David Sinclair, Ph.D.

David Sinclair, Ph.D.

David A. Sinclair, Ph.D. is a Professor in the Department of Genetics at Harvard Medical School and co-Director of the Paul F. Glenn Center for the Biological Mechanisms of Aging. He is best known for his work on understanding why we age and how to slow its effects. He obtained his Ph.D. in Molecular Genetics at the University of New South Wales, Sydney in 1995. He worked as a postdoctoral researcher at M.I.T. with Dr. Leonard Guarente where he co discovered a cause of aging for yeast as well as the role of Sir2 in epigenetic changes driven by genome instability. In 1999 he was recruited to Harvard Medical School where his laboratory’s research has focused primarily on understanding the role of sirtuins in disease and aging, with associated interests in chromatin, energy metabolism, mitochondria, learning and memory, neurodegeneration, and cancer. He has also contributed to the understanding of how sirtuins are modulated by endogenous molecules and pharmacological agents such as resveratrol. Dr. Sinclair is co-founder of several biotechnology companies (Sirtris, Ovascience, Genocea, Cohbar, MetroBiotech, ArcBio, 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 including the CSL Prize, The Australian Commonwealth Prize, Thompson Prize, Helen Hay Whitney Postdoctoral Award, Charles Hood Fellowship, Leukemia Society Fellowship, Ludwig Scholarship, Harvard-Armenise Fellowship, American Association for Aging Research Fellowship, Nathan Shock Award from the National Institutes of Health, Ellison Medical Foundation Junior and Senior Scholar Awards, Merck Prize, Genzyme Outstanding Achievement in Biomedical Science Award, Bio-Innovator Award, David Murdock-Dole Lectureship, Fisher Honorary Lectureship, Les Lazarus Lectureship, Australian Medical Research Medal, The Frontiers in Aging and Regeneration Award, Top 100 Australian Innovators, and TIME magazine’s list of the “100 most influential people in the world”.

Direct Contact

Harvard Medical School
Department of Genetics
77 Avenue Louis Pasteur
Boston MA 02115 USA
Telephone: (617) 432-3931
Fax: (617) 432-6225
Lab Website: http://genetics.med.harvard.edu/sinclair/

Selected Publications

Ultrastructure of the liver microcirculation influences hepatic and systemic insulin activity and provides a mechanism for age-related insulin resistance
Mohamad M, Mitchell SA, Lindsay Wu, Alessandra Warren, White, MY, Cordwell SJ, Boyer D, Nines D, Mach J, Solon-Biet SM, Hilmer SN, Sinclair DA, Simpson SJ, de Cabo R, Le Couteur D, Cogger V. 2016. Aging Cell, in press.

Restoration of normal embryogenesis by mitochondrial supplementation in pig oocytes exhibiting mitochondrial DNA deficiency.
Cagnone GL, Tsai TS, Makanji Y, Matthews P, Gould J, Bonkowski MS, Elgass KD, Wong AS, Wu LE, McKenzie M, Sinclair DA, John JC. Sci Rep. 2016 Mar 18;6:23229. doi: 10.1038/srep23229.
PMID: 26987907 Free PMC Article

Genome Instability.
Rajman LA, Cassidy L, Sinclair DA. (2015).  In Molecular and Cellular Biology of Aging. J. Vijg, J. Campisi and G. Lithgow. Washington, DC. The Gerontological Society of America.

C. elegans lifespan extension by osmotic stress requires FUdR, base excision repair, FOXO, and sirtuins.
Anderson EN, Corkins ME, Li JC, Singh K, Parsons S, Tucey TM, Sorkaç A, Huang H, Dimitriadi M, Sinclair DA, Hart AC. Mech Ageing Dev. 2016 Mar;154:30-42. doi: 10.1016/j.mad.2016.01.004. Epub 2016 Feb 22. PMID: 26854551

When stem cells grow old: phenotypes and mechanisms of stem cell aging.
Schultz MB, Sinclair DA. Development. 2016 Jan 1;143(1):3-14. doi: 10.1242/dev.130633. Review. PMID: 26732838

Controlled DNA double-strand break induction in mice reveals post-damage transcriptome stability.
Kim J, Sturgill D, Tran AD, Sinclair DA, Oberdoerffer P. Nucleic Acids Res. 2015 Dec 19. pii: gkv1482. [Epub ahead of print] PMID: 26687720 Free Article

SIRT1 Limits Adipocyte Hyperplasia through c-Myc Inhibition.
Abdesselem H, Madani A, Hani A, Al-Noubi M, Goswami N, Ben Hamidane H, Billing AM, Pasquier J, Bonkowski MS, Halabi N, Dalloul R, Sheriff MZ, Mesaeli N, ElRayess M, Sinclair DA, Graumann J, Mazloum NA. J Biol Chem. 2016 Jan 29;291(5):2119-35. doi: 10.1074/jbc.M115.675645. Epub 2015 Dec 11. PMID: 26655722 Free PMC Article

Protective effects of sirtuins in cardiovascular diseases: from bench to bedside.
Winnik S, Auwerx J, Sinclair DA, Matter CM. Eur Heart J. 2015 Dec 21;36(48):3404-12. doi: 10.1093/eurheartj/ehv290. Epub 2015 Jun 25. Review. PMID: 26112889 Free PMC Article

