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Reproductive fitness and longevity in Drosophila melanogaster.

It has been suggested that senescence could have evolved by selection of genes with beneficial effects early in life and detrimental ones later in life (pleiotropy theory of the evolution of senescence). To test that theory, the egg production of 322 females of the Oregon strain of Drosophila melanogaster was recorded daily throughout their life. At the individual level, no relation could be detected between early components of fitness and longevity. For the time being it appears that there are no unequivocal reasons to accept the pleiotropy theory of the evolution of senescence.

Aging↗

Education, homeostasis, and longevity.

The effects of education in lengthening life expectancy and reducing disability and disease in old age are examined for neural and hormonal correlates. Hormones and local factors influencing growth, in regulating neural cell death, proliferation, and differentiation, support the view of a "brain reserve capacity" built up during early learning years and capable of affording a protective action (increased threshold to damage) against the losses of normal and abnormal aging. Observation from studies on the effects of estrogen, dexamethasone, and a number of local factors on growth and differentiation of human neuroblastoma cells and of glial cells are supportive of a role for these factors in maintenance of homeostasis at an advanced age. Continuing education and learning is proposed as an effective means to promote longevity and improve life in old age.

Aged↗

Effect of BHA on longevity, antioxygenic enzymes and peroxides in Callosobruchus maculatus.

Life span and antioxygenic enzyme activities of insects reared on optimal BHA concentration (1 mM) soaked seeds were higher than their respective controls. However, the reproductive potential, peroxides and the level of free radicals declined. The increased longevity with BHA could be attributed to its free radical quenching effect, thereby leading to the decreased peroxide levels and the increased antioxygenic enzyme activities of the insects.

Animals↗

Within- and between-strain variability in longevity of inbred and outbred rats under the same environmental conditions.

The analysis of 26 longevity curves of different populations of inbred (Fischer 344) and outbred (Sprague-Dawley) rats highlighted a remarkable between-populations variability in survival parameters. This variability is independent of the breeding characteristics of the strain. The two strains differed in the slope of the survival curves, with Fischer 344 rats showing a higher survival over the second year of life as well as a lower interindividual variability. A model-free approach based on principal component analysis allowed us to quantify these differences and to high-light some limitations of the classical Gompertzian approach.

Animals↗

Interaction between longevity-associated mitochondrial DNA 5178 C/A polymorphism and cigarette smoking on hematological parameters in Japanese men.

Mitochondrial DNA 5178 C/A (mt5178 C/A), namely NADH dehydrogenase subunit 2 237 Leu/Met, polymorphism is as reported in literature associated with longevity and susceptibility to ischemic heart disease or cerebrovascular disorders in the Japanese population. Previous reports suggested that mt5178A genotype exerts antiatherogenic effects. The aim of this study was to investigate whether mt5178 C/A polymorphism is associated with hematological parameters, such as thrombogenic risk factors for myocardial infarction and stroke, in 321 healthy Japanese men. No significant differences were observed between mt5178 C/A genotypes, but in subjects with body mass index (BMI) of < or = 23, this polymorphism influenced the effects of habitual smoking on hematological parameters. Red blood cell (RBC) counts were significantly lower and mean corpuscular hemoglobin (MCH) levels were significantly higher in smokers with mt5178A than nonsmokers with mt5178A. Platelet counts were significantly higher in smokers with mt5178C than nonsmokers with mt5178C. Cigarette consumption was strongly associated with RBC counts, mean corpuscular volume levels, and MCH levels for men with mt5178A, and was associated with platelet counts for those with mt5178C. Moreover, BMI was significantly positively associated with RBC counts and platelet counts only in men with mt5178A, age was significantly negatively associated with RBC counts only in men with mt5178C. These data suggest that mt5178 C/A polymorphism may influence the effects of cigarette smoking on hematological parameters in healthy BMI < or = 23 Japanese men.

Age Factors↗

Angiotensin converting enzyme insertion/deletion polymorphism in sporadic and familial Alzheimer's disease and longevity.

