Lactylation and methylation: Dual epigenetic codes and potential therapeutic targets in myocardial aging.

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.