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A I Yashin

Publications and source records attributed to A I Yashin.

11 recordsLinked to original sources

How long can humans live? Lower bound for biological limit of human longevity calculated from Danish twin data using correlated frailty model.

How long can people live? Opinions of the researchers diverge and debates continue. Is there any systematic way to address this question? In this paper, we suggest an approach to the estimation of the biological limit of human longevity using survival data for twins from different zygocity groups. The approach is based on the genetic model of individual frailty. It combines ideas used in demography and survival analysis with methods of quantitative genetics and genetic epidemiology. The association between the life-spans of related individuals is described by the correlated frailty model of bivariate survival. A version of this model is used in order to estimate heritability of the individual frailty and to calculate the lower bound of human longevity. The limitations of this approach and directions of further research are discussed.

Aged

Mortality among twins after age 6: fetal origins hypothesis versus twin method.

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.

Adolescent

Genetic analysis of durations: correlated frailty model applied to survival of Danish twins.

Population studies of changes in human morbidity and mortality require models which take into account the influence of genetic and environmental factors on life-related durations, such as age at onset of the disease or disability, age at death, etc. In this paper we show how a bivariate survival model based on the concept of correlated individual frailty can be used for the genetic analysis of durations. Six genetic models of frailty are considered and applied to Danish twin survival data. The results of statistical analysis allow us to conclude that at least 50% of variability in individual frailty is determined by environmental factors. The approach suggests a method of estimation of the lower bound for the biological limit of human longevity. Directions for further research are discussed.

Adult

The effects of health histories on stochastic process models of aging and mortality.

A model of human health history and aging, based on a multivariate stochastic process with both continuous diffusion and discrete jump components, is presented. Discrete changes generate non-Gaussian diffusion with time varying continuous state distributions. An approach to calculating transition rates in dynamically heterogeneous populations, which generalizes the conditional averaging of hazard rates done in "fixed frailty" population models, is presented to describe health processes with multiple jumps. Conditional semi-invariants are used to approximate the conditional p.d.f. of the unobserved health history components. This is useful in analyzing the age dependence of mortality and health changes at advanced age (e.g., 95+) where homeostatic controls weaken, and physiological dynamics and survival manifest nonlinear behavior.

Aging

A duality in aging: the equivalence of mortality models based on radically different concepts.

Several alternative mortality models fit Swedish old-age mortality data equally well. The models build on two different concepts of the heterogeneity of individuals in a population. The first concept concerns fixed, genetic differences among individuals in their risk of death. The second concept involves acquired susceptibility to death due to physiological changes and environmental influences. We show that alternative mortality models based on either of these two concepts or some mix of them lead to the same parametric form of observed age-specific death rates. We discuss this duality property of mortality processes and show that even when a mortality model fits the data, the concepts used to construct the model may not be correct.

Adult

A multistate model of fecundability and sterility.

This paper develops a multistate hazards model for estimating fecundability and sterility from data on waiting times to conception. Important features of the model include separate sterile and nonsterile states, a distinction between preexisting sterility and sterility that begins after initiation of exposure, and log-normally distributed fecundability among nonsterile couples. Application of the model to data on first birth intervals from Taiwan, Sri Lanka, and the Amish shows that heterogeneity in fecundability is statistically significant at most ages, but that preexisting sterility and new sterility are unimportant before age 40. These results suggest that sterility may not be an important determinant of natural fertility until later reproductive ages.

Adolescent

The propagation of uncertainty in human mortality processes operating in stochastic environments.

This paper presents a model describing how the uncertainty due to influential exogenous processes combines with stochasticity intrinsic to physiological aging processes and propagates through time to generate uncertainty about the future physiological state of the population. Variance expressions are derived for (a) the future values of the physiological variables under the assumption that external factors evolve under a linear stochastic diffusion process, and (b) the cohort survival functions and cohort life expectancies which reflect the uncertainty in the future values of the physiological variables. The model implies that a major component of uncertainty in forecasts of the physiological characteristics of a closed cohort is due to differential rates of survival associated with different realizations of the external process. This suggests that the limits to forecasting may be different in physiological systems subject to systematic mortality than in physical systems such as weather where the concepts of closed cohorts and of mortality selection have no simple analog.

Aging

Dependent competing risks: a stochastic process model.

Analyses of human mortality data classified according to cause of death frequently are based on competing risk theory. In particular, the times to death for different causes often are assumed to be independent. In this paper, a competing risk model with a weaker assumption of conditional independence of the times to death, given an assumed stochastic covariate process, is developed and applied to cause specific mortality data from the Framingham Heart Study. The results generated under this conditional independence model are compared with analogous results under the standard marginal independence model. Under the assumption that this conditional independence model is valid, the comparison suggests that the standard model overestimates by 4% the effect on life expectancy at age 30 due to the hypothetical elimination of cancer and by 7% the effect for cardiovascular/cerebrovascular disease. By age 80 the overestimates were 11% for cancer and 16% for heart disease. These results suggest the importance of avoiding the marginal independence assumption when appropriate data are available--especially when focusing on mortality at advanced ages.

Adolescent

Mortality and aging in a heterogeneous population: a stochastic process model with observed and unobserved variables.

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.

Aging

Estimating hidden morbidity via its effect on mortality and disability.

The applicability of the theory of partially observed finite-state Markov processes to the study of disease, morbidity, and disability is explored. A method is developed for the continuous updating of parameter estimates over time in longitudinal studies analogous to Kalman filtering in continuous valued continuous time stochastic processes. It builds on a model of filtering of incompletely observed finite-state Markov processes subject to mortality due to Yashin et al. The method of estimation is based on maximum likelihood theory and the incompleteness in the observation of the process is dealt with by applying missing information principles in maximum likelihood estimation.

Aged