Genes and Cells that Influence the Rate of Aging in C. elegans
Cynthia Kenyon (Department of Biophysics and Biochemistry, University of California, San Francisco)
(January 20, 2010 10:30 AM - 11:20 AM)
Aging has long been assumed to be a passive consequence of molecular wear and tear. But it's not so simple. Genetic studies have shown that the aging process, like everything else in biology, is under exquisite regulation, in this case, by a complex, multifaceted hormonal and transcriptional system that affects aging in many species, including humans. In 1993, we showed that changing a single gene in the small roundworm C. elegans can double its lifespan. This gene encodes an insulin/IGF-1 like receptor, which indicates that aging is regulated hormonally. By manipulating genes and cells, we have now been able to extend the lifespan and period of youthfulness of healthy, active C. elegans by six times. We have found that signals from the reproductive system and sensory neurons influence the lifespan of C. elegans, and these processes, too, may be evolutionarily conserved. These signals act, at least in part, to control the expression of a wide variety of subordinate genes, including metabolic, stress response, antimicrobial, and novel genes, whose activities act in a cumulative fashion to determine the lifespan of the animal. Some of these subordinate genes can also influence the progression of age-related disease, including cancer. In this way, this hormone system couples the natural aging process to age-related disease susceptibility.