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Everyone has a chronological age. Because survivorship declines relentlessly in populations with age-specific death rates greater than zero, everyone also has a survivorship age ("s-age"), the age at which a proportion s of the population is still alive. S-ages can be estimated for both periods and cohorts. While trajectories of mortality over chronological ages differ (e.g., across populations, over time, by sex, or by any subpopulation), mortality trajectories over s-ages are similar, a sign that populations experience similar mortality dynamics at specific levels of survivorship. We show that this important demographic regularity holds for 23 sex-specific populations analyzed during a period comprising more than 100 years., (Copyright © 2023 The Authors.)

Why do women live longer than men? Here, we mine rich lodes of demographic data to reveal that lower female mortality at particular ages is decisive-and that the important ages changed around 1950. Earlier, excess mortality among baby boys was crucial; afterward, the gap largely resulted from elevated mortality among men 60+. Young males bear modest responsibility for the sex gap in life expectancy: Depending on the country and time, their mortality accounts for less than a quarter and often less than a 10th of the gap. Understanding the impact on life expectancy of differences between male and female risks of death by age, over time, and across populations yields insights for research on how the lives of men and women differ., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Background: Mortality rates have been reduced by half over the last 60 years for nonagenarians, and the progress is continuing. The greater survival might be due to overtreatment of severely physically and cognitively disabled individuals, which is a big concern for societies and individuals., Methods: The study population comprised two Danish birth cohorts: the 1905 Cohort and the 1915 Cohort. At age 95, all from the two cohorts who were still alive and living in Denmark were invited to participate in a health survey that used the same assessment instrument. A total of 2,670 (56.8%) persons participated in the two surveys and survival was assessed through a 7.3-year follow-up period during which 2,497 (93.5%) had died, and with virtually no loss to follow-up., Results: Despite the increasing chance of surviving to age 95, the 1915 Cohort had significantly better health and functioning than the 1905 Cohort. The survival advantage in the 1915 Cohort continued in the follow-up period after age 95: Median survival length was 2.4 months longer, p = .011. This advantage was not statistically associated with different levels of activities of daily living, physical performance, cognitive functioning, self-rated health and life satisfaction. However, the advantage tended to be more pronounced among people with better health., Conclusions: Life span and health increases among the oldest old. The improvement in survival for 95-year olds born in 1915 compared with 1905 was seen across the whole spectrum of health and functioning, with a tendency towards bigger improvement among those in good health., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Theories about biological limits to life span and evolutionary shaping of human longevity depend on facts about mortality at extreme ages, but these facts have remained a matter of debate. Do hazard curves typically level out into high plateaus eventually, as seen in other species, or do exponential increases persist? In this study, we estimated hazard rates from data on all inhabitants of Italy aged 105 and older between 2009 and 2015 (born 1896-1910), a total of 3836 documented cases. We observed level hazard curves, which were essentially constant beyond age 105. Our estimates are free from artifacts of aggregation that limited earlier studies and provide the best evidence to date for the existence of extreme-age mortality plateaus in humans., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: This study compares handgrip strength and its association with mortality across studies conducted in Moscow, Denmark, and England., Materials: The data collected by the Study of Stress, Aging, and Health in Russia, the Study of Middle-Aged Danish Twins and the Longitudinal Study of Aging Danish Twins, and the English Longitudinal Study of Ageing was utilized., Results: Among the male participants, the age-standardized grip strength was 2 kg and 1 kg lower in Russia than in Denmark and in England, respectively. The age-standardized grip strength among the female participants was 1.9 kg and 1.6 kg lower in Russia than in Denmark and in England, respectively. In Moscow, a one-kilogram increase in grip strength was associated with a 4% (hazard ratio [HR] = 0.96, 95% confidence interval [CI]: 0.94, 0.99) reduction in mortality among men and a 10% (HR = 0.90, 95%CI: 0.86, 0.94) among women. Meanwhile, a one-kilogram increase in grip strength was associated with a 6% (HR = 0.94, 95%CI: 0.93, 0.95) and an 8% (HR = 0.92, 95%CI: 0.90, 0.94) decrease in mortality among Danish men and women, respectively, and with a 2% (HR = 0.98, 95%CI: 0.97, 0.99) and a 3% (HR = 0.97, 95%CI: 0.95, 0.98) reduction in mortality among the English men and women, respectively., Conclusion: The study suggests that, although absolute grip strength values appear to vary across the Muscovite, Danish, and English samples, the degree to which grip strength is predictive of mortality is comparable across national populations with diverse socioeconomic and health profiles and life expectancy levels.

