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PubMed2006

Parental longevity and mortality amongst Japanese men and women: the JACC Study.

OBJECTIVES: To examine whether the risk of mortality varies according to parents' age at death. DESIGN AND SUBJECTS: A large prospective study in Japanese men and women from 45 communities across Japan. A total of 51 485 men and women aged 40-79 years completed self-administered questionnaires at baseline and followed up for 9.6 years. RESULTS: The risk of mortality from stroke, cardiovascular disease, and all causes was 20-30% lower in men and women with fathers who died at age > or = 80 years, compared with those with fathers whose age at death was <60 years. A similar reduction was found when the age at death of mothers was > or = 85 years compared with <65 years. Furthermore, the risk reduction was more evident amongst persons with both parents being long-lived parents compared with those with being short-lived parents, especially for death from cardiovascular disease. CONCLUSIONS: Our findings indicate that parental longevity could be a predictor for reduced risk of mortality from stroke, cardiovascular disease, and all causes for both Japanese men and women.

Adult↗
PubMed2006

Anopheles culicifacies sibling species B and E in Sri Lanka differ in longevity and in their susceptibility to malaria parasite infection and common insecticides.

Members of the Anopheles culicifacies Giles complex (Diptera: Culicidae) are well established as the predominant vectors of malaria in Sri Lanka. Until recently, only sibling species B was reported to be present in Sri Lanka, which was surprising as species B is a poor vector of malaria in India. This was clarified by the identification through Y-chromosome morphology that what was reported as B on the island is really a mixture of B and E. The fecundity, longevity and insecticide resistance of B and E are of relevance to malaria transmission and its control and are reported in this study. The mean egg production of these two sibling species did not differ significantly. The mean age of wild mosquitoes was assessed by the Polovodova technique of observing ovarian dilatations. More of species E than B had three or more dilatations, i.e. had reached an age at which sporozoites could have developed to maturity, although the difference between the species was of borderline significance. Following feeding on Plasmodium vivax or Plasmodium falciparum infected blood, some females of species E developed oocysts but none of species B did so. Both sibling species were found fully susceptible in laboratory tests to lambdacyhalothrin and deltamethrin, but resistant to DDT and partially resistant to malathion.

Age Factors↗
PubMed2006

Use of microarray biomarkers to identify longevity therapeutics.

A number of lines of evidence, including nonhuman primate and human studies, suggest that regulatory pathways similar to those invoked by caloric restriction (CR) may be involved in determining human longevity. Thus, pharmaceuticals capable of mimicking the molecular mechanisms of life- and health-span extension by CR (CR mimetics) may have application to human health. CR acts rapidly, even in late adulthood, to begin to extend life- and health-span in mice. We have linked these effects with rapid changes in the levels of specific gene transcripts in the liver and the heart. Our results are consistent with the rapid effects of caloric intake on the lifespan and/or biochemistry and physiology of Drosophila, rodents, rhesus macaques and humans. To test the hypothesis that existing pharmaceuticals can mimic the physiologic effects of CR, we evaluated the effectiveness of glucoregulatory drugs and putative cancer chemo-preventatives in reproducing the hepatic gene-expression profiles produced by long-term CR (LTCR). We found that 8 weeks of metformin treatment was superior to 8 weeks of CR at reproducing the specific changes in transcript levels produced by LTCR. Consistent with these results, metformin reduces cancer incidence in diabetic humans and ameliorates the onset and severity of metabolic syndrome. Metformin extends the mean and maximum lifespans of female transgenic HER-2/neu mice by 8% and 13.1% in comparison with control mice. Phenformin, a close chemical relative of metformin, extends lifespan and reduces tumor incidence in C3H mice. These results indicate that gene-expression biomarkers can be used to identify promising candidate CR mimetics.

Aging↗
PubMed2005

Economic and policy implications of improving longevity.

With all the rhetoric surrounding the impending "entitlement crisis" produced by the "graying of America," there has been surprisingly little serious analysis of the social and economic implications of increased longevity and the doubling of the number of elderly people that will occur in this country over the next 30 years. This article identifies five critical areas in which the effect of demographic change will be significant. First, patterns of work life and labor-force participation will almost inevitably change. Second, government expenditures now financed largely by payroll and federal income taxes will increase, whereas those financed by state and local property taxes will fall, at least proportionately. Third, the post-World War II pattern of suburbanized, automobile-dependent communities will pose special challenges to serving an aging population, and new adaptations will need to be developed. Fourth, intrafamily caregiving patterns will necessarily change. Fifth, the level of disability and dependence of older people, for which the rate of change is inherently unpredictable, will have a major effect on all these and other phenomena. Whether one views the net effect of all these changes as a positive or a negative, it is necessary to begin thinking a lot harder and more systematically about all of them.

