抑制IL

泰然健康网
2024-12-19 01:57

抑制IL-11信号可延长哺乳动物的健康和寿命

作者：小柯机器人发布时间：2024/7/21 1:10:40

新加坡国立大学Stuart A. Cook等研究人员合作发现，抑制IL-11信号可延长哺乳动物的健康和寿命。该研究于2024年7月17日在线发表于国际一流学术期刊《自然》。

研究人员揭示了IL-11这一IL-6家族的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。随着小鼠的衰老，IL-11在不同的细胞类型和组织中上调，通过调节ERK-AMPK-mTORC1轴来影响细胞、组织和整体水平的衰老病理。Il11或Il11ra1的删除可以防止老年期的代谢衰退、多病和虚弱。

对75周龄的小鼠进行为期25周的抗IL-11治疗可以改善代谢和肌肉功能，降低衰老生物标志物和虚弱程度。在寿命研究中，Il11的基因删除使雄性和雌性小鼠的平均寿命延长了24.9%。从75周龄开始进行抗IL-11治疗直至死亡，使雄性小鼠的中位寿命延长了22.5%，雌性小鼠延长了25%。

这些结果表明，促炎因子IL-11在哺乳动物的健康寿命和寿命中起到重要作用。研究人员认为，当前用于纤维化肺病的早期临床试验中的抗IL-11疗法可能为研究IL-11抑制对老年人衰老病理的影响提供转化机会。

据悉，在健康寿命和寿命方面，ERK、AMPK和mTORC1代表了关键通路，而炎症是一个重要的标志。

附：英文原文

Title: Inhibition of IL-11 signalling extends mammalian healthspan and lifespan

Author: 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., Hbner, Norbert, Petretto, Enrico, Withers, Dominic J., Ho, Lena, Gil, Jesus, Carling, David, Cook, Stuart A.

Issue&Volume: 2024-07-17

Abstract: For healthspan and lifespan, ERK, AMPK and mTORC1 represent critical pathways and inflammation is a centrally important hallmark1,2,3,4,5,6,7. 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.

DOI: 10.1038/s41586-024-07701-9

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