Photo of David A. Sinclair, PhD

David A. Sinclair, PhD

Harvard Medical School

Harvard Medical School
Phone: (617) 432-3931
Fax: (617) 432-6225

Photo of David A. Sinclair, PhD

Harvard Medical School
Phone: (617) 432-3931
Fax: (617) 432-6225

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David A. Sinclair, PhD

Harvard Medical School

EDUCATIONAL TITLES

  • Professor, Genetics, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Publications from Harvard Catalyst Profiles

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  • Amorim JA, Sinclair DA. Measuring PGC-1α and Its Acetylation Status in Mouse Primary Myotubes. Methods Mol Biol 2021; 2310:301-309. PubMed
  • Montay-Gruel P, Zhu Y, Petit B, Leavitt R, Warn M, Giedzinski E, Ollivier J, Sinclair DA, Vozenin MC, Limoli CL. Extracellular Vesicles for the Treatment of Radiation-Induced Normal Tissue Toxicity in the Lung. 2020; 10:602763. PubMed
  • Lu Y, Brommer B, Tian X, Krishnan A, Meer M, Wang C, Vera DL, Zeng Q, Yu D, Bonkowski MS, Yang JH, Zhou S, Hoffmann EM, Karg MM, Schultz MB, Kane AE, Davidsohn N, Korobkina E, Chwalek K, Rajman LA, Church GM, Hochedlinger K, Gladyshev VN, Horvath S, Levine ME, Gregory-Ksander MS, Ksander BR, He Z, Sinclair DA. Reprogramming to recover youthful epigenetic information and restore vision. Nature 2020; 588:124-129. PubMed
  • Schultz MB, Kane AE, Mitchell SJ, MacArthur MR, Warner E, Vogel DS, Mitchell JR, Howlett SE, Bonkowski MS, Sinclair DA. Age and life expectancy clocks based on machine learning analysis of mouse frailty. Nat Commun 2020; 11:4618. PubMed
  • Bolderson E, Burgess JT, Li J, Gandhi NS, Boucher D, Croft LV, Beard S, Plowman JJ, Suraweera A, Adams MN, Naqi A, Zhang SD, Sinclair DA, O'Byrne KJ, Richard DJ. Barrier-to-autointegration factor 1 (Banf1) regulates poly [ADP-ribose] polymerase 1 (PARP1) activity following oxidative DNA damage. Nat Commun 2019; 10:5501. PubMed
  • Palmeira CM, Teodoro JS, Amorim JA, Steegborn C, Sinclair DA, Rolo AP. Mitohormesis and metabolic health: The interplay between ROS, cAMP and sirtuins. Free Radic Biol Med 2019; 141:483-491. PubMed
  • Amano H, Chaudhury A, Rodriguez-Aguayo C, Lu L, Akhanov V, Catic A, Popov YV, Verdin E, Johnson H, Stossi F, Sinclair DA, Nakamaru-Ogiso E, Lopez-Berestein G, Chang JT, Neilson JR, Meeker A, Finegold M, Baur JA, Sahin E. Telomere Dysfunction Induces Sirtuin Repression that Drives Telomere-Dependent Disease. Cell Metab 2019. PubMed
  • Feng J, LaChance A, Sinclair DA, Asgari MM. Multiple basal cell carcinomas in a patient with myotonic dystrophy type 1. BMJ Case Rep 2019. PubMed
  • Kane AE, Sinclair DA. Epigenetic changes during aging and their reprogramming potential. Crit Rev Biochem Mol Biol 2019; 54:61-83. PubMed
  • Kane AE, Sinclair DA. Frailty biomarkers in humans and rodents: Current approaches and future advances. Mech Ageing Dev 2019; 180:117-128. PubMed
  • Kane AE, Sinclair DA, Mitchell JR, Mitchell SJ. Sex differences in the response to dietary restriction in rodents. Curr Opin Physiol 2018; 6:28-34. PubMed
  • Kane AE, Sinclair DA. Sirtuins and NAD in the Development and Treatment of Metabolic and Cardiovascular Diseases. Circ Res 2018; 123:868-885. PubMed
  • Latorre-Muro P, Baeza J, Armstrong EA, Hurtado-Guerrero R, Corzana F, Wu LE, Sinclair DA, López-Buesa P, Carrodeguas JA, Denu JM. Dynamic Acetylation of Phosphoenolpyruvate Carboxykinase Toggles Enzyme Activity between Gluconeogenic and Anaplerotic Reactions. Mol Cell 2018; 71:718-732.e9. PubMed
  • Bonora M, Wieckowski MR, Sinclair DA, Kroemer G, Pinton P, Galluzzi L. Targeting mitochondria for cardiovascular disorders: therapeutic potential and obstacles. Nat Rev Cardiol 2018. PubMed
