Hepatocellular senescence induces multi-organ senescence and dysfunction via TGFβ.

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 transpl

SUBMITTER: Kiourtis C 

PROVIDER: S-EPMC11628396 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature