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Background: The oldest-old (those aged ≥80 years) are the most rapidly growing age group globally, and are most in need of health care and assistance. We aimed to assess changes in mortality, disability in activities of daily living, and physical and cognitive functioning among oldest-old individuals between 1998 and 2008., Methods: We used data from the Chinese Longitudinal Healthy Longevity Study. Three pairs of cohorts aged 80-89 years, 90-99 years, and 100-105 years (in total, 19 528 oldest-old participants) were examined; the two cohorts in each pair were born 10 years apart, with the same age at the time of the assessment in the 1998 and 2008 surveys. Four health outcomes were investigated: annual death rate, Activities of Daily Living (ADL), physical performance in three tests and cognitive function measured by Mini-Mental State Examination (MMSE). We used different tests and multivariate regression analyses to examine the cohort differences., Findings: Controlling for various confounding factors, we noted that annual mortality among oldest-old individuals was substantially reduced between 0·2% and 1·3% in 1998-2008 compared with individuals of the same age born 10 years previously, and that disability according to activities of daily living had significantly reduced annually between 0·8% and 2·8%. However, cognitive impairment in the later cohorts increased annually between 0·7% and 2·2% and objective physical performance capacity (standing up from a chair, picking up a book from the floor, and turning around 360°) decreased anually between 0·4% and 3·8%. We also noted that female mortality was substantially lower than male mortality among the oldest-old, but that women's functional capacities in activities of daily living, cognition, and physical performance were worse than their male counterparts., Interpretation: Advances in medications, lifestyle, and socioeconomics might compress activities of daily living disability, that is, benefits of success, but lifespan extension might expand disability of physical and cognitive functioning as more frail, elderly individuals survive with health problems, that is, costs of success., Funding: National Natural Science Foundation of China, National Institute on Aging/National Institutes of Health, United Nations Funds for Population Activities., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The general health status of a population changes over time, generally in a positive direction. Some generations experience more unfavourable conditions than others. The health of Danish women in the interwar generations is an example of such a phenomenon. The stagnation in their life expectancy between 1977 and 1995 is thought to be related to their smoking behaviour. So far, no study has measured the absolute effect of smoking on the mortality of the interwar generations of Danish women and thus the stagnation in Danish women's life expectancy. We applied a method to estimate age-specific smoking-attributable number of deaths to examine the effect of smoking on the trends in partial life expectancy of Danish women between age 50 and 85 from 1950 to 2012. We compared these trends to those for women in Sweden, where there was no similar stagnation in life expectancy. When smoking-attributable mortality was excluded, the gap in partial life expectancy at age 50 between Swedish and Danish women diminished substantially. The effect was most pronounced in the interwar generations. The major reason for the stagnation in Danish women's partial life expectancy at age 50 was found to be smoking-related mortality in the interwar generations.

Objective: To examine whether older parents in China would benefit more from daughters' care than from sons' emotional care., Method: Analysis of the unique data sets of the Chinese Longitudinal Healthy Longevity Survey conducted in 2002, 2005, and 2008-2009 in 22 provinces., Results: As compared with having son(s), having daughter(s) is significantly more beneficial at older ages in China, with regard to maintaining higher cognitive capacity and reducing mortality risk. Such daughter advantages in providing emotional care to older parents are more profound among the oldest-old aged 80+ as compared with the young-old aged 65 to 79 and surprisingly more profound in rural areas as compared with urban areas, even though son preference is much more common among rural residents., Discussion: We describe how educational campaigns aimed at informing the public about the benefits of daughter(s) for older parents' health outcome could help promote gender equality and reduce traditional son preference, especially in rural China.

The human lifespan has traversed a long evolutionary and historical path, from short-lived primate ancestors to contemporary Japan, Sweden, and other longevity frontrunners. Analyzing this trajectory is crucial for understanding biological and sociocultural processes that determine the span of life. Here we reveal a fundamental regularity. Two straight lines describe the joint rise of life expectancy and lifespan equality: one for primates and the second one over the full range of human experience from average lifespans as low as 2 y during mortality crises to more than 87 y for Japanese women today. Across the primate order and across human populations, the lives of females tend to be longer and less variable than the lives of males, suggesting deep evolutionary roots to the male disadvantage. Our findings cast fresh light on primate evolution and human history, opening directions for research on inequality, sociality, and aging., Competing Interests: The authors declare no conflict of interest.

Despite the importance of trauma in healthspan and lifespan in humans as well as in non-human species, with one important exception the literature in both gerontology and ecology contains virtually no experimental demographic studies concerned with trauma in any species. We used dietary manipulation [full diet (F) versus sugar-only (S)] to produce four levels of frailty in 55-day old tephritid fruit flies (Anastrepha ludens) that were then subject to the trauma of cage transfer stress (n = 900/sex in each of the 4 treatments). The key results included the following: (1) there is a trauma effect caused by the transfer that depends on previous diet before transfer, new diet after transfer and gender of the fly; (2) males are more vulnerable than females; (3) if initial diet was F, flies are relatively immune against the trauma, and the subsequent diet (F or S) does not matter; (4) however if initial diet was S, then the effect of the trauma depends largely on the diet after the transfer; (5) flies transferred from S to F diets do very well in terms of remaining longevity (i.e. greatest remaining longevity), while flies transferred from S to S diet do poorly (i.e. shortest remaining longevity). We discuss both the strengths and weaknesses of this study and implications of the results.

On the basis of the genotypic/phenotypic data from Chinese Longitudinal Healthy Longevity Survey (CLHLS) and Cox proportional hazard model, the present study demonstrates that interactions between carrying FOXO1A-209 genotypes and tea drinking are significantly associated with lower risk of mortality at advanced ages. Such a significant association is replicated in two independent Han Chinese CLHLS cohorts (p = 0.028-0.048 in the discovery and replication cohorts, and p = 0.003-0.016 in the combined dataset). We found the associations between tea drinking and reduced mortality are much stronger among carriers of the FOXO1A-209 genotype compared to non-carriers, and drinking tea is associated with a reversal of the negative effects of carrying FOXO1A-209 minor alleles, that is, from a substantially increased mortality risk to substantially reduced mortality risk at advanced ages. The impacts are considerably stronger among those who carry two copies of the FOXO1A minor allele than those who carry one copy. On the basis of previously reported experiments on human cell models concerning FOXO1A-by-tea-compounds interactions, we speculate that results in the present study indicate that tea drinking may inhibit FOXO1A-209 gene expression and its biological functions, which reduces the negative impacts of FOXO1A-209 gene on longevity (as reported in the literature) and offers protection against mortality risk at oldest-old ages. Our empirical findings imply that the health outcomes of particular nutritional interventions, including tea drinking, may, in part, depend upon individual genetic profiles, and the research on the effects of nutrigenomics interactions could potentially be useful for rejuvenation therapies in the clinic or associated healthy aging intervention programs.

