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PubMed1990

Relationship of reproductive success and median longevity to food intake, in the captive female spider Frontinella pyramitela.

Two biological phenomena (prolongation of life span with dietary restriction, and life shortening with reproductive activity) have been described in several species but treated separately. For captive female bowl and doily spiders (Frontinella pyramitela), data reported by Austad were analyzed in terms of food consumed. "Reproductive success" was defined; its rate of change could be directly equated to food intake. To describe life span, the specific rate of change of median longevity was noted to be negatively proportional to the specific rate of change of food intake. Both reproductive success and changes in median longevity are coupled to food intake in these female spiders, and can be described by quantitative expressions.

Animals↗
PubMed1993

The female longevity phenomenon. Hypotheses on some molecular and cell biology aspects.

The most relevant theories on the sex-dependent longevity at population level are critically re-examined in the light of the knowledge available today on the aging process at cellular and molecular level. The aim of this perspective is to help in the understanding of the cellular and molecular bases of longevity and to indicate the most suitable biological models of investigation.

Animals↗
PubMed1995

How long can humans live? Lower bound for biological limit of human longevity calculated from Danish twin data using correlated frailty model.

How long can people live? Opinions of the researchers diverge and debates continue. Is there any systematic way to address this question? In this paper, we suggest an approach to the estimation of the biological limit of human longevity using survival data for twins from different zygocity groups. The approach is based on the genetic model of individual frailty. It combines ideas used in demography and survival analysis with methods of quantitative genetics and genetic epidemiology. The association between the life-spans of related individuals is described by the correlated frailty model of bivariate survival. A version of this model is used in order to estimate heritability of the individual frailty and to calculate the lower bound of human longevity. The limitations of this approach and directions of further research are discussed.

Aged↗
PubMed1984

Economics and extended longevity: a case study.

Preventive and therapeutic advances have brought life expectancy in the United States to well over 70 years and have shifted mortality causes from acute to chronic diseases, the determinants of which are genetics, lifestyle, the environment, and aging itself. Plausible approaches to chronic disease prevention are likely to increase longevity further, with some foreseeable effects on demographic and economic projections. Primarily, longevity advances would swell forecasts of population size, and would thus have to be met by production advances in order to maintain or improve living standards. This study, a restricted example, considers the probable demographic and economic consequences of a limited prevention program in the context of the Ford Motor Company, based on actual experience and certain expectations up to the year 2000. According to the results, prevention would reduce outlays for life insurance, disability, and health care, but would also generate the higher costs of extending pension plans. Undoubtedly, prevention will continue to be highly ranked in society's pursuit of happiness, and society must prepare to meet its effects with appropriate social and economic policies.

Aged↗
PubMed1990

Body weight and longevity: insurance experience in Japan.

Adverse effects of obesity on health and longevity are widely known in clinical medicine. The author reports here the result of a study on the relationship of body weight and longevity based on the data obtained by the life insurance cohort study in which he participated. The result is summarized below: 1. Mortality by body weight assumed a U-shaped curve with the nadir near the average weight for both men and women. 2. Because the mortality for some causes went upward toward right or reverse with the shift from underweight to overweight, the curve for all-cause mortality became U-shaped. 3. The relationship between hospitalization ratio and body weight showed substantially the same trend although the cause for hospitalization varied. 4. The body weight showing the lowest mortality was slightly heavier than the average body weight in Japan, which was different from North America. 5. Based on Metropolitan Life's principle of lowest mortality, we published Meiji Life's height and weight tables in order to set the standard body weight for the Japanese today.

Body Weight↗
PubMed1982

Components of longevity: developmental and genetic responses to differential childhood mortality.