The Sirt1 activator SRT3025 expands hematopoietic stem and progenitor cells and improves hematopoiesis in Fanconi anemia mice.
Zhang QS, Deater M, Schubert K, Marquez-Loza L, Pelz C, Sinclair DA, Grompe M. Stem Cell Res. 2015 Jul;15(1):130-40. doi: 10.1016/j.scr.2015.05.007. Epub 2015 May 22. PMID: 26046330 Free Article

Correction: nicotinamide impairs entry into and exit from meiosis I in mouse oocytes.
Riepsamen A, Wu L, Lau L, Listijono D, Ledger W, Sinclair DA, Homer H. PLoS One. 2015 Jun 3;10(6):e0130058. doi: 10.1371/journal.pone.0130058. eCollection 2015. No abstract available. PMID: 26038838 Free PMC Article

Interventions to Slow Aging in Humans: Are We Ready?
Longo VD, Antebi A, Bartke A, Barzilai N, Brown-Borg HM, Caruso C, Curiel TJ, de Cabo R, Franceschi C, Gems D, Ingram DK, Johnson TE, Kennedy BK, Kenyon C, Klein S, Kopchick JJ, Lepperdinger G, Madeo F, Mirisola MG, Mitchell JR, Passarino G, Rudolph KL, Sedivy JM, Shadel GS, Sinclair DA, Spindler SR, Suh Y, Vijg J, Vinciguerra M, Fontana L. Aging Cell. 2015 Aug;14(4):497-510. doi: 10.1111/acel.12338. Epub 2015 Apr 22. PMID: 25902704 Free PMC Article

Oogonial stem cells as a model to study age-associated infertility in women.
Garg N, Sinclair DA. Reprod Fertil Dev. 2015 Apr 22. doi: 10.1071/RD14461. [Epub ahead of print] PMID: 25897831

Selective Sirt2 inhibition by ligand-induced rearrangement of the active site.
Rumpf T, Schiedel M, Karaman B, Roessler C, North BJ, Lehotzky A, Oláh J, Ladwein KI, Schmidtkunz K, Gajer M, Pannek M, Steegborn C, Sinclair DA, Gerhardt S, Ovádi J, Schutkowski M, Sippl W, Einsle O, Jung M. Nat Commun. 2015 Feb 12;6:6263. doi: 10.1038/ncomms7263. PMID: 25672491 Free PMC Article

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. PMID: 25308487

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: 10.1111/acel.12273. Epub 2014 Sep 25. PMID: 25257342 Free PMC Article

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: 10.1111/acel.12273. Epub 2014 Sep 25. PMID: 25257342 Free PMC Article

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. PMID: 24931715 Free PMC Article

The "metabolic winter" hypothesis: a cause of the current epidemics of obesity and cardiometabolic disease.
Cronise RJ, Sinclair DA, Bremer AA. Metab Syndr Relat Disord. 2014 Sep;12(7):355-61. doi: 10.1089/met.2014.0027. Epub 2014 Jun 11. PMID: 24918620 Free PMC Article

SIRT2 controls the pentose phosphate switch.
Wu LE, Sinclair DA. EMBO J. 2014 Jun 17;33(12):1287-8. doi: 10.15252/embj.201488713. Epub 2014 May 13. PMID: 24825350 Free PMC Article

SIRT2 induces the checkpoint kinase BubR1 to increase lifespan.
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. EMBO J. 2014 Jul 1;33(13):1438-53. doi: 10.15252/embj.201386907. Epub 2014 May 12. PMID: 24825348 Free PMC Article

The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice.
Solon-Biet SM, McMahon AC, Ballard JW, Ruohonen K, Wu LE, Cogger VC, Warren A, Huang X, Pichaud N, Melvin RG, Gokarn R, Khalil M, Turner N, Cooney GJ, Sinclair DA, Raubenheimer D, Le Couteur DG, Simpson SJ. Cell Metab. 2014 Mar 4;19(3):418-30. doi: 10.1016/j.cmet.2014.02.009. PMID: 24606899 Free Article

The Sirt1 activator SRT3025 provides atheroprotection in Apoe-/- mice by reducing hepatic Pcsk9 secretion and enhancing Ldlr expression.
Miranda MX, van Tits LJ, Lohmann C, Arsiwala T, Winnik S, Tailleux A, Stein S, Gomes AP, Suri V, Ellis JL, Lutz TA, Hottiger MO, Sinclair DA, Auwerx J, Schoonjans K, Staels B, Lüscher TF, Matter CM. Eur Heart J. 2015 Jan 1;36(1):51-9. doi: 10.1093/eurheartj/ehu095. Epub 2014 Mar 6. PMID: 24603306 Free PMC Article

The SIRT1 activator SRT1720 extends lifespan and improves health of mice fed a standard diet.
Mitchell SJ, Martin-Montalvo A, Mercken EM, Palacios HH, Ward TM, Abulwerdi G, Minor RK, Vlasuk GP, Ellis JL, Sinclair DA, Dawson J, Allison DB, Zhang Y, Becker KG, Bernier M, de Cabo R. Cell Rep. 2014 Mar 13;6(5):836-43. doi: 10.1016/j.celrep.2014.01.031. Epub 2014 Feb 27. PMID: 24582957 Free PMC Article

GLTSCR2/PICT1 links mitochondrial stress and Myc signaling.
Yoon JC, Ling AJ, Isik M, Lee DY, Steinbaugh MJ, Sack LM, Boduch AN, Blackwell TK, Sinclair DA, Elledge SJ. Proc Natl Acad Sci U S A. 2014 Mar 11;111(10):3781-6. doi: 10.1073/pnas.1400705111. Epub 2014 Feb 20. PMID: 24556985 Free PMC Article