Background: Histograms are a common tool to estimate densities non-parametrically. They are extensively encountered in health sciences to summarize data in a compact format. Examples are age-specific distributions of death or onset of diseases grouped in 5-years age classes with an open-ended age group at the highest ages. When histogram intervals are too coarse, information is lost and comparison between histograms with different boundaries is arduous. In these cases it is useful to estimate detailed distributions from grouped data., Methods: From an extensive literature search we identify five methods for ungrouping count data. We compare the performance of two spline interpolation methods, two kernel density estimators and a penalized composite link model first via a simulation study and then with empirical data obtained from the NORDCAN Database. All methods analyzed can be used to estimate differently shaped distributions; can handle unequal interval length; and allow stretches of 0 counts., Results: The methods show similar performance when the grouping scheme is relatively narrow, i.e. 5-years age classes. With coarser age intervals, i.e. in the presence of open-ended age groups, the penalized composite link model performs the best., Conclusion: We give an overview and test different methods to estimate detailed distributions from grouped count data. Health researchers can benefit from these versatile methods, which are ready for use in the statistical software R. We recommend using the penalized composite link model when data are grouped in wide age classes.

Health conditions change from year to year, with a general tendency in many countries for improvement. These conditions also change from one birth cohort to another: some generations suffer more adverse events in childhood, smoke more heavily, eat poorer diets, etc., than generations born earlier or later. Because it is difficult to disentangle period effects from cohort effects, demographers, epidemiologists, actuaries, and other population scientists often disagree about cohort effects' relative importance. In particular, some advocate forecasts of life expectancy based on period trends; others favor forecasts that hinge on cohort differences. We use a combination of age decomposition and exchange of survival probabilities between countries to study the remarkable recent history of female life expectancy in Denmark, a saga of rising, stagnating, and now again rising lifespans. The gap between female life expectancy in Denmark vs. Sweden grew to 3.5 y in the period 1975-2000. When we assumed that Danish women born 1915-1945 had the same survival probabilities as Swedish women, the gap remained small and roughly constant. Hence, the lower Danish life expectancy is caused by these cohorts and is not attributable to period effects.

Unlabelled: The open-data scientific philosophy is being widely adopted and proving to promote considerable progress in ecology and evolution. Open-data global data bases now exist on animal migration, species distribution, conservation status, etc. However, a gap exists for data on population dynamics spanning the rich diversity of the animal kingdom world-wide. This information is fundamental to our understanding of the conditions that have shaped variation in animal life histories and their relationships with the environment, as well as the determinants of invasion and extinction. Matrix population models (MPMs) are among the most widely used demographic tools by animal ecologists. MPMs project population dynamics based on the reproduction, survival and development of individuals in a population over their life cycle. The outputs from MPMs have direct biological interpretations, facilitating comparisons among animal species as different as Caenorhabditis elegans, Loxodonta africana and Homo sapiens. Thousands of animal demographic records exist in the form of MPMs, but they are dispersed throughout the literature, rendering comparative analyses difficult. Here, we introduce the COMADRE Animal Matrix Database, an open-data online repository, which in its version 1.0.0 contains data on 345 species world-wide, from 402 studies with a total of 1625 population projection matrices. COMADRE also contains ancillary information (e.g. ecoregion, taxonomy, biogeography, etc.) that facilitates interpretation of the numerous demographic metrics that can be derived from its MPMs. We provide R code to some of these examples., Synthesis: We introduce the COMADRE Animal Matrix Database, a resource for animal demography. Its open-data nature, together with its ancillary information, will facilitate comparative analysis, as will the growing availability of databases focusing on other aspects of the rich animal diversity, and tools to query and combine them. Through future frequent updates of COMADRE, and its integration with other online resources, we encourage animal ecologists to tackle global ecological and evolutionary questions with unprecedented sample size., (© 2016 The Authors. Journal of Animal Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Society.)

Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10(-5)). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity.

An epigenetic profile defining the DNA methylation age (DNAm age) of an individual has been suggested to be a biomarker of aging, and thus possibly providing a tool for assessment of health and mortality. In this study, we estimated the DNAm age of 378 Danish twins, age 30-82 years, and furthermore included a 10-year longitudinal study of the 86 oldest-old twins (mean age of 86.1 at follow-up), which subsequently were followed for mortality for 8 years. We found that the DNAm age is highly correlated with chronological age across all age groups (r = 0.97), but that the rate of change of DNAm age decreases with age. The results may in part be explained by selective mortality of those with a high DNAm age. This hypothesis was supported by a classical survival analysis showing a 35% (4-77%) increased mortality risk for each 5-year increase in the DNAm age vs. chronological age. Furthermore, the intrapair twin analysis revealed a more-than-double mortality risk for the DNAm oldest twin compared to the co-twin and a 'dose-response pattern' with the odds of dying first increasing 3.2 (1.05-10.1) times per 5-year DNAm age difference within twin pairs, thus showing a stronger association of DNAm age with mortality in the oldest-old when controlling for familial factors. In conclusion, our results support that DNAm age qualifies as a biomarker of aging., (© 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Objectives: To determine whether simple functional indicators are predictors of survival prognosis in very old adults., Design: In-person survey conducted over a 3-month period in 1998; assessment of survival over a 15-year follow-up period., Setting: Denmark., Participants: All 3,600 Danes born in 1905 and living in Denmark in 1998, were invited to participate regardless of residence and health; 2,262 (63%) participated in the survey: 1,814 (80.2%) in person and 448 (19.8%) through a proxy., Measurements: Socioeconomic factors, medications and diseases, activities of daily living, physical performance, cognition, depression symptomatology, self-rated health, and all-cause mortality, evaluated as average remaining lifespan and chance of surviving to 100 years., Results: Men aged 92 to 93 had an overall 6.0% chance of surviving to 100 years, whereas the chance for women was 11.4%. Being able to rise without use of hands increased the chance for men to 11.2% (95% confidence interval (CI)=7.7-14.7) and for women to 22.0% (95% CI=18.9-25.1). When combining this with a Mini-Mental State Examination (MMSE) scores from 28 to 30, the chances were 21.7% (95% CI=11.5-31.9) for men and 34.2% (95% CI=24.8-43.5) for women., Conclusion: Chair stand score combined with MMSE score is a quick and easy way to estimate overall chance of survival in very old adults, which is particularly relevant when treatment with potential side effects for nonacute diseases is considered., (© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.)

