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A I Yashin

Publications and source records attributed to A I Yashin.

At least 19 recordsLinked to original sources
PubMed1999

What difference does the dependence between durations make? Insights for population studies of aging.

The interpretation of age-specific changes in hazards, relative risks, genetic parameters and other indicators of aging calculated from data on related individuals should take into account the regularities of bivariate selection. Due to such selection the hazard rate calculated for twins who have survived to a certain age may be lower than for singletons, even if marginal chances of survival for all individuals are the same. In a mixed population of relatives the proportion of pairs with closer family links increases with age, even if all marginal individual chances of survival are the same. The proportion of chronic conditions for MZ twins observed in a cross-sectional study may be different from that of DZ twins. The age-dependence of relative risks calculated in genetic-epidemiological studies of twins does not necessarily reflect changes in genetic influence on individual susceptibility to disease and death during the aging process. The age-related changes in heritability of susceptibility estimated in twin studies may have nothing to do with changes in the genetic determination of diseases with age. These issues are illustrated by empirical graphs together with the results of modeling and statistical analysis.

Aging↗
PubMed1999

Half of the variation in susceptibility to mortality is genetic: findings from Swedish twin survival data.

Molecular epidemiological studies confirm tremendous variability in genetic and environmental susceptibility to disease and death for humans. This variability as well as the roles of genetic and environmental factors in susceptibility to death can be estimated in the analysis of survival data on related individuals (e.g., twins). In this paper, correlated gamma-frailty models are applied to survival data on Swedish twins to estimate genetic parameters in six models of susceptibility. It is shown that the frailty model with additive genetic and nonshared environmental components fits the data best. The estimate of narrow-sense heritability in gamma frailty is about 50%. The results of genetic analysis confirm our earlier findings from the studies of Danish twins that about 50% of individual susceptibility approximated by gamma-distributed frailty is heritable.

Cohort Studies↗
PubMed1998

Biodemographic trajectories of longevity.

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.

Aging↗
PubMed1998

The genetic component of discrete disability traits: an analysis using liability models with age-dependent thresholds.

The presence of familial and genetic effects in the Activities-of-Daily-Life (ADL) data collected in the first wave of the 1995 Longitudinal Study of Aging of Danish Twins (LSADT) older than 75 is tested using multithreshold liability models of disability with age-dependent thresholds. These models are developed for discrete scores represented by five disability scales of male and female Danish twins. The presence of familial effects is revealed in all five scales of disability data for females and in three scales of data for males. Genetic effects are found to be significant in all four levels of aggregation of the Upper Limb-T (T = tiredness) disability scale for females and in the PADL-H (H = need for help) scale for males. Genetic effects are also pronounced in the Mobility-T scale for females and in the Lower Limb-T scale for males and females. For females, the genetic effects in the T-scale seem to be more pronounced than in the H-scale. For males, genetic effects are more pronounced in the H-scale. The estimates for MZ correlations in liability tend to be higher than the estimates for DZ correlations in almost all cases, which suggests that additional genetic effects may be revealed should the sample size of the ADL data be increased.

Activities of Daily Living↗
PubMed1998

Age-related changes of the 3'APOB-VNTR genotype pool in ageing cohorts.

The analysis of seven different age cohorts (697 individuals from 10 to 109 years old) revealed age-related changes in the 3'APOB-VNTR genotype pool. By recoding the 3'APOB-VNTR alleles into three size-classes (small, S, 26-34 repeats; medium, M, 35-39 repeats; large, L, 41-55 repeats), an age-related convex trajectory of the frequency of SS homozygotes was found. The frequency of SS in the genotype pool increased from the group aged 10-19 years (3.06 +/- 1.74%) to that aged 40-49 years (8.51 +/- 4.07%). Then it declined reaching the minimum value in centenarians (1.58 +/- 0.90%). The observed trajectory is in agreement with that expected by assuming crossing of mortality curves relevant to subgroups of individuals having different genotypes.

Adolescent↗
PubMed1998

How heritable is individual susceptibility to death? The results of an analysis of survival data on Danish, Swedish and Finnish twins.

Molecular epidemiological studies confirm a substantial contribution of individual genes to variability in susceptibility to disease and death for humans. To evaluate the contribution of all genes to susceptibility and to estimate individual survival characteristics, survival data on related individuals (eg twins or other relatives) are needed. Correlated gamma-frailty models of bivariate survival are used in a joint analysis of survival data on more than 31,000 pairs of Danish, Swedish and Finnish male and female twins using the maximum likelihood method. Additive decomposition of frailty into genetic and environmental components is used to estimate heritability in frailty. The estimate of the standard deviation of frailty from the pooled data is about 1.5. The hypothesis that variance in frailty and correlations of frailty for twins are similar in the data from all three countries is accepted. The estimate of narrow-sense heritability in frailty is about 0.5. The age trajectories of individual hazards are evaluated for all three populations of twins and both sexes. The results of our analysis confirm the presence of genetic influences on individual frailty and longevity. They also suggest that the mechanism of these genetic influences may be similar for the three Scandinavian countries. Furthermore, results indicate that the increase in individual hazard with age is more rapid than predicted by traditional demographic life tables.

Adult↗
PubMed1997

How frailty models can be used for evaluating longevity limits: taking advantage of an interdisciplinary approach.

In this paper we discuss an approach to the analysis of mortality and longevity limits when survival data on related individuals with and without observed covariates are available. The approach combines the ideas of demography and survival analysis with methods of quantitative genetics and genetic epidemiology. It allows us to analyze the genetic structure of frailty in the Cox-type hazard model with random effects. We demonstrate the implementation of this strategy to survival data on Danish twins. We then evaluate the resulting lower bounds for biological limits of human longevity. Finally, we discuss the limitations of this approach and directions of further research.

Aged↗
PubMed1996

[Mortality among twins after the age of six: the programming hypothesis versus the twin-method].

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.

Adolescent↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1989

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↗
PubMed1986

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↗
PubMed1985

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↗