Effects of the APOE Polymorphism and Age Dynamics of Physiological Variables on Mortality: Insights from the Genetic Stochastic Process Model of Aging

Konstantin G. Arbeev, Duke University
Svetlana V. Ukraintseva, Duke University
Alexander Kulminski, Duke University
Liubov Arbeeva, Duke University
Irina V. Culminskaya, Duke University
Deqing Wu, Duke University

We evaluated effects of the APOE polymorphism (carriers versus noncarriers of the e4 allele) and age trajectories of total cholesterol and diastolic blood pressure on mortality risk in the Framingham Heart Study (original cohort). We found that long-lived carriers and noncarriers have different average age trajectories and long-lived individuals have consistently higher levels and less steep declines at old ages compared to short-lived individuals. We applied the stochastic process model of aging aimed at joint analyses of genetic and nongenetic subsamples of longitudinal data and estimated different aging-related characteristics for carriers and noncarriers which otherwise cannot be evaluated from data. We found that such characteristics as adaptive capacity, mean allostatic trajectories, and U-shapes of mortality as functions of physiological variables differ in carriers and noncarriers. Such observations strongly indicate the presence of a genetic component in respective aging-related mechanisms. Such differences may contribute to patterns of allele- and sex-specific mortality.