With TOR, Less Is More: A Key Role for the Conserved Nutrient-Sensing TOR Pathway in Aging

被引:510
作者
Kapahi, Pankaj [1 ]
Chen, Di [1 ]
Rogers, Anc N. [1 ]
Katewa, Subhash D. [1 ]
Li, Patrick Wai-Lun [1 ]
Thomas, Emma L. [1 ]
Kockel, Lutz [2 ]
机构
[1] Buck Inst Age Res, Novato, CA 94945 USA
[2] Univ Calif San Francisco, Dept Med, Ctr Diabet, San Francisco, CA 94143 USA
基金
美国国家卫生研究院;
关键词
LIFE-SPAN EXTENSION; CELL-CYCLE ARREST; DIETARY RESTRICTION; AUTOPHAGY GENES; S6; KINASE; DEVELOPMENTAL ARREST; CALORIC RESTRICTION; STRESS RESISTANCE; HYPOXIC RESPONSE; RAG GTPASES;
D O I
10.1016/j.cmet.2010.05.001
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Target of rapamycin (TOR) is an evolutionarily conserved nutrient-sensing protein kinase that regulates growth and metabolism in all eukaryotic cells. Studies in flies, worms, yeast, and mice support the notion that the TOR signaling network modulates aging. TOR is also emerging as a robust mediator of the protective effects of various forms of dietary restriction (DR), which can extend life span and slow the onset of certain age-related diseases across species. Here we discuss how modulating TOR signaling slows aging through downstream processes including mRNA translation, autophagy, endoplasmic reticulum (ER) stress signaling, stress responses, and metabolism. Identifying the mechanisms by which the TOR signaling network works as a pacemaker of aging is a major challenge and may help identify potential drug targets for age-related diseases, thereby facilitating healthful life span extension in humans.
引用
收藏
页码:453 / 465
页数:13
相关论文
共 124 条
[1]   Metabolism, ubiquinone synthesis, and longevity [J].
Aguilaniu, H ;
Durieux, J ;
Dillin, A .
GENES & DEVELOPMENT, 2005, 19 (20) :2399-2406
[2]   S6 kinase deletion suppresses muscle growth adaptations to nutrient availability by activating AMP kinase [J].
Aguilar, Victor ;
Alliouachene, Samira ;
Sotiropoulos, Athanassia ;
Sobering, Andrew ;
Athea, Yoni ;
Djouadi, Fatima ;
Miraux, Sylvain ;
Thiaudiere, Eric ;
Foretz, Marc ;
Viollet, Benoit ;
Diolez, Philippe ;
Bastin, Jean ;
Benit, Paule ;
Rustin, Pierre ;
Carling, David ;
Sandri, Marco ;
Ventuar-Clapier, Renee ;
Pende, Mario .
CELL METABOLISM, 2007, 5 (06) :476-487
[3]   New Insights into mTOR Signaling: mTORC2 and Beyond [J].
Alessi, Dario R. ;
Pearce, Laura R. ;
Garcia-Martinez, Juan M. .
SCIENCE SIGNALING, 2009, 2 (67) :pe27
[4]   Metformin slows down aging and extends life span of female SHR mice [J].
Anisimov, Vladimir N. ;
Berstein, Lev M. ;
Egormin, Peter A. ;
Piskunova, Tatiana S. ;
Popovich, Irina G. ;
Zabezhinski, Mark A. ;
Tyndyk, Margarita L. ;
Yurova, Maria V. ;
Kovalenko, Irina G. ;
Poroshina, Tatiana E. ;
Semenchenko, Anna V. .
CELL CYCLE, 2008, 7 (17) :2769-2773
[5]   The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C-elegans [J].
Apfeld, J ;
O'Connor, G ;
McDonagh, T ;
DiStefano, PS ;
Curtis, R .
GENES & DEVELOPMENT, 2004, 18 (24) :3004-3009
[6]   Life extension in the dwarf mouse [J].
Bartke, A ;
Brown-Borg, H .
CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY, VOL 63, 2004, 63 :189-+
[7]   A Human Protein Interaction Network Shows Conservation of Aging Processes between Human and Invertebrate Species [J].
Bell, Russell ;
Hubbard, Alan ;
Chettier, Rakesh ;
Chen, Di ;
Miller, John P. ;
Kapahi, Pankaj ;
Tarnopolsky, Mark ;
Sahasrabuhde, Sudhir ;
Melov, Simon ;
Hughes, Robert E. .
PLOS GENETICS, 2009, 5 (03)
[8]   Skeletal Muscle-Specific Ablation of raptor, but Not of rictor, Causes Metabolic Changes and Results in Muscle Dystrophy [J].
Bentzinger, C. Florian ;
Romanino, Klaas ;
Cloetta, Dimitri ;
Lin, Shuo ;
Mascarenhas, Joseph B. ;
Oliveri, Filippo ;
Xia, Jinyu ;
Casanova, Emilio ;
Costa, Celine F. ;
Brink, Marijke ;
Zorzato, Francesco ;
Hall, Michael N. ;
Rueegg, Markus A. .
CELL METABOLISM, 2008, 8 (05) :411-424
[9]   PML inhibits HIF-1α translation and neoangiogenesis through repression of mTOR [J].
Bernardi, Rosa ;
Guernah, Ilhem ;
Jin, David ;
Grisendi, Silvia ;
Alimonti, Andrea ;
Teruya-Feldstein, Julie ;
Cordon-Cardo, Carlos ;
Simon, M. Celeste ;
Rafii, Shahin ;
Pandolfi, Pier Paolo .
NATURE, 2006, 442 (7104) :779-785
[10]   The TOR (target of rapamycin) signal transduction pathway regulates the stability of translation initiation factor eIF4G in the yeast Saccharomyces cerevisiae [J].
Berset, C ;
Trachsel, H ;
Altmann, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (08) :4264-4269