Senior Scholar Award in Aging
Cynthia J. Kenyon, Ph.D.
University of California - San Francisco

Can the Heat-Shock Response Extend the Lifespan of the Mouse?

During the last decade, remarkable discoveries in the small roundworm C. elegans have shown that aging is regulated hormonally by a regulatory system similar to that of the human insulin and IGF-1 (insulin-like growth factor) endocrine systems. This same endocrine system governs the aging process in fruit flies, and, recent studies show, in mice as well. Together these findings suggest that this system arose early in evolution, before the ancestors of humans and these of other animals diverged from one another. Thus, this system may regulate lifespan in humans as well. One of the ways in which this conserved regulatory system appears to influence lifespan is by increasing the production of proteins that protect cells from oxidative and other forms of damage. Overexpressing some of these genes can lengthen the lifespans of invertebrates. In these studies, we plan to overexpress similar genes in mice, to ask whether this, too, will extend lifespan.

Many diseases, such as cancer and protein-aggregation diseases, are called “diseases of aging” because they occur with a much higher frequency in older individuals. The frequency of these diseases is linked to physiological, not chronological, age. Thus two-year old mice experience high rates of cancer, whereas two-year old dogs or humans, which have much longer mean lifespans, do not. What makes old animals and humans more susceptible to these diseases? One possibility is that damage to cellular proteins can potentiate these diseases. Interestingly, worms and rats that live long because of changes in their insulin/IGF-1 hormone signaling systems, are less susceptible to protein aggregation diseases, and cancer, respectively. To ask whether changes in stress response proteins might link the process of normal aging to age-related diseases, we plan to test the susceptibility of mice that have higher levels of stress-response proteins to several different age-related diseases.

Contact Dr. Kenyon.