Aged↗
PubMed2005

Extraordinary longevity: individual and societal issues.

The likelihood of substantial increases in average life spans and the potential for profound longevity increases (to 100, 110, or 120 years on average) raises a host of societal issues. These include huge increases in the number of old and very old persons, the likelihood of a massive increase in health expenditures for the population aged 65 and older, the potential for outliving financial resources, challenges to the viability of Social Security and pensions, concerns about quality of life, and possible intergenerational antagonisms. If marked increases occur in average life spans worldwide, several billions could be added to world population at eventual stability, and that could become a sustainability issue. To prepare for what is likely to be our demographic future requires a major shift in thinking about this type of complex issue; we must change from a simple linear to a much broader systems approach. Changes in retirement age, strengthening (but then replacing) the Social Security system, retaining older persons in the labor force, mandating retirement savings during working years, and many other actions must be considered in a debate that should start now about life span increase and the future; if we dawdle, we risk the consequences of being unprepared for the dramatic demographic changes that are likely to occur in the coming decades.

Aged↗
PubMed1997

Gene activation, apolipoprotein A-I/high density lipoprotein, atherosclerosis prevention and longevity.

Recent studies in man and human apolipoprotein A-I transgenic animals emphasize the significance of apolipoprotein A-I and high density lipoprotein in antiatherogenesis. Several drugs and other compounds, e.g. phenobarbital, gemfibrozil, fenofibrate, prednisone, estrogen and alcohol, induce apolipoprotein A-I synthesis. They commonly produce serum lipoprotein patterns typical of a low risk of coronary heart disease, and many of them have been found to prevent atherogenesis, reduce coronary heart disease mortality and increase survival. These compounds act against atherosclerosis by using one or several mechanisms that include overexpression of the apolipoprotein A-I gene with an increase in serum apolipoprotein A-I and high density lipoprotein and promotion of reverse cholesterol transport, upregulation of the low density lipoprotein receptor gene with a decrease in serum apolipoprotein B and low density lipoprotein, maintenance of endothelial cell function and protection against thrombosis. They have been found to raise high density lipoprotein cholesterol and apolipoprotein A-I together with a decrease in cholesterol ester transfer protein activity, and to induce hepatic cholesterol 7 alpha-hydroxylase and cholesterol and bile acid elimination from the body. By raising the activities of apolipoprotein A-I/high density lipoprotein-associated paraoxonase and other antioxidative enzymes, the inducers have the capacity to prevent atherogenesis in arterial walls through inhibition of the oxidative modification of low density lipoprotein. Other antiatherogenic vascular actions of high density lipoprotein include interference with low density lipoprotein aggregation and uptake by endothelial cells, and competition with low density lipoprotein for endothelial-localized low density lipoprotein receptors. Apolipoprotein A-I/high density lipoprotein beneficially enhances fibrinolysis, decreases platelet aggregation, increases prostacyclin production and stabilization and prevents atherogenic immune and inflammatory responses. This gene activation or microsomal induction can prevent atherosclerosis and is a basis for tailoring effective new agents and optimal non-invasive therapy against atherosclerotic vascular disease to promote health and enhance longevity.

Animals↗
PubMed1992

Purification and characterization of a protein associated with genetically-determined longevity difference in Drosophila melanogaster.

Earlier studies have shown a correlation between the presence of a 77 kDa protein in the proteins extracted from young adult Drosophila melanogaster (D.m.) and the autosomal longevity allele. A2 at the JmA locus. In this study, a 77 kDa protein has been isolated from pupae of D.m. of a long-lived strain of genotype A2A2, and was purified by DEAE chromatography, ConA column chromatography, and two cycles of gel filtration. The purified protein has a molecular weight of 76,600 (by SDS-PAGE), an isoelectric point of pH 6.5, and molar extinction coefficient A(280(1%) = 18.3. It is a glycoprotein containing 3.3% hexose. Supplementing the food of D.m. with the purified protein at 5 x 10(-4) micrograms/ml, beginning at day 5 after emergence, resulted in an increase in the survival rate and maximal life span of both short-lived and long-lived strains of D.m.

Animals↗
PubMed1991

New surprises in very old places: Civil War nurse leaders and longevity.

While the average woman in the U.S. Civil War times lived to the age of about 40, a group of 17 extraordinary nurses--including Louisa Mae Alcott, Dorothea Dix, and Clara Barton--survived to much older ages. A variety of possible reasons, from social and marital status to altruism and religion, is explored. More than any tangible factor, however, the presence of a "pioneering spirit" seems to be at the root of their longevity.

