David A Sinclair

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi request reprint TPE or not TPE? It's no longer a question
    Jason G Wood
    Dept of Pathology, Harvard Medical School, Boston, MA 02115
    Trends Pharmacol Sci 23:1-4. 2002
  2. pmc Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy
    Angela V Hafner
    Harvard Medical School, Department of Pathology and Glenn Labs for Aging Research, Boston, MA 02115, USA
    Aging (Albany NY) 2:914-23. 2010
  3. pmc Small-molecule allosteric activators of sirtuins
    David A Sinclair
    Glenn Laboratories for the Biological Mechanisms of Aging, Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115 email
    Annu Rev Pharmacol Toxicol 54:363-80. 2014
  4. doi request reprint The longevity of sirtuins
    David Sinclair
    Glenn Laboratories for the Molecular Biology of Aging, Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Cell Rep 2:1473-4. 2012
  5. ncbi request reprint Toward a unified theory of caloric restriction and longevity regulation
    David A Sinclair
    Department of Pathology, Harvard Medical School, 77 Avenue Louis Paster, Boston, MA 02115, USA
    Mech Ageing Dev 126:987-1002. 2005
  6. ncbi request reprint Cell biology. An age of instability
    David A Sinclair
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Science 301:1859-60. 2003
  7. pmc The ageing epigenome: damaged beyond repair?
    David A Sinclair
    The Paul F Glenn Laboratories for the Biological Mechanisms of Ageing, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Ageing Res Rev 8:189-98. 2009
  8. ncbi request reprint Is DNA cut out for a long life?
    David Sinclair
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Sci Aging Knowledge Environ 2003:PE8. 2003
  9. ncbi request reprint Paradigms and pitfalls of yeast longevity research
    David A Sinclair
    Department of Pathology, Harvard Medical School, Boston MA 02115, USA
    Mech Ageing Dev 123:857-67. 2002
  10. ncbi request reprint HST2 mediates SIR2-independent life-span extension by calorie restriction
    Dudley W Lamming
    Paul F Glenn Laboratories for the Biological Mechanisms of Aging, Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Science 309:1861-4. 2005

Research Grants

Collaborators

Detail Information

Publications61

  1. ncbi request reprint TPE or not TPE? It's no longer a question
    Jason G Wood
    Dept of Pathology, Harvard Medical School, Boston, MA 02115
    Trends Pharmacol Sci 23:1-4. 2002
  2. pmc Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy
    Angela V Hafner
    Harvard Medical School, Department of Pathology and Glenn Labs for Aging Research, Boston, MA 02115, USA
    Aging (Albany NY) 2:914-23. 2010
    ....
  3. pmc Small-molecule allosteric activators of sirtuins
    David A Sinclair
    Glenn Laboratories for the Biological Mechanisms of Aging, Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115 email
    Annu Rev Pharmacol Toxicol 54:363-80. 2014
    ....
  4. doi request reprint The longevity of sirtuins
    David Sinclair
    Glenn Laboratories for the Molecular Biology of Aging, Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Cell Rep 2:1473-4. 2012
    ..In this issue of Cell Reports, Banerjee et al. demonstrate that Drosophila Sir2 is necessary for life span extension in response to dietary restriction and that its overexpression in the fat body increases the life span...
  5. ncbi request reprint Toward a unified theory of caloric restriction and longevity regulation
    David A Sinclair
    Department of Pathology, Harvard Medical School, 77 Avenue Louis Paster, Boston, MA 02115, USA
    Mech Ageing Dev 126:987-1002. 2005
    ..This has important implications for how we might develop novel medicines that can harness these newly discovered innate mechanisms of disease resistance and survival...
  6. ncbi request reprint Cell biology. An age of instability
    David A Sinclair
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Science 301:1859-60. 2003
    ..As yeast cells age there is a marked increase in their genetic instability (a hallmark of cancer), which is independent of the mechanism that determines their life-span...
  7. pmc The ageing epigenome: damaged beyond repair?
    David A Sinclair
    The Paul F Glenn Laboratories for the Biological Mechanisms of Ageing, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Ageing Res Rev 8:189-98. 2009
    ....
  8. ncbi request reprint Is DNA cut out for a long life?
    David Sinclair
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Sci Aging Knowledge Environ 2003:PE8. 2003
    ..In this Perspective, I discuss results presented in this month's issue of Aging Cell that address whether the types of DNA damage repaired by the base excision repair pathway cause aging in yeast...
