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

Yang Y, Chen H, Xiang S, Wei Y, Zhang L, Sun A, E X, Wu F, Luo N, Liang F, Wu X, …, 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

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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	2026-10-01
Source	DOI 10.1038/s41392-026-02773-7 · PMID 42736285

Where this study fits

How this study connects to the pathway map, open questions, people and other studies in the Atlas.

Pathway relations

Supports

AMPK inhibits mTORC1

Strongest evidence: A (Animal model) · settled in the literature · Status: Proposed

plausible in people, not shown directly

Cell biochemistry in human and mouse cells (GWI2008) plus one study in aged mice (YAN2026B). Direct Raptor phosphorylation is shown in cells; how much it adds beside the TSC route in living tissue, and in people, is not shown.

People in the Atlas

Yang Yang first author · 1 study in the Atlas

Showed as first author that the liver-secreted protein hepassocin protects against age-related liver senescence and helps the liver regenerate
Xiaoming Yang last author · 1 study in the Atlas

Showed as senior author that the liver-secreted protein hepassocin protects against age-related liver senescence and helps the liver regenerate
Ruizhao Wang 1 study in the Atlas

Built FPTT, fluorescent 'ticker tapes' that record several signalling pathways in living cells over days, and used its mTOR version to follow mTOR activity oscillating through the cell cycle

More: 23 other authors

No profile yet: Chen H, Xiang S, Wei Y, Zhang L, Sun A, E X, Wu F, Luo N, Liang F, Wu X, Wang C, Chen Z, Zhang Q, Chen X, Wu Q, Han Z, Li C, Yin R, Ren G, Li J, Zhao K, Gao H, Yu M

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All 212 studies on mTORC1

Topics

Cellular senescence mTORC1 LKB1 (STK11)Autophagy AMPK

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

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., Chen, H., Xiang, S., Wei, Y., Zhang, L., Sun, A., E, X., Wu, F., Luo, N., Liang, F., Wu, X., Wang, C., Chen, Z., Zhang, Q., Chen, X., Wu, Q., Han, Z., Li, C., Yin, R., Ren, G., Li, J., Zhao, K., Gao, H., Wang, R., Yu, M., & 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 Chen, H. and Xiang, S. and Wei, Y. and Zhang, L. and Sun, A. and E, X. and Wu, F. and Luo, N. and Liang, F. and Wu, X. and Wang, C. and Chen, Z. and Zhang, Q. and Chen, X. and Wu, Q. and Han, Z. and Li, C. and Yin, R. and Ren, G. and Li, J. and Zhao, K. and Gao, H. and Wang, R. and Yu, M. 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}
}

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