This study analyzes the unique datasets of the Chinese Longitudinal Healthy Longevity Survey using logistic regression and controlling for various covariates. Our analyses clearly demonstrate that disabled older parents are more satisfied with care provided by daughters than sons and that older parents enjoy greater filial piety from and better relationships with daughters than sons. The daughter-advantages of enjoying greater filial piety from and better relationships with children are stronger among the oldest-old aged 80+ than the young-old aged 65-79, and surprisingly more profound in rural areas than urban areas, while son-preference is much more prevalent among rural residents. We also discuss why China's rigorous fertility policy until October-2015 and much less-developed pension system in rural areas substantially contribute to sustaining traditional son-preference and a high sex ratio at birth (SRB) when fertility is low. We recommend China take integrative public health policy actions of informing the public that having daughter(s) is beneficial for old age care, developing the rural pension system and implementing the universal two-child policy as soon as possible. We believe that these policy actions would help to reduce son-preference, bring down the high SRB, and enable more future elderly parents to enjoy better care from their children and healthier lives., Competing Interests: Declaration of Conflicting Interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Senescence, the increase in mortality and decline in fertility with age after maturity, was thought to be inevitable for all multicellular species capable of repeated breeding. Recent theoretical advances and compilations of data suggest that mortality and fertility trajectories can go up or down, or remain constant with age, but the data are scanty and problematic. Here, we present compelling evidence for constant age-specific death and reproduction rates in Hydra, a basal metazoan, in a set of experiments comprising more than 3.9 million days of observations of individual Hydra. Our data show that 2,256 Hydra from two closely related species in two laboratories in 12 cohorts, with cohort age ranging from 0 to more than 41 y, have extremely low, constant rates of mortality. Fertility rates for Hydra did not systematically decline with advancing age. This falsifies the universality of the theories of the evolution of aging that posit that all species deteriorate with age after maturity. The nonsenescent life history of Hydra implies levels of maintenance and repair that are sufficient to prevent the accumulation of damage for at least decades after maturity, far longer than the short life expectancy of Hydra in the wild. A high proportion of stem cells, constant and rapid cell turnover, few cell types, a simple body plan, and the fact that the germ line is not segregated from the soma are characteristics of Hydra that may make nonsenescence feasible. Nonsenescence may be optimal because lifetime reproduction may be enhanced more by extending adult life spans than by increasing daily fertility.

Background: This article investigates the importance of regional health care availability for old age survival. Using German reunification as a natural experiment, we show that spatial variation in health care in East Germany considerably influenced the convergence of East German life expectancy toward West German levels., Method: We apply cause-deleted life tables and continuous mortality decomposition for the years 1982-2007 to show how reductions in circulatory mortality among the elderly affected the East German catch-up in life expectancy., Results: Improvements in remaining life expectancy at older ages were first seen in towns with university hospitals, where state-of-the-art services became available first., Conclusion: Our results suggest that the modernization of the health care system had a substantial effect on old-age life expectancy and helped to significantly reduce circulatory diseases as the main cause of death in East Germany.

Purpose: Familial clustering of longevity is well documented and includes both genetic and other familial factors, but the specific underlying mechanisms are largely unknown. We examined whether low incidence of specific cancers is a mechanism for familial clustering of longevity., Methods: The study population of individuals from longevity-enriched families consisted of 3267 offspring from 610 Danish long-lived families defined by two siblings attaining an age of 90 years or more. The offspring of the long-lived siblings were followed from 1968 to 2009. Using high-quality registry data, observed numbers of cancers were compared with expected numbers based on gender-, calendar period-, and age-specific incidence rates in the general population., Results: During the 41-year-follow-up period, a total of 423 cancers occurred in 397 individuals. The standardized incidence ratios (95% confidence interval) for offspring of long-lived individuals were 0.78 (0.70-0.86) for overall cancer; 0.66 (0.56-0.77) for tobacco-related cancer; 0.34 (0.22-0.51) for lung cancer; 0.88 (0.71-1.10) for breast cancer; 0.91 (0.62-1.34) for colon cancer., Conclusions: The low incidence of tobacco-related cancers in long-lived families compared with non-tobacco-related cancers suggests that health behavior plays a central role in lower early cancer incidence in offspring of long-lived siblings in Denmark., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The apparent contradiction that women live longer but have worse health than men, the so called male-female health-survival paradox, is very pronounced in Russia. The present study investigates whether men in Moscow are healthier than women at the level of biomarkers, and whether the associations between biomarkers and subjective health have sex-specific patterns., Materials: Previously collected data in the study of Stress, Aging, and Health in Russia (SAHR, n = 1800) were used to examine sex differences in biomarkers and their associations with physical functioning and self-rated health., Results: The present study found mixed directions and magnitudes for sex differences in biomarkers. Women were significantly disadvantaged with regard to obesity and waist circumference, whereas men had a tendency toward higher prevalence of electrocardiographic abnormalities. No sex differences were indicated in the prevalence of immunological biomarkers, and mixed patterns were found for lipid profiles. Many biomarkers were associated with physical functioning and general health. Obesity and waist circumference were related to lower physical functioning among females only, while major Q-wave abnormalities with high probabilities of myocardial infarction and atrial fibrillation or atrial flutter were associated with physical functioning and self-rated health among males only., Conclusion: No clear patterns of sex differences in prevalence of high-risk levels of biomarkers suggest that the male-female health-survival paradox is weaker at the level of health biomarkers. We found some evidence that certain biomarkers reflecting pathophysiological changes in the organism that do not possess acute health risks, but over many years may lead to physical disability, are associated with physical functioning and self-rated health in women, whereas others reflecting more serious life-threatening pathophysiological changes are associated with physical functioning and self-rated health in men.

Logistic regression analysis based on data from 822 Han Chinese oldest old aged 92+ demonstrated that interactions between carrying FOXO1A-266 or FOXO3-310 or FOXO3-292 and tea drinking at around age 60 or at present time were significantly associated with lower risk of cognitive disability at advanced ages. Associations between tea drinking and reduced cognitive disability were much stronger among carriers of the genotypes of FOXO1A-266 or FOXO3-310 or FOXO3-292 compared with noncarriers, and it was reconfirmed by analysis of three-way interactions across FOXO genotypes, tea drinking at around age 60, and at present time. Based on prior findings from animal and human cell models, we postulate that intake of tea compounds may activate FOXO gene expression, which in turn may positively affect cognitive function in the oldest old population. Our empirical findings imply that the health benefits of particular nutritional interventions, including tea drinking, may, in part, depend upon individual genetic profiles., (© The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Little is known about whether the feeling of happiness follows the age-related decline in physical and mental functioning. The objective of this study was to analyze differences with age in physical and mental functions and in the feeling of happiness among Danes aged 45 years and older., Method: Three Danish population-based surveys including 11,307 participants aged 45+ years, of whom 2411 were in the age group of 90+, were conducted in the period 1995-2001. The participation rate in the three surveys was between 63% and 82% and the same design and the same instrument were used. Self-reported mobility, a cognitive composite score, and a depression symptomatology score including a question about happiness were assessed. T-score metric was used to compare across domains and age groups., Results: Overall, successively older age groups performed worse than the youngest age group (45-49 years), and the estimated linear decline was greater after age 70 than before age 70. For example, when comparing the oldest age group (90+ years) with the youngest, the T-score differences were found to be the largest for the mobility score (men: 40.2, women: 41.4), followed by the cognitive function (men: 22.0, women: 24.9), and the total depression symptomatology score (men: 15.5, women: 17.4). Conversely, the T-score difference in happiness was small (men: 5.6, women: 6.0)., Conclusion: Despite markedly poorer physical and mental functions with increasing age, in this Danish sample age did not seem to affect happiness to a similarly notable extent, although, in this study, cohort and age effects cannot be disentangled.

