Sirtuins - novel therapeutic targets to treat age-associated diseases

被引:378
作者
Lavu, Siva [1 ]
Boss, Olivier [1 ]
Elliott, Peter J. [1 ]
Lambert, Philip D. [1 ]
机构
[1] Sirtris Pharmaceut GSK Co, Cambridge, MA 02139 USA
关键词
D O I
10.1038/nrd2665
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Sirtuins post-translationally modulate the function of many cellular proteins that undergo reversible acetylation-deacetylation cycles, affecting physiological responses that have implications for treating diseases of ageing. Potent small-molecule modulators of sirtuins have shown efficacy in preclinical models of metabolic, neurodegenerative and inflammatory diseases, and so hold promise for drug discovery efforts in multiple therapeutic areas. Here, we discuss current knowledge and data that strengthens sirtuins as a druggable set of enzymes for the treatment of age-associated diseases, including activation of SIRT1 in type 2 diabetes.
引用
收藏
页码:841 / 853
页数:13
相关论文
共 160 条
  • [1] Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase
    Ahuja, Nidhi
    Schwer, Bjoern
    Carobbio, Stefania
    Waltregny, David
    North, Brian J.
    Castronovo, Vincenzo
    Maechler, Pierre
    Verdin, Eric
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (46) : 33583 - 33592
  • [2] Sirt1 regulates aging and resistance to oxidative stress in the heart
    Alcendor, Ralph R.
    Gao, Shumin
    Zhai, Peiyong
    Zablocki, Daniela
    Holle, Eric
    Yu, Xianzhong
    Tian, Bin
    Wagner, Thomas
    Vatner, Stephen F.
    Sadoshima, Junichi
    [J]. CIRCULATION RESEARCH, 2007, 100 (10) : 1512 - 1521
  • [3] Silent information regulator 2α, a longevity factor and class III histone deacetylase, is an essential endogenous apoptosis inhibitor in cardiac myocytes
    Alcendor, RR
    Kirshenbaum, LA
    Imai, S
    Vatner, SF
    Sadoshima, J
    [J]. CIRCULATION RESEARCH, 2004, 95 (10) : 971 - 980
  • [4] Comparative analysis of the effects of resveratrol in two apoptotic models:: Inhibition of complex I and potassium deprivation in cerebellar neurons
    Alvira, D.
    Yeste-Velasco, M.
    Folch, J.
    Verdaguer, E.
    Canudas, A. M.
    Pallas, M.
    Camins, A.
    [J]. NEUROSCIENCE, 2007, 147 (03) : 746 - 756
  • [5] Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration
    Araki, T
    Sasaki, Y
    Milbrandt, J
    [J]. SCIENCE, 2004, 305 (5686) : 1010 - 1013
  • [6] Transcriptional coactivator PGC-1α controls the energy state and contractile function of cardiac muscle
    Arany, Z
    He, HM
    Lin, JD
    Hoyer, K
    Handschin, C
    Toka, O
    Ahmad, F
    Matsui, T
    Chin, S
    Wu, PH
    Rybkin, II
    Shelton, JM
    Manieri, M
    Cinti, S
    Schoen, FJ
    Bassel-Duby, R
    Rosenzweig, A
    Ingwall, JS
    Spiegelman, BM
    [J]. CELL METABOLISM, 2005, 1 (04) : 259 - 271
  • [7] Resveratrol improves health and survival of mice on a high-calorie diet
    Baur, Joseph A.
    Pearson, Kevin J.
    Price, Nathan L.
    Jamieson, Hamish A.
    Lerin, Carles
    Kalra, Avash
    Prabhu, Vinayakumar V.
    Allard, Joanne S.
    Lopez-Lluch, Guillermo
    Lewis, Kaitlyn
    Pistell, Paul J.
    Poosala, Suresh
    Becker, Kevin G.
    Boss, Olivier
    Gwinn, Dana
    Wang, Mingyi
    Ramaswamy, Sharan
    Fishbein, Kenneth W.
    Spencer, Richard G.
    Lakatta, Edward G.
    Le Couteur, David
    Shaw, Reuben J.
    Navas, Placido
    Puigserver, Pere
    Ingram, Donald K.
    de Cabo, Rafael
    Sinclair, David A.
    [J]. NATURE, 2006, 444 (7117) : 337 - 342
  • [8] Cytogenetics and Molecular Genetics of Malignant Gliomas and Medulloblastoma
    Bigner, Sandra H.
    Vogelstein, Bert
    [J]. BRAIN PATHOLOGY, 1990, 1 (01) : 12 - 18
  • [9] SirT1 Regulates Energy Metabolism and Response to Caloric Restriction in Mice
    Boily, Gino
    Seifert, Erin L.
    Bevilacqua, Lisa
    He, Xiao Hong
    Sabourin, Guillaume
    Estey, Carmen
    Moffat, Cynthia
    Crawford, Sean
    Saliba, Sarah
    Jardine, Karen
    Xuan, Jian
    Evans, Meredith
    Harper, Mary-Ellen
    McBurney, Michael W.
    [J]. PLOS ONE, 2008, 3 (03):
  • [10] Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic β cells
    Bordone, L
    Motta, MC
    Picard, F
    Robinson, A
    Jhala, US
    Apfeld, J
    McDonagh, T
    Lemieux, M
    McBurney, M
    Szilvasi, A
    Easlon, EJ
    Lin, SJ
    Guarente, L
    [J]. PLOS BIOLOGY, 2006, 4 (02): : 210 - 220