Weekly administration of rapamycin improves survival and biomarkers in obese male mice on high-fat diet
Version of Record online: 22 MAR 2014
© 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Volume 13, Issue 4, pages 616–622, August 2014
How to Cite
Leontieva, O. V., Paszkiewicz, G. M. and Blagosklonny, M. V. (2014), Weekly administration of rapamycin improves survival and biomarkers in obese male mice on high-fat diet. Aging Cell, 13: 616–622. doi: 10.1111/acel.12211
- Issue online: 29 JUL 2014
- Version of Record online: 22 MAR 2014
- Manuscript Accepted: 2 FEB 2014
- anti-aging agent;
- mammalian or mechanistic target of rapamycin;
Recent discoveries have revealed the key role of mTOR (target of rapamycin) in aging. Furthermore, rapamycin extends lifespan in mice, especially in female mice. Here, we treated obese male mice on high-fat diet with rapamycin given intermittently: either weekly (once a week) or alternating bi-weekly (three injections every other week). While only marginally reducing obesity, intermittent administration of rapamycin significantly extended lifespan. Significance was achieved for weekly treated group and for the three rapamycin-received groups combined. In weekly treatment group, 100% mice were alive by the age of 2 years, whereas 60% of mice died in untreated group by this age. The effect of weekly treatment on survival was highly significant and cannot be fully explained by partial reduction in obesity. Alternating bi-weekly treatments seem to be less effective than weekly treatment, although effects of additional factors (see 'Discussion') may not be excluded. After one year of treatment, all survived mice were sacrificed 8 days after the last administration of rapamycin to avoid its direct interference with parameters examined. Fasting levels of cardiac and hepatic p-S6, a marker of mTORC1 activity, were lower in weekly treatment group compared with control mice. In contrast, levels of p-Akt (S473), glucose, triglycerides and insulin were unchanged, whereas leptin and IGF-1 tended to be lower. Thus, weekly treatment with rapamycin may slow down aging in obese male mice on high-fat diet.