Childhood disease may have far-reaching effects on adult longevity in high-mortality populations. It was earlier reported from demographic analysis of 19th century New England communities that survivors of high-fatality childhood epidemics lived significantly longer than their unstressed counter-parts. As part of a broader survey of agricultural families of western Massachusetts, these data indicate that elevated child mortality is associated with an increase in the average age at death of survivors. This paper examines this selection process and the problem of heritable longevity using cohort data selected from historical epidemics. A series of tests of the selection hypothesis in which an attempt is made to control demographic covariates suggest that widespread childhood infectious disease strengthens survivors in a developmental manner. Whether such episodes also eliminate less fit individuals according to a simple selection model could not be determined. The influence of family formation variables on child loss, and behavioral (fertility) responses to childhood epidemics in these communities are also considered.

Adolescent↗
PubMed1989

Medical and social predictors of longevity in the elderly: total predictive value and interdependence.

In the Dutch Longitudinal Study among the Elderly, a probability sample of 3149 persons from the population of the Netherlands, initial ages 65-99 years, was followed from 1955 for 28 years. Vital status was determined in 1983 for 84% of the original sample. Multivariate regression models were used to predict the realized probability of dying (RPD), a measure of longevity based on actual survival time, sex and age at baseline. Predictor variables included physical, mental and social indicators of health status. The total variance explained was 20.2%. Objective health (rated by the examining physician) showed the strongest relationship with the RPD. Upon removing objective health from the model, 19.5% of the variance remained explained. Separate analyses were performed for (1) bio-medical, physical and mental examination variables, (2) disability and health care use variables, and (3) social and psychological variables; in each case the variance explained was over 11%, demonstrating considerable interdependence among predictors. Across different regression models, bio-medical and disability variables proved to be the most stable predictors of longevity.

Activities of Daily Living↗
PubMedDate not supplied

Age-specific mortality costs of exposure to inbred Drosophila melanogaster in relation to longevity selection.

This article address the hypotheses that selection for early- or late-life fitness changes patterns of reproductive behavior, that this behavior may be dependent on the genetic makeup of the females, and that patterns of male mortality are strongly dependent on the type of females to which they are exposed. Flies selected for late-life reproduction and their associated stocks selected for early reproduction were exposed to flies of the opposite sex from either the same stock or a highly inbred stock. Males of both long- and short-lived stocks showed an increase in early mortality when exposed to inbred females. In addition, when males were exposed to inbred females early in life they showed a lower age-specific mortality rate late in life than males exposed to females from their own stock. Interestingly, females exposed to inbred males showed a significant reduction in mean longevity. Analysis of age-specific mortality revealed that this reduction was brought about as a result of increased early mortality. Interpretation of the results from an analysis of mean longevity not only fails to identify important information--as shown from a demographic analysis of age-specific mortality--but also presents a misleading description of mortality costs.

Animals↗
PubMed1992

Family patterns of coronary heart disease mortality: the Framingham Longevity Study.

Family patterns for age at death were examined in a 40 year follow-up of 5209 men and women (2900 deceased, 2309 living) in the Framingham Study and their parents. Age at death of both mothers and fathers was significantly older for surviving offspring when compared to decreased offspring (p less than 0.0001). When longevity was assessed according to cause of death in the offspring, parental age at death was a significant predictor of death by coronary heart disease (CHD), but not for stroke or cancer. Multiple regression analysis for offspring with sudden CHD death revealed that mother's age at death was a significant predictor of age at sudden CHD death (p less than 0.0003) whereas father's age at death was a significant predictor of age at death in non-sudden CHD death (p less than 0.004). Life table analysis showed longest survival rates associated with both parents surviving to age 75 or older followed by mother only surviving to age 75 or older, then father only, and shortest survival with neither parent surviving to age 75. Longevity appears to be more strongly associated with maternal death age than parental death age. Proportional hazards analysis of risk factors associated with CHD revealed that systolic blood pressure, sex of the individual, and cigarette smoking were the most significant predictors of death age. These findings suggest that familial similarities for death age may be mediated primarily through shared CHD risk factors within families, either genetic or non-genetic.

Adult↗
PubMed2006

Longevity index (LI%) and centenarity index (CI%): new indicators to evaluate the characteristics of aging process in the Italian population.