  9. ncbi request reprint Paradigms and pitfalls of yeast longevity research
    David A Sinclair
    Department of Pathology, Harvard Medical School, Boston MA 02115, USA
    Mech Ageing Dev 123:857-67. 2002
    ..Characterizing this and other mechanisms of yeast aging should help identify additional components of longevity pathways in higher organisms...
  10. ncbi request reprint HST2 mediates SIR2-independent life-span extension by calorie restriction
    Dudley W Lamming
    Paul F Glenn Laboratories for the Biological Mechanisms of Aging, Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Science 309:1861-4. 2005
    ..These findings demonstrate that the maintenance of DNA stability is critical for yeast life-span extension by CR and suggest that, in higher organisms, multiple members of the Sir2 family may regulate life span in response to diet...
  11. ncbi request reprint Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase
    Haim Y Cohen
    Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Science 305:390-2. 2004
    ..Thus, CR could extend life-span by inducing SIRT1 expression and promoting the long-term survival of irreplaceable cells...
  12. ncbi request reprint Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae
    Rozalyn M Anderson
    Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 423:181-5. 2003
    ..We conclude that yeast lifespan extension by calorie restriction is the consequence of an active cellular response to a low-intensity stress and speculate that nicotinamide might regulate critical cellular processes in higher organisms...
  13. ncbi request reprint Yeast life-span extension by calorie restriction is independent of NAD fluctuation
    Rozalyn M Anderson
    Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston MA 02115, USA
    Science 302:2124-6. 2003
    ..Moreover, the activity of Sir2 and its human homologue SIRT1 are not affected by physiological alterations in the NAD+:NADH ratio. These data implicate alternate mechanisms of Sir2 regulation by CR...
  14. pmc Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival
    Hongying Yang
    Department of Pathology, Paul F Glenn Laboratories, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Cell 130:1095-107. 2007
    ..We discuss the relevance of these findings to understanding how nutrition modulates physiology and to the evolution of apoptosis...
  15. pmc Design and synthesis of compounds that extend yeast replicative lifespan
    Hongying Yang
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Aging Cell 6:35-43. 2007
    ..These studies show that it is possible to improve upon naturally occurring STACs based on a number of criteria including lifespan extension...
  16. ncbi request reprint Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1
    Kevin J Bitterman
    Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 277:45099-107. 2002
    ..We discuss the possibility that nicotinamide is a physiologically relevant regulator of Sir2 enzymes...
  17. pmc Carboxamide SIRT1 inhibitors block DBC1 binding via an acetylation-independent mechanism
    Basil P Hubbard
    Department of Genetics, Harvard Medical School, Boston, MA, USA
    Cell Cycle 12:2233-40. 2013
    ..Together, these data show that protein acetylation serves as an endogenous regulatory mechanism for SIRT1-DBC1 binding and illuminate a new path to developing small-molecule modulators of SIRT1. ..
  18. pmc Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging
    Ana P Gomes
    Glenn Labs for the Biological Mechanisms of Aging, Department of Genetics, Harvard Medical School, Boston, MA 02115, USA Center for Neurosciences and Cell Biology, 3004 517 Coimbra, Portugal Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, 3004 517 Coimbra, Portugal
    Cell 155:1624-38. 2013
    ..Thus, a pseudohypoxic state that disrupts PGC-1α/β-independent nuclear-mitochondrial communication contributes to the decline in mitochondrial function with age, a process that is apparently reversible. ..
  19. ncbi request reprint Unlocking the secrets of longevity genes
    David A Sinclair
    Paul F Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, USA
    Sci Am 294:48-51, 54-7. 2006
  20. pmc MSN2 and MSN4 link calorie restriction and TOR to sirtuin-mediated lifespan extension in Saccharomyces cerevisiae
    Oliver Medvedik
    Paul F Glenn Laboratories for the Biological Mechanisms of Aging, Department of Pathology, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS Biol 5:e261. 2007
    ..These findings suggest that TOR and sirtuins may be part of the same longevity pathway in higher organisms, and that they may promote genomic stability during aging...
  21. ncbi request reprint Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase
    Anne Brunet
    Division of Neuroscience, Children s Hospital, and Department of Neurobiology, Center for Blood Research CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA
    Science 303:2011-5. 2004
    ..Thus, one way in which members of the Sir2 family of proteins may increase organismal longevity is by tipping FOXO-dependent responses away from apoptosis and toward stress resistance...
