Epigenetic Regulation of Aging and its Rejuvenation

作者：Yongpan An, Qian Wang, Ke Gao, Chi Zhang, Yanan Ouyang, Ruixiao Li, Ma Zhou, Tong Wu, Lifan Zhou, Zhengwei Xie, Rui Zhang, Guojun Wu · 发表于：MedComm · 年份：2025 · DOI：10.1002/mco2.70369 · 被引用次数：21 · 研究领域：Epigenetics and DNA Methylation、Genetics, Aging, and Longevity in Model Organisms、Single-cell and spatial transcriptomics

Aging increases the global burden of disease, yet its molecular basis remains incompletely understood. Recent studies indicate that reversible epigenetic drift-spanning DNA methylation clocks, histone codes, three-dimensional chromatin, and noncoding RNA networks-constitutes a central regulator of organismal decline and age-related diseases. How these epigenetic layers interact across different tissues-and how best to translate them into therapeutic strategies-are still open questions. This review outlines the specific mechanisms by which epigenetic changes influence aging, highlighting their impact on genomic instability, stem-cell exhaustion, and mitochondrial dysfunction. We critically evaluate emerging rejuvenation strategies-partial OSKM reprogramming, CRISPR-dCas9 epigenome editing, NAD⁺/sirtuin boosters, HDAC inhibitors, microbiota transfer, and precision lifestyle interventions-detailing their efficacy in resetting epigenetic age and restoring tissue homeostasis. Integrating single-cell multiomics and second-generation epigenetic clocks, we propose a roadmap for translating these insights into safe, personalized antiaging medicine.