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Cell senescence

IL-11 as a master regulator of ageing

Nature Reviews Molecular Cell Biology volume 25, page 956 (2024)Cite this article

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The first hint that cellular senescence could be implicated in ageing was described in a study by Hayflick and Moorhead in 1961. They observed — in contrast to what was widely believed at the time — that cultured human primary fibroblasts could undergo a finite number of cell divisions. They named this phenomenon cellular senescence and hypothesised that this mimicked what happened during ageing. However, 50 years had to pass before a functional link between senescence and ageing was established. In an elegant study in 2016, Baker et al. demonstrated that the selective elimination of senescent cells prevents ageing and age-related diseases in mice.

A recent study by Widjaja et al. adds a new layer of complexity to the composition and functionality of the SASP, in particular relating to the pro-inflammatory cytokine IL-11. As IL-11 can activate different pathways that regulate ageing, the authors hypothesize that IL-11 regulates senescence and ageing. They observe a notable upregulation of IL-11 across tissues during ageing in mice, and an association between IL-11 and senescence markers in mice and cultured human cells. They go on to inhibit IL-11 production using a variety of techniques that combine genetic mouse models and therapy treatments and observe a systemic ‘rejuvenation’ effect. For example, inhibition of IL-11 improved metabolism and muscle function, reduced ageing biomarkers and frailty, and led to an increase in lifespan. Furthermore, the authors found that IL-11 inhibition has potent anti-ageing effects in both male and female mice, which suggests that it is a master regulator of senescence and ageing.

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  1. Epigenetic & Cellular Senescence Group; Biomedicine Department, Centre for Biological Research (CIB), Spanish National Research Council (CSIC), Madrid, Spain

    Ana O’Loghlen

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  1. Ana O’Loghlen
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Correspondence to Ana O’Loghlen.

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O’Loghlen, A. IL-11 as a master regulator of ageing. Nat Rev Mol Cell Biol 25, 956 (2024). https://doi.org/10.1038/s41580-024-00793-1

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