A recent, large meta-analysis has reproposed the role of the angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism as a risk factor for Alzheimer's disease (AD). To further investigate the proposed association and to better clarify the role of ACE as a risk factor for AD, we analyzed the genotype and allele frequency distribution of ACE I/D and apolipoprotein E (APOE) gene polymorphisms in 235 Italian patients with sporadic AD, 153 with familial AD (FAD), 192 healthy controls and 111 centenarians. Patients with AD were consecutively gathered from among the outpatients from the Neurology Department at the University of Florence. All 691 subjects were genotyped for ACE and APOE polymorphisms. There were no significant differences in ACE genotypes or allele frequencies in all the studied groups, even after stratification for APOE epsilon4 carrier status. Centenarians show the highest allele D frequency, although the value is not significant, thus suggesting a possible implication of the D allele as an epistatic allele that has pleiotropic age-dependent effects. In conclusion, our data suggest that the ACE allelic variant is not a susceptibility factor in sporadic and familial AD (FAD), nor does it mitigate the effect of the APOE epsilon4 allele in the risk of developing AD. Moreover, our data do not suggest a possible involvement of the D allele in longevity.

Aged↗

Dehydroepiandrosterone, glucose-6-phosphate dehydrogenase, and longevity.

Dehydroepiandrosterone (DHEA) is an abundantly produced adrenal steroid whose biological role has never been clarified. DHEA is a potent uncompetitive inhibitor of mammalian glucose-6-phosphate dehydrogenase (G6PDH) and as a consequence lowers NADPH levels and reduces NADPH-dependent oxygen-free radical production. Overproduction of oxygen-free radicals, or oxidative stress, upregulates inflammation and cellular proliferation and is believed to play a critical role in the development of cancer, atherosclerosis, and Alzheimer's disease, as well as the basic aging process. Both in vitro and in vivo experimental studies strongly indicate that DHEA and related steroids inhibit inflammation and associated epithelial hyperplasia, carcinogenesis, and atherosclerosis, at least in part, through the inhibition of G6PDH and oxygen-free radical formation. Recent epidemiological findings in Sardinian males bearing the Mediterranean variant of G6PDH deficiency are consistent with the hypothesis that reduced G6PDH activity has a beneficial effect on age-related disease development and longevity. Clinical trials with DHEA are encumbered by the high oral doses required as well as the conversion of DHEA into active androgens. The use of less androgenic congeners as well as non-oral formulations may facilitate testing of this class of compounds.

Animals↗

The emerging role of poly(ADP-ribose) polymerase-1 in longevity.

In the present paper, the involvement of the family of poly(ADP-ribose) polymerases (PARPs), and especially of PARP-1, in mammalian longevity is reviewed. PARPs catalyse poly(ADP-ribosyl)ation, a covalent post-translational protein modification in eukaryotic cells. PARP-1 and PARP-2 are activated by DNA strand breaks, play a role in DNA base-excision repair (BER) and are survival factors for cells exposed to low doses of ionising radiation or alkylating agents. PARP-1 is the main catalyst of poly(ADP-ribosyl)ation in living cells under conditions of DNA breakage, accounting for about 90% of cellular poly(ADP-ribose). DNA-damage-induced poly(ADP-ribosyl)ation also functions as a negative regulator of DNA damage-induced genomic instability. Cellular poly(ADP-ribosyl)ation capacity in permeabilised mononuclear blood cells (MNC) is positively correlated with life span of mammalian species. Furthermore PARP-1 physically interacts with WRN, the protein deficient in Werner syndrome, a human progeroid disorder, and PARP-1 and WRN functionally cooperate in preventing carcinogenesis in vivo. Some of the other members of the PARP family have also been revealed as important regulators of cellular functions relating to ageing/longevity. In particular, tankyrase-1, tankyrase-2, PARP-2 as well as PARP-1 have been found in association with telomeric DNA and are able to poly(ADP-ribosyl)ate the telomere-binding proteins TRF-1 and TRF-2, thus blocking their DNA-binding activity and controlling telomere extension by telomerase.

