The strongest human evidence that mTOR inhibition can rejuvenate a specific function of aging - immunity. In 264 elderly people, a low-dose combination that selectively hits TORC1 significantly reduced infections over the following year and boosted antiviral gene expression and flu-vaccine response. The follow-up to Mannick 2014.
| Evidence tier | B Direct human evidence |
| Study type | 2 - Human Clinical Trial |
| Model system | Humans, phase 2a RCT (n=264, elderly) |
| Journal | Science Translational Medicine |
| Year | 2018 |
| Peer reviewed | Yes |
| Source | DOI 10.1126/scitranslmed.aaq1564 · PMID 29997249 |
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 (= 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.
| Intervention | Low-dose mTOR inhibitor (RAD001 + RTB101/BEZ235), 6 weeks |
| Target | TORC1 |
| Model | Human – phase 2a RCT (n=264, elderly) |
| Effect | Combined low-dose TORC1 inhibition enhanced immune function and reduced infection rates in the elderly |