Leonard Pershing Guarente, Ph.D., MIT Novartis Professor of Biology, MIT, Cambridge, MA, USA
Leonard Guarente formerly studied gene regulation in eukaryotes (1980-1995). In these early studies, his lab first purified the TATA-binding protein TBP and
cloned the gene, discovered UASs, identified the first heteromeric transcription factor (HAP2/3/4/5), and provided the first evidence for coactivators.
He then turned his studies to the mechanism of aging and its regulation using yeast and subsequently higher organisms.
His lab began studying aging in 1991 and showed SIR2 is a critical longevity gene in yeast and C. elegans
His lab discovered the novel biochemical activity of the SIR2 gene product ??? NAD-dependent protein deacetylase.
This activity suggested that SIR2 might link diet to aging, addressing the longstanding question of how calorie restriction (CR) slows aging.
His lab established a system to study CR in yeast and showed that CR extended the life span in yeast mother cells by activating SIR2.
More recently, his lab has made several findings regarding the mammalian ortholog of SIR2, SIRT1. Importantly, it controls several physiological processes impacted by CR.
First, Sirt1 renders cells stress resistant by inhibiting pro-apoptotic transcription factors p53 and forkhead.
Second, Sirt1 also regulates many metabolic functions influenced by diet, for example the mobilization of fat from white adipocytes upon food limitation, and
the increase in muscle maintenance during CR. These findings show that the life and health extension by CR are not passive events, but result from the activation of Sirt1,
which then impacts on cellular and organismal processes to deliver the benefits.
More recently, his and other labs have linked SIRT1 to protection against cardiovascular disease, diabetes, cancer, neurodegenerative disease and osteoporosis in mouse models.
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.
His book Ageless Quest (Cold Spring Harbor Press, 2003) describes the pathway of discovery of SIR2 as a key regulator of life span in response to diet.