Small molecule SIRT1 activators for the treatment of aging and age-related diseases.
Hubbard BP, Sinclair DA. Trends Pharmacol Sci. 2014 Mar;35(3):146-54. doi: 10.1016/j.tips.2013.12.004. Epub 2014 Jan 16. Review. PMID: 24439680 Free PMC Article

Geroncogenesis: metabolic changes during aging as a driver of tumorigenesis.
Wu LE, Gomes AP, Sinclair DA. Cancer Cell. 2014 Jan 13;25(1):12-9. doi: 10.1016/j.ccr.2013.12.005. PMID: 24434207 Free PMC Article

Sirtuin1 over-expression does not impact retinal vascular and neuronal degeneration in a mouse model of oxygen-induced retinopathy.
Michan S, Juan AM, Hurst CG, Cui Z, Evans LP, Hatton CJ, Pei DT, Ju M, Sinclair DA, Smith LE, Chen J. PLoS One. 2014 Jan 8;9(1):e85031. doi: 10.1371/journal.pone.0085031. eCollection 2014. PMID: 24416337 Free PMC Article

Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging.
Gomes AP, Price NL, Ling AJ, Moslehi JJ, Montgomery MK, Rajman L, White JP, Teodoro JS, Wrann CD, Hubbard BP, Mercken EM, Palmeira CM, de Cabo R, Rolo AP, Turner N, Bell EL, Sinclair DA. Cell. 2013 Dec 19;155(7):1624-38. doi: 10.1016/j.cell.2013.11.037. PMID: 24360282 Free PMC Article

Small-molecule allosteric activators of sirtuins.
Sinclair DA, Guarente L. Annu Rev Pharmacol Toxicol. 2014;54:363-80. doi: 10.1146/annurev-pharmtox-010611-134657. Epub 2013 Oct 16. Review. PMID: 24160699 Free PMC Article

Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide.
Schmeisser K, Mansfeld J, Kuhlow D, Weimer S, Priebe S, Heiland I, Birringer M, Groth M, Segref A, Kanfi Y, Price NL, Schmeisser S, Schuster S, Pfeiffer AF, Guthke R, Platzer M, Hoppe T, Cohen HY, Zarse K, Sinclair DA, Ristow M. Nat Chem Biol. 2013 Nov;9(11):693-700. doi: 10.1038/nchembio.1352. Epub 2013 Sep 29. PMID: 24077178 Free PMC Article

Measurement of sirtuin enzyme activity using a substrate-agnostic fluorometric nicotinamide assay.
Hubbard BP, Sinclair DA. Methods Mol Biol. 2013;1077:167-77. doi: 10.1007/978-1-62703-637-5_11. PMID: 24014406 Free PMC Article

Resveratrol accelerates erythroid maturation by activation of FoxO3 and ameliorates anemia in beta-thalassemic mice.
Franco SS, De Falco L, Ghaffari S, Brugnara C, Sinclair DA, Matte’ A, Iolascon A, Mohandas N, Bertoldi M, An X, Siciliano A, Rimmelé P, Cappellini MD, Michan S, Zoratti E, Anne J, De Franceschi L. Haematologica. 2014 Feb;99(2):267-75. doi: 10.3324/haematol.2013.090076. Epub 2013 Aug 23. PMID: 23975182 Free PMC Article

Studying the replicative life span of yeast cells.
Sinclair DA. Methods Mol Biol. 2013;1048:49-63. doi: 10.1007/978-1-62703-556-9_5. PMID: 23929097 Free PMC Article

Neuronal sirtuin1 mediates retinal vascular regeneration in oxygen-induced ischemic retinopathy. Chen J, Michan S, Juan AM, Hurst CG, Hatton CJ, Pei DT, Joyal JS, Evans LP, Cui Z, Stahl A, Sapieha P, Sinclair DA, Smith LE. Angiogenesis. 2013 Oct;16(4):985-92. doi: 10.1007/s10456-013-9374-5. Epub 2013 Aug 4. PMID: 23912262 Free PMC Article

Metformin improves healthspan and lifespan in mice.
Martin-Montalvo A, Mercken EM, Mitchell SJ, Palacios HH, Mote PL, Scheibye-Knudsen M, Gomes AP, Ward TM, Minor RK, Blouin MJ, Schwab M, Pollak M, Zhang Y, Yu Y, Becker KG, Bohr VA, Ingram DK, Sinclair DA, Wolf NS, Spindler SR, Bernier M, de Cabo R. Nat Commun. 2013;4:2192. doi: 10.1038/ncomms3192. PMID: 23900241 Free PMC Article

Carboxamide SIRT1 inhibitors block DBC1 binding via an acetylation-independent mechanism.
Hubbard BP, Loh C, Gomes AP, Li J, Lu Q, Doyle TL, Disch JS, Armour SM, Ellis JL, Vlasuk GP, Sinclair DA. Cell Cycle. 2013 Jul 15;12(14):2233-40. doi: 10.4161/cc.25268. PMID: 23892437 Free PMC Article

Germline energetics, aging, and female infertility.
Tilly JL, Sinclair DA. Cell Metab. 2013 Jun 4;17(6):838-50. doi: 10.1016/j.cmet.2013.05.007. Review. PMID: 23747243 Free PMC Article