Gene variants found to associate with human longevity in one population rarely replicate in other populations. The lack of consistent findings may partly be explained by genetic heterogeneity among long-lived individuals due to cohort differences in survival probability. In most high-income countries the probability of reaching e.g. 100years increases by 50-100% per decade, i.e. there is far less selection in more recent cohorts. Here we investigate the cohort specificity of variants in the APOE and FOXO3A genes by comparing the frequencies of the APOE ε4 allele and the minor alleles of two variants in FOXO3A at age 95+ and 100+ in 2712 individuals from the genetically homogeneous Danish birth cohorts 1895-96, 1905, 1910-11, and 1915. Generally, we find a decrease in the allele frequencies of the investigated APOE and FOXO3A variants in individuals from more recent birth cohorts. Assuming a recessive model, this negative trend is significant in 95+ year old individuals homozygous for the APOE ε4 allele (P=0.026) or for the FOXO3A rs7762395 minor allele (P=0.048). For the APOE ε4 allele, the significance is further strengthened when restricting to women (P=0.006). Supportive, but non-significant, trends are found for two of the three tested variants in individuals older than 100years. Altogether, this indicates that cohort differences in selection pressure on survival to the highest ages are reflected in the prevalence of longevity gene variants. Although the effect seems to be moderate, our findings could have an impact on genetic studies of human longevity., (Copyright © 2014 Elsevier Inc. All rights reserved.)

To re-examine the correlation between mtDNA variability and longevity, we examined mtDNAs from samples obtained from over 2200 ultranonagenarians (and an equal number of controls) collected within the framework of the GEHA EU project. The samples were categorized by high-resolution classification, while about 1300 mtDNA molecules (650 ultranonagenarians and an equal number of controls) were completely sequenced. Sequences, unlike standard haplogroup analysis, made possible to evaluate for the first time the cumulative effects of specific, concomitant mtDNA mutations, including those that per se have a low, or very low, impact. In particular, the analysis of the mutations occurring in different OXPHOS complex showed a complex scenario with a different mutation burden in 90+ subjects with respect to controls. These findings suggested that mutations in subunits of the OXPHOS complex I had a beneficial effect on longevity, while the simultaneous presence of mutations in complex I and III (which also occurs in J subhaplogroups involved in LHON) and in complex I and V seemed to be detrimental, likely explaining previous contradictory results. On the whole, our study, which goes beyond haplogroup analysis, suggests that mitochondrial DNA variation does affect human longevity, but its effect is heavily influenced by the interaction between mutations concomitantly occurring on different mtDNA genes., (© 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

In high income countries females outlive men, although they generally report worse health, the so-called male-female health-survival paradox. Russia has one of the world's largest sex difference in life expectancy with a male disadvantage of more than 10 years. We compare components of the paradox between Denmark and Moscow by examining sex differences in mortality and several health measures. The Human Mortality Database and the Russian Fertility and Mortality Database were used to examine sex differences in all-cause death rates in Denmark, Russia, and Moscow in 2007-2008. Self-reported health data were obtained from the Study of Middle-Aged Danish Twins (n = 4,314), the Longitudinal Study of Aging Danish Twins (n = 4,731), and the study of Stress, Aging, and Health in Russia (n = 1,800). In both Moscow and Denmark there was a consistent female advantage at ages 55-89 years in survival and a male advantage in self-rated health, physical functioning, and depression symptomatology. Only on cognitive tests males performed similarly to or worse than women. Nevertheless, Muscovite males had more than twice higher mortality at ages 55-69 years compared to Muscovite women, almost double the ratio in Denmark. The present study showed that despite similar directions of sex differences in health and mortality in Moscow and Denmark, the male-female health-survival paradox is very pronounced in Moscow suggesting a stronger sex-specific disconnect between health indicators and mortality among middle-aged and young-old Muscovites.

Evolution drives, and is driven by, demography. A genotype moulds its phenotype's age patterns of mortality and fertility in an environment; these two patterns in turn determine the genotype's fitness in that environment. Hence, to understand the evolution of ageing, age patterns of mortality and reproduction need to be compared for species across the tree of life. However, few studies have done so and only for a limited range of taxa. Here we contrast standardized patterns over age for 11 mammals, 12 other vertebrates, 10 invertebrates, 12 vascular plants and a green alga. Although it has been predicted that evolution should inevitably lead to increasing mortality and declining fertility with age after maturity, there is great variation among these species, including increasing, constant, decreasing, humped and bowed trajectories for both long- and short-lived species. This diversity challenges theoreticians to develop broader perspectives on the evolution of ageing and empiricists to study the demography of more species.

Background: A rapidly increasing proportion of people in high-income countries are surviving into their tenth decade. Concern is widespread that the basis for this development is the survival of frail and disabled elderly people into very old age. To investigate this issue, we compared the cognitive and physical functioning of two cohorts of Danish nonagenarians, born 10 years apart., Methods: People in the first cohort were born in 1905 and assessed at age 93 years (n=2262); those in the second cohort were born in 1915 and assessed at age 95 years (n=1584). All cohort members were eligible irrespective of type of residence. Both cohorts were assessed by surveys that used the same design and assessment instrument, and had almost identical response rates (63%). Cognitive functioning was assessed by mini-mental state examination and a composite of five cognitive tests that are sensitive to age-related changes. Physical functioning was assessed by an activities of daily living score and by physical performance tests (grip strength, chair stand, and gait speed)., Findings: The chance of surviving from birth to age 93 years was 28% higher in the 1915 cohort than in the 1905 cohort (6·50% vs 5·06%), and the chance of reaching 95 years was 32% higher in 1915 cohort (3·93% vs 2·98%). The 1915 cohort scored significantly better on the mini-mental state examination than did the 1905 cohort (22·8 [SD 5·6] vs 21·4 [6·0]; p<0·0001), with a substantially higher proportion of participants obtaining maximum scores (28-30 points; 277 [23%] vs 235 [13%]; p<0·0001). Similarly, the cognitive composite score was significantly better in the 1915 than in the 1905 cohort (0·49 [SD 3·6] vs 0·01 [SD 3·6]; p=0·0003). The cohorts did not differ consistently in the physical performance tests, but the 1915 cohort had significantly better activities of daily living scores than did the 1905 cohort (2·0 [SD 0·8] vs 1·8 [0·7]; p<0·0001)., Interpretation: Despite being 2 years older at assessment, the 1915 cohort scored significantly better than the 1905 cohort on both the cognitive tests and the activities of daily living score, which suggests that more people are living to older ages with better overall functioning., Funding: Danish National Research Foundation; US National Institutes of Health-National Institute on Aging; Danish Agency for Science, Technology and Innovation; VELUX Foundation., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Death rates for 80+-year-olds are now half of what they were after WWII. The chance of living past 90 years has gone up by roughly 30% per decade for people born in Denmark in 1895, 1905, and 1915 - and the later cohorts are functioning better physically and cognitively. Centenarians are on average functioning physically and cognitively as well as 92-93-year-olds due to selective mortality. A steep increase in the frequency of hospitalization and surgical procedure among 85-100-year-olds is occurring, but there is a lack of knowledge about treatment effects and side effects among the oldest-old.

