Leonard Guarente, Ph.D.
Director at the Leonard Guarente lab at MIT, Novartis Professor of Biology
Since 1982 Leonard has led the Glenn Center for the Biology of Aging Research at MIT, where his research has focused on the genetic and molecular basis of aging — first in model organisms and now in mouse models and humans.
Guarente is best known for his research on the role of sirtuins, a class of proteins that play a key role in regulating metabolic systems in response to stress and aging. In particular, Guarente was the first to identify SIR2 as the gene that controls aging in yeast cells. The mammalian version of SIR2, SIRT1 (and its associated proteins), has since been shown by Guarente and others to play a key role in longevity and metabolic function in mammals.
“What many scientists have repeatedly demonstrated is that if one increases the activity of sirtuins under these [stress or aging] conditions in the laboratory, health benefits accrue to the animal,” Guarente said. “For example, old mice are less prone to diabetes. This has been repeated across multiple animal species, which underscores that sirtuins will be important targets to promote metabolic health in humans as well.”
Guarente’s lab is currently focused on understanding how the human brain aging transcriptional program works and how it is regulated, to pave the way for anti-aging therapeutic strategies for neurodegenerative disease. His team is particularly interested in the role of sirtuins in human brain aging and neurodegeneration. They are investigating the role of sirtuin levels and also sirtuin polymorphisms in regulating human brain aging rates and neurodegenerative disease risk, as well as looking broadly using unbiased genome-wide strategies.
Guarente is the Novartis Professor of Biology at MIT. He holds a B.S. from MIT and a Ph.D. from Harvard.
We combine comprehensive bioinformatics analyses with functional analyses of pathways and genes to study aging in humans and mice. We apply these approaches to identify the major pathways and genes involved in the aging of certain brain regions. We are also studying muscular dystrophy and muscle loss with aging. Ultimately, our findings may guide studies in other organs and lead to a systemic understanding of mammalian aging.
aging critical publications
Wellman AS, Metukuri MR, Kazgan N, Xu X, Xu Q, Ren NSX, Czopik A, Shanahan MT, Kang A, Chen W, Azcarate-Peril MA, Gulati AS, Fargo DC, Guarente L, Li X (2017) Intestinal Epithelial Sirtuin 1 Regulates Intestinal Inflammation During Aging in Mice by Altering the Intestinal Microbiota. Gastroenterology. 153(3):772-786. doi: 10.1053/j.gastro 2017.05.022. Epub 2017 May 26.
Zainabadi K, Liu CJ, Caldwell ALM, Guarente L (2017) SIRT1 is a positive regulator of in vivo bone mass and a therapeutic target for osteoporosis. PLoS One. 12(9):e0185236. doi: 10.1371/journal.pone.0185236.
Dellinger RW, Santos SR, Morris M, Evans M, Alminana D, Guarente L, Marcotulli E (2017) Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study. NPJ Aging Mech Dis.;3:17. doi: 10.1038/s41514-017-0016-9.
Das A*, Huang GX,*, Bonkowski, MS, Longchamp, A, Li C, Schultz MB, Kim LJ, Osborne B, Joshi S, Lu Y, Treviño-Villarreal JH, Kang MJ, Hung TT, Lee B, Williams EO, Igarashi M, Mitchell JR, Wu LE, Turner N, Arany Z, Guarente L, and Sinclair DA (2018) Impairment of an endothelial NAD+-H2S signaling network is a reversible cause of vascular aging. Cell 173, 74-89.
Herskovits AZ, Hunter T, Maxwell, N, Pereira KMK, Whittaker, CA Valdez G, Guarente L (2018). SIRT1 deacetylase and neuromuscular aging in amyotrophic lateral sclerosis. Aging Cell (2018) e12839.