Journals of Gerontology: BioloGical ScienceS

THE world ’ s population is rapidly aging and this has enormous implications for society. Therefore, it is vitally important to understand how and why we age in order to enhance our odds of aging with better health and less disability ( 1). Genetics may account for 10 % – 50 % of the variability in human life span, depending upon the population, but little is known about the effector genes ( 2 – 6). Studies of model organisms have identifi ed several evolutionarily conserved biological pathways that have major infl uence on aging and age-related traits ( 6 – 8). Daf-16, an evolutionarily conserved gene in nematodes was identifi ed among early candidates as a potential modulator of human aging ( 8). On this basis, we tested the hypothesis that the daf-16 human homologue, FOXO3, a gene on chromosome 6 that codes for a forkhead Box O transcription factor, might be important in human aging and longevity ( 9; see Figure 1). W