Adam Lenart

DNA methylation age is associated with mortality in a longitudinal Danish twin study.

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.

The moments of the Gompertz distribution and maximum likelihood estimation of its parameters

The Gompertz distribution is widely used to describe the distribution of adult deaths. Previous works concentrated on formulating approximate relationships to characterise it. However, using the generalised integro-exponential function, exact formulas can be derived for its moment-generating function and central moments. Based on the exact central moments, higher accuracy approximations can be defined for them. In demographic or actuarial applications, maximum likelihood estimation is often used to determine the parameters of the Gompertz distribution. By solving the maximum likelihood estimates analytically, the dimension of the optimisation problem can be reduced to one both in the case of discrete and continuous data. Monte Carlo experiments show that by ML estimation, higher accuracy estimates can be acquired than by the method of moments.

The emergence of longevous populations

Significance Public interest in social and economic equality is burgeoning. We examine a related phenomenon, lifespan equality, using data from charismatic primate populations and diverse human populations. Our study reveals three key findings. First, lifespan equality rises in lockstep with life expectancy, across primate species separated by millions of years of evolution and over hundreds of years of human social progress. Second, industrial humans differ more from nonindustrial humans in these measures than nonindustrial humans do from other primates. Third, in spite of the astonishing progress humans have made in lengthening the lifespan, a male disadvantage in lifespan measures has remained substantial—a result that will resonate with enduring public interest in male–female differences in many facets of life. The human lifespan has traversed a long evolutionary and historical path, from short-lived primate ancestors to contemporary Japan, Sweden, and other longevity frontrunners. Analyzing this trajectory is crucial for understanding biological and sociocultural processes that determine the span of life. Here we reveal a fundamental regularity. Two straight lines describe the joint rise of life expectancy and lifespan equality: one for primates and the second one over the full range of human experience from average lifespans as low as 2 y during mortality crises to more than 87 y for Japanese women today. Across the primate order and across human populations, the lives of females tend to be longer and less variable than the lives of males, suggesting deep evolutionary roots to the male disadvantage. Our findings cast fresh light on primate evolution and human history, opening directions for research on inequality, sociality, and aging.

Rise, stagnation, and rise of Danish women's life expectancy

Significance Life expectancy is the most commonly used measure of health status in a population. Life expectancy has increased rapidly in most western populations over the past two centuries. There has been an ongoing debate about the relative contribution of cohort and period effects on a nation’s life expectancy, but few concrete examples of strong cohort effects exist. In this study, we use demographic approaches to study cohort effects on the life expectancy of Danish women. We identify a clear-cut and strong cohort effect: the case of the interwar generations of Danish women. 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.

Goodness-of-fit tests for the Gompertz distribution

Abstract While the Gompertz distribution is often fitted to lifespan data, testing whether the fit satisfies theoretical criteria is being neglected. Here four goodness-of-fit measures – the Anderson–Darling statistic, the correlation coefficient test, a statistic using moments, and a nested test against the generalized extreme value distributions – are discussed. Along with an application to laboratory rat data, critical values calculated by the empirical distribution of the test statistics are also presented.

Gompertz-Makeham life expectancies: expressions and applications.

In a population of individuals, whose mortality is governed by a Gompertz-Makeham hazard, we derive closed-form solutions to the life-expectancy integral, corresponding to the cases of homogeneous and gamma-heterogeneous populations, as well as in the presence/absence of the Makeham term. Derived expressions contain special functions that aid constructing high-accuracy approximations, which can be used to study the elasticity of life expectancy with respect to model parameters. Knowledge of Gompertz-Makeham life expectancies aids constructing life-table exposures.

Blood DNA methylation age is not associated with cognitive functioning in middle-aged monozygotic twins.

