American Society of Hirudotherapy

Hepatocellular senescence induces multi-organ senescence and dysfunction via TGF

Research article published in Nature cell biology (2024)

Last Updated: June 18, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Research reportGenomics & ProteomicsKiourtis C et al. · Nature cell biology, 2024

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.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

Publication typeJournal ArticleResearch Support, Non-U.S. Gov't
Indexed MeSH termsCellular SenescenceAnimalsHumansHepatocytesLiverTransforming Growth Factor betaSignal TransductionMice, Inbred C57BLMaleMiceDisease Models, Animal

Summary

Cellular senescence is not only associated with ageing but also impacts physiological and pathological processes, such as embryonic development and wound healing.

Why This Matters for Hirudotherapy

This study used liver injury models, genetic models of hepatocyte-specific senescence, and patient data from severe acute liver failure to demonstrate that hepatocellular senescence can spread systemically via TGFβ signaling, inducing senescence and dysfunction in extrahepatic organs such as the kidney. TGFβ inhibition in vivo blocked this inter-organ transmission and prevented renal dysfunction. The article has no direct connection to hirudotherapy or leech secretome research; no leeches or leech-derived molecules are mentioned. The TGFβ pathway is studied here in the context of senescence and multi-organ dysfunction, and the abstract provides no data linking it to any leech-related therapeutic application. Relevance to ASH's domain is absent based on the abstract alone.

Citation

Hepatocellular senescence induces multi-organ senescence and dysfunction via TGF

Kiourtis C et al. · Nature cell biology, 2024

DOI

Added to ASH library: May 27, 2026 · Site last updated: June 18, 2026

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