Rapalogs and mTOR inhibitors as anti-aging therapeutics

被引:487
作者
Lamming, Dudley W. [1 ,2 ,3 ]
Ye, Lan [4 ,5 ]
Sabatini, David M. [1 ,2 ,3 ]
Baur, Joseph A. [4 ,5 ]
机构
[1] MIT, Howard Hughes Med Inst, Dept Biol, Whitehead Inst Biomed Res, Cambridge, MA USA
[2] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA
[3] Broad Inst MIT & Harvard, Cambridge, MA USA
[4] Univ Penn, Perelman Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA
[5] Univ Penn, Perelman Sch Med, Dept Physiol, Philadelphia, PA 19104 USA
关键词
EXTENDS LIFE-SPAN; HEMATOPOIETIC STEM-CELLS; INDUCED CARDIAC-HYPERTROPHY; MESSENGER-RNA TRANSLATION; ACTIVATED PROTEIN-KINASE; GENETICALLY HETEROGENEOUS MICE; HUTCHINSON-GILFORD PROGERIA; RENAL-TRANSPLANT RECIPIENTS; MAMMALIAN TARGET; CAENORHABDITIS-ELEGANS;
D O I
10.1172/JCI64099
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
100103 [病原生物学]; 100218 [急诊医学];
摘要
Rapamycin, an inhibitor of mechanistic target of rapamycin (mTOR), has the strongest experimental support to date as a potential anti-aging therapeutic in mammals. Unlike many other compounds that have been claimed to influence longevity, rapamycin has been repeatedly tested in long-lived, genetically heterogeneous mice, in which it extends both mean and maximum life spans. However, the mechanism that accounts for these effects is far from clear, and a growing list of side effects make it doubtful that rapamycin would ultimately be beneficial in humans. This Review discusses the prospects for developing newer, safer anti-aging therapies based on analogs of rapamycin (termed rapalogs) or other approaches targeting mTOR signaling.
引用
收藏
页码:980 / 989
页数:10
相关论文
共 131 条
[1]
Autophagy is required for extension of yeast chronological life span by rapamycin [J].
Alvers, Ashley L. ;
Wood, Michael S. ;
Hu, Doreen ;
Kaywell, Amelia C. ;
Dunn, William A., Jr. ;
Aris, John P. .
AUTOPHAGY, 2009, 5 (06) :847-849
[2]
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
[3]
Rapamycin increases lifespan and inhibits spontaneous tumorigenesis in inbred female mice [J].
Anisimov, Vladimir N. ;
Zabezhinski, Mark A. ;
Popovich, Irina G. ;
Piskunova, Tatiana S. ;
Semenchenko, Anna V. ;
Tyndyk, Margarita L. ;
Yurova, Maria N. ;
Rosenfeld, Svetlana V. ;
Blagosklonny, Mikhail V. .
CELL CYCLE, 2011, 10 (24) :4230-4236
[4]
Rapamycin Extends Maximal Lifespan in Cancer-Prone Mice [J].
Anisimov, Vladimir N. ;
Zabezhinski, Mark A. ;
Popovich, Irina G. ;
Piskunova, Tatiana S. ;
Semenchenko, Anna V. ;
Tyndyk, Margarita L. ;
Yurova, Maria N. ;
Antoch, Marina P. ;
Blagosklonny, Mikhail V. .
AMERICAN JOURNAL OF PATHOLOGY, 2010, 176 (05) :2092-2097
[5]
Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic mice [J].
Anisimov, VN ;
Berstein, LM ;
Egormin, PA ;
Piskunova, TS ;
Popovich, IG ;
Zabezhinski, MA ;
Kovalenko, IG ;
Poroshina, TE ;
Semenchenko, AV ;
Provinciali, M ;
Re, F ;
Franceschi, C .
EXPERIMENTAL GERONTOLOGY, 2005, 40 (8-9) :685-693
[6]
TOR in the immune system [J].
Araki, Koichi ;
Ellebedy, Ali H. ;
Ahmed, Rafi .
CURRENT OPINION IN CELL BIOLOGY, 2011, 23 (06) :707-715
[7]
mTOR regulates memory CD8 T-cell differentiation [J].
Araki, Koichi ;
Turner, Alexandra P. ;
Shaffer, Virginia Oliva ;
Gangappa, Shivaprakash ;
Keller, Susanne A. ;
Bachmann, Martin F. ;
Larsen, Christian P. ;
Ahmed, Rafi .
NATURE, 2009, 460 (7251) :108-U124
[8]
WORTMANNIN IS A POTENT PHOSPHATIDYLINOSITOL 3-KINASE INHIBITOR - THE ROLE OF PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE IN NEUTROPHIL RESPONSES [J].
ARCARO, A ;
WYMANN, MP .
BIOCHEMICAL JOURNAL, 1993, 296 :297-301
[9]
Screen for Chemical Modulators of Autophagy Reveals Novel Therapeutic Inhibitors of mTORC1 Signaling [J].
Balgi, Aruna D. ;
Fonseca, Bruno D. ;
Donohue, Elizabeth ;
Tsang, Trevor C. F. ;
Lajoie, Patrick ;
Proud, Christopher G. ;
Nabi, Ivan R. ;
Roberge, Michel .
PLOS ONE, 2009, 4 (09)
[10]
Metformin, Independent of AMPK, Induces mTOR Inhibition and Cell-Cycle Arrest through REDD1 [J].
Ben Sahra, Isaam ;
Regazzetti, Claire ;
Robert, Guillaume ;
Laurent, Kathiane ;
Le Marchand-Brustel, Yannick ;
Auberger, Patrick ;
Tanti, Jean-Francois ;
Giorgetti-Peraldi, Sophie ;
Bost, Frederic .
CANCER RESEARCH, 2011, 71 (13) :4366-4372