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Inhibition of IL-11 signalling extends mammalian healthspan and lifespan.
- Source :
-
Nature [Nature] 2024 Aug; Vol. 632 (8023), pp. 157-165. Date of Electronic Publication: 2024 Jul 17. - Publication Year :
- 2024
-
Abstract
- For healthspan and lifespan, ERK, AMPK and mTORC1 represent critical pathways and inflammation is a centrally important hallmark <superscript>1-7</superscript> . 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.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Female
Male
Mice
AMP-Activated Protein Kinases metabolism
Frailty genetics
Frailty metabolism
Frailty prevention & control
Inflammation metabolism
Inflammation drug therapy
Interleukin-11 Receptor alpha Subunit metabolism
Interleukin-11 Receptor alpha Subunit deficiency
Mechanistic Target of Rapamycin Complex 1 metabolism
Mechanistic Target of Rapamycin Complex 1 antagonists & inhibitors
Mice, Inbred C57BL
Humans
Extracellular Signal-Regulated MAP Kinases metabolism
Muscle, Skeletal drug effects
Muscle, Skeletal physiology
Aging drug effects
Aging genetics
Aging metabolism
Aging pathology
Interleukin-11 antagonists & inhibitors
Interleukin-11 deficiency
Interleukin-11 genetics
Interleukin-11 metabolism
Longevity drug effects
Longevity genetics
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4687
- Volume :
- 632
- Issue :
- 8023
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 39020175
- Full Text :
- https://doi.org/10.1038/s41586-024-07701-9