Search

Senescence, the physiological deterioration resulting in an increase in mortality and decline in fertility with age, is widespread in the animal kingdom and has often been regarded as an inescapable feature of all organisms. This essay briefly describes the history of the evolutionary theoretical ideas on senescence. The canonical evolutionary theories suggest that increasing mortality and decreasing fertility should be ubiquitous. However, increasing empirical data demonstrates that senescence may not be as universal a feature of life as once thought and that a diversity of demographic trajectories exists. These empirical observations support theoretical work indicating that a wide range of mortality and fertility trajectories is indeed possible, including senescence, negligible senescence and even negative senescence (improvement). Although many mysteries remain in the field of biogerontology, it is clear that senescence is not inevitable.

After a brief introduction to the background, significance and unique features of the centenarian population in China, we describe the Chinese Longitudinal Healthy Longevity Study (CLHLS), which is the world's largest study of centenarians, nonagenarians, octogenarians, and compatible young-old aged 65-79. Based on the CLHLS data and other relevant studies, we summarize demographic and socioeconomic characteristics as well as self-reported and objectively-tested health indicators of centenarians in China, with an emphasis on gender differences and rural/urban disparities. We then compare five-year-age-specific trajectories of physical and cognitive functions, self-reported health, and life satisfactions from ages 65-69 to 100+, concluding that good psychological resilience and optimism are keys to the exceptional longevity enjoyed by centenarians. We discuss recent findings of novel loci and pathways that are significantly associated with longevity based on the genome-wide association study (GWAS) of the CLHLS centenarian sample, which is 2.7 times as large as prior GWAS of longevity. We also highlight colleagues' and our own studies on longevity candidate genes and gene-environment interaction analyses. Finally, we discuss limitations inherent in our studies of centenarians in China and further research perspectives. After a brief introduction to the background, significance and unique features of the centenarian population in China, we describe the Chinese Longitudinal Healthy Longevity Study (CLHLS), which is the world's largest study of centenarians, nonagenarians, octogenarians, and compatible young-old aged 65-79. Based on the CLHLS data and other relevant studies, we summarize demographic and socioeconomic characteristics as well as self-reported and objectively-tested health indicators of centenarians in China, with an emphasis on gender differences and rural/urban disparities. We then compare five-year-age-specific trajectories of physical and cognitive functions, self-reported health, and life satisfactions from ages 65-69 to 100+, concluding that good psychological resilience and optimism are keys to the exceptional longevity enjoyed by centenarians. We discuss recent findings of novel loci and pathways that are significantly associated with longevity based on the genome-wide association study (GWAS) of the CLHLS centenarian sample, which is 2.7 times as large as prior GWAS of longevity. We also highlight colleagues' and our own studies on longevity candidate genes and gene-environment interaction analyses. Finally, we discuss limitations inherent in our studies of centenarians in China and further research perspectives.

Many common stochastic mortality models can be formulated as a generalized linear model (GLM). When these GLMs are used to model one year-death probabilities, qx, deaths are assumed to be binomially distributed, and the canonical logit link function has been used by default. In this work we present the quantile function of the Generalized Extreme Value distribution as an alternative link function to the standard canonical logit link and show that its theoretical advantages enable a better fit for mortality models in cases when data are highly imbalanced or sparse. We provide an example that shows that this link function also enables superior fits to mortality data at the very highest ages in the case of the Cairns Blake Dowd family of mortality models.

Despite advances in aging research, a multitude of aging models, and empirical evidence for diverse senescence patterns, understanding is lacking of the biological processes that shape senescence, both for simple and complex organisms. We show that for a isogenicEscherichia colibacterial population senescence results from two stochastic processes. A primary random deterioration process within the cell, such as generated by random accumulation of damage, leads to an exponential increase in mortality early in life followed by a late age mortality plateau; a secondary process of stochastic asymmetric transmission of an unknown factor at cell fission influences mortality. This second process is required to explain the difference between the classical mortality plateaus detected for young mothers’ offspring and the near non-senescence of old mothers’ offspring as well as the lack of a mother offspring correlation in age at death. We observed that life span is predominantly determined by underlying stochastic stage dynamics. Our findings support models based on stage-specific actions of alleles for the evolution of senescence. This support might be surprising since these models that have not specifically been developed in the context of simple, single cell organisms. We call for exploration of similar stochastic influences beyond simple organisms.

