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Hypoxia and gerosuppression: The mTOR saga continues

Volume 11, Issue 21   November 1, 2012
Pages 3926 - 3931
http://dx.doi.org/10.4161/cc.21908
Keywords: aging, cancer, mTOR, senescence
Authors: Olga V. Leontieva and Mikhail V. Blagosklonny

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Abstract:
Growth-promoting and nutrient/mitogen-sensing pathways such as mTOR convert p21- and p16-induced arrest into senescence (geroconversion). We have recently demonstrated that hypoxia, especially near-anoxia, suppresses geroconversion. This gerosuppressive effect of hypoxia correlated with inhibition of the mTOR/S6K pathway but not with modulation of the LKB1/AMPK/eEF2 pathway. Here we further show that mTOR inhibition is required for gerosuppression by hypoxia, at least in some cellular models, because depletion of TSC2 abolished mTOR inhibition and gerosupression by hypoxia. Also, in two cancer cell lines resistant to inhibition of mTOR by both p53 and hypoxia, hypoxia did not suppress geroconversion. Therefore, the effects of hypoxia on the oxygen-sensing mTOR pathway and geroconversion are cell type-specific. We also briefly discuss replicative senescence, organismal aging and free radical theory.

Received: August 2, 2012; Accepted: August 20, 2012; Published Online: September 17, 2012

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