Rapamycin increases lifespan and inhibits spontaneous tumorigenesis in inbred female mice

被引：272

作者：

Anisimov, Vladimir N. ^{[1
]}

Zabezhinski, Mark A. ^{[1
]}

Popovich, Irina G. ^{[1
]}

Piskunova, Tatiana S. ^{[1
]}

Semenchenko, Anna V. ^{[1
]}

Tyndyk, Margarita L. ^{[1
]}

Yurova, Maria N. ^{[1
]}

Rosenfeld, Svetlana V. ^{[1
]}

Blagosklonny, Mikhail V. ^{[2
,3
]}

机构：

[1] NN Petrov Oncol Res Inst, Dept Carcinogenesis & Oncogerontol, St Petersburg, Russia

[2] Roswell Pk Canc Inst, Dept Mol & Cellular Biol, Buffalo, NY 14263 USA

[3] Roswell Pk Canc Inst, Dept Cell Stress Biol, Buffalo, NY 14263 USA

来源：

CELL CYCLE | 2011年 / 10卷 / 24期

基金：

俄罗斯基础研究基金会;

关键词：

rapamycin; mTOR; aging; longevity; gerosuppressants; HER-2/NEU TRANSGENIC MICE; SPONTANEOUS MAMMARY-TUMORS; FATAL NEOPLASTIC DISEASES; CELLULAR SENESCENCE; PHARMACOLOGICAL INHIBITION; CALORIE RESTRICTION; DELAYED OCCURRENCE; RIBOSOMAL-PROTEIN; DOWN-REGULATION; MTOR PATHWAY;

D O I：

10.4161/cc.10.24.18486

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The nutrient-sensing TOR (target of rapamycin) pathway is involved in cellular and organismal aging. Rapamycin, an inhibitor of TOR, extends lifespan in yeast, fruit flies and genetically heterogeneous mice. Here, we demonstrate that lifelong administration of rapamycin extends lifespan in female 129/Sv mice characterized by normal mean lifespan of 2 y. Importantly, rapamycin was administrated intermittently (2 weeks per month) starting from the age of 2 mo. Rapamycin inhibited age-related weight gain, decreased aging rate, increased lifespan (especially in the last survivors) and delayed spontaneous cancer. 22.9% of rapamycin-treated mice survived the age of death of the last mouse in control group. Thus we demonstrated for the first time in normal inbred mice that lifespan can be extended by rapamycin. This opens an avenue to develop optimal doses and schedules of rapamycin as an anti-aging modality.

引用

页码：4230 / 4236

页数：7