You are here

Aging Cell DOI:10.1111/acel.12256

Depletion of Rictor, an essential protein component of mTORC2, decreases male lifespan.

Publication TypeJournal Article
Year of Publication2014
AuthorsLamming, DW, Mihaylova, MM, Katajisto, P, Baar, EL, Yilmaz, ÖH, Hutchins, A, Gültekin, Y, Gaither, R, Sabatini, DM
JournalAging Cell
Date Published2014 Oct
KeywordsAnimals, Carrier Proteins, Female, Longevity, Male, Mice, Mice, Inbred C57BL, Multiprotein Complexes, Sex Factors, Signal Transduction, TOR Serine-Threonine Kinases

Rapamycin, an inhibitor of the mechanistic target of rapamycin (mTOR), robustly extends the lifespan of model organisms including mice. We recently found that chronic treatment with rapamycin not only inhibits mTOR complex 1 (mTORC1), the canonical target of rapamycin, but also inhibits mTOR complex 2 (mTORC2) in vivo. While genetic evidence strongly suggests that inhibition of mTORC1 is sufficient to promote longevity, the impact of mTORC2 inhibition on mammalian longevity has not been assessed. RICTOR is a protein component of mTORC2 that is essential for its activity. We examined three different mouse models of Rictor loss: mice heterozygous for Rictor, mice lacking hepatic Rictor, and mice in which Rictor was inducibly deleted throughout the body in adult animals. Surprisingly, we find that depletion of RICTOR significantly decreases male, but not female, lifespan. While the mechanism by which RICTOR loss impairs male survival remains obscure, we find that the effect of RICTOR depletion on lifespan is independent of the role of hepatic mTORC2 in promoting glucose tolerance. Our results suggest that inhibition of mTORC2 signaling is detrimental to males, which may explain in part why interventions that decrease mTOR signaling show greater efficacy in females.


Alternate JournalAging Cell
PubMed ID25059582
PubMed Central IDPMC4172536
Grant ListR00 AG041765 / AG / NIA NIH HHS / United States
K99 AG045144 / AG / NIA NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
R00 AG045144 / AG / NIA NIH HHS / United States
K99 AG041765 / AG / NIA NIH HHS / United States