Search

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

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.

First, we revisit the “life lived equals life left” property for stationary populations and discuss it from a more general perspective. Specifically, we show that identically distributed random age and the remaining lifetime in stationary populations have the same distribution as the equilibrium distribution of the renewal theory. Then we consider specific non-stationary populations that are closed to migration and have a constant birth rate. We obtain some useful inequalities between random age and remaining lifetime for different instants of calendar time. We also discuss the aging properties of populations using different stochastic orders.

1. The open-access scientific philosophy has been widely adopted and proven to promote considerable progress in the fields of ecology and evolution. Open-access global databases now exist on animal migration, the distribution of species, and conservation status, to mention a few. However, a gap exists for databases on population dynamics spanning the rich diversity of the animal kingdom. This information is fundamental to our understanding of the conditions that have shaped variation in animal life histories and their relationships with the environment. Furthermore, an animal population schedules of reproduction and mortality determine its invasive potential, and its risk of local extinction, which are at the core of conservation biology. 2. Matrix population models (MPMs) are among the most widely used demographic tools by animal ecologists. MPMs project population dynamics in terms of reproduction, mortality, and development over the entire life cycle. The results of MPMs have direct biological interpretations, facilitating comparisons among animal species as different as Caenorhabditis elegans, Loxodonta africana and Homo sapiens. 3. Thousand 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 version 1.0.0, an open-source online repository containing data on 402 species worldwide, from 272 studies, with a total of 1,575 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. 4. Synthesis: We introduce the COMADRE Animal Matrix Database, a resource for animal demography. The open access nature of this database, together with its ancillary information will facilitate comparative analysis, as will the growing availability of databases focusing on other traits, 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 statistical power.

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 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

The chance of surviving to the age of 90 has increased markedly over the last 50 years in high-income countries, and will probably continue to rise with successive cohorts.1,2 In the United States, the number of nonagenarians has increased from approximately 230,000 in 1960 to approximately 1.8 million in 2010, and in the five biggest countries in the European Union (Germany, France, the United Kingdom, Italy, Spain) the number has increased from approximately 250,000 to 1.6 million, which is almost 7 times as many nonagenarians, compared with 1.5 times as many people in the total population of these countries in 1960 as in 2010. With this growing number of oldest old adults, ageism has been decreasing in recent decades, and it has now become generally unacceptable to deny medical procedures to people aged 80 and older using advanced age as the sole argument.3 Research has also emerged that investigates medical procedures for very old adults,4–6 but life expectancy for very old adults is still short in most high-income countries, ranging from around 8 to 10 years for 80-year-olds to 4 to 5 years for 90-year-olds (online Table S1).7 Hence, overtreatment of very old adults is still a general concern, and potential side effects of treatment have to be balanced with the overall survival prognosis, which is generally based on the overall chance of survival to a given age or overall life expectancy.8 It has been argued that clinicians should offer to discuss the overall survival prognosis with patients aged 85 and older.8 There is large varivariation in health and life expectancy in very old adults, which also should be taken into consideration before treatment is provided. Comprehensive geriatric assessments exist, but they are generally time-consuming and mostly validated in people aged 70 to 80.9-11 Simple, easy-to-use tools that can help predict the chance of individual survival in very old adults would be useful in clinical decision-making for general practitioners, but only a few studies have investigated factors that predict mortality in very old adults. In a study of 186 Spanish nonagenarians, comorbidity and cognition assessed over a 5-year follow-up period were found to be the best predictors of mortality.12 In a study of 888 Finnish people aged 90 and older, activities of daily living (ADLs), self-rated health, and being institutionalized over a 9-year period were found to be associated with mortality.13 A study of 19,340 Americans, 335 of whom were nonagenarians, showed that functional limitation in nonagenarians was a better predictor of mortality than chronic conditions.14 In a study of 335 Italian people aged 80 and older, walking speed and five-time chair stand test were found to be associated with mortality.15 Walking speed and chair stands has also been shown to predict subsequent disability and mortality in people aged 70 and older.16,17 Unfortunately, most of these studies presented hazard ratios, which can be difficult to use in clinical decision-making and to communicate to people. This study comprised a Danish birth cohort followed from age 92 or 93 until the cohort was almost extinct. The aim was to identify measures that predict remaining lifespan and chance of surviving to 100 years and that can be easily administered in a primary care setting without specialized equipment.

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. Electronic supplementary material The online version of this article (doi:10.1186/s12874-016-0157-8) contains supplementary material, which is available to authorized users.

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.

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.

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.

Background: Demographers have long been interested in how compositional change, e.g., change in age structure, affects population averages. Objective: We want to deepen understanding of how compositional change affects population averages. Results: The difference between two averages of a variable, calculated using alternative weighting functions, equals the covariance between the variable and the ratio of the weighting functions, divided by the average of the ratio. We compare weighted and unweighted averages and also provide examples of use of the relationship in analyses of fertility and mortality. Comments: Other uses of covariances in formal demography are worth exploring.

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.

