2009 July 16; 460(7253): 392–395 | David E. Harrison, Randy Strong, Zelton Dave Sharp, James F. Nelson, Clinton M. Astle, Kevin Flurkey, Nancy L. Nadon, J. Erby Wilkinson, Krystyna Frenkel, Christy S. Carter, Marco Pahor, Martin A. Javors, Elizabeth Fernandez, Richard A. Miller
The study by Harrison et al. investigates the effects of rapamycin, an inhibitor of the mTOR pathway, on lifespan in genetically heterogeneous mice. The research was conducted at three independent test sites: The Jackson Laboratory, the University of Michigan, and the University of Texas Health Science Center. The key findings are that feeding rapamycin to mice starting at 600 days of age significantly extended both median and maximal lifespan in both male and female mice. Specifically, rapamycin increased median lifespan by 9% in males and 14% in females, and extended maximal lifespan by 28% in males and 38% in females. The effects were consistent across all three test sites and were not influenced by differences in diet or health status prior to rapamycin administration. The study also found that rapamycin reduced phosphorylation of the target substrate rpS6 in visceral white adipose tissue, indicating effective mTOR inhibition. These results provide the first evidence of a role for mTOR signaling in regulating mammalian lifespan and suggest that mTOR inhibition could be a promising target for interventions to delay aging and prevent age-related diseases.The study by Harrison et al. investigates the effects of rapamycin, an inhibitor of the mTOR pathway, on lifespan in genetically heterogeneous mice. The research was conducted at three independent test sites: The Jackson Laboratory, the University of Michigan, and the University of Texas Health Science Center. The key findings are that feeding rapamycin to mice starting at 600 days of age significantly extended both median and maximal lifespan in both male and female mice. Specifically, rapamycin increased median lifespan by 9% in males and 14% in females, and extended maximal lifespan by 28% in males and 38% in females. The effects were consistent across all three test sites and were not influenced by differences in diet or health status prior to rapamycin administration. The study also found that rapamycin reduced phosphorylation of the target substrate rpS6 in visceral white adipose tissue, indicating effective mTOR inhibition. These results provide the first evidence of a role for mTOR signaling in regulating mammalian lifespan and suggest that mTOR inhibition could be a promising target for interventions to delay aging and prevent age-related diseases.