Inhibition of IL-11 signalling extends mammalian healthspan and lifespan in research published in the journal Nature.
Female Il11-deleted mice are protected from age-associated obesity, frailty, and metabolic decline. Male mice lives 22.5% longer and female mice 25% longer.
The effects were similar to rapamycin but had less negative effects on liver and other organs when rapamycin is used for extended times. They were able to use monoclonal antibodies with monthly injections to deliver the treatment. There does not seem to any side effects with the blocking of IL-11. It is in human trials for safety.
For healthspan and lifespan, ERK, AMPK and mTORC1 represent critical pathways and inflammation is a centrally important hallmark. Here we examined whether IL-11, a pro-inflammatory cytokine of the IL-6 family, has a negative effect on age-associated disease and lifespan. As mice age, IL-11 is upregulated across cell types and tissues to regulate an ERK–AMPK–mTORC1 axis to modulate cellular, tissue- and organismal-level ageing pathologies. Deletion of Il11 or Il11ra1 protects against metabolic decline, multi-morbidity and frailty in old age. Administration of anti-IL-11 to 75-week-old mice for 25 weeks improves metabolism and muscle function, and reduces ageing biomarkers and frailty across sexes. In lifespan studies, genetic deletion of Il11 extended the lives of mice of both sexes, by 24.9% on average. Treatment with anti-IL-11 from 75 weeks of age until death extends the median lifespan of male mice by 22.5% and of female mice by 25%. Together, these results demonstrate a role for the pro-inflammatory factor IL-11 in mammalian healthspan and lifespan. We suggest that anti-IL-11 therapy, which is currently in early-stage clinical trials for fibrotic lung disease, may provide a translational opportunity to determine the effects of IL-11 inhibition on ageing pathologies in older people.
The major signalling mechanisms that regulate lifespan across species include ERK, STK11 (also known as LKB1), AMPK, mTORC1 and IGF1–insulin modules. These pathways are collectively perturbed in old age to activate hallmarks of ageing, which include mitochondrial dysfunction, inflammation and cellular senescence. In aged organisms, the AMPK–mTORC1 axis is uniquely important for metabolic health, with notable effects in adipose tissue and therapeutic inhibition of mTOR extends lifespan in mice.
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