Animal models have supported the idea that apoptosis and senescence, which are important cellular tumor suppressing mechanisms (1–5), could be antagonistically pleiotropic, that is, these mechanisms protect organisms from early life cancer, but in late life, they accelerate the aging phenotypes and the development of a host of age-related diseases. The role of p53 in activating cell cycle checkpoints and apoptosis has been suggested as a specific mechanism for serving as guardian and suppressor of longevity (6). In particular, p53 mutant mice with augmented p53 activity that display early aging sign and at the same time enhance the resistance to spontaneous tumors compared with wild types (7) have promoted the “better cancer protection–accelerated aging” hypothesis. However, an undefined 20 kb region upstream of the p53 gene was also deleted in the p53 mutant mice, and other mice strains do not confirm this association (3,4). An area that has received particular attention is telomeres and telomerase in cancer and aging. K5-mTert transgenic mice overexpress telomerase in a wide spectrum of tissues, which results in higher incidence of both induced and spontaneous tumors and, accordingly, increased mortality during the first year of life (8). However, despite this elevated tumor incidence and initial lower survival, the K5-mTert mice show a substantial extension of the maximum life span corresponding to a 10% increase in mean life span compared with wild types. This suggests that telomerase overexpression extends both the maximum life span and the cancer risk in mice (8). Notably, telomerase is a key element in most human cancers as well as central in the aging mechanisms in an interplay with p53 and mitochondrial dysfunctioning (9). The data for humans are rather sparse and conflicting; Van Heemst and colleagues (10) performed a meta-analysis of the published literature in 2005, showing that carriers of the TP53 codon 72 Pro/Pro have an increased cancer risk compared with Arg/Arg carriers, but at the same time, a significantly increased survival at the highest age, suggesting that human p53 protects against cancer but at the cost of longevity. Although it is expected that long-lived individuals have a lower cancer incidence (as cancer reduces the chances of exceptional longevity; 11), the family (co)occurrence of cancer and longevity is the optimal design for studying the cancer–longevity trade-offs. A study of 106 families with 295 offspring of centenarians in the New England Centenarian Study (12) compared with a similar-sized control group suggested that the offspring of centenarians had lower all-cause, cardiovascular, and cancer mortality compared with the control offspring. This was a small study, and the risk of socioeconomic confounding was considerable. A more powerful study (13) investigated individuals born from 1830 to 1963 using the Utah-population Database Cohort. The study focused on the effect of familial longevity and familial mortality for 10 of the leading causes of death. It was found that families with greater longevity did not die from causes distinct from other members of the cohort; they died from the same causes at reduced rate. Individuals of longer-lived families had lower mortality rate for most age-related diseases including heart disease, stroke, and diabetes but not from cancer. The study has the drawback of being conducted in a special population (Mormons) and only using cause of death data and not cancer incidence data. In this study, the closest possible relative of long-lived individuals, namely the cotwin of monozygotic (and dizygotic) twins, is used to study the potential cancer–longevity trade-off. The hypothesis is that longevity is positively associated with cancer risk in zero (monozygotic cotwin) and first-degree (dizygotic twins) relatives.

Over the past two centuries, the life expectancy has more than doubled in many countries, for both males and females. The levels of the countries with the highest life expectancies have risen almost linearly. We exploit this regularity by using the classic univariate ARIMA model to forecast future levels of best-practice life expectancy. We then compare two alternative stochastic models for forecasting the gap between the best-practice level and life expectancy in a particular population. One of our approaches is based on the concept of discrete geometric Brownian motion; our other approach relies on a discrete model of geometric mean-reverting processes. A key advantage of our strategy is that the life expectancies forecast for different countries are positively correlated because of their tie to the forecast best-practice line. We provide illustrations based on Italian and US data.

Summary We analyzed MBL2 gene variants in two cohorts of centenarians, octo-nonagenarians and nonagenarians, and in the general population, one from Sardinia Island (Italy), recruited in the frame of the AKea study, and another from Campania (southern Italy), to search for haplotypes related to longevity. We also assessed in vitro the effect of mannose-binding lectin (MBL) on various human cells at different stage of senescence. The frequency of high and null activity haplotypes was significantly lower, and the frequency of intermediate activity haplotype significantly higher in centenarians and in subjects between 80 and 99 years from both the cohorts as compared each to the general population from the same geographic area. Furthermore, serum MBL concentration (also after normalization to serum albumin) was significantly lower in centenarians and in octo- and nonagenarians as compared to the general population, suggesting that intermediate MBL haplotype/activity may be protective. We also demonstrated that in vitro MBL protein bound to senescent IMR90 fibroblasts thereby causing cell lysis, but not to other types of cycle-arrested cells not in senescence. This implicates a novel role of MBL in the clearance of senescent cells.

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.

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. 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.

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.

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. 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.

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 e4 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 e4 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 e4 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 e4 status in 1998, 1546 had died at the end of the 10-year follow-up. Carriers of the ApoE e4 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 e4 allele on mortality with age do not support previous findings of decreased influence ApoE e4 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.

