive self-perceptions of aging.

This research found that older individuals with more positive self-perceptions of aging, measured up to 23 years earlier, lived 7.5 years longer than those with less positive self-perceptions of aging. This advantage remained after age, gender, socioeconomic status, loneliness, and functional health were included as covariates. It was also found that this effect is partially mediated by will to live. The sample consisted of 660 individuals aged 50 and older who participated in a community-based survey, the Ohio Longitudinal Study of Aging and Retirement (OLSAR). By matching the OLSAR to mortality data recently obtained from the National Death Index, the authors were able to conduct survival analyses. The findings suggest that the self-perceptions of stigmatized groups can influence longevity.

Aged↗

An archival prospective study of mental health and longevity.

The relationship between mental health status and longevity was examined in an archival prospective cohort study (N = 1,103) derived from work begun by Lewis Terman in the 1920s. Degree of psychological maladjustment, cumulatively rated by Terman and his colleagues as of 1950, was found to be related to higher risk of all-cause mortality over a 4-decade follow-up period. The differences among causes of death were nonsignificant, but there was some indication that mental health problems were more strongly related to deaths from injury and cardiovascular disease. The overall relationship was significant for men but weaker for women. The effect was not substantially mediated by alcohol consumption, obesity, or cigarette smoking.

Adolescent↗

Playing with pets and longevity among older people.

Models of the relations between contact with pets and better health are examined in an archival prospective study using data derived from the longitudinal study initiated by Terman in 1921 (current N = 343 men, 300 women). In survival analyses of documented longevity, playing with pets in 1977 (M age = 67 years) was not associated with mortality risk through 1991 for the total sample nor for those who were unmarried or those who were less satisfied with their human relationships. Playing with pets was not associated with health-prone attributes or healthy behaviors such as personality, social ties, education, and smoking.

Aged↗

A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans.

A pheromone-induced neurosecretory pathway in Caenorhabditis elegans triggers developmental arrest and an increase in longevity at the dauer diapause stage. The gene age-1 is required for non-dauer development and normal senescence. age-1 encodes a homologue of mammalian phosphatidylinositol-3-OH kinase (PI(3)K) catalytic subunits. Lack of both maternal and zygotic age-1 activity causes dauer formation, whereas animals with maternal but not zygotic age-1 activity develop as non-dauers that live more than twice as long as normal. These data suggest that phosphatidylinositol signalling mediated by AGE-1 protein controls lifespan and the dauer diapause decision.

Amino Acid Sequence↗

The effects of gene-environment interaction on the expression of longevity.

Several previous attempts at selecting for increased life span with Drosophila have failed to obtain a response to selection, and postulate that life span is controlled by non-genetic maternal effects instead of genes. In other experiments, however, populations have responded. This study uses a set of true-breeding long- and short-lived stocks developed by in vitro selection to examine the effect on life span of developmental environment and outcrossing. The expression of genes for life span is shown here to vary as a result of a gene-environment interaction and is strongly affected by the environment during development. The longevity of F1 crosses between long- and short-lived parental lines is additive when the density of larvae is high and unfixed, showing that life span is controlled by genes and not nongenetic maternal effects. But, when numbers of larvae are held low and constant, as in studies where selection fails, life span of crosses and parental lines is greatly restricted. The failure of some previous attempts at selection, therefore, appears to have resulted from the introduction, through experimental design, of strong artifactual environmental effects that limit the phenotypic expression of genes for life span and the effectiveness of selection. Comparison of fecundity in parental and F1 lines shows that selection for increased life span antagonistically reduces early-life fecundity. Short-lived, parental lines, reproduced at an early age in life, lay 22-24 per cent more eggs in the same period than do long-lived lines selected for reproduction at a late age.

Animals↗

The effect of the inactive mutation on longevity, sex, rhythm and resistance to p-cresol in Drosophila melanogaster.

Flies carrying the inactive (iav) mutation exhibit low locomotor activity and poor mating success, both of which are associated with a deficiency in the putative neurotransmitter, octopamine. Several other aspects of the iav mutant phenotype are described here. Male and female iav mutants show a small reduction in longevity but it is not clear whether this is a consequence of the iav mutation or their inactive phenotype. Young iav males show extended attractiveness to older courting males, which supports the notion that the iav gene has a role in post-eclosional maturation. The eclosion rhythm of iav mutants is normal, discounting the possibility of a role for octopamine in the maintenance of circadian rhythm. Flies carrying the iav mutation are highly susceptible to the octopamine analogue p-Cresol. Other phenotypically inactive flies show wild type levels of p-Cresol resistance. This is attributed to the deficiency of octopamine in iav mutants because low octopamine levels may be unable to out-compete the toxic effect of p-Cresol. Some inferences on the possible mode of action of the iav gene product are discussed.

Animals↗