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. 2024 Dec;26(12):2016-2017.
doi: 10.1038/s41556-024-01520-w.

A systemic effect for liver senescence

Kuo Du  1 , David Scott Umbaugh  1 , Rajesh Kumar Dutta  1 , Anna Mae Diehl  2
Affiliations

A systemic effect for liver senescence

Kuo Du et al. Nat Cell Biol. 2024 Dec.

Abstract

A study reveals that senescence induced in the liver can spread systemically to precipitate multi-organ dysfunction. The work identifies TGFβ signaling as a key mediator of this transmission, suggesting therapeutic avenues to prevent multi-organ failure in severe liver diseases.

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Conflict of interest statement

Competing interests: The authors declare no conflicts of interest related to this article.

Figures

Figure 1:
Figure 1:. Senescence spreads from the liver to multiple organs through TGFβ.
Genetic alterations such as MDM2 deletion or KRAS overexpression in hepatocytes result in the upregulation of p21 and hepatocyte senescence. These hepatocytes develop the senescence-associated secretory phenotype (SASP), releasing factors like TGFβ into the circulation. These circulating SASP factors, particularly TGFβ, propagate senescence to distant organs, including the brain, kidneys, and lungs, leading to multi-organ dysfunction.
See this image and copyright information in PMC

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