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 mechanisms that control human longevity. The main obstacle in human studies is that the opportunities for direct experiments with humans are limited and therefore data collection through observations, i.e., epidemiological methods, are 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 environmental and social confounding. To cope with environmental and social confounding, this paper suggests two robust exploratory tests with low risk of artifactual results, based on the analysis of two kinds of genetic influences on human longevity: (1) parental consanguinity, which increases the proportion of homozygotes in offspring, leading to the expression of recessive traits and an increased incidence of multifactorial traits (via increased variance for genetic liability distribution); and (2) advanced paternal age at conception, which is known to be one of the major sources of new mutations in human populations. This paper also describes methodologies to study the role of environmental factors (shared familial environment and early seasonal events) as determinants of human longevity.