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Effects of mTOR Inhibition on Immunosenescence in the Elderly

Mannick, Joan and Del Giudice, Giuseppe and Valiante, Nick and Lattanzi, Maria and Praestgaard, Jens and Huang, Baisong and Lonetto, Michael and Kovarik, John M. and Maecker, Holden and Carson, Simon and Glass, David and Klickstein, Lloyd (2014) Effects of mTOR Inhibition on Immunosenescence in the Elderly. Science Translational Medicine.

Abstract

Abstract: Inhibition of the mTOR pathway extends lifespan in all species studied to date, and in mice delays the onset of aging-related diseases and co-morbidities. However, it is unknown if mTOR inhibition impacts aging in humans. To begin to assess the effects of mTOR inhibition on human aging-related conditions, we evaluated whether the mTOR inhibitor RAD001 ameliorated immunosenescence (the decline in immune function during aging) in elderly volunteers, as assessed by response to influenza vaccination. Our findings suggest that RAD001 enhanced the response to influenza vaccine in elderly volunteers at doses that were relatively well tolerated. RAD001 may enhance immune function in the elderly by reducing the percentage of programmed death (PD)-1-positive CD4 and CD8 T lymphocytes that accumulate with age. These results suggest that mTOR inhibition has beneficial effects on immunosenescence in elderly volunteers. It remains to be determined if mTOR inhibitors improve other aging-related conditions in humans.

Item Type: Article
Keywords: aging, immunosenescence, mTOR, RAD001
Date Deposited: 26 Apr 2016 23:45
Last Modified: 26 Apr 2016 23:45
URI: https://oak.novartis.com/id/eprint/21804

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