Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice

被引：331

作者：

Bitto, Alessandro ^{[1
]}

Ito, Takashi K. ^{[1
]}

Pineda, Victor V. ^{[1
]}

LeTexier, Nicolas J. ^{[1
]}

Huang, Heather Z. ^{[1
]}

Sutlief, Elissa ^{[1
]}

Tung, Herman ^{[1
]}

Vizzini, Nicholas ^{[1
]}

Chen, Belle ^{[1
]}

Smith, Kaleb ^{[1
]}

Meza, Daniel ^{[1
]}

Yajima, Masanao ^{[2
]}

Beyer, Richard P. ^{[3
]}

Kerr, Kathleen F. ^{[4
]}

Davis, Daniel J. ^{[5
]}

Gillespie, Catherine H. ^{[5
]}

Snyder, Jessica M. ^{[6
]}

Treuting, Piper M. ^{[6
]}

Kaeberlein, Matt ^{[1
]}

机构：

[1] Univ Washington, Dept Pathol, Seattle, WA 98195 USA

[2] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA

[3] Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA

[4] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[5] Univ Missouri, Dept Vet Pathobiol, Columbia, MO USA

[6] Univ Washington, Dept Comparat Med, Seattle, WA 98195 USA

来源：

ELIFE | 2016年 / 5卷

基金：

日本学术振兴会;

关键词：

GENETICALLY HETEROGENEOUS MICE; MITOCHONDRIAL DISEASE; MTOR INHIBITION; RESTRICTION; LONGEVITY; SIROLIMUS; WEIGHT; CELLS;

D O I：

10.7554/eLife.16351

中图分类号：

Q [生物科学];

学科分类号：

090105 [作物生产系统与生态工程];

摘要：

The FDA approved drug rapamycin increases lifespan in rodents and delays age-related dysfunction in rodents and humans. Nevertheless, important questions remain regarding the optimal dose, duration, and mechanisms of action in the context of healthy aging. Here we show that 3 months of rapamycin treatment is sufficient to increase life expectancy by up to 60% and improve measures of healthspan in middle-aged mice. This transient treatment is also associated with a remodeling of the microbiome, including dramatically increased prevalence of segmented filamentous bacteria in the small intestine. We also define a dose in female mice that does not extend lifespan, but is associated with a striking shift in cancer prevalence toward aggressive hematopoietic cancers and away from non-hematopoietic malignancies. These data suggest that a short-term rapamycin treatment late in life has persistent effects that can robustly delay aging, influence cancer prevalence, and modulate the microbiome.

引用

页数：17

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