Background: The "male-female health-survival paradox" that women live significantly longer, but have lower physical performance and more adverse health outcomes at older ages than men, is a phenomenon observed everywhere in the world. This study aims to provide an understanding of the "male-female health-survival paradox", through investigating whether genetic associations with longevity are stronger in males or females. Methods: We conducted logistic regression and bio-demographic analyses, using the genome-wide association study (GWAS) datasets including 2,178 centenarians and 2,299 middle-aged controls of Chinese Longitudinal Healthy Longevity Study. Findings: We found that averages of probabilities of longevity, associated with each of the six mutually exclusive groups of 11 male-specific and 11 female-specific top loci (P

Globally, the twenty-first century will witness rapid population ageing. Already in 2050, one out of five persons in the world, and one out of three in Europe, is expected to be 60 or over (UN 2015). Moreover, we have entered into a new stage of population ageing in terms of its causes, which have altered its consequences. In the first stage, lasting until the middle of the twentieth century in developed countries, population ageing was entirely due to the decline in fertility, with Sweden being commonly used as an example (Coale 1957; Bengtsson and Scott 2010; Lee and Zhou 2017). During this stage, the increase in life expectancy was primarily driven by declines in infant and child mortality. It worked in the opposite direction to the fertility decline, making the population younger since it added more years before, than after retirement (Coale 1957; Lee 1994). In the second stage of population ageing, which is the current situation, population ageing is primarily driven by the increase in life expectancy, which is now due to declining old-age mortality. As a result, more years are added after retirement than in working ages (Lee 1994). Could immigration or an upswing in fertility stop population ageing? The short answer is most likely not. The effect of migration on population aging is generally regarded as minor (Murphy 2017), and since population ageing is a global phenomenon, it will be of no general help anyway. A rapid increase in fertility is improbable and, in any case, an increase would take some 25 years before adding to the labor force. Instead, attention has been focused on how to adapt our social systems to the increasing number of elderly per worker – more so since the increase in the elderly-per-worker ratio came in parallel with a rise in per capita costs for the institutional care, home care, and general health care for the elderly.

This note outlines a method for forecasting life expectancy. The method is based on the idea of structured conditional probabilistic estimation; it “scopes” out the range of possibilities the future may hold. I first described this SCOPE method at a workshop organized by Juha Alho several years ago in Finland. It is a kind of scenario method – with probabilities attached to scenarios, with scenarios structured conditionally, and with the possibility of stochastic scenarios. It is a simple method, and it is by no means original; many other people have used a similar approach in various settings. This method might be helpful to those who want to forecast life expectancy. This note summarizes my presentation.

Biodiversity loss is a major challenge. Over the past century, the average rate of vertebrate extinction has been about 100-fold higher than the estimated background rate and population declines continue to increase globally. Birth and death rates determine the pace of population increase or decline, thus driving the expansion or extinction of a species. Design of species conservation policies hence depends on demographic data (e.g., for extinction risk assessments or estimation of harvesting quotas). However, an overview of the accessible data, even for better known taxa, is lacking. Here, we present the Demographic Species Knowledge Index, which classifies the available information for 32,144 (97%) of extant described mammals, birds, reptiles, and amphibians. We show that only 1.3% of the tetrapod species have comprehensive information on birth and death rates. We found no demographic measures, not even crude ones such as maximum life span or typical litter/clutch size, for 65% of threatened tetrapods. More field studies are needed; however, some progress can be made by digitalizing existing knowledge, by imputing data from related species with similar life histories, and by using information from captive populations. We show that data from zoos and aquariums in the Species360 network can significantly improve knowledge for an almost eightfold gain. Assessing the landscape of limited demographic knowledge is essential to prioritize ways to fill data gaps. Such information is urgently needed to implement management strategies to conserve at-risk taxa and to discover new unifying concepts and evolutionary relationships across thousands of tetrapod species.

