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TORC1 inhibition enhances immune function and reduces infections in the elderly.
Sci Transl Med. 2018 Jul 11;10(449). pii: eaaq1564. doi: 10.1126/scitranslmed.aaq1564
Mannick JB, Morris M, Hockey HP, Roma G, Beibel M, Kulmatycki K, Watkins M, Shavlakadze T, Zhou W, Quinn D, Glass DJ, Klickstein LB
Abstract:
Inhibition of the mechanistic target of rapamycin (mTOR) protein kinase extends life span and ameliorates aging-related pathologies including declining immune function in model organisms. The objective of this phase 2a randomized, placebo-controlled clinical trial was to determine whether low-dose mTOR inhibitor therapy enhanced immune function and decreased infection rates in 264 elderly subjects given the study drugs for 6 weeks. A low-dose combination of a catalytic (BEZ235) plus an allosteric (RAD001) mTOR inhibitor that selectively inhibits target of rapamycin complex 1 (TORC1) downstream of mTOR was safe and was associated with a significant (P = 0.001) decrease in the rate of infections reported by elderly subjects for a year after study drug initiation. In addition, we observed an up-regulation of antiviral gene expression and an improvement in the response to influenza vaccination in this treatment group. Thus, selective TORC1 inhibition has the potential to improve immune function and reduce infections in the elderly.
Comment in
* Harnessing TORC to boost the horsepower of aging immune systems. [Sci Immunol. 2018]
* Immune-boost for the elderly. [Nat Rev Immunol. 2018]
Comment in
* Harnessing TORC to boost the horsepower of aging immune systems. [Sci Immunol. 2018]
* Immune-boost for the elderly. [Nat Rev Immunol. 2018]
PMID: 29997249
Free Full-Text: https://stm.sciencemag.org/content/10/449/eaaq1564/tab-pdf
Tags: BEZ235, humans, immunity, infection rate, mTOR, mTORC1, RAD001, rapamycin, vaccination