A mutation in Tubb2b, a human polymicrogyria gene, leads to lethality and abnormal cortical development in the mouse.
Stottmann RW, Donlin M, Hafner A, Bernard A, Sinclair DA, Beier DR. Hum Mol Genet. 2013 Oct 15;22(20):4053-63. doi: 10.1093/hmg/ddt255. Epub 2013 May 31. PMID: 23727838 Free PMC Article

Type 5 adenylyl cyclase increases oxidative stress by transcriptional regulation of manganese superoxide dismutase via the SIRT1/FoxO3a pathway.
Lai L, Yan L, Gao S, Hu CL, Ge H, Davidow A, Park M, Bravo C, Iwatsubo K, Ishikawa Y, Auwerx J, Sinclair DA, Vatner SF, Vatner DE. Circulation. 2013 Apr 23;127(16):1692-701. doi: 10.1161/CIRCULATIONAHA.112.001212. Epub 2013 Mar 27. PMID: 23536361 Free PMC Article

Identification of a SIRT1 mutation in a family with type 1 diabetes.
Biason-Lauber A, Böni-Schnetzler M, Hubbard BP, Bouzakri K, Brunner A, Cavelti-Weder C, Keller C, Meyer-Böni M, Meier DT, Brorsson C, Timper K, Leibowitz G, Patrignani A, Bruggmann R, Boily G, Zulewski H, Geier A, Cermak JM, Elliott P, Ellis JL, Westphal C, Knobel U, Eloranta JJ, Kerr-Conte J, Pattou F, Konrad D, Matter CM, Fontana A, Rogler G, Schlapbach R, Regairaz C, Carballido JM, Glaser B, McBurney MW, Pociot F, Sinclair DA, Donath MY. Cell Metab. 2013 Mar 5;17(3):448-55. doi: 10.1016/j.cmet.2013.02.001. PMID: 23473037 Free PMC Article

Evidence for a common mechanism of SIRT1 regulation by allosteric activators.
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, Armour SM, Michan S, Zhao H, Jiang Y, Sweitzer SM, Blum CA, Disch JS, Ng PY, Howitz KT, Rolo AP, Hamuro Y, Moss J, Perni RB, Ellis JL, Vlasuk GP, Sinclair DA. Science. 2013 Mar 8;339(6124):1216-9. doi: 10.1126/science.1231097. PMID: 23471411 Free PMC Article

A high-confidence interaction map identifies SIRT1 as a mediator of acetylation of USP22 and the SAGA coactivator complex.
Armour SM, Bennett EJ, Braun CR, Zhang XY, McMahon SB, Gygi SP, Harper JW, Sinclair DA. Mol Cell Biol. 2013 Apr;33(8):1487-502. doi: 10.1128/MCB.00971-12. Epub 2013 Feb 4. PMID: 23382074 Free PMC Article

Analysis of 41 cancer cell lines reveals excessive allelic loss and novel mutations in the SIRT1 gene.
Han J, Hubbard BP, Lee J, Montagna C, Lee HW, Sinclair DA, Suh Y. Cell Cycle. 2013 Jan 15;12(2):263-70. doi: 10.4161/cc.23056. Epub 2012 Jan 15. PMID: 23255128 Free PMC Article

Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome.
Escande C, Nin V, Price NL, Capellini V, Gomes AP, Barbosa MT, O’Neil L, White TA, Sinclair DA, Chini EN. Diabetes. 2013 Apr;62(4):1084-93. doi: 10.2337/db12-1139. Epub 2012 Nov 19. PMID: 23172919 Free PMC Article

Guidelines for the use and interpretation of assays for monitoring autophagy.
Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, 2012 Apr;8(4):445-544.

The lifespan extension effects of resveratrol are conserved in the honey bee and may be driven by a mechanism related to caloric restriction.
Rascón B, Hubbard BP, Sinclair DA, Amdam GV. Aging (Albany NY). 2012 Jul;4(7):499-508. PMID: 22868943 Free PMC Article

Sirtuin 1 and sirtuin 3: physiological modulators of metabolism.
Nogueiras R, Habegger KM, Chaudhary N, Finan B, Banks AS, Dietrich MO, Horvath TL, Sinclair DA, Pfluger PT, Tschöp MH. Physiol Rev. 2012 Jul;92(3):1479-514. doi: 10.1152/physrev.00022.2011. Review. PMID: 22811431 Free PMC Article

SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function.
Price NL, Gomes AP, Ling AJ, Duarte FV, Martin-Montalvo A, North BJ, Agarwal B, Ye L, Ramadori G, Teodoro JS, Hubbard BP, Varela AT, Davis JG, Varamini B, Hafner A, Moaddel R, Rolo AP, Coppari R, Palmeira CM, de Cabo R, Baur JA, Sinclair DA. Cell Metab. 2012 May 2;15(5):675-90. doi: 10.1016/j.cmet.2012.04.003. PMID: 22560220 Free PMC Article

The intersection between aging and cardiovascular disease.
North BJ, Sinclair DA. Circ Res. 2012 Apr 13;110(8):1097-108. doi: 10.1161/CIRCRESAHA.111.246876. Review. PMID: 22499900 Free PMC Article

Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium-chain triglyceride oil on life span of genetically heterogeneous mice.
Strong R, Miller RA, Astle CM, Baur JA, de Cabo R, Fernandez E, Guo W, Javors M, Kirkland JL, Nelson JF, Sinclair DA, Teter B, Williams D, Zaveri N, Nadon NL, Harrison DE. J Gerontol A Biol Sci Med Sci. 2013 Jan;68(1):6-16. doi: 10.1093/gerona/gls070. Epub 2012 Mar 26. PMID: 22451473 Free PMC Article

