Mouse and human data link Hepassocin to age-related liver senescence and regeneration
In this abstract, circulating and intrahepatic Hepassocin fell in aged mice and elderly humans; aged Hepassocin-knockout mice showed more cellular senescence and worse liver regeneration after partial hepatectomy, and AMPK-linked signalling was implicated. [1]
Automatic summary · not editorially reviewed
The key findings
Circulating and intrahepatic Hepassocin levels were lower in aged mice and elderly humans, and the post-partial-hepatectomy rise in Hepassocin was blunted in 12-month-old mice. [1]
Aged Hepassocin-knockout mice showed variable hepatic steatosis, exacerbated cellular senescence and impaired autophagy, with severely compromised liver regeneration after partial hepatectomy. [1]
In aged Hepassocin-knockout mice, the AMPK agonist AICAR ameliorated the liver aging phenotype and restored regenerative capacity, and exogenous Hepassocin improved regenerative outcomes in aged wild-type mice. [1]
The source at a glance
- Study type / format
- Abstract of a preclinical mouse study with a human observational comparison
- Population / context
- Aged mice, including Hepassocin-knockout and wild-type mice, and elderly humans.
- Summary based on
- Study abstract
- Original publication
- September 15, 2026
Hepassocin levels in aged mice and elderly humans
The abstract reports lower circulating and intrahepatic Hepassocin (HPS) levels in both aged mice and elderly humans. In 12-month-old mice, the rise in HPS after two-thirds partial hepatectomy (PHx, surgical removal of part of the liver) was markedly reduced. The authors describe HPS as a hepatokine, a liver-produced signalling protein, with known liver-protective functions and little effect on liver homeostasis in adult mice.
Supporting source [1]
Aged HPS-knockout mice: senescence and impaired regeneration
Aged HPS-knockout mice showed variable hepatic steatosis (fatty liver), exacerbated cellular senescence and impaired autophagy. After PHx, liver regeneration was severely compromised: higher mortality, reduced hepatocyte proliferation, delayed recovery of liver mass and worsened disruption of autophagy. Compared with wild-type littermates, aged knockout mice had reduced activation of LKB1 and AMPK and elevated mTOR activity in quiescent and regenerating livers.
Supporting source [1]
AMPK agonist and exogenous HPS in aged mice
Mechanistically, the abstract states that HPS directly activated AMPK in hepatocytes via an ANXA2–ERK–p90RSK–LKB1 signalling cascade. Treatment with the AMPK agonist AICAR ameliorated the liver aging phenotype and restored regenerative capacity in aged HPS-knockout mice. Administration of exogenous HPS improved regenerative outcomes in aged wild-type mice. The authors conclude that HPS is a protective factor against liver senescence through AMPK-dependent mechanisms and suggest HPS signalling as a possible therapeutic target.
Supporting source [1]
How to interpret this
This is an abstract; the full text was not reviewed. Findings come mainly from mouse experiments, including knockout and aged wild-type mice, plus an observation of lower Hepassocin levels in elderly humans. The abstract does not report human sample sizes, study design details or whether raising Hepassocin improves human liver outcomes. Proposed therapeutic strategies are not established treatments.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
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. · europepmc.org · September 15, 2026