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Age (Dordr). 2014 Feb;36(1):199-212. doi: 10.1007/s11357-013-9572-5. Epub 2013 Aug 16.

Contrasting effects of chronic, systemic treatment with mTOR inhibitors rapamycin and metformin on adult neural progenitors in mice.

Author information

1
Neuroscience Graduate Program, Arizona State University, Phoenix, AZ, 85287, USA.

Abstract

The chronic and systemic administration of rapamycin extends life span in mammals. Rapamycin is a pharmacological inhibitor of mTOR. Metformin also inhibits mTOR signaling but by activating the upstream kinase AMPK. Here we report the effects of chronic and systemic administration of the two mTOR inhibitors, rapamycin and metformin, on adult neural stem cells of the subventricular region and the dendate gyrus of the mouse hippocampus. While rapamycin decreased the number of neural progenitors, metformin-mediated inhibition of mTOR had no such effect. Adult-born neurons are considered important for cognitive and behavioral health, and may contribute to improved health span. Our results demonstrate that distinct approaches of inhibiting mTOR signaling can have significantly different effects on organ function. These results underscore the importance of screening individual mTOR inhibitors on different organs and physiological processes for potential adverse effects that may compromise health span.

PMID:
23949159
PMCID:
PMC3889877
DOI:
10.1007/s11357-013-9572-5
[Indexed for MEDLINE]
Free PMC Article

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