Age-related pathology
Tissue- and organ-level ageing phenotypes, graded separately from survival.
Getting ill and frail with age - not the same thing as how long you live. Getting ill and frail with age - not the same thing as how long you live.
Kept separate from Longevity on purpose. LEE2010 measured fat accumulation and muscle and cardiac pathology in flies lacking Sestrin, with no lifespan measurement; healthspan and lifespan are separable endpoints and this Atlas grades them separately.
TL;DR. Age-related pathology appears in 2 curated studies in Oliver's mTOR Atlas: 2 in animal models. No study in people is recorded for it in the Atlas yet. It has 1 interaction in the curated pathway model.
In the pathway model
| Interaction | Mechanism | Evidence | Studies |
|---|---|---|---|
| Sestrin2 inhibits Age-related pathology mechanism: functional-consequence · this link in full · on the map table | The only case in this atlas linking a nutrient sensor to ageing of a whole animal: fruit flies without this sensor build up fat and develop muscle and heart problems, and blocking this pathway or switching on AMPK prevents it. So the sensor holds age-related damage back. Watch what was measured – how sick the flies got, not how long they lived. Losing Drosophila Sestrin produces fat accumulation, mitochondrial dysfunction, muscle degeneration and cardiac malfunction, all prevented by inhibiting TOR or activating AMPK. Sestrin therefore limits age-associated pathology in the fly. Losing Drosophila Sestrin produces fat accumulation, mitochondrial dysfunction, muscle degeneration and cardiac malfunction, all prevented by inhibiting TOR or activating AMPK. Sestrin therefore limits age-associated pathology in the fly. Holds under: Fly only, and the readout is age-related pathology: survival was never measured. No mammalian sensor-to-ageing evidence exists in this corpus. not tested in people · emerging, few independent studies | A | LEE2010 |
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| A | Animal model | 2 |
No direct human evidence in the Atlas for this entity yet — everything below rests on animal or molecular work.
Studies
| Year | Evidence | Study |
|---|---|---|
| 2018 | A | Rapamycin improves healthspan but not inflammaging in nfκb1(-/-) mice. COR2018 Separates two effects of rapamycin that are usually assumed to travel together. In mice with genetically enhanced NF-kB activity, rapamycin showed no benefit in lifespan and no reduction of inflammaging, yet still reduced frailty and improved long-term memory, neuromuscular coordination and tissue architecture, with lower markers of cellular senescence. Healthspan benefit is therefore uncoupled here from suppression of inflammation, which is a boundary condition on the common claim that rapamycin acts on ageing mainly by damping inflammation. Note the mixed result: the healthspan outcomes are positive, the lifespan and inflammaging outcomes are null. |
| 2010 | A | Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies LEE2010 An early study linking Sestrin, later identified as a leucine sensor in mammals, to age-associated pathology in flies (fat accumulation, mitochondrial dysfunction, muscle and cardiac decline), prevented by TOR inhibition or AMPK activation. Sestrin sits in a negative feedback loop: TOR activity drives Sestrin expression, and Sestrin inhibits TOR back. |
Related entities
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