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

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

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.

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.

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

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

Human senescence has been delayed by a decade. This finding, documented in 1994 and bolstered since, is a fundamental discovery about the biology of human ageing, and one with profound implications for individuals, society and the economy. Remarkably, the rate of deterioration with age seems to be constant across individuals and over time: it seems that death is being delayed because people are reaching old age in better health. Research by demographers, epidemiologists and other biomedical researchers suggests that further progress is likely to be made in advancing the frontier of survival - and healthy survival - to even greater ages.

Background: Prior research has revealed large differences in health and mortality across countries, socioeconomic groups, and individuals. Russia experiences one of the world's highest levels of all-cause and cardiovascular mortality, great mortality differences within the population, and a heavy burden of ill health. Psychological stress has been suggested as a likely explanation of health loss and premature death in Russia and Eastern Europe. However, physiological mechanisms connecting stress with health in Russia remain unclear since existing epidemiological data are scarce and limited to conventional risk factors., Method and Design: The survey on Stress Aging and Health in Russia (SAHR) is addressing this knowledge gap by collecting an unusually rich database that includes a wide range of reported information, physical and cognitive health outcomes, and biomarkers in a sample of Muscovite men and women aged 55 and older. The total planned sample size is 2,000 individuals. The sample was randomly selected from epidemiological cohorts formed in Moscow between the mid-1970s and the 1990s and from medical population registers. The baseline data collection was carried out from December 2006 to June 2009. Interviews and medical tests were administered at hospital or at home according to standardized protocol. Questionnaire information includes health, socio-demographic characteristics, economic well-being, cognitive functioning, and batteries on stress and depression. Biomarkers include anthropometry, grip strength, resting ECG, conventional cardiovascular factors of risk such as lipid profile and blood pressure, and other biochemical parameters such as those related to inflammation, glucose and insulin resistance, coagulation, fibrinolysis, and stress hormones. In addition to these measurements, SAHR includes dynamic biomarkers provided by 24-hour ECG (Holter) monitoring. This method continuously registers the beat-to-beat heart rate in naturalistic conditions without restrictions on normal daily activities. It provides information about heart functioning, including heart rate variability and ischemic and arrhythmic events.Re-examination of the study subjects will be conducted in 2009-2011 and will focus on health, functional status, economic conditions, behaviors, and attitudes towards aging. The subjects are also followed up for mortality and non-fatal health events., Discussion: The SAHR will produce a valuable set of established and novel biomarkers combined with self-reported data for the international research community and will provide important insights into factors and biological mechanisms of mortality and health losses in Russia.

Leukocyte telomere length, representing the mean length of all telomeres in leukocytes, is ostensibly a bioindicator of human aging. The authors hypothesized that shorter telomeres might forecast imminent mortality in elderly people better than leukocyte telomere length. They performed mortality analysis in 548 same-sex Danish twins (274 pairs) aged 73-94 years, of whom 204 pairs experienced the death of one or both co-twins during 9-10 years of follow-up (1997-2007). From the terminal restriction fragment length (TRFL) distribution, the authors obtained the mean TRFL (mTRFL) and the mean values of the shorter 50% (mTRFL(50)) and shortest 25% (mTRFL(25)) of TRFLs in the distribution and computed the mode of TRFL (MTRFL). They analyzed the proportions of twin pairs in which the co-twin with the shorter telomeres died first. The proportions derived from the intrapair comparisons indicated that the shorter telomeres predicted the death of the first co-twin better than the mTRFL did (mTRFL: 0.56, 95% confidence interval (CI): 0.49, 0.63; mTRFL(50): 0.59, 95% CI: 0.52, 0.66; mTRFL(25): 0.59, 95% CI: 0.52, 0.66; MTRFL: 0.60, 95% CI: 0.53, 0.67). The telomere-mortality association was stronger in years 3-4 than in the rest of the follow-up period, and it grew stronger with increasing intrapair difference in all telomere parameters. Leukocyte telomere dynamics might help explain the boundaries of the human life span.

