What question did this study set out to answer?

To determine whether localized hepatocellular senescence drives extrahepatic senescence and multi-organ failure, and to identify the molecular mechanism mediating this systemic spread.

November 13, 2024Nature Cell BiologyOpen Access

Hepatocellular senescence induces multi-organ senescence and dysfunction via TGFβ

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Authors

CKChristos KiourtisCancer Research UK MTMaria Terradas-TerradasUniversity of Glasgow LGLucy GeeMayo Clinic

Discussion

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Implication

Translational study demonstrates hepatocellular senescence drives extrahepatic failure in acute liver failure, indicating TGFβ inhibition prevents systemic dysfunction.

Key Points

To determine whether localized hepatocellular senescence drives extrahepatic senescence and multi-organ failure, and to identify the molecular mechanism mediating this systemic spread.
Analyzed liver injury models and genetic mouse models of hepatocyte-specific senescence to evaluate extrahepatic organ damage and dysfunction.
Evaluated clinical cohorts of patients with severe acute liver failure to determine the relationship between hepatocyte senescence and extrahepatic organ failure.
Targeted the TGFβ pathway using in vivo inhibition to test whether blocking this signaling mechanism prevents transmission of senescence to distant organs.
Hepatocyte-specific senescence induced cellular senescence in extrahepatic organs and directly caused systemic organ failure.
Extent of hepatocellular senescence in severe acute liver failure predicted overall disease outcome, requirement for liver transplantation, and onset of extrahepatic organ failure.
In vivo inhibition of TGFβ signaling blocked the transmission of senescence to other organs and prevented liver senescence-induced renal dysfunction.

Cite This Study

Kiourtis et al. (2024) studied this question.

synapsesocial.com/papers/69d7d4a911d83f35e5ae2d50 https://doi.org/10.1038/s41556-024-01543-3

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November 13, 2024Nature Cell BiologyOpen Access

Hepatocellular senescence induces multi-organ senescence and dysfunction via TGFβ

View Full Paper

Ask AI

Bookmark

Authors

CKChristos KiourtisCancer Research UK MTMaria Terradas-TerradasUniversity of Glasgow LGLucy GeeMayo Clinic

Discussion

Member takes

Implication

Translational study demonstrates hepatocellular senescence drives extrahepatic failure in acute liver failure, indicating TGFβ inhibition prevents systemic dysfunction.

Key Points

To determine whether localized hepatocellular senescence drives extrahepatic senescence and multi-organ failure, and to identify the molecular mechanism mediating this systemic spread.
Analyzed liver injury models and genetic mouse models of hepatocyte-specific senescence to evaluate extrahepatic organ damage and dysfunction.
Evaluated clinical cohorts of patients with severe acute liver failure to determine the relationship between hepatocyte senescence and extrahepatic organ failure.
Targeted the TGFβ pathway using in vivo inhibition to test whether blocking this signaling mechanism prevents transmission of senescence to distant organs.
Hepatocyte-specific senescence induced cellular senescence in extrahepatic organs and directly caused systemic organ failure.
Extent of hepatocellular senescence in severe acute liver failure predicted overall disease outcome, requirement for liver transplantation, and onset of extrahepatic organ failure.
In vivo inhibition of TGFβ signaling blocked the transmission of senescence to other organs and prevented liver senescence-induced renal dysfunction.

Cite This Study

Kiourtis et al. (2024) studied this question.

synapsesocial.com/papers/69d7d4a911d83f35e5ae2d50 https://doi.org/10.1038/s41556-024-01543-3

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