Evidence map›Paper›PMID 41604112›Full record

ArticleGeroScience2026

Liver-specific phenotypic aging, behavior and genetic risks, and long-term liver-related outcomes.

Tianhao Wu, Chengnan Guo, Huangbo Yuan, Mingyi Du, Tiejun Zhang, Xingdong Chen, Zhenqiu Liu

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Article in GeroScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Tianhao WuHuman Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Fudan University, Shanghai, 200433, China.
Chengnan GuoDepartment of Epidemiology, School of Public Health, Fudan University, Shanghai, China.
Huangbo YuanFudan University Taizhou Institute of Health Sciences, Taizhou, China.
Mingyi DuHuman Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Fudan University, Shanghai, 200433, China.
Tiejun ZhangDepartment of Epidemiology, School of Public Health, Fudan University, Shanghai, China.
Xingdong ChenFudan University Taizhou Institute of Health Sciences, Taizhou, China. xingdongchen@fudan.edu.cn.
Zhenqiu LiuHuman Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Fudan University, Shanghai, 200433, China. zhenqiuliu@fudan.edu.cn.ORCID http://orcid.org/0000-0002-5244-6894

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Phenotypic age, an aging indicator derived from clinical biomarkers, is associated with morbidities and mortality. However, a liver-specific phenotypic aging indicator is still lacking, and its longitudinal associations with liver-related outcomes, as well as the underlying biological mechanisms, remain elusive. We developed a liver-specific phenotypic age using 11 selected clinical blood markers within the England-White cohort of the UK Biobank and validated this metric in both the Scotland-Wales cohort and Non-White-British cohort. We calculated phenotypic age acceleration (PhenoAgeAccel) and examined its association with long-term liver-related outcomes. We also explored the extent to which liver-specific PhenoAgeAccel mediated the impact of modifiable risk behaviors on liver-related outcomes. The metabolic and proteomic signatures of liver-specific PhenoAgeAccel were subsequently characterized. Liver-specific PhenoAgeAccel was significantly associated with a 1.23- to 2.97-fold increased risks of all-cause mortality and liver-related events. The impact of liver-specific PhenoAgeAccel on liver outcomes were more pronounced in males and in individuals with high genetic risk compared to their respective counterparts, and was stronger than that observed with systemic PhenoAgeAccel. Approximately 10-27% of the associations between risk behaviors and liver-related outcomes were mediated by liver-specific PhenoAgeAccel. Proteomic analysis identified 211 proteins associated with both liver-specific PhenoAgeAccel and liver-related outcomes, of which 22 (e.g., AGXT and SULT2A1) were liver-enriched and significantly mediated this relationship. Liver-specific PhenoAgeAccel is a strong predictor of liver-related outcomes, partially mediates the impact of modifiable behaviors, and is linked to liver-enriched proteins. This accessible tool may enhance risk stratification and support preventive strategies targeting liver health and aging.

Indexed as

Liver agingLiver diseasesMolecular signaturesMortality

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.