If life expectancy – also known as the expectation of life, is the mean life-span of a cohort of newborns if current age-specific death rates remain unchanged – in developed countries were close to an ultimate limit, then increases in record life expectancy – the average length of life in the best-practice population – should slow as the ceiling is asymptotically approached.

La longevite humaine a connu une hausse remarquable depuis 1840. En France, l'esperance de vie a double, passant de 40 ans en 1840 a 82 ans aujourd'hui. L'analyse de la nature de cet accroissement, y compris les progres en termes de survie chez les personnes âgees, apporte un nouvel eclairage sur les transformations economiques, sociales et en matiere de sante ayant eu lieu au cours des deux cents dernieres annees. Il se pourrait que l'avenir de la longevite soit tout aussi remarquable que son passe. Demographes, actuaires, gerontologues et autres experts de la mortalite sont largement en desaccord sur la question de savoir si l'esperance de vie se rapproche d'une limite ineluctable ou si, au contraire, elle continuera d'augmenter aussi rapidement que par le passe. Des methodes de projection plus performantes sont necessaires afin d'anticiper les evolutions economiques, sociales et de sante a venir.Classification JEL : J11, J14.

Summary 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.

Beltrán-Sánchez et al . based their comment on misleading calculations of the maximum survival age. With realistic numbers of people attaining age 105 and the estimated plateau, the Jeanne Calment record is indeed plausible.

Background: Demographers sometimes observe remaining lifespans in populations of individuals of unknown age. Such populations may have an age structure that is approximately stable. To estimate life tables for these populations, it is useful to know the relationship between the number of individuals at a given age a, and the number of individuals that are expected to die a time units after observation. This result has already been described for stationary populations, but here we extend it to stable populations. Results: In a stable population, the population at a given age a is a simple function of the number of deaths at remaining lifespan a, the number of deaths at remaining lifespans a and higher, and the population growth rate. This property, which can be useful when ages are unknown, but individuals are followed until death, permits estimation of the underlying unknown survival schedule of the population and calculation of the usual life table functions and statistics, including the stable age structure. Contribution: The main contribution of this article is to provide a formal proof of the relationship between life lived and life left in stable populations. We also discuss the challenges of applying theoretical relationships to empirical data, especially due to the fact that in real-world applications time is not continuous and some adjustments are necessary to move from a continuous to a discrete-time framework. Two applications, one with simulated data and a second with Swedish data from the 19th century, illustrate these ideas.

Background Adult mortality has been postponed over time to increasingly high ages. However, evidence on past and current health trends has been mixed, and little is known about European disability trends. Methods In a cross-sectional setting, we compared cognitive and physical functioning in same-aged Europeans aged 50+ between 2004–05 (wave 1; n = 18 757) and 2013 (wave 5 refresher respondents; n = 16 696), sourced from the Survey of Health, Ageing and Retirement in Europe (SHARE). Results People in 2013 had better cognitive function compared with same-aged persons in 2004–05, with an average difference of approximately one-third standard deviation. The same level of cognitive function in 2004–05 at age 50 was found in 2013 for people who were 8 years older. There was an improvement in cognitive function in all European regions. Mean grip strength showed an improvement in Northern Europe of 1.00 kg [95% confidence interval (CI) 0.65; 1.35] and in Southern Europe of 1.68 kg (95% CI 1.14; 2.22), whereas a decrease was found in Central Europe (-0.80 kg; 95% CI −1.16; −0.44). We found no overall differences in activities of daily living (ADL), but small improvements in instrumental activities of daily living (IADL) in Northern and Southern Europe, with an improvement in both ADL and IADL from age 70 in Northern Europe. Conclusions Our results indicate that later-born Europeans have substantially better cognitive functioning than earlier-born cohorts. For physical functioning, improvements were less clear, but for Northern Europe there was an improvement in ADL and IADL in the oldest age groups.

