抑制IL-11信號可延長哺乳動物的健康和壽命

作者：小柯機器人 發(fā)布時間：2024/7/21 1:10:40

新加坡國立大學(xué)Stuart A. Cook等研究人員合作發(fā)現(xiàn)，抑制IL-11信號可延長哺乳動物的健康和壽命。該研究于2024年7月17日在線發(fā)表于國際一流學(xué)術(shù)期刊《自然》。

研究人員揭示了IL-11這一IL-6家族的促炎細胞因子是否對與年齡相關(guān)的疾病和壽命有負(fù)面影響。隨著小鼠的衰老，IL-11在不同的細胞類型和組織中上調(diào)，通過調(diào)節(jié)ERK-AMPK-mTORC1軸來影響細胞、組織和整體水平的衰老病理。Il11或Il11ra1的刪除可以防止老年期的代謝衰退、多病和虛弱。

對75周齡的小鼠進行為期25周的抗IL-11治療可以改善代謝和肌肉功能，降低衰老生物標(biāo)志物和虛弱程度。在壽命研究中，Il11的基因刪除使雄性和雌性小鼠的平均壽命延長了24.9%。從75周齡開始進行抗IL-11治療直至死亡，使雄性小鼠的中位壽命延長了22.5%，雌性小鼠延長了25%。

這些結(jié)果表明，促炎因子IL-11在哺乳動物的健康壽命和壽命中起到重要作用。研究人員認(rèn)為，當(dāng)前用于纖維化肺病的早期臨床試驗中的抗IL-11療法可能為研究IL-11抑制對老年人衰老病理的影響提供轉(zhuǎn)化機會。

據(jù)悉，在健康壽命和壽命方面，ERK、AMPK和mTORC1代表了關(guān)鍵通路，而炎癥是一個重要的標(biāo)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

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