SRT1720 improves survival and healthspan of obese mice.
Minor RK, Baur JA, Gomes AP, Ward TM, Csiszar A, Mercken EM, Abdelmohsen K, Shin YK, Canto C, Scheibye-Knudsen M, Krawczyk M, Irusta PM, Martín-Montalvo A, Hubbard BP, Zhang Y, Lehrmann E, White AA, Price NL, Swindell WR, Pearson KJ, Becker KG, Bohr VA, Gorospe M, Egan JM, Talan MI, Auwerx J, Westphal CH, Ellis JL, Ungvari Z, Vlasuk GP, Elliott PJ, Sinclair DA, de Cabo R. Sci Rep. 2011;1:70. doi: 10.1038/srep00070. Epub 2011 Aug 18. Erratum in: Sci Rep. 2013;3():1131. PMID: 22355589 Free PMC Article

An unSIRTain role in longevity.
Accili D, de Cabo R, Sinclair DA. Nat Med. 2011 Nov 7;17(11):1350-1. doi: 10.1038/nm1111-1350.  PMID: 22064411

Berberine protects against high fat diet-induced dysfunction in muscle mitochondria by inducing SIRT1-dependent mitochondrial biogenesis.
Gomes AP, Duarte FV, Nunes P, Hubbard BP, Teodoro JS, Varela AT, Jones JG, Sinclair DA, Palmeira CM, Rolo AP. Biochim Biophys Acta. 2012 Feb;1822(2):185-95. doi: 10.1016/j.bbadis.2011.10.008. Epub 2011 Oct 17. PMID: 22027215 Free PMC Article

Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling.
Beirowski B, Gustin J, Armour SM, Yamamoto H, Viader A, North BJ, Michán S, Baloh RH, Golden JP, Schmidt RE, Sinclair DA, Auwerx J, Milbrandt J. Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):E952-61. doi: 10.1073/pnas.1104969108. Epub 2011 Sep 26. PMID: 21949390 Free PMC Article

SIRT1 deacetylase in SF1 neurons protects against metabolic imbalance.
Ramadori G, Fujikawa T, Anderson J, Berglund ED, Frazao R, Michán S, Vianna CR, Sinclair DA, Elias CF, Coppari R. Cell Metab. 2011 Sep 7;14(3):301-12. doi: 10.1016/j.cmet.2011.06.014. PMID: 21907137 Free PMC Article

Sir2 histone deacetylase prevents programmed cell death caused by sustained activation of the Hog1 stress-activated protein kinase.
Vendrell A, Martínez-Pastor M, González-Novo A, Pascual-Ahuir A, Sinclair DA, Proft M, Posas F. EMBO Rep. 2011 Sep 30;12(10):1062-8. doi: 10.1038/embor.2011.154. PMID: 21836634 Free PMC Article

Negative regulation of STAT3 protein-mediated cellular respiration by SIRT1 protein.
Bernier M, Paul RK, Martin-Montalvo A, Scheibye-Knudsen M, Song S, He HJ, Armour SM, Hubbard BP, Bohr VA, Wang L, Zong Y, Sinclair DA, de Cabo R. J Biol Chem. 2011 Jun 3;286(22):19270-9. doi: 10.1074/jbc.M110.200311. Epub 2011 Apr 5. PMID: 21467030 Free PMC Article

Resveratrol inhibits pathologic retinal neovascularization in Vldlr(-/-) mice.
Hua J, Guerin KI, Chen J, Michán S, Stahl A, Krah NM, Seaward MR, Dennison RJ, Juan AM, Hatton CJ, Sapieha P, Sinclair DA, Smith LE. Invest Ophthalmol Vis Sci. 2011 Apr 25;52(5):2809-16. doi: 10.1167/iovs.10-6496. Print 2011 Apr. PMID: 21282584 Free PMC Article

Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy.
Hafner AV, Dai J, Gomes AP, Xiao CY, Palmeira CM, Rosenzweig A, Sinclair DA. Aging (Albany NY). 2010 Dec;2(12):914-23. PMID: 21212461 Free PMC Article

Dietary restriction: standing up for sirtuins.
Baur JA, Chen D, Chini EN, Chua K, Cohen HY, de Cabo R, Deng C, Dimmeler S, Gius D, Guarente LP, Helfand SL, Imai S, Itoh H, Kadowaki T, Koya D, Leeuwenburgh C, McBurney M, Nabeshima Y, Neri C, Oberdoerffer P, Pestell RG, Rogina B, Sadoshima J, Sartorelli V, Serrano M, Sinclair DA, Steegborn C, Tatar M, Tissenbaum HA, Tong Q, Tsubota K, Vaquero A, Verdin E. Science. 2010 Aug 27;329(5995):1012-3; author reply 1013-4. doi: 10.1126/science.329.5995.1012. No abstract available. PMID: 20798296 Free PMC Article

Characterization of murine SIRT3 transcript variants and corresponding protein products.
Yang Y, Hubbard BP, Sinclair DA, Tong Q. J Cell Biochem. 2010 Nov 1;111(4):1051-8. doi: 10.1002/jcb.22795. PMID: 20677216 Free PMC Article

SIRT1 is essential for normal cognitive function and synaptic plasticity.
Michán S, Li Y, Chou MM, Parrella E, Ge H, Long JM, Allard JS, Lewis K, Miller M, Xu W, Mervis RF, Chen J, Guerin KI, Smith LE, McBurney MW, Sinclair DA, Baudry M, de Cabo R, Longo VD. J Neurosci. 2010 Jul 21;30(29):9695-707. doi: 10.1523/JNEUROSCI.0027-10.2010. PMID: 20660252 Free PMC Article

