At concentrations that inhibit mTOR, resveratrol suppresses cellular senescence

被引:107
作者
Demidenko, Zoya N. [1 ]
Blagosklonny, Mikhail V. [1 ,2 ]
机构
[1] Oncotarget, Albany, NY USA
[2] Ordway Res Inst, Albany, NY USA
关键词
resveratrol; rapamycin; cellular senescence; S6; mTOR; SMALL-MOLECULE ACTIVATORS; SMOOTH-MUSCLE-CELLS; CANCER-CELLS; LIFE-SPAN; APOPTOSIS; ARREST; GROWTH; RESTRICTION; HYPERTROPHY; SIRTUINS;
D O I
10.4161/cc.8.12.8810
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Here we demonstrated that, at cytostatic, near-toxic concentrations, resveratrol inhibited S6 phosphorylation and prevented the senescence morphology in human cells. Using a sensitive functional assay, we found that resveratrol partially prevented loss of the proliferative potential associated with cellular senescence. Resveratrol was less effective than rapamycin, because aging-suppression by resveratrol was limited by its toxicity at high concentrations. We discuss whether concentrations of resveratrol that inhibit mTOR (target of rapamycin) and suppress cellular senescence are clinically achievable and whether partial inhibition of mTOR by resveratrol might be sufficient to affect organismal aging.
引用
收藏
页码:1901 / 1904
页数:4
相关论文
共 32 条
[1]  
Ahmad N, 2001, CLIN CANCER RES, V7, P1466
[2]   An accelerated assay for the identification of lifespan-extending interventions in Drosophila melanogaster [J].
Bauer, JH ;
Goupil, S ;
Garber, GB ;
Helfand, SL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (35) :12980-12985
[3]   Resveratrol improves health and survival of mice on a high-calorie diet [J].
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. .
NATURE, 2006, 444 (7117) :337-342
[4]   Therapeutic potential of resveratrol:: the in vivo evidence [J].
Baur, Joseph A. ;
Sinclair, David A. .
NATURE REVIEWS DRUG DISCOVERY, 2006, 5 (06) :493-506
[5]   Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent [J].
Boocock, David J. ;
Faust, Guy E. S. ;
Patel, Ketan R. ;
Schinas, Anna M. ;
Brown, Victoria A. ;
Ducharme, Murray P. ;
Booth, Tristan D. ;
Crowell, James A. ;
Perloff, Marjorie ;
Gescher, Andreas J. ;
Steward, William P. ;
Brenner, Dean E. .
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2007, 16 (06) :1246-1252
[6]   trans-3,4,5′-trihydroxystibene inhibits hypoxia-inducible factor 1α and vascular endothelial growth factor expression in human ovarian cancer cells [J].
Cao, ZX ;
Fang, J ;
Xia, C ;
Shi, XL ;
Jiang, BH .
CLINICAL CANCER RESEARCH, 2004, 10 (15) :5253-5263
[7]   Resveratrol inhibits cardiac hypertrophy via AMP-activated protein kinase and Akt [J].
Chan, Anita Y. M. ;
Dolinsky, Vernon W. ;
Soltys, Carrie-Lynn M. ;
Viollet, Benoit ;
Baksh, Shairaz ;
Light, Peter E. ;
Dyck, Jason R. B. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (35) :24194-24201
[8]  
Chang BD, 1999, CANCER RES, V59, P3761
[9]   Resveratrol-associated renal toxicity [J].
Crowell, JA ;
Korytko, PJ ;
Morrissey, RL ;
Booth, TD ;
Levine, BS .
TOXICOLOGICAL SCIENCES, 2004, 82 (02) :614-619
[10]   Resveratrol - From basic science to the clinic [J].
Cucciolla, Valeria ;
Borriello, Adriana ;
Oliva, Adriana ;
Galletti, Patrizia ;
Zappia, Vincenzo ;
Della Ragione, Fulvio .
CELL CYCLE, 2007, 6 (20) :2495-2510