Centenarians represent a group of population displaying the most rapid expansion. This progressive increase of the presence of centenarians is a multi-factorial phenomenon, which is due to the improvements of the environmental conditions and the life style and also to the progress of the medical science. In order to obtain a more reliable estimate of the longevity per gender and territorial entities, we propose two new indicators. (i) The ratio between the ultranonagenarians and the total population above 65 years old (called longevity index: LI%); (ii) the ratio between the centenarians and the total population above 90 years old (called centenarity index: CI%). An analysis of the data of the Italian National Office of Statistics (ISTAT, ) using these two indicators demonstrates that the subjects above the age of 90 are more frequent in the regions of Central and Northern Italy, which are more developed regarding the economic conditions and technological progress. Nevertheless, the Southern and Insular regions of Italy have a higher occurrence of centenarians among the ultranonagenarian population, and also a higher prevalence of male centenarians, as compared to the northern regions. This demonstrates that achievement of the threshold of 100 years old does not require only particular socio-economic conditions, but also an adequate climate and environment, as well as a favorable genetic composition.

Aged↗
PubMed2005

C. elegans DAF-12, Nuclear Hormone Receptors and human longevity and disease at old age.

In Caenorhabditis elegans, DAF-12 appears to be a decisive checkpoint for many life history traits including longevity. The daf-12 gene encodes a Nuclear Hormone Receptor (NHR) and is member of a superfamily that is abundantly represented throughout the animal kingdom, including humans. It is, however, unclear which of the human receptor representatives are most similar to DAF-12, and what their role is in determining human longevity and disease at old age. Using a sequence similarity search, we identified human NHRs similar to C. elegans DAF-12 and found that, based on sequence similarity, Liver X Receptor A and B are most similar to C. elegans DAF-12, followed by the Pregnane X Receptor, Vitamin D Receptor, Constitutive Andosteron Receptor and the Farnesoid X Receptor. Their biological functions include, amongst others, detoxification and immunomodulation. Both are processes that are involved in protecting the body from harmful environmental influences. Furthermore, the DAF-12 signalling systems seem to be functionally conserved and all six human NHRs have cholesterol derived compounds as their ligands. We conclude that the DAF-12 signalling system seems to be evolutionary conserved and that NHRs in man are critical for body homeostasis and survival. Genomic variations in these NHRs or their target genes are prime candidates for the regulation of human lifespan and disease at old age.

Aging↗
PubMed2005

Design and analysis in genetic studies of human ageing and longevity.

With the success of the Human Genome Project and taking advantage of the recent developments in high-throughput genotyping techniques as well as in functional genomics, it is now feasible to collect vast quantities of genetic data with the aim of deciphering the genetics of human complex traits. As a result, the amount of research on human ageing and longevity has been growing rapidly in recent years. The situation raises questions concerning efficient choice of study population, sampling schemes, and methods of data analysis. In this article, we summarize the key issues in genetic studies of human ageing and longevity ranging from research design to statistical analyses. We discuss the virtues and drawbacks of the multidisciplinary approaches including the population-based cross-sectional and cohort studies, family-based linkage analysis, and functional genomics studies. Different analytical approaches are illustrated with their performances compared. In addition, important research topics are highlighted together with experiment design and data analyzing issues to serve as references for future studies.

Aging↗
PubMed2005

Correlation of parents' longevity with carotid intima-media thickness in patients attending a Lipid Clinic.

The relationship between carotid intima-media thickness (IMT) and the subject's parents' longevity has been investigated. The association between parents' age at death and IMT was estimated in 593 consecutive patients attending a Lipid Clinic by survival-analysis methods. Average maximum IMT (Avg-IMT), maximum IMT (Max-IMT), clinical and laboratory variables and parental age at death, were assessed. Kaplan-Meier analyses showed significant differences in survival curves, low IMTs being associated with long-lived parents (p=0.0003 and 0.001 by log-rank test for fathers and mothers, respectively). A Cox proportional hazards regression model showed that higher carotid IMT values were associated with father's and mother's deaths at an early age, even after adjusting for conventional cardiovascular risk factors. These data were confirmed after the stratification of patients into younger (<65 y) and older (>/=65 y) or into subjects with and without a family history of dyslipidemia or vascular diseases. In addition, by stratifying subjects into those with no, one or two long-lived parents, we observed a significant trend for the combination of father's and mother's longevity on their offspring's IMTs (p<0.01 and 0.05 for Avg-IMT and Max-IMT, respectively). These data highlight a significant relationship between carotid artery IMT and a familial predisposition to be long-lived that is independent of the individual's vascular risk profile.

