Mannick · Science translational medicine 2018 · Phase 2a randomized controlled trial · n=264

TORC1 inhibition enhances immune function and reduces infections in the elderly.

Cited 505 times in the scientific literature.

Level 2 - randomized trial

Phase 2a randomized placebo-controlled clinical trial

PubMed 29997249 · doi:10.1126/scitranslmed.aaq1564 · record verified 2026-08-28

What was done

A phase 2a randomized, placebo-controlled clinical trial evaluated whether 6 weeks of low-dose mTOR inhibitor therapy (a combination of catalytic inhibitor BEZ235 and allosteric inhibitor RAD001 targeting TORC1) could enhance immune response and reduce infections in 264 elderly participants followed for 1 year after study drug initiation.

What was found

Low-dose selective TORC1 inhibition was safe and significantly reduced the rate of reported infections over the 1-year follow-up compared to placebo (P = 0.001). The intervention also led to up-regulation of antiviral gene expression and improved response to influenza vaccination. Specific baseline rates, relative risks, and numerical vaccine titers were not provided in the abstract.

Why it matters

This trial suggests that short-term pharmacological targeting of aging biology (TORC1 pathway) can clinically enhance immune function and reduce infection burden in older adults.

Limits

The abstract lacks exact event counts, absolute effect sizes, confidence intervals, and safety event numbers. Infections appear to be subject-reported, and the study was a phase 2a trial requiring validation in larger confirmatory phase 3 studies.

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