Significance Women live longer than men in nearly all populations today. Some research focuses on the biological origins of the female advantage; other research stresses the significance of social factors. We studied male–female survival differences in populations of slaves and populations exposed to severe famines and epidemics. We find that even when mortality was very high, women lived longer on average than men. Most of the female advantage was due to differences in mortality among infants: baby girls were able to survive harsh conditions better than baby boys. These results support the view that the female survival advantage is modulated by a complex interaction of biological environmental and social factors., Women in almost all modern populations live longer than men. Research to date provides evidence for both biological and social factors influencing this gender gap. Conditions when both men and women experience extremely high levels of mortality risk are unexplored sources of information. We investigate the survival of both sexes in seven populations under extreme conditions from famines, epidemics, and slavery. Women survived better than men: In all populations, they had lower mortality across almost all ages, and, with the exception of one slave population, they lived longer on average than men. Gender differences in infant mortality contributed the most to the gender gap in life expectancy, indicating that newborn girls were able to survive extreme mortality hazards better than newborn boys. Our results confirm the ubiquity of a female survival advantage even when mortality is extraordinarily high. The hypothesis that the survival advantage of women has fundamental biological underpinnings is supported by the fact that under very harsh conditions females survive better than males even at infant ages when behavioral and social differences may be minimal or favor males. Our findings also indicate that the female advantage differs across environments and is modulated by social factors.

Mortality rates level off at extreme age The demography of human longevity is a contentious topic. On the basis of high-quality data from Italians aged 105 and older, Barbi et al. show that mortality is constant at extreme ages but at levels that decline somewhat across cohorts. Human death rates increase exponentially up to about age 80, then decelerate, and plateau after age 105. Science , this issue p. 1459

Females survive better than males in populations under stressful conditions, such as famines, epidemics, and slavery (1). Delanghe et al. (2) identify a biological mechanism that might partly explain this finding. They emphasize that women generally have smaller body iron stores than men, and therefore are less prone to develop conditions such as scurvy or siderophilic infections. This could … [↵][1]1To whom correspondence should be addressed. Email: jwv{at}demogr.mpg.de. [1]: #xref-corresp-1-1

Importance: Sex differences in genetic associations with human longevity remain largely unknown; investigations on this topic are important for individualized health care. Objective: To explore sex differences in genetic associations with longevity. Design, Setting, and Participants: This population-based case-control study used sex-specific genome-wide association study and polygenic risk score (PRS) analyses to examine sex differences in genetic associations with longevity. Five hundred sixty-four male and 1614 female participants older than 100 years were compared with a control group of 773 male and 1526 female individuals aged 40 to 64 years. All were Chinese Longitudinal Healthy Longevity Study participants with Han ethnicity who were recruited in 1998 and 2008 to 2014. Main Outcomes and Measures: Sex-specific loci and pathways associated with longevity and PRS measures of joint effects of sex-specific loci. Results: Eleven male-specific and 11 female-specific longevity loci (P < 10 -5) and 35 male-specific and 25 female-specific longevity loci (10 -5≤ P < 10 -4) were identified. Each of these loci's associations with longevity were replicated in north and south regions of China in one sex but were not significant in the other sex (P =.13-.97), and loci-sex interaction effects were significant (P -5) and US women (P = 4.6 × 10 -5) but not significant in Chinese and US men. The associations of the loci rs2622624 of the ABCG2 gene were replicated in Chinese women (P = 6.8 × 10 -5) and European women (P =.003) but not significant in both Chinese and European men. Eleven male-specific pathways (inflammation and immunity genes) and 34 female-specific pathways (tryptophan metabolism and PGC-1α induced) were significantly associated with longevity (P -5) and 35 male-specific and 25 female-specific loci (10 -5≤P < 10 -4) were jointly replicated across north and south discovery and target samples. Analyses using the combined data set of north and south showed that these 4 groups of sex-specific loci were jointly and significantly associated with longevity in one sex (P = 2.9 × 10 -70to 1.3 × 10 -39) but not jointly significant in the other sex (P =.11 to.70), while interaction effects between PRS and sex were significant (P = 4.8 × 10 -50to 1.2 × 10 -16). Conclusion and Relevance: The sex differences in genetic associations with longevity are remarkable, but have been overlooked by previously published genome-wide association studies on longevity. This study contributes to filling this research gap and provides a scientific basis for further investigating effects of sex-specific genetic variants and their interactions with environment on healthy aging, which may substantially contribute to more effective and targeted individualized health care for male and female elderly individuals.

