Lifespan benefits for the combination of rapamycin plus acarbose and for captopril in genetically heterogeneous mice

Strong R, Miller RA, Cheng CJ, Nelson JF, Gelfond J, Allani SK, Diaz V, Dorigatti AO, Dorigatti J, Fernandez E, Galecki A, …, Harrison DE · 2022 · Aging Cell · Atlas ID STR2022

What this study shows

NIA Interventions Testing Program C2017 cohort. In MALE mice, rapamycin plus acarbose started at 9 months produced a longer lifespan than either of the two prior ITP cohorts treated with rapamycin alone, suggesting the combination is more potent than its components used separately. In FEMALES the combination was neither better nor worse than rapamycin alone, which the authors relate to the limited survival benefit acarbose alone had shown in earlier female cohorts. Captopril gave a small but significant lifespan increase in females (4-5%). CAVEAT (important for how this is cited): the rapamycin-only comparison is HISTORICAL, against prior cohorts, not a concurrent rapamycin-only arm in the same experiment, so 'more potent than either component' is the authors' suggestion rather than a within-experiment randomised comparison.

Abstract

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Mice bred in 2017 and entered into the C2017 cohort were tested for possible lifespan benefits of (R/S)-1,3-butanediol (BD), captopril (Capt), leucine (Leu), the Nrf2-activating botanical mixture PB125, sulindac, syringaresinol, or the combination of rapamycin and acarbose started at 9 or 16 months of age (RaAc9, RaAc16). In male mice, the combination of Rapa and Aca started at 9 months and led to a longer lifespan than in either of the two prior cohorts of mice treated with Rapa only, suggesting that this drug combination was more potent than either of its components used alone.

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At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Genetically heterogeneous UM-HET3 mice, three test sites (ITP C2017 cohort)); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Genetically heterogeneous UM-HET3 mice, three test sites (ITP C2017 cohort)
Journal	Aging Cell
Year	2022
Peer reviewed	—
Record last updated	2026-10-01
Source	DOI 10.1111/acel.13724 · PMID 36179270 · Free full text (PMC9741502)

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	Rapamycin + acarbose combination; captopril; (R/S)-1,3-butanediol; leucine; PB125; sulindac; syringaresinol
Target	mTORC1 (rapamycin); alpha-glucosidase / glucose absorption (acarbose)
Model	Mouse
Effect	Rapamycin + acarbose from 9 months outlived prior rapamycin-only cohorts in males; no added benefit over rapamycin alone in females

In the Atlas

Open questions that cite this study

Cited as supporting evidence for the open question Does the larger rapamycin benefit in female mice survive equal drug exposure, and is it set by hormones or by chromosomes?.
Cited as supporting evidence for the open question Rapamycin + AMPK-axis drugs (acarbose / metformin): a male-mouse survival signal from cross-cohort comparison, untested in humans.

Cite this paper

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Strong, R., Miller, R. A., Cheng, C. J., Nelson, J. F., Gelfond, J., Allani, S. K., Diaz, V., Dorigatti, A. O., Dorigatti, J., Fernandez, E., Galecki, A., Ginsburg, B., Hamilton, K. L., Javors, M. A., Kornfeld, K., Kaeberlein, M., Kumar, S., Lombard, D. B., Lopez-Cruzan, M., Miller, B. F., Rabinovitch, P., Reifsnyder, P., Rosenthal, N. A., Bogue, M. A., Salmon, A. B., Suh, Y., Verdin, E., Weissbach, H., Newman, J., Maccchiarini, F., & Harrison, D. E. (2022). Lifespan benefits for the combination of rapamycin plus acarbose and for captopril in genetically heterogeneous mice. Aging Cell. https://doi.org/10.1111/acel.13724

@article{STR2022,
  author       = {Strong, R. and Miller, R. A. and Cheng, C. J. and Nelson, J. F. and Gelfond, J. and Allani, S. K. and Diaz, V. and Dorigatti, A. O. and Dorigatti, J. and Fernandez, E. and Galecki, A. and Ginsburg, B. and Hamilton, K. L. and Javors, M. A. and Kornfeld, K. and Kaeberlein, M. and Kumar, S. and Lombard, D. B. and Lopez-Cruzan, M. and Miller, B. F. and Rabinovitch, P. and Reifsnyder, P. and Rosenthal, N. A. and Bogue, M. A. and Salmon, A. B. and Suh, Y. and Verdin, E. and Weissbach, H. and Newman, J. and Maccchiarini, F. and Harrison, D. E.},
  title        = {{Lifespan benefits for the combination of rapamycin plus acarbose and for captopril in genetically heterogeneous mice}},
  journal      = {Aging Cell},
  year         = {2022},
  doi          = {10.1111/acel.13724},
  note         = {PMID: 36179270},
}

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 STR2022) [Data set]. https://mtor-atlas.org/study/STR2022/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_STR2022,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record STR2022},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/STR2022/},
  doi          = {10.5281/zenodo.22059963}
}

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