  22. pmc The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth
    Ron Firestein
    Paul F Glenn Laboratories for the Biological Mechanisms of Aging, Department of Pathology, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 3:e2020. 2008
    ..Taken together, these observations show that SIRT1 suppresses intestinal tumor formation in vivo and raise the prospect that therapies targeting SIRT1 may be of clinical use in beta-catenin-driven malignancies...
  23. pmc SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging
    Philipp Oberdoerffer
    Department of Pathology and Glenn Labs for Aging Research, Harvard Medical School, Boston, MA 02115, USA
    Cell 135:907-18. 2008
    ..Thus, DNA damage-induced redistribution of SIRT1 and other chromatin-modifying proteins may be a conserved mechanism of aging in eukaryotes...
  24. pmc The role of protein arginine methylation in the formation of silent chromatin
    Michael C Yu
    Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 20:3249-54. 2006
    ..These data suggest a model whereby protein arginine methylation affects the establishment and maintenance of silent chromatin...
  25. ncbi request reprint Small molecules that regulate lifespan: evidence for xenohormesis
    Dudley W Lamming
    Harvard Medical School, Department of Pathology, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Mol Microbiol 53:1003-9. 2004
    ..In this way, organisms can prepare in advance for a deteriorating environment and/or loss of food supply...
  26. pmc Nampt/PBEF/Visfatin: a regulator of mammalian health and longevity?
    Hongying Yang
    Department of Pathology, Paul F Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, 77 Ave Louis Pasteur, Boston, MA, USA
    Exp Gerontol 41:718-26. 2006
    ..We propose that there is a functional equivalent of PNC1 in mammals called Nampt (a.k.a. PBEF/Visfatin), a stress-responsive gene that would coordinately regulate metabolism, cell defenses, and resistance to diseases of aging...
  27. pmc Longevity regulation in Saccharomyces cerevisiae: linking metabolism, genome stability, and heterochromatin
    Kevin J Bitterman
    Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Microbiol Mol Biol Rev 67:376-99, table of contents. 2003
    ..We also present the specific methods used to study aging and longevity regulation in S. cerevisiae...
  28. ncbi request reprint Resveratrol improves health and survival of mice on a high-calorie diet
    Joseph A Baur
    Department of Pathology, Paul F Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
    Nature 444:337-42. 2006
    ..These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity-related disorders and diseases of ageing...
  29. pmc Neuronal sirtuin1 mediates retinal vascular regeneration in oxygen-induced ischemic retinopathy
    Jing Chen
    Department of Ophthalmology, Boston Children s Hospital, Harvard Medical School, Boston, MA, USA
    Angiogenesis 16:985-92. 2013
    ....
  30. doi request reprint Measurement of sirtuin enzyme activity using a substrate-agnostic fluorometric nicotinamide assay
    Basil P Hubbard
    Department of Genetics, Harvard Medical School, Boston, MA, USA
    Methods Mol Biol 1077:167-77. 2013
    ..The assay is amenable to any substrate and any modification removed by sirtuins. The assay may also be used to measure glycohydrolase (e.g., CD38) and ADP-ribosyltransferase activity (e.g., mARTs and PARPs)...
  31. pmc Evidence for a common mechanism of SIRT1 regulation by allosteric activators
    Basil P Hubbard
    Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Science 339:1216-9. 2013
    ..In primary cells reconstituted with activation-defective SIRT1, the metabolic effects of STACs were blocked. Thus, SIRT1 can be directly activated through an allosteric mechanism common to chemically diverse STACs...
  32. pmc SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function
    Nathan L Price
    Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, Boston, MA 02115, USA
    Cell Metab 15:675-90. 2012
    ..Together these data indicate that SIRT1 plays an essential role in the ability of moderate doses of resveratrol to stimulate AMPK and improve mitochondrial function both in vitro and in vivo...
  33. ncbi request reprint Caloric restriction and life span determination of yeast cells
    Oliver Medvedik
    Pharmacology Department, Harvard Medical School, Boston, MA, USA
    Methods Mol Biol 371:97-109. 2007
    ..cerevisiae (6-8)...
  34. pmc SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis
    Dohoon Kim
    Howard Hughes Medical Institute, Picower Insitute for Learning and Memory, RIKEN MIT Neuroscience Research Center, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Boston, MA, USA
    EMBO J 26:3169-79. 2007
    ..Thus, SIRT1 constitutes a unique molecular link between aging and human neurodegenerative disorders and provides a promising avenue for therapeutic intervention...