Heute sterben die Menschen im Durchschnitt zehn Jahre spater als noch vor 40 Jahren – und zwar nicht, weil ihr korperlicher Verfall sich uber eine langere Zeit hinzoge, sondern weil sie bei besserer Gesundheit alt werden.

Life expectancy is highly correlated over time among countries and between males and females. These associations can be used to improve forecasts. Here we propose a method for forecasting female life expectancy based on analysis of the gap between female life expectancy in a country compared with the record level of female life expectancy in the world. Second, to forecast male life expectancy, the gap between male life expectancy and female life expectancy in a country is analysed. We present these results for various developed countries. We compare our results with forecasts based on the Lee–Carter approach and the Cairns–Blake–Dowd strategy. We focus on forecasting life expectancy at age 0 and remaining life expectancy at age 65.

The chapter on observed death rates illustrates why demographic rates need to be adjusted by the number of person years lived and shows surface maps of such “raw” death rates for a few selected national populations. One can easily see that random fluctuations can turn out be problematic for smaller populations as they may lead to misinterpretations.

The second chapter specifies how a Lexis diagram is constructed and shows that cohorts are depicted on the 45∘ line. It briefly discusses the so-called identification problem of standard methods of age-, period-, and cohort analysis and explains how those effects look like in the Lexis diagram. The chapter concludes with a brief history of the depiction of population dynamics in three dimensions.

Rates of mortality improvement, as presented in the previous two chapters, are an excellent tool to illustrate mortality dynamics. They can not be directly translated to contributions to changes in life expectancy. Using Arriaga’s decomposition approach, we plot maps for selected countries from the Human Mortality Database, showing which ages contributed most to the respective change in life expectanc over time.

Surface maps of unsmoothed and smoothed mortality data have been used widely before. In this chapter, we present surface plots of rates of mortality improvement (“ROMI”), which are the derivative of age-specific mortality with respect to time. They have been introduced rather recently. By showing a large set of surface maps for countries from the Human Mortality Database, we argue that those ROMI plots are better able to detect period and cohort effects than standard mortality surface maps.

Many causes of death have a clear seasonal pattern. Circulatory and respiratory diseases, which comprise about half of all deaths, have a peak in winter and lowest mortality during summer. Data by cause of death, age, and calendar time (month and year) provided by the National Center for Health Statistics allow an analysis how seasonality has changed over age and time. Using a two-dimensional decomposition and smoothing approach, we show how the amplitude and the phase of selected causes of death have developed since the late 1950s.

This chapter summarizes our main findings, it shows that the tools presented in this monograph can not only be applied to mortality but also to fertility, migration, or any kind of variable that can be classified by age and calendar time.

Introduction: Why do we visualize data and what is this book about? The introductory chapter describes the three rationales to visualize data: exploration, confirmation and presentation, and discusses the developments in computer hardware, software and connectivity that were instrumental for the recent increased interest in visualizing data.

This chapter shows that ROMI plots, as presented in the previous chapter, can not only be employed for mortality from all-causes but also for cause-specific mortality. They allow us to demonstrate that the slow increase in life expectancy among women in the United States during the 1980s and 1990s can not be attributed to heart diseases or stroke. Instead, mortality from respiratory diseases and from lung cancer, the latter featuring a pronounced cohort effect, suppressed faster gains in life expectancy.

The surface maps of the previous chapter showed that random fluctuations can be quite large. The present chapter on smoothing mortality data explains how we smoothed the observed mortality with P-splines. We illustrate our smoothing results with the same set of countries as in the previous chapter for unsmoothed data.

