Rapamycin

Assembled from 18 blocks · 1 evidence · 13 related

1. Story
2. A macrolide isolated from a Streptomyces species found in soil on Rapa Nui, used clinically as an immunosuppressant in transplantation, and the most robust pharmacological lifespan extender known in mammals. It inhibits mTOR, the nutrient-sensing kinase complex whose deregulation is one of the hallmarks of ageing, which places it mechanistically adjacent to caloric restriction. The National Institute on Aging's Interventions Testing Program reported in 2009 that rapamycin extended median lifespan in genetically heterogeneous mice even when started at twenty months of age — the equivalent of a human in their sixties — with the effect somewhat larger in females than males. The result has been replicated across doses and strains. Its human position is unresolved: the immunosuppressive dose used in transplantation is not obviously the dose that would be relevant, no adequately powered human trial of ageing endpoints has been run, and off-label use has run well ahead of the evidence.
3. Knowledge
4. Caloric restriction
5. Rapamycin
6. Connections
7. Caloric restriction
8. NIA Interventions Testing Program
9. Rapamycin extends mouse lifespan when started in late life
10. Model organism lifespan research
11. CALERIE (Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy)
12. Rapamycin
13. Caloric restriction extends rodent lifespan
14. Wisconsin reports that caloric restriction reduces age-related mortality in rhesus monkeys
15. The NIA rhesus study reports no significant survival benefit
16. CALERIE reports two-year results in humans
17. Evidence
18. Supports the late-life lifespan extension by rapamycin replicated across the Interventions Testing Program's three sites. V55 verification basis: not retrieved; the specific percentage extensions and the sex difference are unchecked and are therefore not quoted numerically in the objects citing this record.