Background and Aims: Studies examining predictors of survival among the oldest-old have primarily focused on objective measures, such as physical function and health status. Only a few studies have examined the effect of personality traits on survival, such as optimism. The aim of this study was to examine whether an optimistic outlook predicts survival among the oldest-old., Methods: The Danish 1905 Cohort Survey is a nationwide, longitudinal survey comprising all individuals born in Denmark in 1905. At baseline in 1998, a total of 2,262 persons aged 92 or 93 agreed to participate in the intake survey. The baseline in-person interview consisted of a comprehensive questionnaire including physical functioning and health, and a question about whether the respondent had an optimistic, neutral or pessimistic outlook on his or her own future., Results: During the follow-up period of 12 years (1998-2010) there were 2,239 deaths (99 %) in the 1905 Cohort Survey. Univariable analyses revealed that optimistic women and men were at lower risk of death compared to their neutral counterparts [HR 0.82, 95 % CI (0.73-0.93) and 0.81, 95 % CI (0.66-0.99), respectively]. When confounding factors such as baseline physical and cognitive functioning and disease were taken into account the association between optimism and survival weakened in both sexes, but the general pattern persisted. Optimistic women were still at lower risk of death compared to neutral women [HR 0.85, 95 % CI (0.74-0.97)]. The risk of death was also decreased for optimistic men compared to their neutral counterparts, but the effect was non-significant [HR 0.91, 95 % CI (0.73-1.13)]., Conclusion: An optimistic outlook appears to be a significant predictor of survival among the oldest-old women. It may also be a significant predictor for men but the sample size is small.

Objective: to examine whether the Danish 1905 cohort members had more active hospital treatment than the 1895 cohort members from ages 85 to 99 years and whether it results in higher in-hospital and post-operative mortality., Methods: in the present register-based follow-up study the complete Danish birth cohorts born in 1895 (n = 12,326) and 1905 (n = 15,477) alive and residing in Denmark at the age of 85 were followed from ages 85 to 99 years with regard to hospitalisations and all-cause and cause-specific surgical procedures, as well as in-hospital and post-operative mortality., Results: the 1905 cohort members had more frequent hospital admissions and operations, but they had a shorter length of hospital stay than the 1895 cohort at all ages from 85 to 99 years. The increase in primary prosthetic replacements of hip joint was observed even within the 1895 cohort: no patients were operated at ages 85-89 years versus 2.2-3.6% at ages 95-99 years. Despite increased hospitalisation and operation rates, there was no increase in post-operative and in-hospital mortality rates in the 1905 cohort. These patterns were similar among men and women., Conclusions: the observed patterns are compatible with more active treatment of the recent cohorts of old-aged persons and reduced age inequalities in the Danish healthcare system. No increase in post-operative mortality suggests that the selection of older patients eligible for a surgical treatment is likely to be based on the health status of old-aged persons and the safety of surgical procedures rather than chronological age.

Allostatic load theory implies a relationship between exposure to psychological stress and multi-system physiological dysregulation. We used data from population-based samples of men and women in Russia (Moscow; n = 1800; age, mean 68.6 years), Taiwan (n = 1036; 65.6 years) and the United States (US; n = 1054; 58.0 years) -- which are likely to vary widely with respect to levels of stress exposure and biological markers -- to determine the magnitude of the association between perceived stress and physiological dysregulation. The measure of overall dysregulation was based on 15 markers including standard cardiovascular/metabolic risk factors as well as markers of inflammation and neuroendocrine activity. Subjective psychological stress was measured by the perceived stress scale. Only the Moscow sample demonstrated a positive association with overall dysregulation in both sexes. In the US, we found an association among women but not men. Among the Taiwanese, who report the lowest perceived stress, there was no association in women but an unexpected inverse relationship in men. The effects also varied across system-level subscores: the association with perceived stress was most consistent for standard cardiovascular/metabolic factors. Perceived stress was associated with inflammation and neuroendocrine activity in some samples. Although the evidence that perceived stress is the primary source of physiological dysregulation is generally modest, it was stronger in Russia where the level of perceived stress was particularly high. For Russia only, we had information about heart function based on a 24 h ambulatory electrocardiogram; perceived stress was consistently associated with heart rate dysregulation in Russian men and women.

In this study, we investigated 102 single-nucleotide polymorphisms (SNPs) covering the common genetic variation in 16 genes recurrently regarded as candidates for human longevity: APOE; ACE; CETP; HFE; IL6; IL6R; MTHFR; TGFB1; APOA4; APOC3; SIRTs 1, 3, 6; and HSPAs 1A, 1L, 14. In a case-control study of 1,089 oldest-old (ages 92-93) and 736 middle-aged Danes, the minor allele frequency (MAF) of rs769449 (APOE) was significantly decreased in the oldest-old, while the MAF of rs9923854 (CETP) was significantly enriched. These effects were supported when investigating 1,613 oldest-old (ages 95-110) and 1,104 middle-aged Germans. rs769449 was in modest linkage equilibrium (R (2)=0.55) with rs429358 of the APOE-ε4 haplotype and adjusting for rs429358 eliminated the association of rs769449, indicating that the association likely reflects the well-known effect of rs429358. Gene-based analysis confirmed the effects of variation in APOE and CETP and furthermore pointed to HSPA14 as a longevity gene. In a longitudinal study with 11 years of follow-up on survival in the oldest-old Danes, only one SNP, rs2069827 (IL6), was borderline significantly associated with survival from age 92 (P-corrected=0.064). This advantageous effect of the minor allele was supported when investigating a Dutch longitudinal cohort (N=563) of oldest-old (age 85+). Since rs2069827 was located in a putative transcription factor binding site, quantitative RNA expression studies were conducted. However, no difference in IL6 expression was observed between rs2069827 genotype groups. In conclusion, we here support and expand the evidence suggesting that genetic variation in APOE, CETP, and IL6, and possible HSPA14, is associated with human longevity.

