TORC1 INHIBITION AS A POTENTIAL IMMUNOTHERAPY TO REDUCE INFECTIONS IN THE ELDERLY

Abstract

Inhibition of the mTOR pathway has extended lifespan and delayed or ameliorated aging-related conditions in yeast, worms, flies and mice. As a first step towards determining whether mTOR inhibitors have beneficial effects on aging and related conditions in humans, we demonstrated previously that low or intermittent mTOR inhibitor therapy improved immune function in elderly subjects as assessed by response to influenza vaccination. We now have extended these findings and demonstrated that a combination of an allosteric (everolimus) and catalytic (RTB101) mTOR inhibitor not only improved the response to influenza vaccination, but also was associated with a significant decrease in the rate of infections reported by elderly subjects for a year following study drug initiation. Thus a low dose combination of the mTOR Inhibitors RTB101 and everolimus may be efficacious as an immunotherapy to reduce infections, a leading cause of death in the elderly.