Longevity Genes: From Primitive Organisms to Humans

AN early indication that not only environmental and behavioral factors but also genes can influence the rate of aging of individuals within a species comes from the identification of long-lived strains of fruit flies (1,2). A more recent indication was the observation that, among breeds of dogs, longevity inversely correlates with body size (3,4). Both of these observations suggest the existence of genes that can affect longevity. Such genes have been variously called longevity assurance genes, longevity enabling genes, longevity-associated genes, longevity genes, or gerontogenes. In this report we will use the term “longevity genes.” Because longevity genes may mean different things to different people, it is important to sort out the nuances of different kinds of genes at the beginning. Longevity genes may manifest themselves in a variety of ways, including the following: ... Whereas the over-expression or ablation of almost any gene may decrease life expectancy, the intention here is to focus on genetic changes that increase life expectancy or shorten life expectancy, if they do so with indications of premature aging. We suggest that these genes be sorted into distinct theoretical categories. Seven categories are described below with comments, where appropriate, about the nature and quantity of human genes that might be found in these categories. [Since this workshop, George Martin has published 2 review articles that also review classes of gene action with respect to longevity (5,6).]