TORC1 inhibition enhances immune function and reduces infections in the elderly

Mannick JB, Morris M, Hockey HP, Roma G, Beibel M, Kulmatycki K, Watkins M, Shavlakadze T, Zhou W, Quinn D, Glass DJ, Klickstein LB · 2018 · Science Translational Medicine · Atlas ID MAN2018

What this study shows

A phase 2a RCT in 264 older adults: 6 weeks of a low-dose combination of BEZ235 (a catalytic PI3K/mTOR inhibitor) and everolimus (RAD001) was associated with fewer reported infections over the following year, plus higher antiviral gene expression and a better flu-vaccine response. The later phase 3 trial of RTB101 (BEZ235) alone (MAN2021) did not confirm a clinical benefit.

Cited on mTOR drugs in development: RTB101

Abstract

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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.

Read the full abstract on PubMed →

At a glance

Evidence type	H Human study Marked H because it is direct evidence from a human clinical trial or human cohort; the code names the kind of study, not its quality -- a small, well-run trial is still H.
Study type	2 - Human Clinical Trial
Model system	Humans, phase 2a RCT (n=264, elderly)
Journal	Science Translational Medicine
Year	2018
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1126/scitranslmed.aaq1564 · PMID 29997249

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

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

In the Atlas

Open questions that cite this study

Cited as supporting evidence for the open question A sensor/autophagy biomarker panel as a surrogate endpoint for human trials.
Cited as supporting evidence for the open question Is there a low-dose mTOR schedule whose immune effects come out favourable, compartment by compartment?.

Answers that reference this study

Discussed in the plain-language answer What are rapamycin's side effects?.

Cite this paper

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Mannick, J. B., Morris, M., Hockey, H. P., Roma, G., Beibel, M., Kulmatycki, K., Watkins, M., Shavlakadze, T., Zhou, W., Quinn, D., Glass, D. J., & Klickstein, L. B. (2018). TORC1 inhibition enhances immune function and reduces infections in the elderly. Science Translational Medicine. https://doi.org/10.1126/scitranslmed.aaq1564

@article{MAN2018,
  author       = {Mannick, J. B. and Morris, M. and Hockey, H. P. and Roma, G. and Beibel, M. and Kulmatycki, K. and Watkins, M. and Shavlakadze, T. and Zhou, W. and Quinn, D. and Glass, D. J. and Klickstein, L. B.},
  title        = {{TORC1 inhibition enhances immune function and reduces infections in the elderly}},
  journal      = {Science Translational Medicine},
  year         = {2018},
  doi          = {10.1126/scitranslmed.aaq1564},
  note         = {PMID: 29997249},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record MAN2018) [Data set]. https://mtor-atlas.org/study/MAN2018/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_MAN2018,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record MAN2018},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/MAN2018/},
  doi          = {10.5281/zenodo.22059963}
}

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