The epigenetic clock, also known as DNA methylation age (DNAmAge), represents age-related changes of DNA methylation at multiple sites of the genome and is suggested to be a biomarker for biological age. Elevated blood DNAmAge is associated with all-cause mortality, with the strongest effects reported in a recent intrapair twin study where epigenetically older twins had increased mortality risk in comparison to their co-twins. In the study presented here, we hypothesize that DNAmAge in blood is associated with cross-sectional and longitudinal cognitive abilities in middle-aged individuals. In 486 monozygotic twins, we investigated the association of DNAmAge, difference between DNAmAge and chronological age and age acceleration with cognition. Despite using a powerful paired twin design, we found no evidence for association of blood DNAmAge with cognitive abilities. This observation was confirmed in unpaired analyses, where DNAmAge initially correlated with cognitive abilities, until adjusting for chronological age. Overall, our study shows that for middle-aged individuals DNAmAge calculated in blood does not correlate with cognitive abilities.

Two stochastic processes shape diverse senescence patterns in a single-cell organism

Despite advancements in aging research, we lack basic understanding of the biological processes that shape senescence. Here, we show that for a simple isogenic bacterial system, Escherichia coli, in a controlled environment, senescence results from two stochastic processes: a primary random deterioration process within the cell underlying classical senescence patterns; and a secondary process of stochastic asymmetric transmission of a factor influencing mortality at cell fission. This second process is required to explain the near non-senescence of old mothers offspring and the lack of a mother offspring correlation in age at death. We observed that life span is predominantly determined by underlying stochastic stage dynamics. Our findings do not support evolutionary postulates that base their reasoning on the age-specific action of alleles, but could support stage-specific actions of alleles. One Sentence Summary Senescence in bacteria is driven by two stochastic processes that produce large variation in lifespan among isogenic individuals. Contributions U.K.S. planned, performed, analyzed, and directed the experiments, and prepared and finalized drafts of the manuscript; M.N., performed experiments; A.L., X.S. analyzed data; F.T., A.B.L., J.V. and all other authors discussed the results and wrote the manuscript. Competing financial interests The authors declare no competing financial interests

Complexity of the relationship between life expectancy and overlap of lifespans

Longevity has long been recognised as a key facilitator of reciprocal altruism because repeated cooperation of partners hinges on mutual survival. Although demographic tools can be used to quantify mutual survival and expected overlapping lifespans, studies on the evolutionary theory of cooperation take only limited advantage of demography. Overlap of lifespans depends on variation in survival across ages and can be high or low independently of high or low life expectancies. Here we develop formal demographic measures to study the complex relationships between shared life expectancy of two birth cohort peers, the proportion of their lives that they can expect to overlap, and longevity. We simulate age-specific mortality schedules using a Siler model to reveal how infant and senescent mortality, along with age-independent mortality, affect the relationship between the proportion of life shared and life expectancy. We find that while the proportion of life shared can vary vastly for similar life expectancies, almost all changes to mortality schedules that result in higher life expectancies also result in higher proportions of life shared. A distinct exception occurs if life expectancy increases due to lowering the rate of senescence. In this case the proportion of life shared decreases. Our work shows that almost all selective pressures that result in higher life expectancies also result in a larger proportion of life shared. Therefore, selective forces that extend life also improve the chances that a cooperative system would be stable in terms of reciprocal interactions. Since reciprocal interactions may also reduce mortality and result in a feedback loop with the evolution of longevity, our measures and findings can be used for future cross-species comparisons that aim to disentangle predecessor and successor in the evolution of longevity and cooperation.

New light on Roman census papyri through semi-automated record linkage

ABSTRACT The census documents from Roman Egypt form the best documentary source of demographic information for the Roman Empire. Earlier collections (Bagnall and Frier 2006; Bagnall, Frier, and Rutherford 1997) have shown that some individuals and households appear more than once within this body of evidence. This article demonstrates how semi-automated record linkage provides an efficient and systematic way of producing linkages between early historical documentary sources that are fragmentary. The process yielded more linkages with generally high probability values than previously employed linkage-by-hand methods. As the added examples show, semi-automated record linkage also proved to be a useful method to fill gaps in papyri by transferring information from one record to the other. As such, it provides new opportunities for papyrologists and epigraphers working with fragmented materials pertaining to the ancient Greco-Roman world.