Cynthia J. Kenyon
University of California, San Francisco
Election Year: 2003
Primary Section: 26, Genetics
Secondary Section: 22, Cellular and Developmental Biology
Membership Type: Member
Our laboratory discovered that the C. elegans homolog of the human insulin and IGF-1 receptors regulates the lifespan of C. elegans, thus demonstrating that aging is controlled hormonally. We showed that inhibiting receptor activity doubles lifespan and greatly extends youthfulness by changing the expression of downstream antioxidant, antimicrobial, chaperone, and metabolic genes. Our work has now led to the discovery that mammalian aging is also regulated hormonally by insulin and IGF-1 endocrine systems, and has catalyzed a fundamental shift in the way we view the aging process, from one that is inevitable and intractable to one that is plastic and subject to regulation. These long-lived mutants have been found to be resistant to several age-related diseases. Thus our work has raised the possibility of a new therapeutic strategy based on the ability to postpone the onset of age-related disease by slowing the aging process itself. By altering two hormone systems in the same animal-the insulin/IGF-1 system, and a second pathway we discovered that is controlled by the reproductive system, we can increase the lifespans of healthy, vigorous animals by six fold, demonstrating that truly remarkable extensions lifespan are possible.