Dr. Guarente received his B. S. from MIT and his Ph. D. at Harvard, under the supervision of Jon Beckwith. He trained as a postdoctoral fellow at...
Dr. Guarente received his B. S. from MIT and his Ph. D. at Harvard, under the supervision of Jon Beckwith. He trained as a postdoctoral fellow at Harvard with Mark Ptashne and has been on the faculty of MIT since 1981, where he is the Novartis Professor of Biology. He is author of more than 190 scientific papers.
His lab first discovered the novel biochemical activity of the SIR2 gene product – NAD-dependent deacetylase. This activity suggested that SIR2 was a regulator that sensed metabolism, thereby linking diet to the regulation of aging. This finding provided a possible answer to the longstanding question of how calorie restriction (CR) works mechanistically to slow aging. It would also explain why SIR2 genes are universal in fighting aging – being able to link the pace of aging to diet confers a selective advantage. His lab quickly established a system of studying CR in yeast and showed that moderate CR extended the life span in yeast mother cells by activating SIR2. This activation requires up-regulation of electron transport, which increases the NAD/NADH ratio. It was subsequently shown by others that life span extension by CR in Drosophila requires the fly SIR2 gene.
In addition, his lab has linked mammalian SIRT proteins (sirtuins) to CR more directly by showing that SIRT4 is regulated by CR to govern glucose homeostasis, and that SIRT1 is required for at least one effect of CR in mice, enhanced physical activity. He is intrigued by the possibility that sirtuins are agents that can modulate the major diseases of aging in response to CR, thereby opening a new therapeutic strategy. He would like to test whether changes in the activity of SIRT1 (and possibly other SIRT genes) can mitigate diseases broadly in mouse models, and work through the mechanisms involved. These studies may potentiate new categories of drugs to combat diseases and extend human health span