Publications

Latest publication 08/18/2024

Inhibition of IL-11 signalling extends mammalian healthspan and lifespan

For healthspan and lifespan, ERK, AMPK and mTORC1 represent critical pathways and inflammation is a centrally important hallmark1-7. Here we...

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    [title] => Inhibition of IL-11 signalling extends mammalian healthspan and lifespan
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Authors
Widjaja, Anissa A., Lim, Wei-Wen, Viswanathan, Sivakumar, Chothani, Sonia, Corden, Ben, Dasan, Cibi Mary, Goh, Joyce Wei Ting, Lim, Radiance, Singh, Brijesh K., Tan, Jessie, Pua, Chee Jian, Lim, Sze Yun, Adami, Eleonora, Schafer, Sebastian, George, Benjamin L., Sweeney, Mark, Xie, Chen, Tripathi, Madhulika, Sims, Natalie A., Hübner, Norbert, Petretto, Enrico, Withers, Dominic J., Ho, Lena, Gil, Jesus, Carling, David, Cook, Stuart A.

 Lab

Journal
Nature
Abstract
For healthspan and lifespan, ERK, AMPK and mTORC1 represent critical pathways and inflammation is a centrally important hallmark1-7. 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. IL-11 is identified as a key regulator of ERK-AMPK-mTORC1 signalling, metabolism, inflammation and age-related disease and lifespan in mouse and human.
Keywords/Topics
inhibition;signalling;extends;mammalian;healthspan;lifespan;represent;critical;pathways;inflammation
BIOSEB Instruments Used:
Grip strength test (BIO-GS4)
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New features GS4 - 2023: Color display with permanent backlight screen for easier reading, reset by footswitch, Improved battery time, Larger data memory of 500 values, Animal counter, USB port (charging/data transfer)

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