A blueprint for developing therapeutic approaches that increase healthspan and delay death.
Le Couteur DG, Sinclair DA. J Gerontol A Biol Sci Med Sci. 2010 Jul;65(7):693-4. doi: 10.1093/gerona/glq048. Epub 2010 Apr 7. No abstract available. PMID: 20375077

Impact papers on aging in 2009.
Blagosklonny MV, Campisi J, Sinclair DA, Bartke A, Blasco MA, Bonner WM, Bohr VA, Brosh RM Jr, Brunet A, Depinho RA, Donehower LA, Finch CE, Finkel T, Gorospe M, Gudkov AV, Hall MN, Hekimi S, Helfand SL, Karlseder J, Kenyon C, Kroemer G, Longo V, Nussenzweig A, Osiewacz HD, Peeper DS, Rando TA, Rudolph KL, Sassone-Corsi P, Serrano M, Sharpless NE, Skulachev VP, Tilly JL, Tower J, Verdin E, Vijg J. Aging (Albany NY). 2010 Mar;2(3):111-21. Epub 2010 Mar 23. Review. PMID: 20351400 Free PMC Article

Aging: past, present and future.
Blagosklonny MV, Campisi J, Sinclair DA. Aging (Albany NY). 2009 Jan 7;1(1):1-5. No abstract available. PMID: 20157590 Free PMC Article

Inhibition of mammalian S6 kinase by resveratrol suppresses autophagy.
Armour SM, Baur JA, Hsieh SN, Land-Bracha A, Thomas SM, Sinclair DA. Aging (Albany NY). 2009 Jun 3;1(6):515-28. PMID: 20157535 Free PMC Article

SIRT1 mRNA expression may be associated with energy expenditure and insulin sensitivity.
Rutanen J, Yaluri N, Modi S, Pihlajamäki J, Vänttinen M, Itkonen P, Kainulainen S, Yamamoto H, Lagouge M, Sinclair DA, Elliott P, Westphal C, Auwerx J, Laakso M. Diabetes. 2010 Apr;59(4):829-35. doi: 10.2337/db09-1191. Epub 2010 Jan 27. PMID: 20107110 Free PMC Article

Mammalian sirtuins: biological insights and disease relevance.
Haigis MC, Sinclair DA. Annu Rev Pathol. 2010;5:253-95. doi: 10.1146/annurev.pathol.4.110807.092250. Review. PMID: 20078221 Free PMC Article

The ageing epigenome: damaged beyond repair?
Sinclair DA, Oberdoerffer P. Ageing Res Rev. 2009 Jul;8(3):189-98. doi: 10.1016/j.arr.2009.04.004. Epub 2009 May 9. Review. PMID: 19439199 Free PMC Article

Biochemical characterization, localization, and tissue distribution of the longer form of mouse SIRT3.
Jin L, Galonek H, Israelian K, Choy W, Morrison M, Xia Y, Wang X, Xu Y, Yang Y, Smith JJ, Hoffmann E, Carney DP, Perni RB, Jirousek MR, Bemis JE, Milne JC, Sinclair DA, Westphal CH. Protein Sci. 2009 Mar;18(3):514-25. doi: 10.1002/pro.50. PMID: 19241369 Free PMC Article

NQR1 controls lifespan by regulating the promotion of respiratory metabolism in yeast.
Jiménez-Hidalgo M, Santos-Ocaña C, Padilla S, Villalba JM, López-Lluch G, Martín-Montalvo A, Minor RK, Sinclair DA, de Cabo R, Navas P. Aging Cell. 2009 Apr;8(2):140-51. doi: 10.1111/j.1474-9726.2009.00461.x. Epub 2009 Feb 23. PMID: 19239415 Free PMC Article

SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging.
Oberdoerffer P, Michan S, McVay M, Mostoslavsky R, Vann J, Park SK, Hartlerode A, Stegmuller J, Hafner A, Loerch P, Wright SM, Mills KD, Bonni A, Yankner BA, Scully R, Prolla TA, Alt FW, Sinclair DA. Cell. 2008 Nov 28;135(5):907-18. doi: 10.1016/j.cell.2008.10.025. PMID: 19041753 Free PMC Article

Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span.
Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, Swindell WR, Kamara D, Minor RK, Perez E, Jamieson HA, Zhang Y, Dunn SR, Sharma K, Pleshko N, Woollett LA, Csiszar A, Ikeno Y, Le Couteur D, Elliott PJ, Becker KG, Navas P, Ingram DK, Wolf NS, Ungvari Z, Sinclair DA, de Cabo R. Cell Metab. 2008 Aug;8(2):157-68. doi: 10.1016/j.cmet.2008.06.011. Epub 2008 Jul 3. PMID: 18599363 Free PMC Article

Xenohormesis: sensing the chemical cues of other species.
Howitz KT, Sinclair DA. Cell. 2008 May 2;133(3):387-91. doi: 10.1016/j.cell.2008.04.019. PMID: 18455976 Free PMC Article

The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth.
Firestein R, Blander G, Michan S, Oberdoerffer P, Ogino S, Campbell J, Bhimavarapu A, Luikenhuis S, de Cabo R, Fuchs C, Hahn WC, Guarente LP, Sinclair DA. PLoS One. 2008 Apr 16;3(4):e2020. doi: 10.1371/journal.pone.0002020. PMID: 18414679 Free PMC Article