Adolescent↗
PubMed2006

SMK-1, an essential regulator of DAF-16-mediated longevity.

Insulin/IGF-1 signaling (IIS) regulates aging in worms, flies, and mice through a well-characterized, highly conserved core set of components. IIS also regulates early developmental decisions, the reproductive status of the animal, innate immunity, and stress-resistance functions. In C. elegans, the sole insulin/IGF-1 receptor, DAF-2, negatively regulates the FOXO transcription factor, DAF-16. We report here on a new component of the IIS longevity pathway, SMK-1, which specifically influences DAF-16-dependent regulation of the aging process in C. elegans by regulating the transcriptional specificity of DAF-16 activity. Localization analysis of DAF-16 places SMK-1 downstream of DAF-16's phosphorylation-dependent relocation to the nucleus. Physiological and transcription analyses indicate that smk-1 is required for the innate immune, UV, and oxidative stress but not the thermal stress functions of DAF-16. SMK-1 therefore plays a role in longevity by modulating DAF-16 transcriptional specificity without affecting other processes regulated by IIS.

Aging↗
PubMed2004

Paraoxonase polymorphisms PON1 192 and 55 and longevity in Italian centenarians and Irish nonagenarians. A pooled analysis.

BACKGROUND: PON1, an arylesterase, associated with high density lipoprotein (HDL), protects low density lipoprotein (LDL) against oxidative modification. Common polymorphisms PON1 55 (L/M) and 192 (Q/R) in the PON1 gene associate with atherosclerosis and heart disease. Because long-lived people seem protected from premature vascular death, we conducted a pooled statistical analysis to assess any association between these polymorphisms and longevity in a large combined group of Italian centenarians and octo/nonagenarians from Northern Ireland (NI). MATERIALS AND METHODS: Separated DNA was available from 1479 subjects from Italy and Northern Ireland (NI). In Italy 308 centenarians (males 67, females 241, mean age 100.8, SD2.1 years) and 579 young controls (males 347, females 232, mean age 40.7, SD 12.7 years) were included in the study. In NI, 296 octo/nonagenarians (males 92, females 204, mean age 89.8, SD 5.7 years) and 296 young sex-matched subjects (mean age 13.0, SD 1.4 years) had available DNA. PON1 55 (L/M) and 192 (Q/R) polymorphisms were studied using a PCR-RFLP approach. RESULTS: There was a significant difference in PON1 192 genotypes in Italian centenarians compared to younger controls (X(2)= 6.8, df = 2 p= 0.03) and a similar but non significant trend between octo/nonagenarian and young subjects in NI (X(2) = 4.0, df=2, p=0.14). Using logistic regression analysis on the combined Italian and Irish datasets, there was a small survival advantage for centenarian and octo/nonagenarian subjects who were heterozygous for PON1 192 R allele, (OR 1.3, CI 1-1.6; p=0.04 with a stepwise increase for RR homozygous subjects (OR 1.7, CI 1.1-2.6; p = 0.02) compared to QQ subjects. Comparing R and Q alleles there was a survival advantage for octo/nonagenarian/centenarian subjects who carried the R allele (OR 1.3, CI 1.1-1.5; p = 0.007) but there was no sex-specific effect p =0.77) LL, LM and MM genotypes of PON 55 polymorphisms showed similar frequencies in Italy (39.9, 47.0, 13.1%) and Ireland (39.5, 48.6, 11.9%) with no age or sex-related differences. The PON1 192R/Q and PON55L/M loci were in strong linkage disequilibrium with a Lewontin's D' coefficient -0.928 (elderly) and -0.965 (young). There was a significant difference in haplotype frequency of these linked loci in older compared to younger subjects (Likelihood Ratio X(2) = 9.60, df = 3, p= 0.02). CONCLUSION: These data suggest a modest association between the 192R allele and longevity in two very elderly populations in two European countries. Being homozygous for 192 RR further enhances survival advantage but this effect was not found to be sex specific. This finding is of interest because the 192R allele has previously been associated with increased risk of coronary heart disease. On the other hand, the 192R allele shows higher enzymatic activity, using paraoxon as substrate, and we postulate that its role in the metabolism of potentially toxic chemicals or other metabolic pathways may be important in survival to very old age.

