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Lecture Abstract:
Over the past decade, we have discovered that like mammals, the nematode C. elegans uses an insulin signaling pathway to control its metabolism and longevity. This analysis has revealed striking conservation of molecular mechanisms at many steps in the pathway, suggesting that insulin regulation of longevity and metabolism is ancient and universal. This discovery that an insulin pathway regulates lifespan and metabolism immediately suggested a concordance with studies of mammalian lifespan: it is reminiscent of the increase in mouse and rat lifespan that is induced by low calorie diets, which reduce insulin levels. We have also found that insulin signaling in the nervous system is key to lifespan. The regulation of when we die from hormones released by the brain is analogous to the regulation of other life stage events, such as puberty and menopause, by signaling centers from the brain such as the hypothalamus. The molecular genetic dissection of the insulin pathway has also been important for understanding and treating diabetes, a disease of insulin signaling deficits. Our finding that the major effector of insulin signaling in C. elegans is the FOXO transcription factor conserved in mammals refocused the mammalian insulin signaling field on those transcriptional cascades from the previous focus on glucose transporter responses. The new genes of the insulin pathway that have emerged from these studies represent new targets for diabetes drug development. Functional genomic analyses using RNAi libraries of every C. elegans gene now allows a systematic study of metabolism and aging. We have surveyed the 18,000 genes for their action in regulation of longevity and fat deposition. This analysis gives a global view of the molecular machines that operate in these pathways. In the case of aging, it is now clear that insulin signaling is the most potent gene inactivation that can increase C. elegans lifespan. These gene lists reveal the many steps in energy regulation, including metabolic enzymes that store and mobilize fat, as well as hormonal signals from fat stores to satiety centers in the brain. A neuroendocrinology of energy balance and longevity is emerging from these studies.

Gary Ruvkun is co-director of the MBL’s Molecular Biology of Aging Course and a professor of genetics at Harvard Medical School. His research on the nematode worm, C. elegans, led to numerous discoveries in the fields of microRNA, RNA interference, and longevity.

Dr. Ruvkun received an A.B. in biophysics from the University of California at Berkeley in 1973 and a Ph.D. in Biophysics from Harvard University in 1982. Through 1985 he conducted postdoctoral research with Bob Horvitz, who received the 2002 Nobel Prize in Physiology or Medicine, at Massachusetts Institute of Technology, and Walter Gilbert, a recipient of the 1980 Nobel Prize in Chemistry, at Harvard. He joined the staff at Harvard Medical School in 1985.

In addition to his research, Dr. Ruvkun is editor of the journal Developmental Biology, and is part of the Harvard Microbial Science Initiative Organizing Committee and the Harvard Origins of Life Initiative. He was on the National Institutes of Health Advisory Council on Aging between 2004 and 2007.

Among Dr. Ruvkun’s numerous honors include an NIH Merit Award, a Benjamin Franklin Medal, a Warren Triennial Prize and, most recently, a Gairdner International Prize. He gave the 2003 Presidential Lecture at the Society for Neuroscience Annual Meeting as well as the 2003 NIH Director's Lecture.

Gerald Weissmann will introduce Dr. Ruvkun. Dr. Weissmann received his M.D. from New York University (NYU) School of Medicine in 1954 and served post-doctoral fellowships in Biochemistry with Severo Ochoa (NYU) and Cell Biology with Dame Honor Fell (Cambridge). From 1973 to 2000, he served as Director of NYU School of Medicine's Division of Rheumatology and is currently Research Professor of Medicine (Emeritus) and the Director of the Biotechnology Study Center at NYU School of Medicine and is editor-in chief of The FASEB Journal. A former president of the American College of Rheumatology and the Harvey Society, Dr. Weissmann is also a Fellow of the AAAS and the New York Academy of Sciences. He was elected to the Accademia Nazionale dei Lincei (Rome) in 2002. Dr. Weissmann is on the Advisory Board of the Ellison Medical Foundation. He was Co-Founder (with E.C. Whitehead) and a Director of The Liposome Company from 1982 to 2000. Dr. Weissmann has a longtime association with the MBL. He is a former investigator and instructor in the MBL's Physiology Course and is currently an MBL Trustee in the Class of 2009. Dr. Weissmann has received the Paul Klemperer Medal, the Princeton Liposome Research Award, the Presidential Gold Medal of the American College of Rheumatology, the MBL Centennial Award (with James Wyngaarden and DeWitt Stetten, Jr.), the Gruber Cancer Research award (with Emil Frei, III), and the Alessandro Robecchi International Prize for Rheumatology in 1972. His eight books of essays range from The Woods Hole Cantata (1985) to Galileo's Gout (2007).

About the Joshua Lederberg Lecture:
The Joshua Lederberg Lecture is sponsored by The Ellison Medical Foundation in honor of Joshua S. Lederberg, Ph.D., Nobel Laureate and founding Chair of the Ellison Medical Foundation Scientific Advisory Board. Dr. Lederberg's insight, energy, and creativity were essential to the creation and successful development of The Ellison Medical Foundation over its first ten years.