  35. pmc Small molecule SIRT1 activators for the treatment of aging and age-related diseases
    Basil P Hubbard
    Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Trends Pharmacol Sci 35:146-54. 2014
    ....
  36. pmc GLTSCR2/PICT1 links mitochondrial stress and Myc signaling
    JOHN C YOON
    Department of Genetics, Harvard Medical School, Boston, MA 02115
    Proc Natl Acad Sci U S A 111:3781-6. 2014
    ..GLTSCR2 controls cellular proliferation and metabolism via the transcription factor Myc, and is induced by mitochondrial stress, suggesting it may constitute a significant component of the mitochondrial signaling pathway. ..
  37. pmc The intersection between aging and cardiovascular disease
    Brian J North
    Glenn Laboratories for the Biological Mechanisms of Aging, Department of Genetics, Harvard Medical School, Boston, MA, USA
    Circ Res 110:1097-108. 2012
    ....
  38. pmc SIRT1 is essential for normal cognitive function and synaptic plasticity
    Shaday Michan
    Paul F Glenn Laboratories, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Neurosci 30:9695-707. 2010
    ..In contrast, mice with high levels of SIRT1 expression in brain exhibited regular synaptic plasticity and memory. We conclude that SIRT1 is indispensable for normal learning, memory, and synaptic plasticity in mice...
  39. ncbi request reprint Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosis
    Haim Y Cohen
    Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115 USA
    Mol Cell 13:627-38. 2004
    ..We demonstrate that increased acetylation of Ku70 disrupts the Ku70-Bax interaction and coincides with cytoplasmic accumulation of CBP. These results shed light on the role of acetyltransferases as tumor suppressors...
  40. ncbi request reprint The role of nuclear architecture in genomic instability and ageing
    Philipp Oberdoerffer
    Department of Pathology, Paul F Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts, USA
    Nat Rev Mol Cell Biol 8:692-702. 2007
    ....
  41. pmc Mammalian sirtuins: biological insights and disease relevance
    Marcia C Haigis
    Glenn Laboratories for the Molecular Biology of Aging, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Annu Rev Pathol 5:253-95. 2010
    ..This review summarizes and discusses the advances of the past decade and the challenges that will confront the field in the coming years...
  42. ncbi request reprint Manipulation of a nuclear NAD+ salvage pathway delays aging without altering steady-state NAD+ levels
    Rozalyn M Anderson
    Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 277:18881-90. 2002
    ..We propose a model in which increased flux through the NAD(+) salvage pathway is responsible for the Sir2-dependent extension of life span...
  43. ncbi request reprint SIRT2 induces the checkpoint kinase BubR1 to increase lifespan
    Brian J North
    Department of Genetics, Paul F Glenn Laboratories for the Biological Mechanisms of Aging Harvard Medical School, Boston, MA, USA
    EMBO J 33:1438-53. 2014
    ..Together, these data indicate that further exploration of the potential of SIRT2 and NAD(+) to delay diseases of aging in mammals is warranted. ..
  44. doi request reprint Studying the replicative life span of yeast cells
    David A Sinclair
    Paul F Glenn Laboratories for the Molecular Biology of Aging, Harvard Medical School, Boston, MA, USA
    Methods Mol Biol 1048:49-63. 2013
    ..cerevisiae (Petes, Cell 19:765-774, 1980; Sinclair and Guarente, Cell 91:1033-1042, 1997; Defossez et al., Mol Cell 3:447-455, 1999)...
  45. pmc Germline energetics, aging, and female infertility
    Jonathan L Tilly
    Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Cell Metab 17:838-50. 2013
    ....
  46. pmc Inhibition of mammalian S6 kinase by resveratrol suppresses autophagy
    Sean M Armour
    Department of Pathology and Paul F Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, Boston, MA 02115, USA
    Aging (Albany NY) 1:515-28. 2009
    ..These data indicate that S6K1 is important for the full induction of autophagy in mammals and raise the possibility that some of the beneficial effects of resveratrol are due to modulation of S6K1 activity...
  47. pmc A high-confidence interaction map identifies SIRT1 as a mediator of acetylation of USP22 and the SAGA coactivator complex
    Sean M Armour
    Department of Genetics and The Paul F Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, Boston, Massachusetts, USA
    Mol Cell Biol 33:1487-502. 2013
    ..Our results indicate an important role of SIRT1-mediated deacetylation in regulating the formation of DUBm subcomplexes within the larger SAGA complex...