What is Xenohormesis?
Baur JA, Sinclair DA. Am J Pharmacol Toxicol. 2008 Mar 31;3(1):152-159. PMID: 26949380

David A. Sinclair, Ph.D is interviewed by Vicki Glaser.
Sinclair DA. Rejuvenation Res. 2008 Feb;11(1):265-8. doi: 10.1089/rej.2008.0694. No abstract available. PMID: 18279035

Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes.
Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, Jin L, Boss O, Perni RB, Vu CB, Bemis JE, Xie R, Disch JS, Ng PY, Nunes JJ, Lynch AV, Yang H, Galonek H, Israelian K, Choy W, Iffland A, Lavu S, Medvedik O, Sinclair DA, Olefsky JM, Jirousek MR, Elliott PJ, Westphal CH. Nature. 2007 Nov 29;450(7170):712-6. PMID: 18046409 Free PMC Article

MSN2 and MSN4 link calorie restriction and TOR to sirtuin-mediated lifespan extension in Saccharomyces cerevisiae.
Medvedik O, Lamming DW, Kim KD, Sinclair DA. PLoS Biol. 2007 Oct 2;5(10):e261. PMID: 17914901 Free PMC Article

Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival.
Yang H, Yang T, Baur JA, Perez E, Matsui T, Carmona JJ, Lamming DW, Souza-Pinto NC, Bohr VA, Rosenzweig A, de Cabo R, Sauve AA, Sinclair DA. Cell. 2007 Sep 21;130(6):1095-107. PMID: 17889652 Free PMC Article

Bax-inhibiting peptide protects cells from polyglutamine toxicity caused by Ku70 acetylation.
Li Y, Yokota T, Gama V, Yoshida T, Gomez JA, Ishikawa K, Sasaguri H, Cohen HY, Sinclair DA, Mizusawa H, Matsuyama S. Cell Death Differ. 2007 Dec;14(12):2058-67. Epub 2007 Sep 21. PMID: 17885668 Free Article

The role of nuclear architecture in genomic instability and ageing.
Oberdoerffer P, Sinclair DA. Nat Rev Mol Cell Biol. 2007 Sep;8(9):692-702. Review. PMID: 17700626

Caloric restriction and life span determination of yeast cells.
Medvedik O, Sinclair DA. Methods Mol Biol. 2007;371:97-109. PMID: 17634577

SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer’s disease and amyotrophic lateral sclerosis.
Kim D, Nguyen MD, Dobbin MM, Fischer A, Sananbenesi F, Rodgers JT, Delalle I, Baur JA, Sui G, Armour SM, Puigserver P, Sinclair DA, Tsai LH. EMBO J. 2007 Jul 11;26(13):3169-79. Epub 2007 Jun 21. PMID: 17581637 Free PMC Article

The role of protein arginine methylation in the formation of silent chromatin.
Yu MC, Lamming DW, Eskin JA, Sinclair DA, Silver PA. Genes Dev. 2006 Dec 1;20(23):3249-54. PMID: 17158743 Free PMC Article

Design and synthesis of compounds that extend yeast replicative lifespan.
Yang H, Baur JA, Chen A, Miller C, Adams JK, Kisielewski A, Howitz KT, Zipkin RE, Sinclair DA. Aging Cell. 2007 Feb;6(1):35-43. Epub 2006 Dec 5. Erratum in: Aging Cell. 2007 Aug;6(4):593. Adams, Jeffrey K [added]; Kisielewski, Anne [added]; Howitz, Konrad T [added]; Zipkin, Robert E [added]. PMID: 17156081 Free PMC Article

Sirtuins: a conserved key unlocking AceCS activity.
North BJ, Sinclair DA. Trends Biochem Sci. 2007 Jan;32(1):1-4. Epub 2006 Dec 1. PMID: 17141505 Free PMC Article

Resveratrol improves health and survival of mice on a high-calorie diet.
Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA. Nature. 2006 Nov 16;444(7117):337-42. Epub 2006 Nov 1. PMID: 17086191

Nampt/PBEF/Visfatin: a regulator of mammalian health and longevity?
Yang H, Lavu S, Sinclair DA. Exp Gerontol. 2006 Aug;41(8):718-26. Epub 2006 Jul 13. Review. PMID: 16842957 Free PMC Article

Therapeutic potential of resveratrol: the in vivo evidence.
Baur JA, Sinclair DA. Nat Rev Drug Discov. 2006 Jun;5(6):493-506. Epub 2006 May 26. Review. PMID: 16732220

Life-span extension in yeast.
Sinclair DA, Lin SJ, Guarente L. Science. 2006 Apr 14;312(5771):195-7; author reply 195-7. No abstract available. PMID: 16614198

Unlocking the secrets of longevity genes.
Sinclair DA, Guarente L. Sci Am. 2006 Mar;294(3):48-51, 54-7. No abstract available. PMID: 16502611

Design, synthesis, and biological evaluation of sirtinol analogues as class III histone/protein deacetylase (Sirtuin) inhibitors.
Mai A, Massa S, Lavu S, Pezzi R, Simeoni S, Ragno R, Mariotti FR, Chiani F, Camilloni G, Sinclair DA. J Med Chem. 2005 Dec 1;48(24):7789-95. PMID: 16302818