Animals↗

Longevity, lipotoxicity and leptin: the adipocyte defense against feasting and famine.

In this review, we propose that actions of the lipid-lowering, apoptosis-inhibiting effects of certain "longevity genes" oppose the life-shortening consequences of lipotoxicity and lipoapoptosis. We note that lipotoxicity occurs whenever leptin action is deficient, or whenever satiety is overridden, as in forced or voluntary overfeeding ("supersizing"). The role of hyperleptinemia, we suggest, is to extend survival during famine by permitting the storage of surplus calories in adipocytes without concomitant injury to nonadipose tissues from ectopic lipid deposits. It achieves this lipid partitioning by (1) restraining the level of overnutrition so as not to exceed the available adipocyte storage space and (2) enhancing oxidation of any ectopic lipid overflow: The mechanisms of lipoapoptosis are discussed, and the possibility that metabolic syndrome is the human equivalent of rodent lipotoxicity is suggested.

Adipocytes↗

Chronomics for chronoastrobiology with immediate spin-offs for life quality and longevity.

Effects of geomagnetic disturbance on heart rate variability (HRV), the 1/f fractal scaling in particular, are being assessed in adults living at high latitude, where magnetic storms are more frequent and more intense than at lower latitudes. The latter may constitute a signal or a proxy, and possibly a mechanism underlying both undesirable and desirable effects, depending upon circumstances yet to be elucidated. Any circadecadal stage-dependence of morbidity and/or mortality from certain conditions such as myocardial infarctions remains to be studied in both adult and pediatric populations. Further work could thus examine whether any associations of geomagnetic disturbances may account, at least in part, through effects upon the circulation, for long-term infra-annual changes, possibly anchored in the population's gene pool, observed in a number of anthropologic measurements at birth as well as in other population statistics. In order to assess the development of several chronome components of the electrocardiogram (ECG), around-the-clock ambulatory ECG were recorded from 19 infants (25 days-3 months of age), 22 children (3-9 years of age), 18 boys and girls (10-14 years of age), pubertal boys (15-20 years of age), and 10 young men (21-29 years of age). Time- and frequency-domain measures of HRV were obtained by spectral analysis, using the maximal entropy method (MEM). The frequency of detection of the circadian, circasemidian and circaoctohoran components, with periods of about 24, 12 and 8 h, respectively, was compared among the five groups for several HRV endpoints, notably 1/f fractal scaling, total spectral power within a 5-min span, and its distribution into several frequency regions. A circadian component is already detectable in a sizeable proportion of infants and children for most of the HRV indices considered. The incidence of detection of the circadian component increases with age for the spectral power in different frequency regions, notably around 10.5 s ("LF") and around 3.6 s ("HF"); it peaks around puberty for 1/f in our data; and it did not detectably change with age for the total spectral power. Similar changes with age are not observed for the circasemidian or circaoctohoran components. The latter characterizes primarily 1/f and less so the about 3.6 s power ("HF"). Several aspects of the HRV chronome may thus develop differently as a function of age. In 2000, we began a community-based study named "Longitudinal Investigation of Longevity and Aging in Hokkaido County (LILAC study)". The ambulatory blood pressure (BP) of middle-aged subjects, aged 40-74 years, was monitored 7-day/24-h, and the cardiovascular and neurobehavioral functions of elderly people above 75 years were evaluated. Our goal was the prevention of stroke and myocardial infarction and the decline in cognitive function of the elderly in a community. Of 115 elderly people recruited in a longitudinal community-based study in 2000, 72 completed yearly follow-ups in 2002. A cardiovascular score based on BP, pulse wave velocity, and 1-h ECG-based HRV endpoints served to distinguish between normal, mildly disordered, or disordered participants. A comparison of cognitive function in 2002 vs. 2000, assessed with the MMSE, HDSR, the Up & Go and Functional Reach tests, gauged any effect of social intervention. Cognitive function was maintained or improved, especially for people suffering from hypertension, tachycardia, or a decreased HRV, suggesting that cardiovascular function is a major factor affecting cognitive function.