This review examines sex differences in health and survival, with a focus on the Nordic countries. There is a remarkable discrepancy between the health and survival of the sexes: men are physically stronger and have fewer disabilities, but have substantially higher mortality at all ages compared with women: the so-called male-female health-survival paradox. A number of proposed explanations for this paradox are rooted in biological, social, and psychological interpretations. It is likely to be due to multiple causes that include fundamental biological differences between the sexes such as genetic factors, immune system responses, hormones, and disease patterns. Behavioral differences such as risk-taking and reluctance to seek and comply with medical treatment may also play a role. Another consideration is that part of the difference may be due to methodological challenges, such as selective non-participation and under-reporting of health problems, and delayed seeking of treatment by men. The Nordic countries provide a unique opportunity for such studies, as they have good-quality data in their national health registers, which cover the whole population, and a long tradition of high participation rates in surveys.

Objective: Over the last half century the mortality rates in Denmark for females above age 80 have declined dramatically whereas the decline for males have been modest, resulting in a change in sex-ratio for centenarians from 2 to 5. Here we investigate whether this mortality pattern is mainly explained by period effects, cohort effects or both. This can provide clues for where to search for causes behind the changes in sex differential in mortality seen in many Western countries during the last decades., Methods: Age-period-cohort study of mortality for all Danish women and men aged 79-98 during the period 1949-2006., Outcome Measures: Relative risks for deaths and second order differences for exploration of the nonlinear variation., Results: Both the overall trends in mortality differences and the fluctuations in mortality for both men and women were better explained by period effects than by cohort effects. The observed rates were better described by the age, period and cohort model than by other models., Conclusions: Our results suggest that causes for both the overall increased difference in mortality and the short term fluctuations in mortality rates are primarily to be found in the period dimension. Cohort effects on the mortality of the oldest Danish women and men played a significant but minor role compared to period effects.

Life expectancy has increased at a steady pace in industrialized countries over the last 160 years. A slowdown is not evident: Since 1950 the number of people celebrating their 100th birthdays has at least doubled each decade. This increase in survival is the result of economic developments, social improvements and advances in medicine. Although the belief that old-age mortality is intractable remains widespread, life expectancy is not approaching a limit. Rather, the evidence suggests that ageing is plastic and that survival can be extended by various genetic changes and non-genetic interactions. Increases in life expectancy are largely attributed to improvements in old-age survival. It is a reasonable scenario that life expectancy will rise further in coming decades, supported by advances in the prevention, diagnosis and treatment of age-related diseases. If the trend continues, life expectancy in Germany will rise to over 90 years in the first half of this century. Many official forecasts, however, have assumed lower figures which can have severe consequences both for public and private decision making.

Negative senescence is characterized by a decline in mortality with age after reproductive maturity, generally accompanied by an increase in fecundity. Hamilton (1966) ruled out negative senescence: we adumbrate the deficiencies of his model. We review empirical studies of various plants and some kinds of animals that may experience negative senescence and conclude that negative senescence may be widespread, especially in indeterminate-growth species for which size and fertility increase with age. We develop optimization models of life-history strategies that demonstrate that negative senescence is theoretically possible. More generally, our models contribute to understanding of the evolutionary and demographic forces that mold the age-trajectories of mortality, fertility and growth.

Objectives: : To elucidate whether well-known predictions of mortality are reduced or even reversed, or whether mortality is a stochastic process in the oldest old., Design: : A multidimensional survey of the Danish 1905 cohort conducted in 1998 with follow-up of vital status after 15 months., Setting: : Denmark., Participants: : All Danes born in 1905, irrespective of physical and mental status were approached. Two thousand two hundred sixty-two persons of 3,600 participated in this survey., Measurements: : Professional interviewers collected data concerning sociodemographic factors, smoking, alcohol consumption, body mass index, physical and cognitive performance, and health during a visit at the participant's residency. Cox regression models were used to evaluate predictors of mortality., Results: : Five hundred seventy-nine (25.7%) of the 2,249 participants eligible for the analysis died during the 15 months follow-up. Multivariate analyses showed that marital status, education, smoking, obesity, consumption of alcohol, and number of self-reported diseases were not associated with mortality. Disability and cognitive impairment were significant risk factors in men and women. In addition poor self-rated health was associated with an increase in mortality in women., Conclusion: : In the oldest old, several known predictors of mortality, such as sociodemographic factors, smoking, and obesity, have lost their importance, but a high disability level, poor physical and cognitive performance, and self-rated health (women only), predict mortality, which shows that mortality in the oldest old is not a stochastic process.

