英国格拉斯哥大学Thomas G. Bird小组发现，肝细胞衰老通过TGFβ诱导多脏器衰老和功能障碍。这一研究成果于2024年11月13日在线发表在国际学术期刊《自然—细胞生物学》上。

研究人员通过肝损伤模型和肝细胞特异性衰老的遗传模型，展示了肝脏衰老诱导的外肝器官衰老和相关器官功能障碍。在重症急性肝衰竭患者中，研究人员发现肝细胞衰老的程度能够预测，疾病的结局、是否需要肝脏移植以及外肝器官衰竭的发生。

研究人员确定了TGFβ通路是衰老在全身传播的关键介导因子，并展示了TGFβ在体内的抑制可以阻止衰老向其他器官的传播，从而防止肝衰老引起的肾功能障碍。

这些结果突出了器官特异性衰老的系统性后果，这种衰老在不依赖衰老的情况下，有助于多脏器功能障碍的发生。

据了解，细胞衰老不仅与衰老相关，还影响生理和病理过程，如胚胎发育和创伤愈合。衰老细胞分泌的因子会影响它们的微环境，并可局部诱导衰老的扩散。急性重症肝病与肝细胞衰老相关，并且常常进展为多脏器衰竭。然而，为什么会发生后者仍不清楚。

附：英文原文

Title: Hepatocellular senescence induces multi-organ senescence and dysfunction via TGFβ

Author: Kiourtis, Christos, Terradas-Terradas, Maria, Gee, Lucy M., May, Stephanie, Georgakopoulou, Anastasia, Collins, Amy L., OSullivan, Eoin D., Baird, David P., Hassan, Mohsin, Shaw, Robin, Tan, Ee Hong, Mller, Miryam, Engelmann, Cornelius, Andreola, Fausto, Hsieh, Ya-Ching, Reed, Lee H., Borthwick, Lee A., Nixon, Colin, Clark, William, Hanson, Peter S., Sumpton, David, Mackay, Gillian, Suzuki, Toshiyasu, Najumudeen, Arafath K., Inman, Gareth J., Campbell, Andrew, Barry, Simon T., Quaglia, Alberto, Morris, Christopher M., LeBeau, Fiona E. N., Sansom, Owen J., Kirschner, Kristina, Jalan, Rajiv, Oakley, Fiona, Bird, Thomas G.

Issue&Volume: 2024-11-13

Abstract: Cellular senescence is not only associated with ageing but also impacts physiological and pathological processes, such as embryonic development and wound healing. Factors secreted by senescent cells affect their microenvironment and can induce spreading of senescence locally. Acute severe liver disease is associated with hepatocyte senescence and frequently progresses to multi-organ failure. Why the latter occurs is poorly understood. Here we demonstrate senescence development in extrahepatic organs and associated organ dysfunction in response to liver senescence using liver injury models and genetic models of hepatocyte-specific senescence. In patients with severe acute liver failure, we show that the extent of hepatocellular senescence predicts disease outcome, the need for liver transplantation and the occurrence of extrahepatic organ failure. We identify the TGFβ pathway as a critical mediator of systemic spread of senescence and demonstrate that TGFβ inhibition in vivo blocks senescence transmission to other organs, preventing liver senescence induced renal dysfunction. Our results highlight the systemic consequences of organ-specific senescence, which, independent of ageing, contributes to multi-organ dysfunction.

DOI: 10.1038/s41556-024-01543-3

Source: https://www.nature.com/articles/s41556-024-01543-3