Multi-omics perspectives on mitochondrial vulnerability in the aging liver: biological modules and translational implications
- 1School of Medicine, Zhejiang Chinese Medical University , ,
- 2Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University , , ,
- 3Graduate School of Engineering Biology, Korea Advanced Institute of Science and Technology , ,
Abstract
Chronological age alone is an incomplete proxy for the biological heterogeneity of the aging liver. Mitochondrial vulnerability may provide a mechanistic link between biological aging and the loss of hepatic resilience under metabolic, toxic, and ischemic stress. Accumulating multi-omics evidence suggests that hepatic aging is best understood as a set of coordinated pathway-level disturbances rather than through isolated biomarkers. Transcriptomic, proteomic, and metabolomic studies converge on five interrelated biological modules: lipid stress, diminished oxidative reserve, proteostatic strain, inflammatory sensitization, and reduced recovery capacity. These modules are interconnected through impaired mitochondrial metabolic flexibility, redox buffering, organelle crosstalk, and quality-control mechanisms. Age-associated changes may remain partly compensated at baseline but become more apparent during metabolic overload, ischemia-reperfusion injury, cold preservation, or ex vivo machine perfusion. Building on cross-species evidence, this Review organizes current findings into a modular framework and examines how mitochondrial vulnerability may connect physiological liver aging with metabolic and ischemic stress. Transplantation and machine perfusion are discussed as stress-exposed settings for evaluating candidate tissue- and fluid-based readouts. Although most omics-derived signals remain insufficiently validated for clinical decision-making, a mitochondrial-centered interpretation may help prioritize biologically coherent mechanisms and improve the translational study of aging-related liver vulnerability.
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BibTeX
@article{chen2026multiomics,
title = {{Multi-omics perspectives on mitochondrial vulnerability in the aging liver: biological modules and translational implications}},
author = {Hanxi Chen and Weiwei Lu and Kainan Wang and Rui Fang and Sunjae Lee and Shi Chen and Zhengtao Liu},
journal = {Frontiers in cell and developmental biology},
year = {2026},
month = oct,
doi = {10.3389/fcell.2026.1954948},
url = {https://europepmc.org/article/PMC/PMC13716950},
note = {CC BY},
}
RIS
TY - JOUR
TI - Multi-omics perspectives on mitochondrial vulnerability in the aging liver: biological modules and translational implications
AU - Hanxi Chen
AU - Weiwei Lu
AU - Kainan Wang
AU - Rui Fang
AU - Sunjae Lee
AU - Shi Chen
AU - Zhengtao Liu
PY - 2026
DA - 2026/10/15
JO - Frontiers in cell and developmental biology
DO - 10.3389/fcell.2026.1954948
UR - https://europepmc.org/article/PMC/PMC13716950
AB - Chronological age alone is an incomplete proxy for the biological heterogeneity of the aging liver. Mitochondrial vulnerability may provide a mechanistic link between biological aging and the loss of hepatic resilience under metabolic, toxic, and ischemic stress. Accumulating multi-omics evidence suggests that hepatic aging is best understood as a set of coordinated pathway-level disturbances rather than through isolated biomarkers. Transcriptomic, proteomic, and metabolomic studies converge on five interrelated biological modules: lipid stress, diminished oxidative reserve, proteostatic strain, inflammatory sensitization, and reduced recovery capacity. These modules are interconnected through impaired mitochondrial metabolic flexibility, redox buffering, organelle crosstalk, and quality-control mechanisms. Age-associated changes may remain partly compensated at baseline but become more apparent during metabolic overload, ischemia-reperfusion injury, cold preservation, or ex vivo machine perfusion. Building on cross-species evidence, this Review organizes current findings into a modular framework and examines how mitochondrial vulnerability may connect physiological liver aging with metabolic and ischemic stress. Transplantation and machine perfusion are discussed as stress-exposed settings for evaluating candidate tissue- and fluid-based readouts. Although most omics-derived signals remain insufficiently validated for clinical decision-making, a mitochondrial-centered interpretation may help prioritize biologically coherent mechanisms and improve the translational study of aging-related liver vulnerability.
SN - 2296-634X
ER -