Review: epigenetic information loss and circadian decline in liver aging
This review links epigenetic information loss and age-related weakening of circadian clock robustness (chronosenescence) in liver aging, with the NAD/SIRT1 axis as a hub; it notes that causal evidence in humans is limited and most rejuvenation strategies remain preclinical or early translational. [1]
Automatic summary · not editorially reviewed
The key findings
The review describes liver aging as involving progressive functional decline and increased susceptibility to metabolic diseases, with some aspects reflecting partially reversible disruption of epigenetic and circadian regulatory programs. [1]
Chronosenescence is defined in the review as age-related deterioration of circadian clock robustness, and the NAD/SIRT1 axis is discussed as a hub linking these processes with energy metabolism. [1]
The review states that direct causal evidence in humans remains limited and most rejuvenation-oriented strategies remain preclinical or early translational. [1]
The source at a glance
- Study type / format
- Narrative review (abstract)
- Population / context
- Liver aging biology, as synthesized in a review
- Summary based on
- Study abstract
- Original publication
- June 1, 2026
Liver aging as partly reversible regulatory disruption
The review states that liver aging involves progressive functional decline and greater susceptibility to metabolic diseases. It argues that some aspects reflect partially reversible disruption of epigenetic and circadian regulatory programs rather than exclusively irreversible molecular damage. It focuses on two interlinked drivers: epigenetic information loss and chronosenescence, defined as age-related deterioration of circadian clock robustness. The NAD/SIRT1 axis is presented as a central hub connecting these processes with energy metabolism.
Supporting source [1]
Synthesized methods and proposed therapeutic strategies
The review synthesizes evidence from foundational studies and recent advances in single-cell multiomics, spatial transcriptomics and CRISPR epigenetic editing technologies. It evaluates emerging therapeutic strategies: lifestyle intervention, NAD restoration, chronotherapy, partial cellular reprogramming, chemical reprogramming and extracellular vesicle-based approaches, with emphasis on their current translational maturity and limitations. The integrated analysis highlights spatial heterogeneity of liver aging and supports mechanistic links between epigenetic remodeling, circadian disruption, NAD decline, inflammation and metabolic dysfunction.
Supporting source [1]
Limited human causal evidence and preclinical status
Experimental studies suggest that selected regulatory features of liver aging can be modified, but the review states that direct causal evidence in humans remains limited and most rejuvenation-oriented strategies remain preclinical or early translational. It presents a unified framework for understanding liver aging as a disorder of regulatory information and temporal coordination and a cautious translational roadmap for identifying modifiable nodes. Clinical application, it stresses, will require rigorous validation of safety, durability, delivery, patient selection and long-term outcomes.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. This is a review synthesizing other studies, not new human data. The abstract reports no sample sizes, follow-up or outcome measures, and it states that direct causal evidence in humans is limited and most rejuvenation strategies are preclinical or early translational.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Xu X, Li H, Li J, Huang M. · europepmc.org · June 1, 2026