Deleting S6K1 (a direct mTORC1 effector) extended lifespan and protected against age-related bone, immune, and motor decline in mice.
| Evidence tier | C Animal in vivo |
| Study type | 4 - Animal Study |
| Model system | Mouse (S6K1 knockout) |
| Journal | Science |
| Year | 2009 |
| Peer reviewed | Yes |
| Source | DOI 10.1126/science.1177221 · PMID 19797661 · Free full text (PMC4954603) |
Caloric restriction (CR) protects against aging and disease, but the mechanisms by which this affects mammalian life span are unclear. We show in mice that deletion of ribosomal S6 protein kinase 1 (S6K1), a component of the nutrient-responsive mTOR (mammalian target of rapamycin) signaling pathway, led to increased life span and resistance to age-related pathologies, such as bone, immune, and motor dysfunction and loss of insulin sensitivity. Deletion of S6K1 induced gene expression patterns similar to those seen in CR or with pharmacological activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK), a conserved regulator of the metabolic response to CR. Our results demonstrate that S6K1 influences healthy mammalian life-span and suggest that therapeutic manipulation of S6K1 and AMPK might mimic CR and could provide broad protection against diseases of aging.
| Intervention | Genetic (S6K1 knockout) |
| Target | S6K1 / mTOR |
| Model | Mouse (S6K1 KO) |
| Effect | S6K1 deletion extends lifespan and confers resistance to age-related pathologies (especially in females) |