Sinclair

David Sinclair is an Australian biologist and genetics professor best known for his research into the biology of lifespan extension and treatment of the diseases associated with aging. He is the Co-Director of the Paul F. Glenn Laboratories for the Biological Mechanisms of Aging at Harvard Medical School, where he has been a tenured professor since 1999.

After earning his Bachelor of Science degree with Honors from the University of New South Wales, Sydney, Sinclair received a Ph.D. in Molecular Genetics in 1995 and then completed postdoctoral research at the Massachusetts Institute of Technology in the lab of Leonard Guarente.

In Guarente’s lab, Sinclair’s work contributed to the discovery that genome instability induces changes in gene regulation that may drive the aging process in mammals. At Harvard, Sinclair’s laboratory studies molecular mechanisms and small molecules that slow the pace of aging and age-related diseases. His focus is on longevity genes and pharmacological approaches that increase the body’s natural defenses against diseases such as cancer, Alzheimer’s, infertility, Type II diabetes and obesity. Approaches include biophysics, biochemistry, cell culture, and mouse models. In 2002, Sinclair’s lab discovered a key role of NADᶧ biosynthesis in aging. Sinclair is also credited with the “Mitochondrial Oasis Hypothesis,” which asserts that the energetics and NADᶧ content of mitochondria determine cell survival in the face of genotoxic stress such as DNA damage, independent of the state of the cytoplasm or nucleus. In 2004, Sinclair co-founded Sirtis Pharmaceuticals with Christopher Westphal to develop drugs that harness the body’s own defenses against diseases of aging. In 2007, GlaxoSmithKline acquired Sirtis for $720 million.

Sinclair has 94 publications in peer-reviewed journals since 2002. Some of the most recent include: “Measuring PGC-1α and its acetylation status in mouse primary myotubes.” Gomes AP, Sinclair DA. Methods Mol Biol. 2015;1241:49-57. doi: 10.1007/978-1-4939-1875-1_5; “Dietary restriction involves NAD(+) -dependent mechanisms and a shift toward oxidative metabolism.” Moroz N, Carmona JJ, Anderson E, Hart AC, Sinclair DA, Blackwell TK. Aging Cell. 2014 Dec;13(6):1075-85. doi: 0.1111/ acel.12273. Epub 2014 Sep 25. “Aging-like phenotype and defective lineage specification in SIRT1-deleted hematopoietic stem and progenitor cells.” Rimmelé P, Bigarella CL, Liang R, Izac B, Dieguez-Gonzalez R, Barbet G, Donovan M, Brugnara C, Blander JM, Sinclair DA, Ghaffari S. Stem Cell Reports. 2014 Jun 6;3(1):44-59. doi: 10.1016/j.stemcr.2014.04.015. eCollection 2014 Jul 8; and “SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass.” Mercken EM, Mitchell SJ, Martin-Montalvo A, Minor RK, Almeida M, Gomes AP, Scheibye-Knudsen M, Palacios HH, Licata JJ, Zhang Y, Becker KG, Khraiwesh H, González-Reyes JA, Villalba JM, Baur JA, Elliott P, Westphal C, Vlasuk GP, Ellis JL, Sinclair DA, Bernier M, de Cabo R. Aging Cell. 2014 Oct;13(5):787-96. doi: 10.1111/acel.12220. Epub 2014 Jun 16.

Sinclair has received more than two dozen awards, including the Australian Commonwealth Prize, a Helen Hay Whitney Fellowship, a Leukemia and Lymphoma Fellowship, the Merck Prize, a MERIT Award from the National Institutes of Health, the Genzyme Outstanding Achievement in Biomedical Science Award, the Denham Harman Award in Biogerontology, and was included in the 2014 TIME magazine list of the 100 “most influential people in the world.”