The landmark synthesis showing that eating less (dietary restriction) and dialing down nutrient-sensing pathways - mTOR and growth hormone/IGF-1 - extend healthy lifespan by the SAME conserved mechanisms from yeast to monkeys to humans. This is the paper that frames why mTOR sits at the crossroads of diet and aging.
| Evidence tier | D Mechanistic / in vitro / review |
| Study type | Narrative Review |
| Model system | Review (yeast to humans) |
| Journal | Science |
| Year | 2010 |
| Peer reviewed | Yes |
| Source | DOI 10.1126/science.1172539 · PMID 20395504 · Free full text (PMC3607354) |
When the food intake of organisms such as yeast and rodents is reduced (dietary restriction), they live longer than organisms fed a normal diet. A similar effect is seen when the activity of nutrient-sensing pathways is reduced by mutations or chemical inhibitors. In rodents, both dietary restriction and decreased nutrient-sensing pathway activity can lower the incidence of age-related loss of function and disease, including tumors and neurodegeneration. Dietary restriction also increases life span and protects against diabetes, cancer, and cardiovascular disease in rhesus monkeys, and in humans it causes changes that protect against these age-related pathologies. Tumors and diabetes are also uncommon in humans with mutations in the growth hormone receptor, and natural genetic variants in nutrient-sensing pathways are associated with increased human life span. Dietary restriction and reduced activity of nutrient-sensing pathways may thus slow aging by similar mechanisms, which have been conserved during evolution. We discuss these findings and their potential application to prevention of age-related disease and promotion of healthy aging in humans, and the challenge of possible negative side effects.
| Intervention | Not applicable (review – dietary restriction / nutrient-sensing inhibition) |
| Target | Nutrient-sensing pathways (incl. TOR, insulin/IGF) |
| Model | Review (yeast to humans) |
| Effect | Dietary restriction and reduced nutrient-sensing activity extend lifespan and reduce age-related disease |