Hepassocin prevents age-related liver senescence and facilitates liver regeneration by activating AMPK

Yang Y, Yang X · 2026 · Signal Transduction and Targeted Therapy · Atlas ID YAN2026B

What this study shows

Hepassocin (HPS/FGL1), a hepatokine, activates AMPK via an ANXA2-ERK-p90RSK-LKB1 cascade, restraining mTOR activity. Aged HPS-knockout mice show reduced LKB1/AMPK activation and elevated mTOR activity, impaired autophagy, exacerbated cellular senescence, and severely compromised liver regeneration after partial hepatectomy. AMPK agonist AICAR or exogenous HPS rescued the aging/regeneration phenotype.

Abstract

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Liver aging significantly impairs hepatic function and regenerative capacity, increasing the risk of morbidity and mortality from chronic liver diseases. Identifying molecular regulators of these processes may reveal promising therapeutic targets. Although Hepassocin (HPS), a hepatokine with known hepatoprotective functions, has minimal effects on liver homeostasis in adult mice, its role in long-term liver maintenance remains unclear. In this study, we observed a decrease in circulating and intrahepatic HPS levels in both aged mice and elderly humans.

Read the full abstract on PubMed →

At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Aged mice (12-month-old) and Hepassocin(Fgl1)-knockout mice, partial-hepatectomy liver regeneration model; correlative human liver tissue (aged vs young)); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Aged mice (12-month-old) and Hepassocin(Fgl1)-knockout mice, partial-hepatectomy liver regeneration model; correlative human liver tissue (aged vs young)
Journal	Signal Transduction and Targeted Therapy
Year	2026
Peer reviewed	Yes
Record last updated	2026-09-23
Source	DOI 10.1038/s41392-026-02773-7 · PMID 42736285

Extracted findings

Intervention	Hepassocin (HPS/FGL1) genetic knockout; exogenous HPS administration; AMPK agonist AICAR
Target	AMPK (via ANXA2-ERK-p90RSK-LKB1 axis); mTOR activity
Model	Mouse (aged, 12-month, HPS-knockout); human liver tissue (correlative)
Effect	HPS activates AMPK/LKB1 and restrains mTOR; aged HPS-KO mice show elevated mTOR activity, impaired autophagy, exacerbated senescence and failed liver regeneration; AICAR or exogenous HPS rescues the phenotype

Cite this paper

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Yang, Y., & Yang, X. (2026). Hepassocin prevents age-related liver senescence and facilitates liver regeneration by activating AMPK. Signal Transduction and Targeted Therapy. https://doi.org/10.1038/s41392-026-02773-7

@article{YAN2026B,
  author       = {Yang, Y. and Yang, X.},
  title        = {{Hepassocin prevents age-related liver senescence and facilitates liver regeneration by activating AMPK}},
  journal      = {Signal Transduction and Targeted Therapy},
  year         = {2026},
  doi          = {10.1038/s41392-026-02773-7},
  note         = {PMID: 42736285},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record YAN2026B) [Data set]. https://mtor-atlas.org/study/YAN2026B/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_YAN2026B,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record YAN2026B},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/YAN2026B/},
  doi          = {10.5281/zenodo.22059963}
}