The major signalling mechanisms regulating lifespan include ERK, STK11, AMPK, mTORC1, and IGF1-insulin pathways, perturbed in old age to activate ageing hallmarks like mitochondrial dysfunction, inflammation. AMPK-mTORC1 axis is crucial in aging's metabolic health, notably in adipose tissue. Therapeutic mTOR inhibition extends mouse lifespan.
IL-11, a pro-inflammatory IL-6 family member, is implicated in age-related pathologies and lifespan reduction due to its ability to activate ERK-mTORC1 and JAK-STAT3, upregulated in older individuals and involved in senescence.
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