Clear evidence exists for heritability of human longevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome-wide linkage scan thus far reported. Linkage analyses included 2118 nonagenarian Caucasian sibling pairs that have been enrolled in 15 study centers of 11 European countries as part of the Genetics of Healthy Aging (GEHA) project. In the joint linkage analyses, we observed four regions that show linkage with longevity; chromosome 14q11.2 (LOD = 3.47), chromosome 17q12-q22 (LOD = 2.95), chromosome 19p13.3-p13.11 (LOD = 3.76), and chromosome 19q13.11-q13.32 (LOD = 3.57). To fine map these regions linked to longevity, we performed association analysis using GWAS data in a subgroup of 1228 unrelated nonagenarian and 1907 geographically matched controls. Using a fixed-effect meta-analysis approach, rs4420638 at the TOMM40/APOE/APOC1 gene locus showed significant association with longevity (P-value = 9.6 × 10(-8) ). By combined modeling of linkage and association, we showed that association of longevity with APOEε4 and APOEε2 alleles explain the linkage at 19q13.11-q13.32 with P-value = 0.02 and P-value = 1.0 × 10(-5) , respectively. In the largest linkage scan thus far performed for human familial longevity, we confirm that the APOE locus is a longevity gene and that additional longevity loci may be identified at 14q11.2, 17q12-q22, and 19p13.3-p13.11. As the latter linkage results are not explained by common variants, we suggest that rare variants play an important role in human familial longevity., (© 2013 The Authors Aging Cell © 2013 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.)

Over the last 60 years, the resources and the research in the Danish Twin Registry (DTR) have periodically been summarized. Here, we give a short overview of the DTR and a more comprehensive description of new developments in the twenty-first century. First, we outline our experience over the last decade of combining questionnaire and survey data with national demographic, social, and health registers in Statistics Denmark. Second, we describe our most recent data collection effort, which was conducted during the period 2008-2011 and included both in-person assessments of 14,000+ twins born 1931-1969 and sampling of biological material, hereby expanding and consolidating the DTR biobank. Third, two examples of intensively studied twin cohorts are given. The new developments in the DTR in the last decade have facilitated the ongoing research and laid the groundwork for new research directions.

Semelparous organisms have a simple life cycle characterized by immediate death after reproduction. We assume that semelparous life histories can be separated into a juvenile non-reproductive period followed by an adult period during which reproduction is possible. We derive formulae for the optimal age and size at reproduction and for the optimal size of the offspring (e.g., seeds). Our main contribution is to determine the conditions under which the optimal size of the offspring does not depend on the optimal size at reproduction and vice versa.

Limited to 1,000 words, we address some serious technical mistakes and factual errors, as well as the misleading quotations in the section of Olshansky's and Carnes' article that attacks some of our joint research., (Copyright © 2012 S. Karger AG, Basel.)

Life expectancy is increasing in most countries and has exceeded 80 in several, as low-mortality nations continue to make progress in averting deaths. The health and economic implications of mortality reduction have been given substantial attention, but the observed malleability of human mortality has not been placed in a broad evolutionary context. We quantify the rate and amount of mortality reduction by comparing a variety of human populations to the evolved human mortality profile, here estimated as the average mortality pattern for ethnographically observed hunter-gatherers. We show that human mortality has decreased so substantially that the difference between hunter-gatherers and today's lowest mortality populations is greater than the difference between hunter-gatherers and wild chimpanzees. The bulk of this mortality reduction has occurred since 1900 and has been experienced by only about 4 of the roughly 8,000 human generations that have ever lived. Moreover, mortality improvement in humans is on par with or greater than the reductions in mortality in other species achieved by laboratory selection experiments and endocrine pathway mutations. This observed plasticity in age-specific risk of death is at odds with conventional theories of aging.

The goal of this study is to estimate the prevalence of MetS, together with its components and correlates, among elderly Russians. Our population-based sample included randomly selected residents of Moscow aged 55 and older: 955 women with an average age of 67.6, and 833 men with an average age of 68.9. MetS was defined according to National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII). The prevalence of MetS was found to be 41.7% in women and 26.8% in men. It tended to decrease with age in men, but not in women. MetS was inversely related to education in women, but not in men. The most prevalent individual components of MetS were as follows: hypertension (64.4%), abdominal obesity (55%), and decreased high density lipoprotein cholesterol (HDL C) (46%) for women; and hypertension (71%) and fasting hyperglycemia (35.2%) for men. An elevated level of triglycerides (TG) was the rarest MetS component, affecting 23.5% of women and 22.1% of men. The higher female prevalence of MetS was attributable to abdominal obesity. MetS was found to be associated with markers of insulin resistance (IR), low-grade inflammation, and insufficient fibrinolysis. Although the metabolic burden is an important contributor to high levels of ill-health and cardiovascular mortality among elderly Russians (especially women), it does not explain why cardiovascular mortality is much higher in Russia than in other industrialized countries., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Here we explore association with human longevity of common genetic variation in three major candidate pathways: GH/IGF-1/insulin signaling, DNA damage signaling and repair and pro/antioxidants by investigating 1273 tagging SNPs in 148 genes composing these pathways. In a case-control study of 1089 oldest-old (age 92-93) and 736 middle-aged Danes we found 1 pro/antioxidant SNP (rs1002149 (GSR)), 5 GH/IGF-1/INS SNPs (rs1207362 (KL), rs2267723 (GHRHR), rs3842755 (INS), rs572169 (GHSR), rs9456497 (IGF2R)) and 5 DNA repair SNPs (rs11571461 (RAD52), rs13251813 (WRN), rs1805329 (RAD23B), rs2953983 (POLB), rs3211994 (NTLH1)) to be associated with longevity after correction for multiple testing. In a longitudinal study with 11 years of follow-up on survival in the oldest-old Danes we found 2 pro/antioxidant SNPs (rs10047589 (TNXRD1), rs207444 (XDH)), 1 GH/IGF-1/INS SNP (rs26802 (GHRL)) and 3 DNA repair SNPs (rs13320360 (MLH1), rs2509049 (H2AFX) and rs705649 (XRCC5)) to be associated with mortality in late life after correction for multiple testing. When examining the 11 SNPs from the case-control study in the longitudinal data, rs3842755 (INS), rs13251813 (WRN) and rs3211994 (NTHL1) demonstrated the same directions of effect (p<0.05), while rs9456497 (IGF2R) and rs1157146 (RAD52) showed non-significant tendencies, indicative of effects also in late life survival. In addition, rs207444 (XDH) presented the same direction of effect when inspecting the 6 SNPs from the longitudinal study in the case-control data, hence, suggesting an effect also in survival from middle age to old age. No formal replications were observed when investigating the 11 SNPs from the case-control study in 1613 oldest-old (age 95-110) and 1104 middle-aged Germans, although rs11571461 (RAD52) did show a supportive non-significant tendency (OR=1.162, 95% CI=0.927-1.457). The same was true for rs10047589 (TNXRD1) (HR=0.758, 95%CI=0.543-1.058) when examining the 6 SNPs from the longitudinal study in a Dutch longitudinal cohort of oldest-old (age 85+, N=563). In conclusion, the present candidate gene based association study, the largest to date applying a pathway approach, not only points to potential new longevity loci, but also underlines the difficulties of replicating association findings in independent study populations and thus the difficulties in identifying universal longevity polymorphisms., (Copyright © 2012 Elsevier Inc. All rights reserved.)

