Abstract: Series 100, Lecture 2

The Harvey Lectures Series 100 (2004—2005)

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Lecture #2: Thursday, November 18, 2004 — Time and Location

From Worms to Mammals: Regulation of Lifespan by Insulin/IGF-1 Signaling

Cynthia Kenyon, PhD

Herbert Boyer Professor of Biochemistry and Biophysics
Director, Hillblom Centers for the Biology of Aging
Department of Biochemistry and Biophysics

University of California, San Francisco

San Francisco, California

Aging has long been assumed to be a passive consequence of molecular wear and tear, counteracted by the force of natural selection. But it's not so simple. Our discoveries in C. elegans have led to the realization that the aging process, like everything else in biology, is under exquisite regulation, in this case, by a complex, multifaceted and evolutionarily conserved insulin/IGF-1 endocrine system. Changing single genes in this system can prolong youthfulness dramatically and double the lifespan of the C. elegans. Signals from the reproductive system also influence lifespan, and if reproductive signaling and insulin/IGF-1 signaling are altered in the same animals, lifespan is increased by six fold. We have found that perturbing insulin/IGF-1 signaling increases lifespan by influencing downstream transcriptional regulators, which, in turn, coordinate the expression of a wide variety of subordinate genes, including stress response, antimicrobial, and novel genes, whose activities act in a cumulative fashion. Some of these subordinate genes can also influence the rate of onset of protein-aggregation disease. In this way, this endocrine system can couple the natural aging process to susceptibility to an age-related disease.