Purpose: Studies of younger individuals have suggested an association between ACE genotype and physical and cognitive performance. Using a longitudinal study of elderly twins we studied the association between ACE genotype and physical and cognitive functioning and survival in old age., Methods: Participants were 684 twins aged 73+ years from the 1997 and 1999 surveys of the Longitudinal Study of Aging Danish Twins. Cognitive skills were assessed by the MMSE, while physical abilities were determined through self-report in 1997 and through both self-report and measurement of performance in two physical tasks in 1999. Survival status was obtained through linkage with a national death register., Results: Neither physical nor cognitive performance was associated with ACE genotype at baseline in 1997, or at follow-up in 1999. For participants in both surveys longitudinal changes in these skills did not depend on ACE genotype. The relative risk of dying was increased in II compared with the DI and DD genotype with relative risks of 1.6 (95 percent confidence intervals 1.1-2.5) and 1.3 (0.8-2.1), respectively., Conclusion: We found no substantial effects of ACE genotype on physical and cognitive performance, or rate of change among elderly. Persons with the D allele may have a lower mortality at older ages.

Despite differences in research traditions, the disciplines of genetics, epidemiology, and demography are becoming increasingly integrated in health-related research. The enormous development within genetic technology, with the possibility of genotyping thousands of variants from small samples of biological material obtained by non-invasive methods, now makes it feasible to include genetic information in epidemiologic and demographic studies. Simultaneously, new insight can be obtained from hybrids of methods and data from the three disciplines. This paper illustrates how a genetic observation combined with demographic insight and a modified genetic-epidemiologic design (a twin study) provides evidence that part of the sex difference in survival can be attributed to the fact that females have two X chromosomes and males have only one, a result that is of potential interest for genetics, epidemiology, and demography.

We developed a method to estimate genotype-specific average relative mortality risk, R, from genotype distributions in cross-sectional studies of people belonging to different age-groups, and applied the method to new data from a study of apolipoprotein E genotypes (apoE) in 177 Danish centenarians and data from a study of 40-year-old Danish men. Twenty-one percent of the centenarians were epsilon 2-carriers (genotypes epsilon 2 epsilon 2 and epsilon 3 epsilon 2) and 15% were epsilon 4-carriers (genotypes epsilon 4 epsilon 4 and epsilon 4 epsilon 3) compared to 13 and 29%, respectively, of the young men. The R-values were 0.95 (95% CI 0.88 to 1.02) for epsilon 2-carriers and 1.13 (95% CI 1.05 to 1.22) for epsilon 4-carriers, using epsilon 3 epsilon 3- and epsilon 4 epsilon 2 genotypes as reference. Corresponding values for epsilon 4-carriers were obtained by using published data from a French and a Finnish study of centenarians, whereas the values for epsilon 2-carriers were about 0.90 with these data. The method to estimate mortality risk and the results associate with the view that the apoE gene is a "frailty gene." On the other hand, if odds ratios are used to summarize data from studies of this kind, they are more impressive and may propagate the misconception that apoE is a "longevity gene"., (Copyright 2000 Wiley-Liss, Inc.)

The declining prevalence of left-handed individuals with increasing age has led to two main avenues of hypotheses; the association is due either (1) to a birth cohort effect and/or an age effect caused by a switch to right-handedness with advancing age or (2) to mortality selection that reduces survival in left-handed individuals, or both. It is uncertain whether a cohort or age effect can explain the decline in age-related prevalence, and conflicting evidence exists in favor of the mortality hypothesis. We compared mortality in a subgroup of 118 opposite-handed twin pairs by counting in how many instances the right-handed twin died first. There was no evidence of differential survival between right-handed and non-right-handed individuals in the entire 1900-1910 cohort. With respect to the number of right-handed twins who died first, there was no material disadvantage among those who were not right-handed. In 60% (95% confidence interval = 49.0-71.5%) of dizygotic pairs, the right-handed twins died first. In 50% of monozygotic pairs, right-handed twins died first. The prevalence of not being right-handed was higher among males (9.2%) than females (6.5%); there was a similar frequency of non-right-handedness in monozygotic (8.0%) and dizygotic (7.8%) twins. We did not find evidence of excess mortality among non-right-handed adult twins in this follow-up study.