This chapter describes the major data sets used in this monograph: The Human Mortality Database, data from the National Center for Health Statistics of the United States for the analysis of causes of death, and the individual-level, longitudinal data of the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute of the United States. The latter is used to illustrate the dynamics of cancer survival.

While previous chapters focused only on the event of death, this chapter investigates the dynamics over age and time for the duration between being diagnosed with a specific cancer and death. We use five year survival as our indicator of survival in general, disease-specific survival and relative survival for selected cancer sites such as breast cancer, colorectal cancer, lung cancer or pancreatic cancer. The major impact of the stage of the tumor at the time of diagnosis for survival is illustrated using stage 1 and stage 4 of colorectal cancer as an example.

Objectives The purpose of this study was to explore the pattern of mortality above the age of 100 years. In particular, we aimed to examine whether Scandinavian data support the theory that mortality reaches a plateau at particularly old ages. Whether the maximum length of life increases with time was also investigated. Methods The analyses were based on individual level data on all Swedish and Danish centenarians born from 1870 to 1901; in total 3006 men and 10 963 women were included. Birth cohort-specific probabilities of dying were calculated. Exact ages were used for calculations of maximum length of life. Whether maximum age changed over time was analysed taking into account increases in cohort size. Results The results confirm that there has not been any improvement in mortality among centenarians in the past 30 years and that the current rise in life expectancy is driven by reductions in mortality below the age of 100 years. The death risks seem to reach a plateau of around 50% at the age 103 years for men and 107 years for women. Despite the rising life expectancy, the maximum age does not appear to increase, in particular after accounting for the increasing number of individuals of advanced age. Conclusion Mortality among centenarians is not changing despite improvements at younger ages. An extension of the maximum life span and a sizeable extension of life expectancy both require reductions in mortality above the age of 100 years. This article is protected by copyright. All rights reserved.

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. 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.

Based on sex-stratified genome-wide association study (GWAS) of Han Chinese, 2,178 centenarians and 2,299 middle-aged controls, we identified 11 male- and 12 female-specific independent loci that are significantly associated with longevity (P-5), replicated in independent North and South regions in one sex, but are not significant (P>0.05) in the other sex. We found that the association of rs60210535 at LINC00871 with longevity replicated well between Chinese females (P=4.6x10-5) and U.S. females (P=9.0x10-5), but was not significant in both Chinese and U.S. males (P>0.05). We discovered that 11 male-specific and 34 female-specific pathways are significantly associated with longevity (PFDR) P-5 in one sex, P>0.05 in other sex), 44/58 male/female strong loci (10-5≤P-4 in one sex, P>0.4 or P>0.35 in other sex), and 191/311 male/female moderate loci (10-4≤P-3 in one sex, P>0.75 or P>0.7 in other sex) are jointly and highly associated with longevity exceeding a significance level P10-8 in one sex, but not jointly associated with longevity in the other sex (P>0.05). Our integrated PRS and novel sex-specific genetic relative benefit/loss ratio analyses indicate that females’ genetic constitution favors longevity more than males’. Further interdisciplinary collaborative efforts are warranted, such as replications from other populations, international meta-analyses with much larger sample size, lab tests, and in silico functional validations. Significance Statement: On average, women live significantly longer lives than men but they have lower physical performance and more adverse health outcomes at older ages compared to men: patterns that signify the male-female health-survival paradox (1). Research on sex differences in health and mortality has proliferated, but has yet to achieve a good understanding of the effects of genetic variants on the sex gap in longevity and health. Based on sex-stratified genome-wide association analysis (GWAS) of Han Chinese including centenarians with a sample size 2.7 times as large as other published largest single GWAS on longevity involving centenarians (2), the present study aims to contribute a better understanding of sex differences in genetic associations with longevity.

