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

Wu JJ, Finkel T et al. · 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	2026-08-22
Source	DOI 10.1016/j.celrep.2013.07.030 · PMID 23994476 · Free full text (PMC3784301)

Extracted findings

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 Sex dimorphism in mTOR-longevity responses is pervasive and sometimes direction-flipping.

Cite this paper

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Wu, J. J., et al. (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 Finkel, T. and others},
  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}
}