In a heterogeneous cohort, the change with age in the force of mortality or some other kind of hazard or intensity of attrition depends on how the hazard changes with age for the individuals in the cohort and on how the composition of the cohort changes due to the loss of those most vulnerable to attrition. Here we prove that the change with age for the cohort equals the average of the change in the hazard for the individuals in the cohort minus the variance in the hazard across individuals. The variance captures the compositional change. This very general and remarkably elegant relationship can be applied to understand and to analyze changes with age in many kinds of demographic hazards, including, e.g., the lifetable aging rate or the intensity of first births.

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).

In a stationary population, the change with age in some characteristic at a point in time, summed over all the individuals in the population, equals the change in this characteristic, from the start to the end of the lifetime of each individual, averaged over all lifetimes of the individuals in the cohort.

Udgivelsesdato: May-7 OBJECTIVE: The study was conducted to examine sex differences in the initial level and rate of change in physical function and grip strength. METHOD: The baseline survey included 2,262 Danes born in 1905 and alive in 1998 and followed-up in 2000, 2003, and 2005. Hence, the authors fully used the power of having a cohort with multiple assessments in late life and virtually complete follow-up of lifespan (through December 2008). Latent growth curve modeling was used. RESULTS: Men had higher initial levels and rates of decline in strength score and grip strength. Lifespan was positively correlated with intercepts and slopes. DISCUSSION: The Danish data suggested that the longest-living individuals have higher initial levels of strength score and grip strength and smaller rate of change. The data further suggested that the initial level of strength score and grip strength was more predictive of mortality than the rate of change was, and the predictive effects were similar in men and women.

Humans, and many other species, suffer senescence: mortality increases and fertility decreases with adult age. Some species, however, enjoy sustenance: mortality and fertility remain constant. Here we develop simple but general evolutionary-demographic models to explain the conditions that favor senescence vs. sustenance. The models illustrate how mathematical demography can deepen understanding of the evolution of aging. (ProQuest: ... denotes formulae omitted.) 1. Introduction Why do humans deteriorate with age? And why is this senescence common across many species-but not all species? A brief answer is that we grow decrepit because we continually suffer damage and because some but not all of the damage is repaired. The cumulative imbalance between damage and repair produces senescence; with mortality rising and fertility falling with age (Kirkwood 1981; Baudisch 2008). The more an organism invests in repair, the less the organism will degenerate with age. If repair is sufficient, then the organism can maintain itself. Such sustenance, however, is costly and requires resources the organism could otherwise invest in greater reproduction. Darwinian evolution optimizes this trade-off for each species-producing age-specific trajectories of mortality and fertility that depend on the species' bauplan and environment (Stearns 1992; Roff 2002). Kirkwood pioneered this important perspective on aging and developed it focusing on senescence (Kirkwood 1977). This article builds on Kirkwood's core idea and expands it to explain when sustenance is optimal. Until recently it was generally thought that the evolutionary theory of aging implied that senescence is inevitable for multicellular iteroparous species (Medawar 1952; Williams 1957; Hamilton 1966). Many gerontologists assumed this was the case and the view is still widely held. As Williams observed, however, "it is indeed remarkable that after a seemingly miraculous feat of morphogenesis a complex metazoan should be unable to perform the much simpler task of merely maintaining what is already formed" (Williams 1957: 398). Over the last decades, field and laboratory studies have demonstrated that some organisms suffer negligible senescence over the course of life (Finch 1990; 2009; Vaupel et al. 2004). Notable examples are queens in eusocial species (Holldobler and Wilson 1990; Keller and Genoud 1997; Keller 1998; Carey 2001) and hydra (Martinez 1998). And recently it has been found that sustenance can be an optimal evolutionary strategy under some conditions (Baudisch 2008). This article develops simple evolutionary-demographic models that yield general conditions for sustenance vs. senescence. The models aim to capture the gist of why evolution favors either sustenance or senescence. We focus on species that potentially would be able to achieve sustenance if sufficient resources are diverted from reproduction to maintenance. We simplify the models as much as we can while retaining some minimal realism about the basic cornerstones of the life cycle of a species. In particular, we focus on age-invariant vs. increasing mortality over adult ages. We assume that fertility is constant over age. This assumption might seem too drastic, but as a first step in studying senescence vs. sustenance, it is reasonable to focus on one process - mortality - instead of two. Senescence can be captured by an increase in mortality over adult ages and sustenance by an age-invariant mortality pattern. Relaxing the constant-fertility assumption in models to be developed in the future will permit study of mortality and fertility senescence together. In our models, age zero is defined as reproductive maturity. 2. A model with constant fertility and increasing mortality Evolution favors sustenance over senescence if Darwinian fitness of the former strategy exceeds that of the latter. Thus, if a strategy of sustenance corresponds to a fitness of Ro and that of senescence to R*, evolution favors sustenance over senescence if Ro > R*. …