We consider items that are incepted into operation having already a random initial age and define the corresponding remaining lifetime. We show that these lifetimes are identically distributed when the age distribution is equal to the equilibrium distribution of the renewal theory. Then we develop the population studies approach to the problem and generalize the setting in terms of stationary and stable populations of items. We obtain new stochastic comparisons for the corresponding population ages and remaining lifetimes that can be useful in applications. Copyright © 2014 John Wiley & Sons, Ltd.

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. 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. 100. years 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 100. years.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.

Fishing causes dramatic changes in the age and size structure of fish stocks. In particular, the targeting of the largest and oldest individuals in a stock changes the age and size distribution of that stock. A large female produces a higher quantity of eggs than a young female because of its larger size, but recent laboratory evidence further indicates that large females also produce eggs of higher quality, a phenomenon known as maternal effects. However, most traditional management models assume that all female fish contribute equally per unit biomass to future recruitment. Here we investigate whether this assumption is valid by calculating the impact of maternal effects both before and after accounting for density-dependent effects. We find that the contribution of large individuals to reproduction is much more pronounced for unfished than for fished stocks. Fisheries reference points are largely unaffected by maternal effects. Our results indicate that the incorporation of maternal effects into impact assessments of fisheries is not expected to change advice substantially. Important exceptions are stocks whose demography is very vulnerable to fishing (and which therefore have low fishing reference points) for which maternal effects are relevant and necessary to consider. Resume : La peche entraine des modifications drastiques de la structure par âge et par taille des stocks de poissons. Le ciblage des individus les plus grands et les plus âges au sein d'un stock, en particulier, modifie les distributions d'âges et de tailles dans ce stock. Si une grosse femelle produit une plus grande quantite d'œufs qu'une jeune femelle en raison de sa plus grande taille, de recentes observations en laboratoire indiquent aussi que les grosses femelles produisent des œufs de meilleure qualite, soit le phenomene des effets maternels. Cependant, la plupart des modeles de gestion traditionnels partent du principe que la contribution au recrutement futur par unite de biomasse est la meme pour tous les poissons femelles. Nous examinons la validite de cette hypothese en calculant l'incidence des effets maternels avant et apres l'integration d'effets dependant de la densite. Nous constatons que la contribution de gros individus ala reproduction est beaucoup plus prononcee dans les stocks non exploites que dans les stocks exploites. Les effets maternels n'ont pas une grande incidence sur les points de reference pour les peches. Nos resultats indiquent que l'integration des effets maternels aux evaluations des impacts des peches ne devrait pas avoir une incidence significative sur les avis concernant les peches. Les stocks dont la demographie est tres vulnerable ala peche (et qui sont donc caracterises par des points de reference tres faibles) constituent d'importantes exceptions pour lesquelles il est donc pertinent et necessaire de tenir compte des effets maternels. (Traduit par la Redaction)

The aims of this study are to analyse the two-way association between women fertility and longevity, and parental transmission of longevity. The wealth of information gathered in the AKeA2—demographic survey on Sardinian centenarians—have been used by applying Logistic Regression Models. For the association between longevity and fertility, we find evidence that *long livers benefit from factors related to the timing of fertility (in particular the age at birth of the last child) that the literature suggests may foster longevity. Regarding the association with parental transmission, it seems to have significant effects for women but not for men. We always found that a higher birth order decreases the probability of becoming a centenarian. There is a negative effect of a higher father age at birth on the longevity of female offspring. The latter suggests that long-lived women seem to have been favoured both by their own late fertility and young paternal age at the moment of their own procreation.

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.

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. 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.

Has the maximum human lifespan been reached? The current record stands at 122 years, 164 days and has held for over 20 years and is more than four and three quarter years higher than the previous record. The value and persistence of this record have surprised some researchers, with some even questioning its veracity. There have been previous attempts in the literature to answer questions about how long this record might stand and whether it is truly exceptional but the focus has been mainly on the record ages, using ad hoc tools. This article contributes in two new ways. First we study lifespan records via the (inter-) record times and second we make use of specific tools from statistical Records Theory. We find that the occurrence of the present record was not surprising. We estimate around a 25% chance that the record would have survived until now and around a one in five chance that it will survive until 2050, demonstrating remarkable persistence.