Attitude of Health Personnel↗
PubMed2002

Membrane fatty acid unsaturation, protection against oxidative stress, and maximum life span: a homeoviscous-longevity adaptation?

Aging is a progressive and universal process originating endogenously that manifests during postmaturational life. Available comparative evidence supporting the mitochondrial free radical theory of aging consistently indicates that two basic molecular traits are associated with the rate of aging and thus with the maximum life span: the presence of low rates of mitochondrial oxygen radical production and low degrees of fatty acid unsaturation of cellular membranes in postmitotic tissues of long-lived homeothermic vertebrates in relation to those of short-lived ones. Recent research shows that steady-state levels of free radical-derived damage to mitochondrial DNA (mtDNA) and, in some cases, to proteins are lower in long- than in short-lived animals. Thus, nonenzymatic oxidative modification of tissue macromolecules is related to the rate of aging. The low degree of fatty acid unsaturation in biomembranes of long-lived animals may confer advantage by decreasing their sensitivity to lipid peroxidation. Furthermore, this may prevent lipoxidation-derived damage to other macromolecules. Taking into account the fatty acid distribution pattern, the origin of the low degree of membrane unsaturation in long-lived species seems to be the presence of species-specific desaturation pathways that determine membrane composition while an appropriate environment for membrane function is maintained. Mechanisms that prevent or decrease the generation of endogenous damage during the evolution of long-lived animals seem to be more important than trying to intercept those damaging agents or repairing the damage already inflicted. Here, the physiological meaning of these findings and the effects of experimental manipulations such as dietary stress, caloric restriction, and endocrine control in relation to aging and longevity are discussed.

Aging↗
PubMed2002

The first six years at the National Institute for Longevity Sciences, Japan.

The National Institute for Longevity Sciences (NILS) of Japan opened on July 7, 1995, 15 years after the Science Council of Japan recommended the establishment of the National Center for Aging and Geriatric Illnesses (the provisional name for NILS) in 1980. During the first four years of operation, 8 separate research departments, containing 21 laboratories, were established. NILS has both research departments for biomedical sciences, such as dementia research, molecular genetics, and geriatric research, and also departments of gerontechnology and the care of the elderly, which engage in research directed toward the comprehensive improvement of the health and well- being of the elderly. On July 9, 1995, the day of the opening ceremonies, NILS employed only three staff members, including the director general. At the end of fiscal year 2000 (March 31, 2001), the institute comprised a staff of more than 200 people, including 30 senior science staff and about 50 junior scientists. The Japanese government has recently decided to expand NILS to double its present size by the end of fiscal year 2004 (March 2005).

Academies and Institutes↗
PubMedDate not supplied

Effects of enalapril on exercise tolerance and longevity in dogs with heart failure produced by iatrogenic mitral regurgitation.

This study was conducted to evaluate the effects of enalapril on exercise capacity and longevity in dogs with left-sided heart failure produced by iatrogenic mitral regurgitation. After surgical creation of mitral regurgitation, 18 dogs were allocated into replicates according to exercise capacities. One dog in each replicate received placebo, and the other received 0.5 mg/kg of enalapril sid for 9 days and bid thereafter. Exercise tolerance was studied after 10, 19, 52 to 53, and 80 to 81 days, respectively. Finally, the percentage of dogs in each group that survived 357 days was compared. The duration of exercise for dogs in the placebo and enalapril groups did not differ at baseline (P > .1) or after 19 days (P > .1). Dogs that received enalapril had significantly reduced (P < .001) exercise tolerance at day 10, and significantly increased (P = .002) exercise tolerance at days 52 to 53 and 80 to 81 when compared with controls. At 357 days, 22% of dogs receiving placebo were alive, compared with 67% of dogs receiving enalapril; however, these differences were not statistically significant (P = .124). This study shows that enalapril increases exercise tolerance in dogs with left-sided heart failure induced by iatrogenic mitral regurgitation.

Animals↗
PubMed2003

The future of human longevity--how important are markets and innovation?

In a hearing before the United States Senate Special Committee on Aging, a well-respected demographer warns that there is no evidence of slowing in the long-term rise in best-practice life expectancy in developed countries. The author discusses how these findings will affect the future of Social Security and argues for a larger, more focused effort with respect to longevity research by demographers, epidemiologists, and economists.

Female↗
PubMed2005

Interfering with longevity.

Several recent studies have highlighted how RNA interference has advanced aging-related research in Caenorhabditis elegans. Two new genome-wide RNAi-based screens together identified more than 100 new candidate longevity genes. RNAi has also greatly facilitated the functional validation of several large-scale gene expression profiling studies. Furthermore, RNAi is flexible and can be administered at different times throughout life; this feature has been exploited to analyze the temporal requirement of genes in life-span determination.

