Increased mammalian lifespan and a segmental and tissue-specific slowing of aging after genetic reduction of mTOR expression

Wu JJ, Liu J, Chen EB, Wang JJ, Cao L, Narayan N, Fergusson MM, Rovira II, Allen M, Springer DA, Lago CU, …, Finkel T · 2013 · Cell reports · Atlas ID WUX2013

What this study shows

Genetically reduced mTOR increases mouse lifespan with tissue-specific slowing of aging.

Abstract

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We analyzed aging parameters using a mechanistic target of rapamycin (mTOR) hypomorphic mouse model. Mice with two hypomorphic alleles are viable but express mTOR at approximately 25% of wild-type levels. These animals demonstrate reduced mTORC1 and mTORC2 activity and exhibit an approximately 20% increase in median survival. While these mice are smaller than wild-type mice, they do not demonstrate any alterations in normalized food intake, glucose homeostasis, or metabolic rate. Consistent with their increased lifespan, the mice exhibited a reduction in a number of aging tissue biomarkers.

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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: Mouse (mTOR hypomorph)); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Mouse (mTOR hypomorph)
Journal	Cell reports
Year	2013
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1016/j.celrep.2013.07.030 · PMID 23994476 · Free full text (PMC3784301)

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	Genetic (mTOR hypomorph, ~25% expression)
Target	mTORC1 & mTORC2
Model	Mouse (mTOR hypomorph)
Effect	Genetic reduction of mTOR extends median lifespan ~20% with segmental, tissue-specific slowing of aging
Dose	mTOR protein reduced to approximately 25% of wild type levels
Sample size	males: n=17 (mTOR Δ/Δ), n=10 (WT); females: n=26 (mTOR Δ/Δ), n=24 (WT); combined: n=43 (mTOR Δ/Δ), n=34 (WT)
Effect size	Median survival increased by 22% for males (p=0.02) and 19% for females (p=0.047); overall median survival 30.3 months for mTOR Δ/Δ vs 26.2 months for WT (p=0.0057)
Limitations	Higher euthanasia rate for mTOR Δ/Δ mice due to severe infections (37% vs 17% WT, p<0.01); exacerbated age-dependent decrease in trabecular bone volume and increased age-dependent infections (mouth, eye, skin) in mTOR Δ/Δ mice

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?.

Cite this paper

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Wu, J. J., Liu, J., Chen, E. B., Wang, J. J., Cao, L., Narayan, N., Fergusson, M. M., Rovira, I. I., Allen, M., Springer, D. A., Lago, C. U., Zhang, S., DuBois, W., Ward, T., deCabo, R., Gavrilova, O., Mock, B., & Finkel, T. (2013). Increased mammalian lifespan and a segmental and tissue-specific slowing of aging after genetic reduction of mTOR expression. Cell reports. https://doi.org/10.1016/j.celrep.2013.07.030

@article{WUX2013,
  author       = {Wu, J. J. and Liu, J. and Chen, E. B. and Wang, J. J. and Cao, L. and Narayan, N. and Fergusson, M. M. and Rovira, I. I. and Allen, M. and Springer, D. A. and Lago, C. U. and Zhang, S. and DuBois, W. and Ward, T. and deCabo, R. and Gavrilova, O. and Mock, B. and Finkel, T.},
  title        = {{Increased mammalian lifespan and a segmental and tissue-specific slowing of aging after genetic reduction of mTOR expression}},
  journal      = {Cell reports},
  year         = {2013},
  doi          = {10.1016/j.celrep.2013.07.030},
  note         = {PMID: 23994476},
}

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 WUX2013) [Data set]. https://mtor-atlas.org/study/WUX2013/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_WUX2013,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record WUX2013},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/WUX2013/},
  doi          = {10.5281/zenodo.22059963}
}

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