Short-term treatment with rapamycin and dietary restriction have overlapping and distinctive effects in young mice

Wilson C. Fok, Yiqiang Zhang, Adam B. Salmon, Arunabh Bhattacharya, Rakesh Gunda, Dean Jones, Walter Ward, Kathleen Fisher, Arlan Richardson, Viviana I. Pérez

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Because rapamycin, an inhibitor of the nutrient sensor mammalian target of rapamycin, and dietary restriction both increase life span of mice, it has been hypothesized that they act through similar mechanisms. To test this hypothesis, we compared various biological parameters in dietary restriction mice (40% food restriction) and mice fed rapamycin (14 ppm). Both treatments led to a significant reduction in mammalian target of rapamycin signaling and a corresponding increase in autophagy. However, we observed striking differences in fat mass, insulin sensitivity, and expression of cell cycle and sirtuin genes in mice fed rapamycin compared with dietary restriction. Thus, although both treatments lead to significant downregulation of mammalian target of rapamycin signaling, these two manipulations have quite different effects on other physiological functions suggesting that they might increase life span through a common pathway as well as pathways that are altered differently by dietary restriction and rapamycin.

Original languageEnglish (US)
Pages (from-to)108-116
Number of pages9
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume68
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

  • Autophagy
  • Dietary restriction
  • Gene expression
  • Rapamycin
  • mTOR

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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