Old-age survival has increased substantially since 1950. Death rates decelerate with age for insects, worms, and yeast, as well as humans. This evidence of extended postreproductive survival is puzzling. Three biodemographic insights--concerning the correlation of death rates across age, individual differences in survival chances, and induced alterations in age patterns of fertility and mortality--offer clues and suggest research on the failure of complicated systems, on new demographic equations for evolutionary theory, and on fertility-longevity interactions. Nongenetic changes account for increases in human life-spans to date. Explication of these causes and the genetic license for extended survival, as well as discovery of genes and other survival attributes affecting longevity, will lead to even longer lives.

Nutrition early in life may influence adult mortality. The fetal-origins hypothesis suggests that nourishment before birth and during the individual's infancy programs the development of risk factors for several important diseases of middle and old age. The present study was designed to evaluate the impact of extreme nutritional deprivation in utero and during infancy and early childhood on mortality in later life. The authors analyzed the survival of the cohorts born in Finland during the severe 1866-1868 famine and during the 5 years immediately preceding and 5 years immediately following the famine. The study included 331,932 individuals born prior to the famine, 161,744 born during the famine, and 323,321 born after the famine. The authors assessed survival by cohorts from birth to age 17 years and from age 17 to 40, 60, and 80 years, as well as average length of life after age 80 years. Survival from birth to age 17 years was significantly lower in cohorts born before and during the famine than in the cohorts born after the famine (males, 0.566 vs. 0.671, a difference of 0.105 (95% confidence interval (CI) 0.102-0.108); females, 0.593 vs. 0.692, a difference of 0.099 (95% CI 0.096-0.102)). At subsequent ages, including old age, mortality was practically identical in the famine-born cohorts and in the five cohorts born before and after the crisis. For both males and females, survival from 17 to 80 years and mean remaining lifetime at age 80 years were very similar across the 13 cohorts studied. These findings suggest that, although cohorts subjected to prolonged and extreme nutritional deprivation in utero and during infancy and early childhood suffer an immediate rise in mortality, after the crisis has passed, they carry no aftereffects that influence their survival in later life.

According to the foetal-origins hypothesis the risk of adult morbidity and mortality is heightened by intrauterine growth retardation. Twins, and in particular monozygotic twins, experience growth retardation in utero. A total of 8495 twin individuals born 1870-1900 in Denmark were followed through 1991 and death rates were calculated on a cohort basis. Deaths rates for twins and the general population were not significantly different except for females aged 60-89: mortality for female twins in this age group was 1.14 times (SE 0.03) higher than the general population. Female dizygotic twins experienced death rates 1.77 times (SE 0.18) higher than monozygotic twins at ages 30-59. Otherwise, mortality for monozygotic and dizygotic twins did not consistently differ after age six. The findings in the present study suggest that the foetal-origins hypothesis is not true for the intrauterine growth retardation experienced by twins.

Objective: To test the validity of the fetal origins hypothesis and the classic twin method., Design: Follow up study of pairs of same sex twins in which both twins survived to age 6., Setting: Denmark., Subjects: 8495 twin individuals born 1870-1900, followed through to 31 December 1991., Main Outcome Measures: Mortality calculated on a cohort basis., Results: Mortality among twins and the general population was not significantly different except among females aged 60-89, in whom mortality among twins was 1.14 times (SE 0.03) higher than in the general population. Mortality among female dizygotic twins was 1.77 times (0.18) higher than among monozygotic twins at age 30-59. Otherwise, mortality for monozygotic and dizygotic twins did not consistently differ after age 6., Conclusion: According to the fetal origins hypothesis the risk of adult morbidity and mortality is heightened by retardation in intrauterine growth. Twins, and in particular monozygotic twins, experience growth retardation in utero. The findings in the present study suggest that the fetal origins hypothesis is not true for the retardation in intrauterine growth experienced by twins. Furthermore, the data are inconsistent with the underlying assumption of a recent claim that the classic twin method is invalid for studies of adult diseases. The present study is, however, based on the one third of all pairs of twins in which both twins survived to age 6. The possible impact of this selection can be evaluated in future studies of cohorts of younger twins with lower perinatal and infant mortality.

Experimental systems that are amenable to genetic manipulation can be used to address fundamental questions about genetic and nongenetic determinants of longevity. Analysis of large cohorts of ten genotypes of Drosophila melanogaster raised under conditions that favored extended survival has revealed variation between genotypes in both the slope and location of age-specific mortality curves. More detailed examination of a single genotype showed that the mortality trajectory was best fit by a two-stage Gompertz model, with no age-specific increase in mortality rates beyond 30 days after emergence. These results are contrary to the limited life-span paradigm, which postulates well-defined, genotype-specific limits on life-span and brief periods of intense and rapidly accelerating mortality rates at the oldest age.