INCREASES in longevity of the general population worldwide are an unprecedented phenomenon with significant health and social impact. Although environmental factors have led to an increase in life span, there is ample evidence that genetic factors are involved in extreme longevity both in humans (1–7) and in other organisms (8). The protective genetic factors that lead to longevity are likely to involve fundamental processes of aging that may be different from those associated with early mortality or premature onset of age-related diseases in younger individuals. The mechanisms of aging in humans are far from understood, but available evidence suggests that several pathways—inflammation, oxidative stress and stress responses, cellular senescence, DNA damage and repair, and the growth hormone or insulin-like growth factor and insulin (GH, IGF, INS) axis—may play key roles (9–12). Model organisms suggest that inhibiting the GH, IGF, or INS axis, which is involved in regulating cell proliferation, cell death, wound repair, and metabolism, may promote longevity by reducing oxidative stress and slowing the rate of cell replication and the accumulation of somatic-cell DNA mutations (13). There is also evidence for other important pathways such as the heat-shock proteins and heat-shock factors that are highly conserved across species and play a role in prolongevity transcription pathways. Clinical and epidemiological investigations, including candidate gene studies, have suggested that inflammation pathways may affect life span and risk of age-related conditions such as cardiovascular disease (CVD) and its risk factors (14–19). A combination of multiple genetic variants may be required for an individual to achieve exceptional longevity, which may account in part for its rarity. Two previous studies have used whole-genome screening to identify genetic variants associated with longevity (20,21). In a linkage analysis, the earliest report (20) identified a locus on chromosome 4 that has not been replicated. A recent report from the Framingham Heart Study (FHS) (22) identified modest associations between longevity (or age at death) and single-nucleotide polymorphisms (SNPs) in or near important candidate genes, including FOXO1A, GAPDH, KL, LEPR, PON1, PSEN1, SOD2, and WRN, but none of the associations achieved conventional levels of statistical significance; the sample size was modest, and the genotyping platform did not cover the genome well by current standards. The advent of genome-wide association studies (GWAS) has successfully led to the discovery of novel genetic variants that have strong evidence for replication and that are outside of traditional candidate gene regions for several common diseases (23–29). The detection of novel genetic variants associated with longevity holds the promise to provide important insights to biologic pathways in the aging process and thus the potential to develop innovative strategies to promote a long and healthy life. We conducted a meta-analysis of GWAS findings for longevity within an international consortium of four longitudinal community-based cohort studies that followed adults over many years. Longevity was defined as survival to age 90 years or older, and a comparison group was drawn from each cohort. Furthermore, we identified two independent cohorts of long-lived individuals, the Leiden Longevity Study cohort and the Danish 1905 cohort, to evaluate initial findings for the strongest allelic associations for longevity in a second discovery stage.

Die Wahrscheinlichkeit, dass Menschen ein hohes Alter erreichen, ist im vergangenen Jahrhundert in den industrialisierten Landern erheblich gestiegen. Sinkende Geburten- und Sterberaten haben zu einer veranderten Bevolkerungsstruktur gefuhrt. In den kommenden Jahrzehnten wird die Bevolkerung in Deutschland rasch altern. Diese neue demografische Lage erfordert Anpassungen und Umdenken auf personlicher und sozialpolitischer Ebene. Wir argumentieren, dass die Forderung von Bildung uber alle Lebensphasen und Bevolkerungsgruppen hinweg im Zentrum der Anpassungsstrategien stehen muss. Das gilt beispielsweise in Bezug auf Gesundheit, denn kunftige Belastungen der sozialen Sicherungssysteme und die gesamtwirtschaftliche Leistungsfahigkeit hangen auch davon ab, in welchem Gesundheitszustand die wachsende Zahl alterer Menschen sein wird. Bildung kann ein gesundheitsforderndes Verhalten unterstutzen und damit die Chancen erhohen, dass ein Mensch ein langes, aktives Leben fuhren kann. Zudem kommen Aus- und Weiterbildung durch den demografischen Wandel eine noch hohere Bedeutung im Arbeitsleben zu, da durch die Veranderungen in der Bevolkerungsstruktur eine Verlangerung der Lebensarbeitszeit und eine gleichmasigere Verteilung der Arbeit uber den Lebenslauf notwendig werden. Bildung ist eine Investition, die sich auch und gerade bei der Aussicht auf ein langes Leben lohnt und das Fundament bildet, auf dem Menschen ihr Leben eigenverantwortlich fuhren, sich personlich und beruflich entwickeln und ihren Lebensunterhalt sichern konnen.

There is a unique threshold age separating early deaths from late deaths such that averting an early death decreases life disparity, but averting a late death increases inequality in lifespans.

This is an expanded version of comments on the future of the demography of aging at an invited session of the 2008 annual meeting of the Population Association of America. In an introduction, John Haaga offers reasons for a revival of interest in population aging, including greater realization of plasticity in aging trajectories at both individual and societal levels. Linda Martin proposes that population scientists working in aging emulate those studying fertility and family planning in previous decades, learning from interventions (in this case, aimed at increasing retirement savings and reducing disability at older ages). Changes in family structure will increasingly affect new cohorts of the elderly, and Linda Waite speculates on the ways in which changes in the economy, medicine, and the legal environment could affect the social context for aging. Research on mortality at older ages is “alive and well” asserts James Vaupel, who sets out six large questions on mortality trends and differentials over time and across species. Lastly, Wolfgang Lutz expands the scope of projections, showing the considerable uncertainty about the timing and pace of population aging in the developing world and the effects on future elderly of the increases in educational attainment in much of the world during the second half of the twentieth century.