  • Longchamp A, Mirabella T, Arduini A, MacArthur MR, Das A, Treviño-Villarreal JH, Hine C, Ben-Sahra I, Knudsen NH, Brace LE, Reynolds J, Mejia P, Tao M, Sharma G, Wang R, Corpataux JM, Haefliger JA, Ahn KH, Lee CH, Manning BD, Sinclair DA, Chen CS, Ozaki CK, Mitchell JR. Amino Acid Restriction Triggers Angiogenesis via GCN2/ATF4 Regulation of VEGF and HS Production. Cell 2018; 173:117-129.e14. PubMed
  • Schultz MB, Lu Y, Braidy N, Sinclair DA. Assays for NAD-Dependent Reactions and NAD Metabolites. Methods Mol Biol 2018; 1813:77-90. PubMed
  • Uddin GM, Youngson NA, Doyle BM, Sinclair DA, Morris MJ. Nicotinamide mononucleotide (NMN) supplementation ameliorates the impact of maternal obesity in mice: comparison with exercise. Sci Rep 2017; 7:15063. PubMed
  • Li J, Bonkowski MS, Moniot S, Zhang D, Hubbard BP, Ling AJ, Rajman LA, Qin B, Lou Z, Gorbunova V, Aravind L, Steegborn C, Sinclair DA. A conserved NAD(+) binding pocket that regulates protein-protein interactions during aging. Science 2017; 355:1312-1317. PubMed
  • Bustamante S, Jayasena T, Richani D, Gilchrist RB, Wu LE, Sinclair DA, Sachdev PS, Braidy N. Quantifying the cellular NAD+ metabolome using a tandem liquid chromatography mass spectrometry approach. Metabolomics 2017; 14:15. PubMed
  • Van Meter M, Simon M, Tombline G, May A, Morello TD, Hubbard BP, Bredbenner K, Park R, Sinclair DA, Bohr VA, Gorbunova V, Seluanov A. JNK Phosphorylates SIRT6 to Stimulate DNA Double-Strand Break Repair in Response to Oxidative Stress by Recruiting PARP1 to DNA Breaks. Cell Rep 2016; 16:2641-50. PubMed
  • Bonkowski MS, Sinclair DA. Slowing ageing by design: the rise of NAD(+) and sirtuin-activating compounds. Nat Rev Mol Cell Biol 2016. PubMed
  • Wu LE, Sinclair DA. Restoring stem cells - all you need is NAD(.) Cell Res 2016. PubMed
  • Schultz MB, Sinclair DA. Why NAD(+) Declines during Aging: It's Destroyed. Cell Metab 2016; 23:965-6. PubMed
  • Kim J, Sturgill D, Tran AD, Sinclair DA, Oberdoerffer P. Controlled DNA double-strand break induction in mice reveals post-damage transcriptome stability. Nucleic Acids Res 2016; 44:e64. PubMed
  • Anderson EN, Corkins ME, Li JC, Singh K, Parsons S, Tucey TM, Sorkaç A, Huang H, Dimitriadi M, Sinclair DA, Hart AC. C. elegans lifespan extension by osmotic stress requires FUdR, base excision repair, FOXO, and sirtuins. Mech Ageing Dev 2016; 154:30-42. PubMed
  • Uddin GM, Youngson NA, Sinclair DA, Morris MJ. Head to Head Comparison of Short-Term Treatment with the NAD(+) Precursor Nicotinamide Mononucleotide (NMN) and 6 Weeks of Exercise in Obese Female Mice. Front Pharmacol 2016; 7:258. PubMed
  • Cagnone GL, Tsai TS, Makanji Y, Matthews P, Gould J, Bonkowski MS, Elgass KD, Wong AS, Wu LE, McKenzie M, Sinclair DA, John JC. Restoration of normal embryogenesis by mitochondrial supplementation in pig oocytes exhibiting mitochondrial DNA deficiency. Sci Rep 2016; 6:23229. PubMed
  • 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. SIRT1 Limits Adipocyte Hyperplasia Through c-Myc Inhibition. J Biol Chem 2015. PubMed
  • Zhang QS, Deater M, Schubert K, Marquez-Loza L, Pelz C, Sinclair DA, Grompe M. The Sirt1 activator SRT3025 expands hematopoietic stem and progenitor cells and improves hematopoiesis in Fanconi anemia mice. 2015; 15:130-40. PubMed
  • Gomes AP, Sinclair DA. Measuring PGC-1α and its acetylation status in mouse primary myotubes. Methods Mol Biol 2015; 1241:49-57. PubMed
  • 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. Selective Sirt2 inhibition by ligand-induced rearrangement of the active site. Nat Commun 2015; 6:6263. PubMed
