Genetically reduced mTOR increases mouse lifespan with tissue-specific slowing of aging.
| Evidence tier | C Animal in vivo |
| Study type | 4 - Animal Study |
| Model system | Mouse (mTOR hypomorph) |
| Journal | Cell reports |
| Year | 2013 |
| Peer reviewed | Yes |
| Source | DOI 10.1016/j.celrep.2013.07.030 · PMID 23994476 · Free full text (PMC3784301) |
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. Functional assessment suggested that, as these mice age, they exhibit a marked functional preservation in many, but not all, organ systems. Thus, in a mammalian model, while reducing mTOR expression markedly increases overall lifespan, it affects the age-dependent decline in tissue and organ function in a segmental fashion.
| 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 |