Centenarians surpass the current human life expectancy with about 20-25 years. However, whether centenarians represent healthy aging still remains an open question. Previous studies have been hampered by a number of methodological shortcomings such as a cross-sectional design and lack of an appropriate control group. In a longitudinal population-based cohort, it was examined whether the centenarian phenotype may be a useful model for healthy aging. The study was based on a complete follow up of 39,945 individuals alive in the Danish 1905 birth cohort on January 1, 1977 identified through the Danish Civil Registration System (DCRS). Data from the Danish Demographic Database and The Danish National Patient Register (in existence since 1977) were used. The 1905 cohort was followed up from 1977 through 2004 with respect to hospitalizations and number of hospital days. Survival status was available until December 2006. Danish centenarians from the 1905 cohort were hospitalized substantially less than their shorter-lived contemporaries at the same point in time during the years 1977 through 2004. For example, at age 71-74, the proportion of nonhospitalized centenarians was 80.5% compared with 68.4% among individuals who died in their early 80s. This trend was evident in both sexes. As a result of their lower hospitalization rates and length of stay in hospital compared with their contemporaries, who died at younger ages, Danish centenarians represent healthy agers. Centenarians constitute a useful study population in the search for fixed traits associated with exceptional longevity, such as genotype.

For the species that have been most carefully studied, mortality rises with age and then plateaus or declines at advanced ages, except for yeast. Remarkably, mortality for yeast can rise, fall and rise again. In the present study we investigated (i) if this complicated shape could be modulated by environmental conditions by measuring mortality with different food media and temperature; (ii) if it is triggered by biological heterogeneity by measuring mortality in stationary phase in populations fractionated into subpopulations of young, virgin cells, and replicatively older, non-virgin cells. We also discussed the results of a staining method to measure viability instead of measuring the number of cells able to exit stationary phase and form a colony. We showed that different shapes of age-specific death rates were observed and that their appearance depended on the environmental conditions. Furthermore, biological heterogeneity explained the shapes of mortality with homogeneous populations of young, virgin cells exhibiting a simple shape of mortality in conditions under which more heterogeneous populations of older cells or unfractionated populations displayed complicated death rates. Finally, the staining method suggested that cells lost the capacity to exit stationary phase and to divide long before they died in stationary phase. These results explain a phenomenon that was puzzling because it appeared to reflect a radical departure from mortality patterns observed for other species.

It is well known that life expectancy can be expressed as an integral of the survival curve. The reverse - that the survival function can be expressed as an integral of life expectancy - is also true.

Mortality data for 30 mostly developed countries available in the Kannisto–Thatcher Database on Old-Age Mortality (KTDB) are drawn on to assess the pace of decline in death rates at ages 80 years and above. As of 2004 this database recorded 37 million persons at these ages, including 130,000 centenarians (more than double the number in 1990). For men, the probability of surviving from age 80 to age 90 has risen from 12 percent in 1950 to 26 percent in 2002; for women, the increase has been from 16 percent to 38 percent. In the lowest-mortality country, Japan, life expectancy at age 80 in 2006 is estimated to be 6.5 years for men and 11.3 years for women. For selected countries, average annual percent declines in age-specific death rates over the preceding ten years are calculated for single-year age groups 80 to 99 and the years 1970 to 2004. The results are presented in Lexis maps showing the patterns of change in old-age mortality by cohort and period, and separately for men and women. The trends are not favorable in all countries: for example, old-age mortality in the United States has stagnated since 1980. But countries with exceptionally low mortality, like Japan and France, do not show a deceleration in death rate declines. It is argued that life expectancy at advanced ages may continue to increase at the same pace as in the past.

Udgivelsesdato: 2008-Sep-9 Late-life loss of independence in daily living is a central concern for the aging individual and for society. The implications of increased survival to advanced age may be different at the population level than at the individual level. Here we used a longitudinal multi-assessment survey of the entire Danish 1905 cohort from 1998 to 2005 to assess the loss of physical and cognitive independence in the age range of 92 to 100 years. Multiple functional outcomes were studied, including independence, which was defined as being able to perform basic activities of daily living without assistance from other persons and having a MiniMental State Examination (MMSE) score of 23 or higher. In the aggregate, the 1905 cohort had only a modest decline in the proportion of independent individuals at the 4 assessments between age 92 and 100 years: 39%, 36%, 32%, and 33%, with a difference between first and last assessment of 6% [95% confidence interval (CI), -1-14%]. For participants who survived until 2005, however, the prevalence of independence was reduced by more than a factor of 2, from 70% in 1998 to 33% in 2005 (difference, 37%; 95% CI, 28-46%). Similar results were obtained for the other functional outcomes. Analyses of missing data resulting from nonresponse and death suggest that the discrepancy between the population trajectory and the individual trajectory is caused by increased mortality among dependent individuals. For the individual, long life brings an increasing risk of loss of independence. For society, mortality reductions are not expected to result in exceptional levels of disability in cohorts of the very old.