A stochastic differential equation model is developed to clarify the interaction of debilitation, recuperation, selection, and aging. The model yields various insights about the lingering mortality consequences of disasters such as wars, famines, and epidemics that may weaken the survivors. A key result is that debilitation and selection are interdependent: debilitation that increases population heterogeneity will result in subsequent selection; selection, by altering the distribution of population heterogeneity, will influence the impact of debilitating events.

The authors construct contour maps of Italian male and female mortality rates for ages 0-79 for the years 1870-1979 using life table data from published sources. The maps "display persistent global and prominent local patterns of mortality, simultaneously over age, by period, and for cohorts." Previously documented aspects of the evolution of Italian mortality are highlighted graphically, and new areas for study are indicated. (summary in FRE, ITA), (excerpt)

Life table methods are developed for populations whose members differ in their endowment for longevity. Unlike standard methods, which ignore such heterogeneity, these methods use different calculations to construct cohort, period, and individual life tables. The results imply that standard methods overestimate current life expectancy and potential gains in life expectancy from health and safety interventions, while underestimating rates of individual aging, past progress in reducing mortality, and mortality differentials between pairs of populations. Calculations based on Swedish mortality data suggest that these errors may be important, especially in old age.

The authors examine how sensitive the estimates of heterogeneity in the mortality risks in a population are to the choices of two types of function, "one describing the age-specific rate of increase of mortality risks for individuals and the other describing the distribution of mortality risks across individuals." U.S. data from published Medicare mortality rates for the period 1968-1978 are used to analyze total mortality among the aged. "In addition, national vital statistics data for the period 1950-1977 were used to analyze adult lung cancer mortality. For these data, the estimates of structural parameters were less sensitive to reasonable choices of the heterogeneity distribution (gamma vs. inverse Gaussian) than to reasonable choices of the hazard rate function (Gompertz vs. Weibull).", (excerpt)

Methods are presented which produce Maximum Likelihood Estimates (MLE) of the degree of heterogeneity in individual mortality risks under a variety of assumptions about the age trajectory of those mortality risks. With these estimates of the degree of population heterogeneity it is possible to adjust comparisons of mortality risks across populations for the effects of population heterogeneity, differential mortality selection, and different age trajectories of the force of mortality. These methods are demonstrated by applying a variety of standard assumptions about the age trajectory of the force of mortality to the analysis of a broad range of cohort mortality data for the U.S. and Swedish populations. The estimates of the degree of heterogeneity, produced under all of the selected force of mortality models, consistently indicated a considerable degree of heterogeneity in mortality risks.

"As a cohort of people, animals, or machines ages, the individuals at highest risk tend to die or exit first. This differential selection can produce patterns of mortality for the population as a whole that are surprisingly different from the patterns for subpopulations or individuals. Naive acceptance of observed population patterns may lead to erroneous policy recommendations if an intervention depends on the response of individuals. Furthermore, because patterns at the individual level may be simpler than composite population patterns, both theoretical and empirical research may be unnecessarily complicated by failure to recognize the effects of heterogeneity.", (excerpt)

How will progress against mortality affect the size and age composition of the United States population over the next century? To gain some insight into this question, three scenarios are examined: no future progress against mortality; steady reductions in mortality at all ages at a rate of 2 per cent per year; and a radical breakthrough in the year 2000 that cuts mortality in half. All three scenarios substantially shift the composition of the US population toward older ages, steady progress resulting in the most radical change. If mortality is reduced 2 per cent per year, by 2080 almost two-fifths of the population would be above age 65 and the number of centenarians would approach 19 million. The social, economic, and public health consequences of this new demography, although speculative and uncertain, are so important that detailed analysis and planning are warranted.

Various multivariate stochastic process models have been developed to represent human physiological aging and mortality. These efforts are extended by considering the effects of observed and unobserved state variables on the age trajectory of physiological parameters. This is done by deriving the Kolmogorov-Fokker-Planck equations describing the distribution of the unobserved state variables conditional on the history of the observed state variables. Given some assumptions, it is proved that the distribution is Gaussian. Strategies for estimating the parameters of the distribution are suggested based on an extension of the theory of Kalman filters to include systematic mortality selection. Various empirical applications of the model to studies of human aging and mortality as well as to other types of "failure" processes in heterogeneous populations are discussed.