Inhibition of IL-11 signalling extends mammalian healthspan and lifespan

Widjaja, Anissa A.; Lim, Wei‐Wen; Viswanathan, Siva; Chothani, Sonia; Corden, Ben; Dasan, Cibi Mary; Goh, Joyce Wei Ting; Lim, Radiance; Singh, Brijesh Kumar; Tan, Jessie; Pua, Chee Jian; Lim, Sze Yun; Adami, Eleonora; Schäfer, Sebastian; George, Benjamin L.; Sweeney, Mark; Xie, Chen; Tripathi, Madhulika; Sims, Natalie A.; Hübner, Norbert; Petretto, Enrico; Withers, Dominic J.; Ho, Lena; Gil, Jesús; Carling, David; Cook, Stuart A.

doi:10.1038/s41586-024-07701-9

articleNatureJul 17, 2024HYBRID OA

Inhibition of IL-11 signalling extends mammalian healthspan and lifespan

AAAnissa A. Widjaja WLWei‐Wen Lim SVSiva Viswanathan SCSonia Chothani BCBen Corden

National University of Singapore · Duke-NUS Medical School · +10 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

. 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…

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Topics & keywords

Topics

Keywords

mTORC1
AMPK
Inflammation
Cell biology
Biology
Signalling pathways
MAPK/ERK pathway
Signalling

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