David Sinclair, Ph.D., AO
Professor in the Department of Genetics at Harvard Medical School & co-Director of the Paul F. Glenn Center for the Biological Mechanisms of Aging
Dr. Sinclair is a co-founder of several biotechnology companies (Sirtris, Ovascience, Genocea, Cohbar, MetroBiotech, ArcBio, Life Biosciences, Liberty Biosecurity) and is on the boards of several others. He is also co-founder and co-chief editor of the journal, Aging. His work is featured in five books, two documentary movies, 60 Minutes, Morgan Freeman’s “Through the Wormhole” and other media. He is an inventor on 35 patents and has received more than 25 awards and honors.
Sirtuins and NAD+. Sirtuins are protein-modifying enzymes that respond to changing NAD+ levels and to caloric restriction (CR) with associated interests in chromatin, energy metabolism, mitochondria, learning and memory, neurodegeneration, and cancer.
The Sinclair lab was the first one to identify a role for NAD+ biosynthesis in regulation of lifespan and first showed that sirtuins are involved in CR in mammals. Sinclair has identified molecules that activate SIRT1 (a type of sirtuin) such as resveratrol and studied how they improve metabolic function using a combination of genetic, enzymological, biophysical and pharmacological approaches.
Sinclair has also demonstrated that miscommunication between the mitochondrial and nuclear genomes is a cause of age-related physiological decline and that relocalization of chromatin factors in response to DNA breaks may be a cause of aging.
Awards and Honors
The CSL Prize, The Australian Commonwealth Prize, Thompson Prize, Helen Hay Whitney Postdoctoral Award, Merck Prize, Genzyme Outstanding Achievement in Biomedical Science Award, Bio-Innovator Award, Nathan Shock Award from the National Institutes of Health, Ellison Medical Foundation Junior and Senior Scholar Awards, Australian Medical Research Medal, The Frontiers in Aging and Regeneration Award, Charles Hood Fellowship, Leukemia Society Fellowship, Ludwig Scholarship, Harvard-Armenise Fellowship, American Association for Aging Research Fellowship, David Murdock-Dole Lectureship, Fisher Honorary Lectureship, Les Lazarus Lectureship, Top 100 Australian Innovators, and TIME magazine’s list of the “100 most influential people in the world”.
aging critical publications
Li, J., Bonkowski MS, Moniot S, Zhang D, Hubbard BP, Ling, AJY, Rajman LA, Qin B., Lou Z., Gorbunova V, L Aravind, Steegborn C. and Sinclair, DA. A conserved NAD+ binding pocket that regulates protein-protein interactions during aging. 2017 Science, 355(6331):1312-1317.
Mitchell, S.J., Bernier, M. - 11 authors - Elliås J.L., Elliott, P., Frederick, D.W., Bohr, V., Brenner, C., Sinclair, D.A., Sauve, A.A., Baur, J.A., and de Cabo, R. Impact of chronic nicotinamide supplementation on health and survival in mice. 2017 Cell Metabolism, 27, 667–676
Das, A., Huang, G.X., Bonkowski, M.S., Longchamp, A., Li, C., Schultz, M.B., 14 authors, Guarente, L.P., Sinclair, D.A. Impairment of an endothelial NAD+-H2S signaling network is a reversible cause of vascular aging. 2018. Cell, 173(1):74-89
Longchamp, A., Mirabella, T. Das, A., Hine, C., Brace, L., Ben-Sahra, I., Knudsen, N, Treviño-Villarreal, J.H., Mejia, P., Tao, M., Sharma, G., Wang, J., Corpataux, J-M., Haefliger, J.A. Ahn, KH., Lee, C-H., Brendan D. Manning, Sinclair, D.A. Christopher Chen, C. Keith Ozaki, and James R. Mitchell. Amino acid restriction triggers angiogenesis via GCN2/ATF4 regulation of VEGF and H2S production. 2018. Cell, 173(1):117-129
Rajman L., Chwalek, K. and Sinclair, DA. Therapeutic potential of NAD-boosting molecules: the in vivo evidence. 2018. Cell Metabolism, 27(3):529-547