  48. pmc Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling
    Bogdan Beirowski
    Department of Genetics, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 108:E952-61. 2011
    ..These results demonstrate that Sirt2 controls an essential polarity pathway in SCs during myelin assembly and provide insights into the association between intracellular metabolism and SC plasticity...
  49. pmc Prolyl isomerase Pin1 regulates neuronal differentiation via β-catenin
    Kazuhiro Nakamura
    Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
    Mol Cell Biol 32:2966-78. 2012
    ....
  50. ncbi request reprint Therapeutic potential of resveratrol: the in vivo evidence
    Joseph A Baur
    Paul F Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
    Nat Rev Drug Discov 5:493-506. 2006
    ..Here, we provide a comprehensive and critical review of the in vivo data on resveratrol, and consider its potential as a therapeutic for humans...
  51. pmc Analysis of 41 cancer cell lines reveals excessive allelic loss and novel mutations in the SIRT1 gene
    Jeehae Han
    Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA
    Cell Cycle 12:263-70. 2013
    ..We conclude that allelic loss or mutations in the SIRT1 gene occur prevalently during tumorigenesis, supporting the assertion that SIRT1 may serve as a tumor suppressor...
  52. pmc Berberine protects against high fat diet-induced dysfunction in muscle mitochondria by inducing SIRT1-dependent mitochondrial biogenesis
    Ana P Gomes
    Center for Neurosciences and Cell Biology, Department of Life Sciences, University of Coimbra 3004 517 Coimbra, Portugal
    Biochim Biophys Acta 1822:185-95. 2012
    ..Taken together, these data reveal an important role for SIRT1 and mitochondrial biogenesis in the preventive effects of BBR on diet-induced insulin resistance...
  53. pmc Sirtuins: a conserved key unlocking AceCS activity
    Brian J North
    Department of Pathology, Paul F Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Trends Biochem Sci 32:1-4. 2007
    ..These findings highlight a metabolic regulatory network controlled by sirtuins that has implications for the mechanisms of calorie restriction and modulation of mammalian lifespan...
  54. pmc Resveratrol inhibits pathologic retinal neovascularization in Vldlr(-/-) mice
    Jing Hua
    Department of Ophthalmology, Harvard Medical School, Children s Hospital, Boston, Massachusetts 02115, USA
    Invest Ophthalmol Vis Sci 52:2809-16. 2011
    ..In this study, the authors evaluate the therapeutic potential of resveratrol, a plant polyphenol, in Vldlr(-/-) mice as a model for MacTel...
  55. ncbi request reprint Sirtuin activators mimic caloric restriction and delay ageing in metazoans
    Jason G Wood
    Department of Pathology, Harvard Medical School, 77 Ave Louis Pasteur, Boston, Massachusetts 02115, USA
    Nature 430:686-9. 2004
    ..Lifespan extension is dependent on functional Sir2, and is not observed when nutrients are restricted. Together these data indicate that STACs slow metazoan ageing by mechanisms that may be related to caloric restriction...
  56. pmc Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span
    Kevin J Pearson
    Laboratory of Experimental Gerontology, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA
    Cell Metab 8:157-68. 2008
    ..Our findings indicate that resveratrol treatment has a range of beneficial effects in mice but does not increase the longevity of ad libitum-fed animals when started midlife...
  57. pmc Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes
    Jill C Milne
    Sirtris Pharmaceuticals Inc, 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
    Nature 450:712-6. 2007
    ..Thus, SIRT1 activation is a promising new therapeutic approach for treating diseases of ageing such as type 2 diabetes...
  58. ncbi request reprint Life-span extension in yeast
    David A Sinclair
    Science 312:195-7; author reply 195-7. 2006
  59. ncbi request reprint Design, synthesis, and biological evaluation of sirtinol analogues as class III histone/protein deacetylase (Sirtuin) inhibitors
    Antonello Mai
    Dipartimento di Studi Farmaceutici, Istituto Pasteur, Fondazione Cenci Bolognetti, Universita degli Studi di Roma La Sapienza, P le A Moro 5, 00185 Roma, Italy
    J Med Chem 48:7789-95. 2005
    ..3-13 times less potent than sirtinol, whereas the 2'-carboxamido analogue was totally inactive. Both (R)- and (S)-sirtinol had similar inhibitory effects on the yeast and human enzymes, demonstrating no enantioselective inhibitory effect...
