REVIEW article
Front. Pharmacol.
Sec. Pharmacogenetics and Pharmacogenomics
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1699296
This article is part of the Research TopicAdvancements in Pharmacological Epigenetics for Aging and Age-related DiseasesView all 4 articles
Epigenetic Pharmacology in Aging: From Mechanisms to Therapies for Age-Related Disorders
Provisionally accepted
Haikuan Yu1
Taojin Feng2Chengcheng Zhang3Zhouguang Jiao4Wenkai Fan5Rongxian Jiang1Dewen Kong1
Fubing Li3*- 1the 927th Hospital of Joint Logistics Support Force of People's Liberation Army of China, Puer, China
- 2Fourth Medical Center of PLA General Hospital, Beijing, China
- 3920th Hospital of People's Liberation Army Joint Logistic Support Force, Kunming, China
- 4NHC Key Laboratory of Human Disease Comparative Medicine, Institute of Laboratory Animal Sciences, Peking Union Medicine College, Chinese Academy of Medical Sciences,, Beijing, China
- 5Pu’er University, Puer, 665000, P. R. China, Puer, China
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Aging is a multidimensional process regulated by the interplay of genetic and environmental factors, with epigenetic alterations serving as a central regulatory hub. Aberrant DNA methylation patterns, dysregulation of histone-modifying enzymes (e.g., SIRT1, EZH2), and non-coding RNA-mediated mechanisms collectively remodel gene expression networks, impacting critical pathways such as cellular senescence and mitochondrial homeostasis. This establishes an "environment-epigenome-disease" causal axis, closely associated with pathologies including β-amyloid deposition in Alzheimer's disease, atherosclerosis, immunosenescence, osteoporosis, sarcopenia, and tumorigenesis. Capitalizing on the reversible nature of epigenetic modifications, pharmacological epigenetics has emerged as a cutting-edge field for intervening in aging and age-related diseases. Targeting key epigenetic modifiers such as DNA methyltransferases and histone deacetylases enables the modulation of disease-associated epigenetic states, providing a promising avenue for therapeutic intervention in aging and age-related diseases. This review synthesizes the molecular mechanisms of epigenetic regulation in aging, their role in age-related diseases, and advances in pharmacological epigenetics — from basic research to clinical translation. It further situates key challenges such as target specificity, long-term safety, and tissue-specific delivery within a translational framework, aiming to inform strategies for the diagnosis and intervention of age-related conditions.
Keywords: Aging, epigenetics, age-related diseases, Pharmacological epigenetics, DNA Methylation, histone modification, non-coding RNA, Epigenetic modifiers
Received: 04 Sep 2025; Accepted: 15 Oct 2025.
Copyright: © 2025 Yu, Feng, Zhang, Jiao, Fan, Jiang, Kong and Li. 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: Fubing Li, lfbingwilson@sohu.com
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