Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction

Richard A. Miller, David E. Harrison, Clinton M. Astle, Elizabeth Fernandez, Kevin Flurkey, Melissa Han, Martin A Javors, Xinna Li, Nancy L. Nadon, James F Nelson, Scott Pletcher, Adam Salmon, Zelton D Sharp, Sabrina Van Roekel, Lynn Winkleman, John R Strong

Research output: Contribution to journalArticle

227 Citations (Scopus)

Abstract

Rapamycin, an inhibitor of mTOR kinase, increased median lifespan of genetically heterogeneous mice by 23% (males) to 26% (females) when tested at a dose threefold higher than that used in our previous studies; maximal longevity was also increased in both sexes. Rapamycin increased lifespan more in females than in males at each dose evaluated, perhaps reflecting sexual dimorphism in blood levels of this drug. Some of the endocrine and metabolic changes seen in diet-restricted mice are not seen in mice exposed to rapamycin, and the pattern of expression of hepatic genes involved in xenobiotic metabolism is also quite distinct in rapamycin-treated and diet-restricted mice, suggesting that these two interventions for extending mouse lifespan differ in many respects.

Original languageEnglish (US)
Pages (from-to)468-477
Number of pages10
JournalAging Cell
Volume13
Issue number3
DOIs
StatePublished - 2014

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Sirolimus
Diet
Xenobiotics
Sex Characteristics
Phosphotransferases
Gene Expression
Liver
Pharmaceutical Preparations

Keywords

  • Aging
  • Caloric restriction
  • Glucose
  • IGF-1
  • Insulin
  • Longevity
  • Mouse
  • MTOR
  • Rapamycin
  • Xenobiotic metabolism

ASJC Scopus subject areas

  • Cell Biology
  • Aging

Cite this

Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction. / Miller, Richard A.; Harrison, David E.; Astle, Clinton M.; Fernandez, Elizabeth; Flurkey, Kevin; Han, Melissa; Javors, Martin A; Li, Xinna; Nadon, Nancy L.; Nelson, James F; Pletcher, Scott; Salmon, Adam; Sharp, Zelton D; Van Roekel, Sabrina; Winkleman, Lynn; Strong, John R.

In: Aging Cell, Vol. 13, No. 3, 2014, p. 468-477.

Research output: Contribution to journalArticle

Miller, RA, Harrison, DE, Astle, CM, Fernandez, E, Flurkey, K, Han, M, Javors, MA, Li, X, Nadon, NL, Nelson, JF, Pletcher, S, Salmon, A, Sharp, ZD, Van Roekel, S, Winkleman, L & Strong, JR 2014, 'Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction', Aging Cell, vol. 13, no. 3, pp. 468-477. https://doi.org/10.1111/acel.12194
Miller, Richard A. ; Harrison, David E. ; Astle, Clinton M. ; Fernandez, Elizabeth ; Flurkey, Kevin ; Han, Melissa ; Javors, Martin A ; Li, Xinna ; Nadon, Nancy L. ; Nelson, James F ; Pletcher, Scott ; Salmon, Adam ; Sharp, Zelton D ; Van Roekel, Sabrina ; Winkleman, Lynn ; Strong, John R. / Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction. In: Aging Cell. 2014 ; Vol. 13, No. 3. pp. 468-477.
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