  • Moroz N, Carmona JJ, Anderson E, Hart AC, Sinclair DA, Blackwell TK. Dietary restriction involves NAD⁺ -dependent mechanisms and a shift toward oxidative metabolism. Aging Cell 2014. PubMed
  • Rimmelé P, Bigarella CL, Liang R, Izac B, Dieguez-Gonzalez R, Barbet G, Donovan M, Brugnara C, Blander JM, Sinclair DA, Ghaffari S. Aging-like phenotype and defective lineage specification in SIRT1-deleted hematopoietic stem and progenitor cells. Stem Cell Reports 2014; 3:44-59. PubMed
  • 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. PubMed
  • Yoon JC, Ling AJ, Isik M, Lee DY, Steinbaugh MJ, Sack LM, Boduch AN, Blackwell TK, Sinclair DA, Elledge SJ. GLTSCR2/PICT1 links mitochondrial stress and Myc signaling. Proc Natl Acad Sci U S A 2014; 111:3781-6. PubMed
  • Wu LE, Gomes AP, Sinclair DA. Geroncogenesis: metabolic changes during aging as a driver of tumorigenesis. Cancer Cell 2014; 25:12-9. PubMed
  • Sinclair DA, Guarente L. Small-molecule allosteric activators of sirtuins. Annu Rev Pharmacol Toxicol 2014; 54:363-80. PubMed
  • 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. Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide. Nat Chem Biol 2013; 9:693-700. PubMed
  • Hubbard BP, Loh C, Gomes AP, Li J, Lu Q, Doyle TL, Disch JS, Armour SM, Ellis JL, Vlasuk GP, Sinclair DA. Carboxamide SIRT1 inhibitors block DBC1 binding via an acetylation-independent mechanism. Cell Cycle 2013; 12:2233-40. PubMed
  • 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. Metformin improves healthspan and lifespan in mice. Nat Commun 2013; 4:2192. PubMed
  • Sinclair DA. Studying the replicative life span of yeast cells. Methods Mol Biol 2013; 1048:49-63. PubMed
  • Hubbard BP, Sinclair DA. Measurement of sirtuin enzyme activity using a substrate-agnostic fluorometric nicotinamide assay. Methods Mol Biol 2013; 1077:167-77. PubMed
  • Nakamura K, Kosugi I, Lee DY, Hafner A, Sinclair DA, Ryo A, Lu KP. Prolyl isomerase Pin1 regulates neuronal differentiation via β-catenin. Mol Cell Biol 2012; 32:2966-78. PubMed
  • 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. Negative regulation of STAT3 protein-mediated cellular respiration by SIRT1 protein. J Biol Chem 2011. PubMed
  • Yang Y, Hubbard BP, Sinclair DA, Tong Q. Characterization of murine SIRT3 transcript variants and corresponding protein products. J Cell Biochem 2010; 111:1051-8. PubMed
  • 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. Dietary restriction: standing up for sirtuins. Science 2010; 329:1012-3; author reply 1013-4. PubMed
  • 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. SIRT1 is essential for normal cognitive function and synaptic plasticity. J Neurosci 2010; 30:9695-707. PubMed
  • Le Couteur DG, Sinclair DA. A blueprint for developing therapeutic approaches that increase healthspan and delay death. J Gerontol A Biol Sci Med Sci 2010; 65:693-4. PubMed
  • 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. SIRT1 mRNA Expression May Be Associated with Energy Expenditure and Insulin Sensitivity. Diabetes 2010; 59:829-35. PubMed
  • Blagosklonny MV, Campisi J, Sinclair DA, Bartke A, Blasco MA, Bonner WM, Bohr VA, Brosh RM, 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. Impact papers on aging in 2009. Aging (Albany NY) 2010; 2:111-21. PubMed
  • Haigis MC, Sinclair DA. Mammalian sirtuins: biological insights and disease relevance. Annu Rev Pathol 2010; 5:253-95. PubMed
  • Sinclair DA,Oberdoerffer P. The ageing epigenome: damaged beyond repair? Ageing Res Rev 2009; 8:189-98. PubMed