HST2 mediates SIR2-independent life-span extension by calorie restriction.
Lamming DW, Latorre-Esteves M, Medvedik O, Wong SN, Tsang FA, Wang C, Lin SJ, Sinclair DA. Science. 2005 Sep 16;309(5742):1861-4. Epub 2005 Jul 28. PMID: 16051752 Free Article

Toward a unified theory of caloric restriction and longevity regulation.
Sinclair DA. Mech Ageing Dev. 2005 Sep;126(9):987-1002. Review. PMID: 15893363

Small molecules that regulate lifespan: evidence for xenohormesis.
Lamming DW, Wood JG, Sinclair DA. Mol Microbiol. 2004 Aug;53(4):1003-9. Review. PMID: 15306006 Free Article

Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase.
Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, Howitz KT, Gorospe M, de Cabo R, Sinclair DA. Science. 2004 Jul 16;305(5682):390-2. Epub 2004 Jun 17. PMID: 15205477 Free Article

Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosis.
Cohen HY, Lavu S, Bitterman KJ, Hekking B, Imahiyerobo TA, Miller C, Frye R, Ploegh H, Kessler BM, Sinclair DA. Mol Cell. 2004 Mar 12;13(5):627-38. PMID: 15023334 Free Article

Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase.
Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE, Mostoslavsky R, Cohen HY, Hu LS, Cheng HL, Jedrychowski MP, Gygi SP, Sinclair DA, Alt FW, Greenberg ME. Science. 2004 Mar 26;303(5666):2011-5. Epub 2004 Feb 19. PMID: 14976264 Free Article

Yeast life-span extension by calorie restriction is independent of NAD fluctuation.
Anderson RM, Latorre-Esteves M, Neves AR, Lavu S, Medvedik O, Taylor C, Howitz KT, Santos H, Sinclair DA. Science. 2003 Dec 19;302(5653):2124-6. Epub 2003 Nov 6. PMID: 14605207 Free Article

Cell biology. An age of instability.
Sinclair DA. Science. 2003 Sep 26;301(5641):1859-60. PMID: 14512612

Longevity regulation in Saccharomyces cerevisiae: linking metabolism, genome stability, and heterochromatin.
Bitterman KJ, Medvedik O, Sinclair DA. Microbiol Mol Biol Rev. 2003 Sep;67(3):376-99, table of contents. Review. PMID: 12966141 Free PMC Article

Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan.
Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA. Nature. 2003 Sep 11;425(6954):191-6. Epub 2003 Aug 24. PMID: 12939617

Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae.
Anderson RM, Bitterman KJ, Wood JG, Medvedik O, Sinclair DA. Nature. 2003 May 8;423(6936):181-5. PMID: 12736687

Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1.
Bitterman KJ, Anderson RM, Cohen HY, Latorre-Esteves M, Sinclair DA. J Biol Chem. 2002 Nov 22;277(47):45099-107. Epub 2002 Sep 23. PMID: 12297502 Free Article

Paradigms and pitfalls of yeast longevity research.
Sinclair DA. Mech Ageing Dev. 2002 Apr 30;123(8):857-67. Review. PMID: 12044934

Manipulation of a nuclear NAD+ salvage pathway delays aging without altering steady-state NAD+ levels.
Anderson RM, Bitterman KJ, Wood JG, Medvedik O, Cohen H, Lin SS, Manchester JK, Gordon JI, Sinclair DA. J Biol Chem. 2002 May 24;277(21):18881-90. Epub 2002 Mar 7. Erratum in: J Biol Chem. 2013 Aug 16;288(33):24160. PMID: 11884393 Free Article

TPE or not TPE? It’s no longer a question.
Wood JG, Sinclair DA. Trends Pharmacol Sci. 2002 Jan;23(1):1-4. Review. No abstract available. PMID: 11804639

Recombination-mediated lengthening of terminal telomeric repeats requires the Sgs1 DNA helicase.
Cohen H, Sinclair DA. Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3174-9. Epub 2001 Mar 6. PMID: 11248051 Free PMC Article

Yeast aging research: recent advances and medical relevance.
Sinclair DA. Cell Mol Life Sci. 1999 Nov 30;56(9-10):807-16. Review. PMID: 11212340

MEC1-dependent redistribution of the Sir3 silencing protein from telomeres to DNA double-strand breaks.
Mills KD, Sinclair DA, Guarente L. Cell. 1999 May 28;97(5):609-20. PMID: 10367890 Free Article

Molecular biology of aging.
Johnson FB, Sinclair DA, Guarente L. Cell. 1999 Jan 22;96(2):291-302. Review. No abstract available. PMID: 9988222 Free Article

Molecular mechanisms of yeast aging.
Sinclair DA, Mills K, Guarente L. Trends Biochem Sci. 1998 Apr;23(4):131-4. Review. PMID: 9584615

Extrachromosomal rDNA circles—a cause of aging in yeast.
Sinclair DA, Guarente L. Cell. 1997 Dec 26;91(7):1033-42. PMID: 9428525 Free Article

Accelerated aging and nucleolar fragmentation in yeast sgs1 mutants.
Sinclair DA, Mills K, Guarente L. Science. 1997 Aug 29;277(5330):1313-6. PMID: 9271578 Free Article

Redistribution of silencing proteins from telomeres to the nucleolus is associated with extension of life span in S. cerevisiae.
Kennedy BK, Gotta M, Sinclair DA, Mills K, McNabb DS, Murthy M, Pak SM, Laroche T, Gasser SM, Guarente L. Cell. 1997 May 2;89(3):381-91. PMID: 9150138 Free Article