Harvard Medical School
Improving survival in space: The Sinclair lab is working on improving the resiliance of human and non-human life beyond Earth. We utilize genetic and pharmacological means to identify technologies that provide resistance of lifeforms to insults, including long-term exposure to ionizing radiation and low gravity. One of our major focuses is on maintaining and improving human health beyond Earth. A key asset is a mouse strain we have engineered to simulate the conditions of space travel, resulting in impairments in cognition, bone density and muscle strength among others. Using this model and other systems we have identified novel agents and approaches that show promise in slowing and even reversing the long-term impact of space travel and colonization.
Publications
North BJ, Rosenberg MA, Jeganathan KB, Hafner AV, Michan S, Dai J, Baker DJ, Cen Y, Wu LE, Sauve AA, van Deursen JM, Rosenzweig A, Sinclair DA. SIRT2 induces the checkpoint kinase BubR1 to increase lifespan. EMBO J. 2014 33:1438-51. PMCID: PMC4194088
Gomes, A.P., Price N.L., Lin A.Y, Moslehi, J., Montgomery, M., Rajman, L., White, J.P., Teodoro, J.S., Wran, C.D., Hubbard, B.P., Mercken, E.M., Palmeira, C., de Cabo, R., Rolo, A.P., Turner, N., Bell, E. and Sinclair, D.A. Declining NAD+ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell 2013 155(7):1624-38. PMCID: PMC4076149
Hubbard, BP., Gomes, AP., Dai, H., Li, J., Case, AW., Considine, T., Riera, TV., Lee, JE., E, Sy., Lamming, DW., Pentelute, BL., Schuman, ER., Stevens, LA., Ling, AJ., …. Ellis, JL., Vlasuk, GP., and Sinclair, DA. Evidence for a common mechanism of SIRT1 regulation by allosteric activators. 2013. Science, Vol. 339: 1216-1219. PMID: 23471411
Armour, SM., Bennett, EJ., Braun, CR., Zhang, XY., McMahon, SB., Gygi, SP., Harper, JW., and Sinclair, DA. A high-confidence interaction map identifies SIRT1 as a mediator of acetylation of USP22 and the SAGA coactivator complex. 2013. Molecular Cell Biology, epub, Feb 4. PMCID: PMC3624249
Rascón B, Hubbard BP, Sinclair DA, Amdam GV. The lifespan extension effects of resveratrol are conserved in the honey bee and may be driven by a mechanism related to caloric restriction. Aging, 2012, 4(7):499-508. PMCID: PMC3433935