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REVIEW article

Front. Cell Dev. Biol.
Sec. Cell Death and Survival
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1548015

Involvement of SIRT1-mediated Aging in Liver Diseases

Provisionally accepted
  • 1 First Affiliated Hospital of Jilin University, Changchun, China
  • 2 Jilin University, Changchun, Hebei Province, China

The final, formatted version of the article will be published soon.

    Liver disease is a significant global health issue, responsible for millions of deaths annually. Aging, characterized by the gradual decline in cellular and physiological functions, impairs tissue regeneration, increases susceptibility to liver diseases, and leads to a decline in liver health. Silent information regulator 1 (SIRT1), a NAD⁺-dependent deacetylase, has emerged as a pivotal factor in modulating age-related changes in the liver. SIRT1 preserves liver function by regulating essential aging-related pathways, including telomere maintenance, epigenetic modifications, cellular senescence, intercellular communication, inflammation, and mitochondrial function. Notably, SIRT1 levels naturally decline with age, contributing to liver disease progression and increased vulnerability to injury. This review summarizes the regulatory role of SIRT1 in aging and its impact on liver diseases such as liver fibrosis, alcoholic associated liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), and metabolic dysfunction-associated steatohepatitis (MASH), hepatocellular carcinoma (HCC). We also discuss emerging therapeutic approaches, including SIRT1 activators, gene therapy, and nutritional interventions, which are evaluated for their potential to restore SIRT1 function and mitigate liver disease progression. Finally, we highlight future research directions to optimize SIRT1-targeted therapies for clinical applications in age-related liver conditions.

    Keywords: SIRT1, Aging, cellular senescence, Liver Diseases, therapeutic approaches

    Received: 19 Dec 2024; Accepted: 27 Jan 2025.

    Copyright: © 2025 Zhang, Gong, Tao, Zhai, Huang and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Sixi Zhang, First Affiliated Hospital of Jilin University, Changchun, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.