Inhibition of IL-11 Signaling Extends Lifespan and Healthspan in Mammals

Core Concepts

Inhibition of the pro-inflammatory cytokine IL-11 can extend healthspan and lifespan in mice.

Abstract

The article examines the role of the pro-inflammatory cytokine IL-11 in the aging process and its impact on healthspan and lifespan in mammals. As mice age, IL-11 levels increase across cell types and tissues, regulating an ERK-AMPK-mTORC1 axis that contributes to cellular, tissue, and organismal-level aging pathologies.

The key findings are:

• Deletion of Il11 or Il11ra1 (the IL-11 receptor) protects against metabolic decline, multi-morbidity, and frailty in old age.
• Administration of anti-IL-11 antibodies to 75-week-old mice for 25 weeks improves metabolism, muscle function, and reduces aging biomarkers and frailty in both sexes.
• Genetic deletion of Il11 extends the lifespan of mice by 24.9% on average.
• Treatment with anti-IL-11 antibodies from 75 weeks of age until death extends the median lifespan of male mice by 22.5% and female mice by 25%.

The authors suggest that anti-IL-11 therapy, currently in early-stage clinical trials for fibrotic lung disease, may provide a translational opportunity to target aging pathologies in older people.

Stats

Genetic deletion of Il11 extended the lifespan of mice by 24.9% on average.
Treatment with anti-IL-11 antibodies from 75 weeks of age until death extended the median lifespan of male mice by 22.5% and female mice by 25%.

Quotes

"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."
"Together, these results demonstrate a role for the pro-inflammatory factor IL-11 in mammalian healthspan and lifespan."

Key Insights Distilled From

Inhibition of IL-11 signalling extends mammalian healthspan and lifespan - Nature

by Anissa A. Wi... at www.nature.com 07-17-2024

https://www.nature.com/articles/s41586-024-07701-9

Deeper Inquiries

What are the specific mechanisms by which IL-11 inhibition leads to improved healthspan and lifespan in mammals?

IL-11 inhibition exerts its beneficial effects on healthspan and lifespan through multiple mechanisms. Firstly, IL-11 is involved in regulating the ERK–AMPK–mTORC1 axis, which plays a crucial role in cellular and tissue aging processes. By inhibiting IL-11 signaling, the dysregulation of these pathways is mitigated, leading to improved metabolic function, reduced multi-morbidity, and enhanced muscle function in aging mammals. Additionally, IL-11 inhibition helps in reducing inflammation, a key hallmark of aging, thereby protecting against age-associated diseases and frailty. These combined effects contribute to extending healthspan and lifespan in mammals.

How do the effects of IL-11 inhibition on aging compare to other known longevity interventions, such as caloric restriction or genetic manipulations?

IL-11 inhibition presents a unique approach to promoting longevity compared to other interventions like caloric restriction or genetic manipulations. While caloric restriction has been shown to extend lifespan by altering nutrient-sensing pathways and metabolic processes, IL-11 inhibition targets the inflammatory aspect of aging, which is a central hallmark of age-related diseases. Genetic manipulations, on the other hand, often involve altering specific genes or pathways to influence aging processes. IL-11 inhibition, by modulating the ERK–AMPK–mTORC1 axis and reducing inflammation, offers a distinct mechanism to improve healthspan and lifespan in mammals. Combining IL-11 inhibition with other interventions may potentially have synergistic effects on longevity, warranting further research in this area.

Could targeting IL-11 signaling have broader implications for the treatment of age-related diseases beyond just extending lifespan?

Targeting IL-11 signaling holds promise for addressing a wide range of age-related diseases beyond simply extending lifespan. Since IL-11 is involved in regulating various pathways associated with aging, inhibiting its signaling could have profound effects on mitigating age-related metabolic decline, frailty, and other pathologies. By improving metabolism, muscle function, and reducing aging biomarkers, IL-11 inhibition may offer therapeutic benefits for conditions such as sarcopenia, metabolic disorders, and frailty in older individuals. Furthermore, the anti-inflammatory effects of IL-11 inhibition could have implications for age-related inflammatory diseases, neurodegenerative disorders, and cardiovascular conditions. Therefore, targeting IL-11 signaling has the potential to not only extend lifespan but also improve the quality of life and reduce the burden of age-related diseases in the aging population.