Udgivelsesdato: 2008-Feb To investigate the genetic contribution to familial similarity in longevity, we set up a novel experimental design where cousin-pairs born from siblings who were concordant or discordant for the longevity trait were analyzed. To check this design, two chromosomal regions already known to encompass longevity-related genes were examined: 6p21.3 (genes TNFalpha, TNFbeta, HSP70.1) and 11p15.5 (genes SIRT3, HRAS1, IGF2, INS, TH). Population pools of 1.6, 2.3 and 2.0 million inhabitants were screened, respectively, in Denmark, France and Italy to identify families matching the design requirements. A total of 234 trios composed by one centenarian, his/her child and a child of his/her concordant or discordant sib were collected. By using population-specific allele frequencies, we reconstructed haplotype phase and estimated the likelihood of Identical By Descent (IBD) haplotype sharing in cousin-pairs born from concordant and discordant siblings. In addition, we analyzed haplotype transmission from centenarians to offspring, and a statistically significant Transmission Ratio Distortion (TRD) was observed for both chromosomal regions in the discordant families (P=0.007 for 6p21.3 and P=0.015 for 11p15.5). In concordant families, a marginally significant TRD was observed at 6p21.3 only (P=0.06). Although no significant difference emerged between the two groups of cousin-pairs, our study gave new insights on the hindrances to recruiting a suitable sample to obtain significant IBD data on longevity-related chromosomal regions. This will allow to dimension future sampling campaigns to study-genetic basis of human longevity.European Journal of Human Genetics (2008) 16, 236-242; doi:10.1038/sj.ejhg.5201950; published online 7 November 2007.

Studies in fertility in the industrialized world primarily focus on the decline in average fertility and the determinants of this trend (Bongaarts 2002; UN Population Division 2003; Morgan 2003; Caldwell and Schindlmayr 2003). Variation in fertility within a population is used in an instrumental manner to link birth rates to explanatory variables by means of regressions and de compositions. The recent comprehensive work by Frejka and Sard?n (2004) reviewed changes in completed cohort fertility in industrialized countries and related them to changing age and parity patterns. The present study is interested primarily in the inter-individual diversity in fertility according to the parity distributions of women. This way of think ing about the inter-individual diversity is related to the concentration (or Lorenz) curve, showing what proportion of women have what proportion of children. Such a curve would demonstrate, for example, that 30 percent of American women born in 1931-32 have half of the children born to this cohort, while half of these women have 75 percent of the children. At the same time, 62 percent of children born to this cohort were born to mothers with four or more children, while only 3 percent were born to mothers with one child. These quantities describe something that might be called a division of labor in the matter of fertility (Vaupel and Goodwin 1987). The division of labor concept can be expressed also by an average inter-individual difference in childbearing "productivity" among women. It can be shown, for example, that the average difference between any pair of women (including women who remained childless) from the 1931-32 American cohort in the number

16. Reverse mortgage insurance would protect the lender just as conventional mortgage insurance does. However, the nature of the risk is quite different. In the latter case a borrower's death may make the loan a nonperforming one, while in the former the borrower's long life may put the lender at risk. 17. See Jacobs and Weissert, op. cit.; Garnett, Robert, and Guttentag, Jack, "The Reverse-Shared-Appreciation Mortgage," Housing Finance Review, 3(1) (Jan. 1984): 63-84. 18. Another advantage of being married is that a spouse is available to provide informal care in the home if the need arises. 19. Firman, James, "Reforming Community Care for the Elderly and the Disabled," Health Affairs, 11(1) (Spring 1983): 66-82. Frail elderly homeowners in California have taken out reverse mortgage loans for this purpose. See Kenny, Kathleen, and Belling, Bronwyn, "Home Equity Conversion: A Counseling Model," The Gerontologist, to appear.

The author notes that the new use that the U.S. Congress has established for the census namely the allocation of revenue sharing and other grants requires exactitude and does not fit with the probability models that have been so effective in other fields. He concludes that as long as the census count is reasonably close to actuality as revealed by the checks now in use its acceptance for this purpose is reasonable. The need for external quality control is indicated but it should be on the institution itself and not on individual census results. (ANNOTATION)