Cardiovascular Diseases↗

Populations, longevity, mortality and fecundity of Chrysoperla carnea (Neuroptera, Chrysopidae) from olive-orchards with different agricultural management systems.

The influence that different styles of olive-orchard management (conventional, integrated, and organic) exert on the predator Chrysoperla carnea has been studied to strengthen this insect's role in the integrated management against pests. For this, the adult chrysopid populations were determined by McPhail traps, and laboratory examinations were made of certain biological characteristics of the first generation of adults captured in each of the olive orchards studied. The chrysopid populations increasing significantly during some months in the integrated and organic olive orchard. The most abundant species in all the zones was C. carnea, representing 95% of all captures in the conventional olive orchard. It was found that the larvae from the integrated olive orchard took longer to develop, while the pupae from the organic orchard evolved most rapidly to adulthood. The highest mortality rate was for larvae in the conventional olive orchard. The fecundity of the females from the organic orchards was significantly greater, presumably due to their greater longevity and shorter pre-oviposition period. These results can be used to improve conservation strategies and to increase C. carnea populations and their predatory activity.

Agriculture↗

Sexual cooperation: mating increases longevity in ant queens.

Divergent reproductive interests of males and females often cause sexual conflict . Males of many species manipulate females by transferring seminal fluids that boost female short-term fecundity while decreasing their life expectancy and future reproductivity . The life history of ants, however, is expected to reduce sexual conflict; whereas most insect females show repeated phases of mating and reproduction, ant queens mate only during a short period early in life and undergo a lifelong commitment to their mates by storing sperm . Furthermore, sexual offspring can only be reared after a sterile worker force has been built up . Therefore, the males should also profit from a long female lifespan. In the ant Cardiocondyla obscurior, mating indeed has a positive effect on the lifetime reproductive success of queens. Queens that mated to either one fertile or one sterilized male lived considerably longer and started laying eggs earlier than virgin queens. Only queens that received viable sperm from fertile males showed increased fecundity. The lack of a trade-off between fecundity and longevity is unexpected, given evolutionary theories of aging . Our data instead reveal the existence of sexual cooperation in ants.

Animals↗

Heat shock response by EBV-immortalized B-lymphocytes from centenarians and control subjects: a model to study the relevance of stress response in longevity.

'Successful aging', i.e. the ability to attain old age in relatively good health, is believed to be related to the capability to cope with different environmental stresses. Independently of their specific differentiation, all body cells respond to hyperthermia and other stresses with the production of Heat Shock Proteins (HSPs) that play an important role in cell survival. We investigated the heat shock response in B-lymphoid cell lines from 44 centenarians and 23 younger subjects, by studying both HSP70 synthesis and cell survival after hyperthermic treatment. Interestingly, no significant difference could be found between the two age groups as far as HSP70 synthesis was concerned; moreover, cell lines from centenarians appeared to be less prone to heat-induced apoptosis than lines from younger controls. These results, which are in contrast with previous findings showing an age-related decrease of the HSP70 synthesis and of hyperthermic response, corroborate the above mentioned hypothesis that the biological success of centenarians is due to the preservation of the capability to cope with stresses. An A/C polymorphism identified in the promoter region of HSP70-1 gene had been previously shown to affect the probability to attain longevity in females. To investigate if this effect was related to any influence of this polymorphism on HSP70 protein synthesis the correlation between A/C polymorphism and protein synthesis was investigated. We found that cells from AA centenarian females displayed a lower synthesis of HSP70.

Adult↗

Investigation of KIR diversity in immunosenescence and longevity within the Irish population.

Natural killer (NK) cells play a pivotal role in the innate immune response. During the ageing process, variations occur in NK cell number and function. The cytolytic activity of NK cells is controlled by an array of activating and inhibitory cell surface receptors, including the killer cell immunoglobulin-like receptors (KIRs). In the present study, genetic diversity of the KIR loci was analysed with respect to successful ageing in the Irish population. A PCR-SSOP KIR gene identification system was employed to determine the frequency of the named KIR genes/pseudogenes and KIR genotypes within a healthy aged cohort and young control group. Although, two KIR genes (2DS3, 2DL5) displayed an initial increased frequency in the aged group, the significance of this association was lost when repeated in a second cohort. In view of the lack of studies to date, investigating the role of the KIR gene system in healthy ageing, further analysis of KIR diversity is required to fully elucidate it's role in respect to age-related disease and longevity.