In mammalian females, one of the two X chromosomes is inactivated in early embryonic life. Females are therefore mosaics for two cell populations, one with the maternal and one with the paternal X as the active X chromosome. A skewed X inactivation is a marked deviation from a 50:50 ratio. In populations of women past 55-60 years of age, an increased degree of skewing (DS) is found. Here the association between age-related skewing and mortality is analyzed in a 13-year follow-up study of 500 women from three cohorts (73-100 years of age at intake). Women with low DS had significantly higher mortality than the majority of women who had a more skewed DS (hazard ratio: 1.30; 95% CI: 1.04-1.64). The association between X inactivation and mortality was replicated in dizygotic twin pairs for which the co-twin with the lowest DS also had a statistically significant tendency to die first in the twin pairs with the highest intra-pair differences in DS (proportion: 0.71; 95% CI: 0.52-0.86). Both results suggest that lower DS is associated with higher mortality. We therefore propose that age-related skewing may be partly due to a population selection with lower mortality among those with higher DS.

Is senescence the adaptive result of tradeoffs between younger and older ages or the nonadaptive burden of deleterious mutations that act at older ages? To shed new light on this unresolved question we combine adaptive and nonadaptive processes in a single model. Our model uses Penna's bit-strings to capture different age-specific mutational patterns. Each pattern represents a genotype and for each genotype we find the life history strategy that maximizes fitness. Genotypes compete with each other and are subject to selection and to new mutations over generations until equilibrium in gene-frequencies is reached. The mutation-selection equilibrium provides information about mutational load and the differential effects of mutations on a life history trait--the optimal age at maturity. We find that mutations accumulate only at ages with negligible impact on fitness and that mutation accumulation has very little effect on the optimal age at maturity. These results suggest that life histories are largely determined by adaptive processes. The non-adaptive process of mutation accumulation seems to be unimportant at evolutionarily relevant ages.

Background: Studies show that the U.S. foreign-born population has lower mortality than the native-born population before age 65. Until recently, the lack of data prohibited reliable comparisons of U.S. mortality by nativity at older ages. This study provides reliable estimates of U.S. foreign-born and native-born mortality at ages 65 and older at the end of the 20(th) century. Life expectancies of the U.S. foreign born are compared to other developed nations and the foreign-born contribution to total life expectancy (TLE) in the United States is assessed., Methods: Newly available data from Medicare Part B records linked with Social Security Administration files are used to estimate period life tables for nearly all U.S. adults aged 65 and older in 1995. Age-specific survival differences and life expectancies are examined in 1995 by sex, race, and place of birth., Results: Foreign-born men and women had lower mortality at almost every age from 65 to 100 compared to native-born men and women. Survival differences by nativity were substantially greater for blacks than whites. Foreign-born blacks had the longest life expectancy of all population groups (18.73 [95% confidence interval {CI}, 18.15-19.30] years at age 65 for men and 22.76 [95% CI, 22.28-23.23] years at age 65 for women). The foreign-born population increased TLE in the United States at older ages, and by international comparison, the U.S. foreign born were among the longest-lived persons in the world., Conclusion: Survival estimates based on reliable Medicare data confirm that foreign-born adults have longer life expectancy at older ages than native-born adults in the United States.

In 2004, the integrated European project GEHA (Genetics of Healthy Ageing) was initiated with the aim of identifying genes involved in healthy ageing and longevity. The first step in the project was the recruitment of more than 2500 pairs of siblings aged 90 years or more together with one younger control person from 15 areas in 11 European countries through a coordinated and standardised effort. A biological sample, preferably a blood sample, was collected from each participant, and basic physical and cognitive measures were obtained together with information about health, life style, and family composition. From 2004 to 2008 a total of 2535 families comprising 5319 nonagenarian siblings were identified and included in the project. In addition, 2548 younger control persons aged 50-75 years were recruited. A total of 2249 complete trios with blood samples from at least two old siblings and the younger control were formed and are available for genetic analyses (e.g. linkage studies and genome-wide association studies). Mortality follow-up improves the possibility of identifying families with the most extreme longevity phenotypes. With a mean follow-up time of 3.7 years the number of families with all participating siblings aged 95 years or more has increased by a factor of 5 to 750 families compared to when interviews were conducted. Thus, the GEHA project represents a unique source in the search for genes related to healthy ageing and longevity., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: To determine the contribution of progress in averting premature deaths to the increase in life expectancy and the decline in lifespan variation., Design: International comparison of national life table data from the Human Mortality Database., Setting: 40 developed countries and regions, 1840-2009., Population: Men and women of all ages., Main Outcome Measure: We use two summary measures of mortality: life expectancy and life disparity. Life disparity is a measure of how much lifespans differ among individuals. We define a death as premature if postponing it to a later age would decrease life disparity., Results: In 89 of the 170 years from 1840 to 2009, the country with the highest male life expectancy also had the lowest male life disparity. This was true in 86 years for female life expectancy and disparity. In all years, the top several life expectancy leaders were also the top life disparity leaders. Although only 38% of deaths were premature, fully 84% of the increase in life expectancy resulted from averting premature deaths. The reduction in life disparity resulted from reductions in early-life disparity, that is, disparity caused by premature deaths; late-life disparity levels remained roughly constant., Conclusions: The countries that have been the most successful in averting premature deaths have consistently been the life expectancy leaders. Greater longevity and greater equality of individuals' lifespans are not incompatible goals. Countries can achieve both by reducing premature deaths.

Patterns of diversity in age at death are examined using e (†), a dispersion measure that equals the average expected lifetime lost at death. We apply two methods for decomposing differences in e (†). The first method estimates the contributions of average levels of mortality and mortality age structures. The second (and newly developed) method returns components produced by differences between age- and cause-specific mortality rates. The United States is close to England and Wales in mean life expectancy but has higher life expectancy losses and lacks mortality compression. The difference is determined by mortality age structures, whereas the role of mortality levels is minor. This is related to excess mortality at ages under 65 from various causes in the United States. Regression on 17 country-series suggests that e (†) correlates with income inequality across countries but not across time. This result can be attributed to dissimilarity between the age- and cause-of-death structures of temporal mortality reduction and intercountry mortality variation. It also suggests that factors affecting overall mortality decrease differ from those responsible for excess lifetime losses in the United States compared with other countries. The latter can be related to weaknesses of health system and other factors resulting in premature death from heart diseases, amenable causes, accidents and violence.