Background: The Gompertz force of mortality (hazard function) is usually expressed in terms of a, the initial level of mortality, and b, the rate at which mortality increases with age. Objective: We express the Gompertz force of mortality in terms of b and the old-age modal age at death M, and present similar relationships for other widely-used mortality models. Our objective is to explain the advantages of using the parameterization in terms of M. Methods: Using relationships among life table functions at the modal age at death, we express the Gompertz force of mortality as a function of the old-age mode. We estimate the correlation between the estimators of old (a and b) and new (M and b) parameters from simulated data. Results: When the Gompertz parameters are statistically estimated from simulated data, the correlation between estimated values of b and M is much less than the correlation between estimated values of a and b. For the populations in the Human Mortality Database, there is a negative association between a and b and a positive association between M and b. Conclusions: Using M, the old-age mode, instead of a, the level of mortality at the starting age, has two major advantages. First, statistical estimation is facilitated by the lower correlation between the estimators of model parameters. Second, estimated values of M are more easily comprehended and interpreted than estimated values of a. Background: The Gompertz force of mortality (hazard function) is usually expressed in terms of a, the initial level of mortality, and b, the rate at which mortality increases with age.Objective: We express the Gompertz force of mortality in terms of b and the old-age modal age at death M, and present similar relationships for other widely-used mortality models. Our objective is to explain the advantages of using the parameterization in terms of M.Methods: Using relationships among life table functions at the modal age at death, we express the Gompertz force of mortality as a function of the old-age mode. We estimate the correlation between the estimators of old (a and b) and new (M and b) parameters from simulated data.Results: When the Gompertz parameters are statistically estimated from simulated data, the correlation between estimated values of b and M is much less than the correlation between estimated values of a and b. For the populations in the Human Mortality Database, there is a negative association between a and b and a positive association between M and b.Conclusions: Using M, the old-age mode, instead of a, the level of mortality at the starting age, has two major advantages. First, statistical estimation is facilitated by the lower correlation between the estimators of model parameters. Second, estimated values of M are more easily comprehended and interpreted than estimated values of a.

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.

Summary: Schedules of survival, growth and reproduction are key life-history traits. Data on how these traits vary among species and populations are fundamental to our understanding of the ecological conditions that have shaped plant evolution. Because these demographic schedules determine population growth or decline, such data help us understand how different biomes shape plant ecology, how plant populations and communities respond to global change and how to develop successful management tools for endangered or invasive species. Matrix population models summarize the life cycle components of survival, growth and reproduction, while explicitly acknowledging heterogeneity among classes of individuals in the population. Matrix models have comparable structures, and their emergent measures of population dynamics, such as population growth rate or mean life expectancy, have direct biological interpretations, facilitating comparisons among populations and species. Thousands of plant matrix population models have been parameterized from empirical data, but they are largely dispersed through peer-reviewed and grey literature, and thus remain inaccessible for synthetic analysis. Here, we introduce the compadre Plant Matrix Database version 3.0, an open-source online repository containing 468 studies from 598 species world-wide (672 species hits, when accounting for species studied in more than one source), with a total of 5621 matrices. compadre also contains relevant ancillary information (e.g. ecoregion, growth form, taxonomy, phylogeny) that facilitates interpretation of the numerous demographic metrics that can be derived from the matrices. Synthesis. Large collections of data allow broad questions to be addressed at the global scale, for example, in genetics (genbank), functional plant ecology (try, bien, d3) and grassland community ecology (nutnet). Here, we present compadre, a similarly data-rich and ecologically relevant resource for plant demography. Open access to this information, its frequent updates and its integration with other online resources will allow researchers to address timely and important ecological and evolutionary questions. Synthesis: Large collections of data sets allow broad questions to be addressed at the global scale, for example, in genetics (genbank), functional plant ecology (try, bien, d3) and grassland community ecology (nutnet). Here, we present compadre, a similarly data-rich and ecologically relevant resource for plant demography. Open access to this information, its frequent updates and its integration with other online resources will allow researchers to address timely and important ecological and evolutionary questions.

This article aims to describe in a unified framework all plateau-generating random effects models in terms of (i) plausible distributions for the hazard (baseline mortality) and the random effect (unobserved heterogeneity, frailty) as well as (ii) the impact of frailty on the baseline hazard. Mortality plateaus result from multiplicative (proportional) and additive hazards, but not from accelerated failure time models. Frailty can have any distribution with regularly-varying-at-0 density and the distribution of frailty among survivors to each subsequent age converges to a gamma distribution. In a multiplicative setting the baseline cumulative hazard can be represented as the inverse of the negative logarithm of any completely monotone function. If the plateau is reached, the only meaningful solution at the plateau is provided by the gamma-Gompertz model. This article aims to describe in a unified framework all plateau-generating random effects models in terms of (i) plausible distributions for the hazard (baseline mortality) and the random effect (unobserved heterogeneity, frailty) as well as (ii) the impact of frailty on the baseline hazard. Mortality plateaus result from multiplicative (proportional) and additive hazards, but not from accelerated failure time models. Frailty can have any distribution with regularly-varying-at-0 density and the distribution of frailty among survivors to each subsequent age converges to a gamma distribution. In a multiplicative setting the baseline cumulative hazard can be represented as the inverse of the negative logarithm of any completely monotone function. If the plateau is reached, the only meaningful solution at the plateau is provided by the gamma-Gompertz model.

The Danish Twin Registry is the oldest national twin register in the world, initiated in 1954, and, by the end of 2005, contained more than 75,000 twin pairs born in the between 1870 and 2004. The Danish Twin Registry is used as a source for studies on the genetic influence on normal variation in clinical parameters associated with the metabolic syndrome and cardiovascular diseases, clinical studies of specific diseases, and aging and age-related health problems. The combination of survey data, clinical data and linkage to national health-related registers enables follow-up studies of both the general twin population and twins from clinical studies. This paper summarizes the newest extension of the register and gives examples of new developments and phenotypes studied.