  60. ncbi request reprint Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan
    Konrad T Howitz
    BIOMOL Research Laboratories, Inc, 5120 Butler Pike, Plymouth Meeting, Pennsylvania 19462, USA
    Nature 425:191-6. 2003
    ..We discuss possible evolutionary origins of this phenomenon and suggest new lines of research into the therapeutic use of sirtuin activators...
  61. doi request reprint David A. Sinclair, Ph.D is interviewed by Vicki Glaser
    David A Sinclair
    Rejuvenation Res 11:265-8. 2008

Research Grants23

  1. Yeast screens for genetic & chemical mimetics of CR
    David Sinclair; Fiscal Year: 2006
    ..The longer-term goal is to test the genes and compounds we identify for their ability to extend life span in C. elegans. The knowledge gained should serve to guide searches for compounds that retard aging in mammals. ..
  2. NAD+ control of transcriptional silencing and longevity
    David Sinclair; Fiscal Year: 2006
    ..As far as we are aware, our approach to understanding this fundamental regulatory network is unique. ..
  3. Role of Sgs1 DNA helicase in telomere maintenance
    David Sinclair; Fiscal Year: 2002
    ....
  4. Role of Chromatin in Genomic Maintenance
    David Sinclair; Fiscal Year: 2009
    ....
  5. Yeast screens for genetic & chemical mimetics of CR
    David Sinclair; Fiscal Year: 2005
    ..The longer-term goal is to test the genes and compounds we identify for their ability to extend life span in C. elegans. The knowledge gained should serve to guide searches for compounds that retard aging in mammals. ..
  6. NAD+ control of transcriptional silencing and longevity
    David Sinclair; Fiscal Year: 2007
    ..As far as we are aware, our approach to understanding this fundamental regulatory network is unique. ..
  7. SIRT as a regulator of health and lifespan of mammals
    David Sinclair; Fiscal Year: 2007
    ....
  8. SIRT as a regulator of health and lifespan of mammals
    David Sinclair; Fiscal Year: 2009
    ....
  9. SIRT as a regulator of health and lifespan of mammals
    David A Sinclair; Fiscal Year: 2010
    ....
  10. Role of Sgs1 DNA helicase in telomere maintenance
    David Sinclair; Fiscal Year: 2001
    ....
  11. Role of Sgs1 DNA helicase in telomere maintenance
    David Sinclair; Fiscal Year: 2005
    ....
  12. Yeast screens for genetic & chemical mimetics of CR
    David Sinclair; Fiscal Year: 2002
    ..The longer-term goal is to test the genes and compounds we identify for their ability to extend life span in C. elegans. The knowledge gained should serve to guide searches for compounds that retard aging in mammals. ..
  13. NAD+ control of transcriptional silencing and longevity
    David Sinclair; Fiscal Year: 2003
    ..As far as we are aware, our approach to understanding this fundamental regulatory network is unique. ..
  14. Yeast screens for genetic & chemical mimetics of CR
    David Sinclair; Fiscal Year: 2003
    ..The longer-term goal is to test the genes and compounds we identify for their ability to extend life span in C. elegans. The knowledge gained should serve to guide searches for compounds that retard aging in mammals. ..
  15. Role of Sgs1 DNA helicase in telomere maintenance
    David Sinclair; Fiscal Year: 2003
    ....
  16. NAD+ control of transcriptional silencing and longevity
    David Sinclair; Fiscal Year: 2004
    ..As far as we are aware, our approach to understanding this fundamental regulatory network is unique. ..
  17. Role of Sgs1 DNA helicase in telomere maintenance
    David Sinclair; Fiscal Year: 2004
    ....
  18. Yeast screens for genetic & chemical mimetics of CR
    David Sinclair; Fiscal Year: 2004
    ..The longer-term goal is to test the genes and compounds we identify for their ability to extend life span in C. elegans. The knowledge gained should serve to guide searches for compounds that retard aging in mammals. ..
  19. NAD+ control of transcriptional silencing and longevity
    David Sinclair; Fiscal Year: 2005
    ..As far as we are aware, our approach to understanding this fundamental regulatory network is unique. ..
  20. Role of Chromatin in Genomic Maintenance
    David A Sinclair; Fiscal Year: 2010
    ....