  • Armour SM, Baur JA, Hsieh SN, Land-Bracha A, Thomas SM, Sinclair DA. Inhibition of mammalian S6 kinase by resveratrol suppresses autophagy. Aging (Albany NY) 2009; 1:515-28. PubMed
  • Jimenez-Hidalgo M,Santos-Ocana C,Padilla S,Villalba JM,Lopez-Lluch G,Martin-Montalvo A,Minor RK,Sinclair DA,de Cabo R,Navas P. NQR1 controls lifespan by regulating the promotion of respiratory metabolism in yeast. Aging Cell 2009; 8:140-51. PubMed
  • 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. Biochemical characterization, localization, and tissue distribution of the longer form of mouse SIRT3. Protein Sci 2009; 18:514-25. PubMed
  • 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. SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging. Cell 2008; 135:907-18. PubMed
  • 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. Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab 2008; 8:157-68. PubMed
  • 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. The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth. PLoS ONE 2008; 3:e2020. PubMed
  • Li Y, Yokota T, Gama V, Yoshida T, Gomez JA, Ishikawa K, Sasaguri H, Cohen HY, Sinclair DA, Mizusawa H, Matsuyama S. Bax-inhibiting peptide protects cells from polyglutamine toxicity caused by Ku70 acetylation. Cell Death Differ 2007; 14:2058-67. PubMed
  • 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. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature 2007; 450:712-6. PubMed
  • Barbosa MT, Soares SM, Novak CM, Sinclair D, Levine JA, Aksoy P, Chini EN. The enzyme CD38 (a NAD glycohydrolase, EC 3.2.2.5) is necessary for the development of diet-induced obesity. FASEB J 2007; 21:3629-39. PubMed
  • Medvedik O, Lamming DW, Kim KD, Sinclair DA. MSN2 and MSN4 link calorie restriction and TOR to sirtuin-mediated lifespan extension in Saccharomyces cerevisiae. PLoS Biol 2007; 5:e261. PubMed
  • 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. Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival. Cell 2007; 130:1095-107. PubMed
  • Oberdoerffer P, Sinclair DA. The role of nuclear architecture in genomic instability and ageing. Nat Rev Mol Cell Biol 2007; 8:692-702. PubMed
  • 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. SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis. EMBO J 2007; 26:3169-79. PubMed
  • Calabrese EJ, Bachmann KA, Bailer AJ, Bolger PM, Borak J, Cai L, Cedergreen N, Cherian MG, Chiueh CC, Clarkson TW, Cook RR, Diamond DM, Doolittle DJ, Dorato MA, Duke SO, Feinendegen L, Gardner DE, Hart RW, Hastings KL, Hayes AW, Hoffmann GR, Ives JA, Jaworowski Z, Johnson TE, Jonas WB, Kaminski NE, Keller JG, Klaunig JE, Knudsen TB, Kozumbo WJ, Lettieri T, Liu SZ, Maisseu A, Maynard KI, Masoro EJ, McClellan RO, Mehendale HM, Mothersill C, Newlin DB, Nigg HN, Oehme FW, Phalen RF, Philbert MA, Rattan SI, Riviere JE, Rodricks J, Sapolsky RM, Scott BR, Seymour C, Sinclair DA, Smith-Sonneborn J, Snow ET, Spear L, Stevenson DE, Thomas Y, Tubiana M, Williams GM, Mattson MP. Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework. Toxicol Appl Pharmacol 2007; 222:122-8. PubMed
  • Syrzycka M, McEachern LA, Kinneard J, Prabhu K, Fitzpatrick K, Schulze S, Rawls JM, Lloyd VK, Sinclair DA, Honda BM. The pink gene encodes the Drosophila orthologue of the human Hermansky-Pudlak syndrome 5 (HPS5) gene. Genome 2007; 50:548-56. PubMed
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Visualize Collaborations
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Similar Members

DF/HCC members that share similar concepts* with David A. Sinclair, PhD but have yet to coauthor a publication with this researcher.

* Concepts are MeSH terms, automatically derived from member publications

Similar Members