Rapamycin increases lifespan and inhibits spontaneous tumorigenesis in inbred female mice

The nutrient-sensing TO R (target of rapamycin) pathway is involved in cellular and organismal aging. Rapamycin, an inhibitor of TO R, extends lifespan in yeast, fruit flies and genetically heterogeneous mice. Here, we demonstrate that lifelong administration of rapamycin extends lifespan in female...

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Published in:Cell cycle (Georgetown, Tex.) Tex.), 2011-12, Vol.10 (24), p.4230-4236
Main Authors: 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
Format: Article
Language:English
Subjects:
Aging - drug effects
Animals
Binding
Biology
Bioscience
Body Temperature
Calcium
Cancer
Cell
Cell Transformation, Neoplastic - drug effects
Cycle
Estrus - drug effects
Female
Landes
Longevity - drug effects
Mice
Mice, 129 Strain
Organogenesis
Proteins
Sirolimus - pharmacology
Statistics, Nonparametric
Survival Analysis
Weight Gain - drug effects
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Summary:The nutrient-sensing TO R (target of rapamycin) pathway is involved in cellular and organismal aging. Rapamycin, an inhibitor of TO R, 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.
ISSN:1538-4101
1551-4005
DOI:10.4161/cc.10.24.18486