For healthspan and lifespan, ERK, AMPK and mTORC1 represent critical pathways and inflammation is a centrally important hallmark^{1,2,3,4,5,6,7}. 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.

对于健康寿命和寿命而言，ERK、AMPK 和 mTORC1 代表关键途径，而炎症是一个重要的核心标志^{1,2,3,4,5,6,7} 。在这里，我们检查了 IL-11（IL-6 家族的一种促炎细胞因子）是否对与年龄相关的疾病和寿命有负面影响。随着小鼠年龄的增长，IL-11 在细胞类型和组织中上调，以调节 ERK-AMPK-mTORC1 轴，从而调节细胞、组织和有机体水平的衰老病理。 Il11或Il11ra1的缺失可以防止代谢下降、多种疾病和老年虚弱。对 75 周龄小鼠施用抗 IL-11 药物 25 周，可以改善新陈代谢和肌肉功能，并减少不同性别的衰老生物标志物和虚弱程度。在寿命研究中， Il11基因缺失使雌雄小鼠的寿命平均延长了 24.9%。从 75 周龄直至死亡，使用抗 IL-11 治疗可使雄性小鼠的中位寿命延长 22.5%，雌性小鼠的中位寿命延长 25%。总之，这些结果证明了促炎因子 IL-11 在哺乳动物健康和寿命中的作用。我们认为，目前正处于纤维化肺病早期临床试验阶段的抗 IL-11 疗法可能会提供一个转化机会，以确定 IL-11 抑制对老年人衰老病理的影响。