Epidemiology of human longevity: The search for appropriate methodology

In contrast to the remarkable progress in genetics of aging of such animal models as yeast, nematodes, and Drosophila, little is known about mechanism s that control human longevity. The main obstacle in human studies is that the opportunities for direct experiments with humans are limited and theref ore data collection through observations, i.e., epidemiological methods, ar e particularly important. To advance scientific knowledge in this area, it is also important to broaden the arsenal of concepts and methods for human longevity studies and to develop alternative tactics to cope with environme ntal and social confounding. To cope with environmental and social confound ing, this paper suggests two robust exploratory tests with low risk of arti factual results, based on the analysis of two kinds of genetic influences o n human longevity: (1) parental consanguinity, which increases the proporti on of homozygotes in offspring, leading to the expression of recessive trai ts and an increased incidence of multifactorial traits (via increased varia nce for genetic liability distribution); and (2) advanced paternal age at c onception, which is known to be one of the major sources of new mutations i n human populations. This paper also describes methodologies to study the r ole of environmental factors (shared familial environment and early seasona l events) as determinants of human longevity.