Adult↗

Association analysis between longevity in the Japanese population and polymorphic variants of genes involved in insulin and insulin-like growth factor 1 signaling pathways.

Recent studies have demonstrated a significant association between mutations in genes involved in the insulin/IGF1 signaling pathway and extension of the life span of model organisms. In this study which compared 122 Japanese semisupercentenarians (older than 105) with 122 healthy younger controls, we examined polymorphic variations of six genes which are involved in insulin/IGF1 signaling. These genes were FOXO1A, INSR, IRS1, PIK3CB, PIK3CG, and PPARGC1A. We investigated the possible association of each gene locus and longevity by haplotype-based association analyses using 18 SNPs from public databases and the published literature. One INSR haplotype, which was comprised of 2 SNPs in linkage disequilibrium, was more frequent in semisupercentenarians than in younger controls.

Adult↗

Blood type B might imply longevity.

The aim of the present study was to investigate the association between blood groups and life expectancy. We compared frequencies of ABO blood group in 269 centenarians (persons over 100 years) living in Tokyo and those in regionally matched controls (n=7153). Frequencies of blood types A, O, B, and AB in centenarians were 34.2, 28.3, 29.4, and 8.2%, respectively, while those in controls were 38.6, 30.1, 21.9, and 9.4%, respectively. Blood type B was observed more frequently in centenarians than in controls (chi(2)=8.41, P=0.04). This tendency also was true in comparison between centenarians and 118 elderly old individuals of the 7153. Approximate one-third of the centenarians were free from serious diseases such as malignancy. However, blood types were not associated with such medical records. Our findings suggest that blood type B might be associated with exceptional longevity. Responsible mechanisms need to be investigated.

ABO Blood-Group System↗

Temperature-dependent trade-offs between longevity and fertility in the Drosophila mutant, methuselah.

Single gene, hypomorphic mutations which extend the life spans of cold-blooded animals, such as the methuselah (mth) mutation in the fruit fly, Drosophila melanogaster, may have additional, deleterious effects on overall fitness. The hypotheses tested here were: (i) that the extension of life span by mth might be temperature-dependent, and (ii) that it might be associated with depression of reproductive output, physical activity, or the rate of metabolism. The effect of mth on life span was smaller in magnitude than reported previously, and it was both sex-specific and temperature-dependent. Female longevity was increased only at 29 degrees C, whereas for male flies the extension of mean life span diminished progressively from 15-25% 25-29 degrees C to 2% at 18 degrees C, and the survival time at 4 degrees C was decreased by 22-39%. Conversely, the lifetime reproductive output of mth mutants was decreased at 29 degrees C, but increased at 18-22 degrees C. The walking speed of mth flies was significantly elevated, but mth had no effect on the rate of oxygen consumption at 25 degrees C. Collectively, the results demonstrate that where the life span is extended, there is an offsetting effect on reproductive output, suggesting that mth induces trade-off effects and is not a direct, mechanistic regulator of the aging process.

Animals↗

Why females live longer than males? Importance of the upregulation of longevity-associated genes by oestrogenic compounds.

Females live longer than males in many mammalian species, including humans. Mitochondria from females produce approximately half the amount of H(2)O(2) than males. We have found that females behave as double transgenics overexpressing both superoxide dismutase and glutathione peroxidase. This is due to oestrogens that act by binding to the estrogen receptors and subsequently activating the mitogen activated protein (MAP) kinase and nuclear factor kappa B (NF-kappaB) signalling pathways. Phytoestrogens mimic the protective effect of oestradiol using the same signalling pathway. The critical importance of upregulating antioxidant genes, by hormonal and dietary manipulations, in order to increase longevity is discussed.

Animals↗