Animals↗
PubMed2003

Steroid control of longevity in Drosophila melanogaster.

Ecdysone, the major steroid hormone of Drosophila melanogaster, is known for its role in development and reproduction. Flies that are heterozygous for mutations of the ecdysone receptor exhibit increases in life-span and resistance to various stresses, with no apparent deficit in fertility or activity. A mutant involved in the biosynthesis of ecdysone displays similar effects, which are suppressed by feeding ecdysone to the flies. These observations demonstrate the importance of the ecdysone hormonal pathway, a new player in regulating longevity.

Animals↗
PubMed2003

OutFOXing the grim reaper: novel mechanisms regulating longevity by forkhead transcription factors.

Studies in the nematode Caenhorhabditis elegans have contributed to understanding the mechanisms that control life-span and aging. Recent experiments have employed RNAi to knock down gene expression, microarray analysis to identify genes involved in the insulin/insulin-like growth factor pathway, and bioinformatics screening to identify new Forkhead-regulated genes. The results from these experiments suggest that members of the Forkhead transcription factor family along with heat shock factors may coordinately regulate production of small heat shock proteins to control how cell stress influences life-span, and provide new links between metabolism and longevity, as well as indicate that antimicrobial genes may be involved in the aging process.

Animals↗
PubMedDate not supplied

Longevity of men capable of prolonged vigorous physical exercise: a 32 year follow up of 2259 participants in the Dutch eleven cities ice skating tour.

OBJECTIVE: To compare the long term survival of a group of athletes taking prolonged vigorous physical exercise to that of the general population. DESIGN: Follow up of a cohort of participants in the Dutch eleven cities ice skating tour (a race and recreational tour) over a distance of 200 kilometers. SETTING: Data on participation from the organising committee and data on mortality from all municipalities in The Netherlands. SUBJECTS: 2259 Male athletes. MAIN OUTCOME MEASURES: Comparison of all cause mortality in male participants in the tour with that in the general population of The Netherlands. RESULTS: The standardised mortality ratio for all participants during 32 years of follow up was 0.76 (95% confidence interval 0.68 to 0.85), and 0.90 (0.48 to 1.44) for participants in the race, and 0.72 (0.60 to 0.86) for participants in the recreational tour who finished within the time limit. CONCLUSIONS: The capacity for prolonged and vigorous physical exercise, particularly if the exercise is recreational, is a strong indicator of longevity.

Adult↗
PubMedDate not supplied

Handedness and longevity: archival study of cricketers.

OBJECTIVE: To test whether handedness is associated with a change in longevity. DESIGN: Archival survey. SETTING: British Isles. SUBJECTS: All first class cricketers born before 1961 whose bowling hand was specified (right, n = 5041; left, n = 1132) in a comprehensive encyclopaedia. MAIN OUTCOME MEASURES: Bowling hand and life span. RESULTS: Regression analysis of the 5960 players born between 1840 and 1960 (3387 dead, 2573 alive) showed no significant relation between mortality and handedness (P = 0.3). Left handedness was, however, associated with an increased likelihood of death from unnatural causes (P = 0.03, log hazard 0.37, 95% confidence interval 0.04 to 0.70). This effect was especially related to deaths during warfare (P = 0.009, log hazard 0.53, 0.13 to 0.92). CONCLUSION: Left handedness is not, in general, associated with an increase in mortality.

Cause of Death↗
PubMed1988

High density lipoprotein cholesterol and longevity.

In the Twin Cities Prospective Study, executive men aged 45 to 55 and "healthy" at the entry examinations in 1948 were re-examined yearly to 1975. Follow-up through 1983 lost only one man. High density lipoprotein cholesterol (HDL) in the serum was measured in 1955 with a method checked with recent standard methods. Among 217 men, 130 were dead by 1983, 56 from coronary heart disease (CHD) and 27 from neoplasms. Survivors did not differ in mean HDL from the men who died but they had higher values than the men dead from CHD. Men dead from neoplasms had significantly higher HDL than men dead from CHD. Men dying early did not differ in HDL from those dying later but they had higher blood pressures. HDL was unrelated to age at death from all causes but was related to age at death from CHD. HDL was not related to age, total cholesterol, smoking, or respiratory function but was negatively correlated with measures of body fatness. Multiple regression and multiple logistic analyses showed no difference in HDL between survivors and men dead from all causes, but men dead from CHD tended to have lower HDL. The data indicate that longevity is not related to HDL in middle age.

Age Factors↗