This paper aims to discuss the validation and family determinants affecting the longevity of Sardinian centenarians, using a genealogical approach. This preliminary study presents the first results of a genealogical tree reconstruction of selected centenarians aged 105 and over, from certain areas. These are mostly situated in the province of Nuoro, an area with the highest rate of centenarians and where the female-to-male sex ratio tends to be male-biased. An accurate centenarian age validation was performed that required a meticulous examination of numerous civil status records and parish registers. An important finding was that longevity occurs among the ascendants of a particular branch of the family. The data used are still provisional but, should it apply to other validated cases, it would provide empirical evidence of a genetic component in longevity. A more thorough examination of the data available may yield deeper insights into the role played by endogamy and consanguinity.

Theories of the evolution of senescence state that symmetrically dividing organisms do not senesce. However, this view is challenged by experimental evidence. We measured by immunofluorescence the occurrence and intensity of protein carbonylation in single and symmetrically dividing cells of Schizosaccharomyces pombe. Cells of S. pombe show different levels of carbonylated proteins. Most cells have little damage, a few show a lot, an observation consistent with the gradual accumulation of carbonylation over time. At reproduction, oxidized proteins are shared between the two resulting cells. These results indicate that S. pombe does age, but does so in a different way from other studied species. Damaged cells give rise to damaged cells. The fact that cells with no or few carbonylated proteins constitute the main part of the population can explain why, although age is not reset to zero in one of the cells during division, the pool of young cells remains large enough to prevent the rapid extinction of the population.

OBJECTIVES: To evaluate the extent to which relationships between apolipoprotein E, cognitive functioning, and survival in people aged 60 to 80 persist into advanced old age. DESIGN: Examine the effect of apolipoprotein E genotypes on baseline cognitive functioning, cognitive decline over 5 years, and survival in a cohort of 1,551 nonagenarians. SETTING: The Danish 1905 birth cohort. PARTICIPANTS: One thousand five hundred fifty-one nonagenarians from the Danish 1905 birth cohort. MEASUREMENTS: Cognitive functioning was assessed using the Mini-Mental State Examination (MMSE) and five brief cognitive tests (cognitive composite). RESULTS: The subjects were stratified into four groups by occurrence of a protective (epsilon2) or a risk (epsilon4) apo E allele (epsilon22 and epsilon23, epsilon33, epsilon24 and epsilon34, epsilon44). At intake, the mean scores for the three genotype groups were 22.1, 21.8, 21.4, and 21.0 for MMSE and 0.10, 0.07, -0.02, and 0.30 for the cognitive composite, respectively. Growth-curve analyses showed that, although individuals carrying at least one epsilon4 allele had slightly lower MMSE scores and declined slightly more rapidly over time, this effect was not statistically significant and was not apparent in scores on the cognitive composite. In subjects whose functioning was relatively well preserved (those still living and able to participate in the assessment, and whose cognitive functioning had declined less than 4 points on the MMSE), epsilon4 frequencies tended to decline at subsequent waves (P=.03, chi-square test for trend), but epsilon4 had no significant survival disadvantage (hazard ratio=1.11 (95% confidence interval=0.99-1.25; P=.07). CONCLUSION: Apo E genotype has a small effect on the probability of remaining a well-functioning nonagenarian but no separately detectable effect on cognitive functioning, cognitive decline, or survival.

Background: The consistent findings of a negative correlationbetween telomere length and replicative potential of cultured cells,as well as a decreasing telomere length in a number of differenttissues in humans with age, have led to the suggestion that telomeresplay a role in cellular aging in vivo and ultimately even in organismalaging. Furthermore, one small longitudinal study of elderlyindividuals has suggested that longer telomeres are associated withbetter survival.Methods: Telomere length was measured as mean terminal restrictionfragment length on blood cells from 812 persons, age 73 to 101years, who participated in population-based surveys in 1997–1998.Among the participants were 652 twins. The participants werefollowed up through the Danish Civil Registration system untilJanuary 2005, at which time 412 (51%) were dead.Results: Univariate Cox regression analyses revealed that longertelomeres were associated with better survival (hazard ratios 0.8995% confidence interval 0.76 –1.04 per 1 kb in males and 0.790.72– 0.88 per 1 kb in females, respectively). However, includingage in the analyses changed the estimates to 0.97 (0.83–1.14) and0.93 (0.85–1.03), respectively. Intrapair comparison showed thatamong 175 twin pairs in which at least one died during follow up,it was the twin with the shorter telomere length who died first in 97(55%) of the pairs (95% confidence interval 48 – 63%). We couldnot confirm the recently reported negative correlation between telomerelength and obesity or between telomere length and smoking.Conclusion: This longitudinal study of the elderly and oldest olddoes not support the hypothesis that telomere length is a predictorfor remaining lifespan once age is controlled for.