Adult↗
PubMed2004

Gender specific association of genetic variation in peroxisome proliferator-activated receptor (PPAR)gamma-2 with longevity.

Long-lived subjects have been shown to have peculiar anthropometric features (i.e. lower body mass index (BMI)) and metabolic parameters (i.e. improved insulin sensitivity). Life style and a genetic background potentially protective against the age-related metabolic derangement might contribute to such a particular phenotype. Peroxisome proliferator-activated receptor (PPAR)gamma-2 is an important regulator of adipose tissue metabolism, insulin sensitivity and inflammatory response. Thus, the potential role of genetic variability at Pro/Ala loci of PPARG gene on longevity was studied in 222 long-lived subjects and 250 aged subjects. We found a different Pro/Ala genotype frequency distribution between long-lived and aged men subjects, long-lived men having an increased frequency of Pro/Ala genotype (20 vs 8.5%); no differences was found when allele and genotype distribution of Pro/Ala gene polymorphism were analyzed in the two age group of women. Interestingly, subjects with Pro/Ala polymorphism had significantly lower BMI than Ala/Ala and Pro/Pro polymorphism. In conclusion, our study demonstrated that paraoxonase Pro/Ala gene polyporphism is associated with human longevity. Such an effect is probably due to the effect of Pro/Ala polymorphism on body composition and appears to be gender specific.

Adult↗
PubMed2005

The insulin/IGF-1 signaling in mammals and its relevance to human longevity.

Hormones, like insulin and insulin-like growth factor 1 (IGF-1), are thought to be deeply involved with longevity. Lower species have been the source for most of our current knowledge on the role of the insulin/IGF-1 signaling in modulating lifespan. This hormonal system may have originated from a very early common ancestor and is involved in many functions that are necessary for metabolism, growth, and fertility in animal models like flies, nematodes and mammalians. Disruption of the insulin/IGF-1 receptor in nematodes and flies increases lifespan significantly. With evolution, mammals developed two well characterized hormonal systems: insulin and growth hormone (GH)/IGF-1, with different metabolic and developmental functions. Abnormalities in the insulin signaling pathway generate age-related diseases and increased mortality, whereas the GH/IGF-1 axis could potentially modulate longevity in many species. In this review we briefly describe the lifespan regulatory role of the insulin/IGF-1 signaling of nematodes, flies and rodent models and compare it with the human equivalent.

Animals↗
PubMed2005

Biodemography of a long-lived tephritid: reproduction and longevity in a large cohort of female Mexican fruit flies, Anastrepha ludens.

Age of sexual maturity, daily and lifetime reproductive rates, and life span were recorded in a laboratory cohort of Mexican fruit flies consisting of over 1100 females maintained individually. The results revealed that, relative to the medfly, the Mexfly is slower maturing (14 vs 17 days), more fecund (1400 vs 650-1100 eggs/female), and longer lived (50 vs 35 days). The results reinforced the generality of several earlier findings on the medfly including the deceleration of mortality at older ages and the weakness of the correlation between the rate of egg laying at early ages and both subsequent reproduction and remaining longevity. Discussion includes perspectives on the role of artificial selection in shaping the demographic traits of the mass-reared strain of Mexfly used in this study, as well as the overall significance of large scale biodemographic studies in understanding aging and longevity.

Aging↗