The Genetics of Human Longevity

Human longevity is at least partly heritable, and the progeroid syndromes of accelerated aging have genetic causes. In addition, there are human homologues to many of these genes that affect lifespan in model organisms. In people, longevity genes might slow the rate of age-related changes in cells, increase resistance to environmental stresses like infection and injury, and reduce the risk of many age-related conditions. This article reviews several genetic pathways that appear to be involved in the aging process and longevity, including genes involved in the progeroid syndromes, telomeres and telomerase, caloric restriction, stress resistance and oxidative damage, mitochondrial DNA, insulin signaling, and inflammation. It concludes with a discussion of the analytic challenges that face investigators in this area. The Genetics of Human Longevity 2 Genetic differences partly explain why long-lived people cluster in families. Studies comparing life expectancy in twins and other family members have found that up to 25% of the variation in human lifespan is heritable (1, 2); the remaining 75 % is due t