Niu Qian-Qian, Xi Yu-Ting, Guo Ya-Qi, Piao Zheng-Ji, Zhang Chun-Rui, Li Tian-Yao, Li Dan-Jie, Li Peng, Yin Ya-Ling, Lim Vuanghao, Kamal Nik Nur Syazni Nik Mohamed
Advanced Medical and Dental Institute, Universiti Sains Malaysia, Penang 13200, Malaysia; School of Basic Medical Sciences, Henan Medical University, Xinxiang 453003, China.
College of Pharmacy, Henan Medical University, Xinxiang 453003, China.
Ageing Res Rev. 2025 Dec;112:102849. doi: 10.1016/j.arr.2025.102849. Epub 2025 Jul 30.
Combating aging has become a central challenge in the life sciences, and myocardial aging, as a fundamental pathological process underlying the development and progression of various cardiovascular diseases, has become a key area in anti-aging research. In recent years, lactylation and methylation, two metabolism-dependent epigenetic modifications, have garnered increasing attention in the context of myocardial aging. Lactylation, mediated by lactate accumulation due to metabolic dysregulation, modifies lysine residues on both histone and non-histone proteins, thereby participating in the regulation of gene transcription, metabolic homeostasis, and inflammatory responses. In parallel, methylation affects gene expression, metabolic remodeling, and mitochondrial function through DNA, RNA, and histone modifications. This review systematically summarizes the regulatory mechanisms of lactylation and methylation in myocardial aging, with a particular focus on their interplay in histone and non-histone protein modification, metabolic regulation, and signaling pathway integration. Furthermore, we evaluate the potential of these reversible modifications as early epigenetic biomarkers and discuss multilayered intervention strategies targeting both lactylation and methylation. Such strategies highlight their translational potential in delaying myocardial aging and mitigating cardiovascular disease. Precisely modulating lactylation and methylation may offer novel theoretical frameworks and therapeutic targets for the prevention and treatment of myocardial aging.
对抗衰老已成为生命科学的核心挑战，而心肌衰老作为各种心血管疾病发生和发展的基本病理过程，已成为抗衰老研究的关键领域。近年来，乳酸化和甲基化这两种依赖代谢的表观遗传修饰在心肌衰老背景下受到越来越多关注。乳酸化由代谢失调导致的乳酸积累介导，修饰组蛋白和非组蛋白上的赖氨酸残基，从而参与基因转录、代谢稳态和炎症反应的调节。与此同时，甲基化通过DNA、RNA和组蛋白修饰影响基因表达、代谢重塑和线粒体功能。本综述系统总结了乳酸化和甲基化在心肌衰老中的调控机制，特别关注它们在组蛋白和非组蛋白修饰、代谢调节及信号通路整合中的相互作用。此外，我们评估了这些可逆修饰作为早期表观遗传生物标志物的潜力，并讨论了针对乳酸化和甲基化的多层干预策略。此类策略凸显了它们在延缓心肌衰老和减轻心血管疾病方面的转化潜力。精确调节乳酸化和甲基化可能为心肌衰老的预防和治疗提供新的理论框架和治疗靶点。