We analyze trends in best-practice life expectancy among female cohorts born from 1870 to 1950. Cohorts experience declining rather than constant death rates, and cohort life expectancy usually exceeds period life expectancy. Unobserved mortality rates in non-extinct cohorts are estimated using the Lee-Carter model for mortality in 1960–2008. Best-practice cohort and period life expectancies increased nearly linearly. Across cohorts born from 1870 to 1920 the annual increase in cohort length of life was 0.43 years. Across calendar years from 1870 to 2008, the annual increase was 0.28 years. Cohort life expectancy increased from 53.7 years in the 1870 cohort to 83.8 years in the 1950 cohort. The corresponding cohort/period longevity gap increased from 1.2 to 10.3 years. Among younger cohorts, survival to advanced ages is substantially higher than could have been anticipated by period mortality regimes when these cohorts were young or middle-aged. A large proportion of the additional expected years of life are being lived at ages 65 and older. This substantially changes the balance between the stages of the life cycle.

Background. The study aimed to examine sex differences in healthcare use before and after widowhood to investigate whether reduced healthcare use among widowers compared with widows may partially explain excess mortality and more adverse health outcomes among men than women after spousal loss. Methods. All individuals alive and aged at least 60 years in 1996 and who became widowed in the period from 1996 to 2003 were selected from the 5% sample of the total Danish population and all Danish twins. The healthcare use was assessed as the average daily all-cause and major system-specific medication use and the average annual number of visits to general physicians (GPs). Results. The average daily use of all-cause and major system-specific medications, as well as the number of GP visits increased over the period from 1 year before and up to 5 years after a spouse's death, but there were no sex-specific patterns in the trajectories of medication use and number of GP visits after conjugal loss. Conclusion. We found little support for the hypothesis that reduced healthcare use contributes to the explanation of more adverse health outcomes after conjugal loss in men compared with women in Denmark.

Based on data from 760 centenarians and 1060 middle-age controls (all Han Chinese), this article contributes biodemographic insights and syntheses concerning the magnitude of effects of the FOXO genotypes on longevity. We also estimate independent and joint effects of the genotypes of FOXO1A and FOXO3A genes on long-term survival, considering carrying or not-carrying the minor allele of the single-nucleotide polymorphism of another relevant gene. We found substantial gender differences in the independent effects; positive effects of FOXO3A and negative effects of FOXO1A largely compensate each other if one carries both, although FOXO3A has a stronger impact. Ten-year follow-up cohort analysis shows that at very advanced ages 92-110, adjusted for various confounders, positive effects of FOXO3A on survival remain statistically significant, but no significant effects of FOXO1A alone; G × G interactions between FOXO1A-209 and FOXO3A-310 or FOXO3A-292 decrease survival likelihood by 32%-36% (p < .05); G × E interactions between FOXO1A-209 and regular exercise increase survival likelihood by 31%-32% (p < .05).

Studies of Nordic twins suggest an increased genetic influence on mortality with age. Contrary to this, the heterogeneity hypothesis predicts that the mortality of individuals carrying a 'frail' or 'risky' genotype in a population will approach that of noncarriers with age because of selection pressure. The ApoE ε4 allele is associated with an increased mortality risk, and its effect has been suggested to decrease with age. Here, we investigated the effect of ApoE ε4 allele on survival in a sample of the healthiest and long-lived Danes. The study population comprised Danes born in 1905 and a replicate sample of the 1895 cohort. For the 1905 cohort, a total of 350 carriers and 1256 noncarriers of the ApoE ε4 allele were followed from 1998 until death or end of follow-up. Cox regression models were used for the analysis. Of the 1606 persons with known ApoE ε4 status in 1998, 1546 had died at the end of the 10-year follow-up. Carriers of the ApoE ε4 allele had an increased mortality compared to noncarriers, and the influence of ApoE status on mortality increased in the age interval 92-103. For the covariates sex and independency status, the difference in relative risk of death between groups decreased with advancing age. Our findings of increasing influence of ApoE ε4 allele on mortality with age do not support previous findings of decreased influence ApoE ε4 allele on mortality with age, and alternative models such as the multifactorial threshold models should be considered for understanding the genetic effects on mortality at advanced age., (© 2010 The Authors. Aging Cell © 2010 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.)

The present study aims to compare the direction and magnitude of sex differences in mortality and major health dimensions across Denmark, Japan and the US. The Human Mortality Database was used to examine sex differences in age-specific mortality rates. The Danish twin surveys, the Danish 1905-Cohort Study, the Health and Retirement Study, and the Nihon University Japanese Longitudinal Study of Aging were used to examine sex differences in health. Men had consistently higher mortality rates at all ages in all three countries, but they also had a substantial advantage in handgrip strength compared with the same-aged women. Sex differences in activities of daily living (ADL) became pronounced among individuals aged 85+ in all three countries. Depression levels tended to be higher in women, particularly, in Denmark and the HRS, and only small sex differences were observed in the immediate recall test and Mini-Mental State Exam. The present study revealed consistent sex differentials in survival and physical health, self-rated health and cognition at older ages, whereas the pattern of sex differences in depressive symptoms was country-specific.

Background: Genome-wide association studies (GWAS) may yield insights into longevity., Methods: We performed a meta-analysis of GWAS in Caucasians from four prospective cohort studies: the Age, Gene/Environment Susceptibility-Reykjavik Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Longevity was defined as survival to age 90 years or older (n = 1,836); the comparison group comprised cohort members who died between the ages of 55 and 80 years (n = 1,955). In a second discovery stage, additional genotyping was conducted in the Leiden Longevity Study cohort and the Danish 1905 cohort., Results: There were 273 single-nucleotide polymorphism (SNP) associations with p < .0001, but none reached the prespecified significance level of 5 x 10(-8). Of the most significant SNPs, 24 were independent signals, and 16 of these SNPs were successfully genotyped in the second discovery stage, with one association for rs9664222, reaching 6.77 x 10(-7) for the combined meta-analysis of CHARGE and the stage 2 cohorts. The SNP lies in a region near MINPP1 (chromosome 10), a well-conserved gene involved in regulation of cellular proliferation. The minor allele was associated with lower odds of survival past age 90 (odds ratio = 0.82). Associations of interest in a homologue of the longevity assurance gene (LASS3) and PAPPA2 were not strengthened in the second stage., Conclusion: Survival studies of larger size or more extreme or specific phenotypes may support or refine these initial findings.

Heterogeneity within a population is a pervasive challenge for studies of individual life-histories. Population-level patterns in age-specific reproductive success can be broken down into relative contributions from selective disappearance, selective appearance of individuals into the study population, and average change in performance for survivors (average ontogenetic development). In this article, we provide an exact decomposition. We apply our formula to data on the reproductive performance of a well characterized population of common terns (Sterna hirundo). We show that improvements with age over most of adult life and senescence at old ages are primarily due to a genuine change in the mean among surviving individuals rather than selective disappearance or selective appearance of individuals. Average ontogenetic development accounts for approximately 87% of the overall age-specific population change.