Aging is identified as a significant risk factor for chronic diseases, particularly in the context of myocardial aging, which involves various cell types and contributes to cardiovascular issues like heart failure and myocardial infarction.

Key factors driving cardiomyocyte aging include abnormal mitochondrial dynamics, metabolic dysfunction, and increased levels of reactive oxygen species (ROS), all of which contribute to DNA damage and epigenetic changes.

Lactylation, a post-translational modification, involves the addition of a lactyl group to lysine residues and is associated with metabolic changes, especially under pathological conditions that lead to lactate accumulation, disrupting cardiomyocyte function.

Methylation, another critical modification, is facilitated by methyltransferases and is essential for regulating chromatin structure, transcriptional activity, and mitochondrial function, thus playing a vital role in cellular aging.

The interaction between lactylation and methylation in cardiomyocytes reveals an antagonistic relationship at the histone level, while they exhibit complementary roles in non-histone protein modifications.

The review highlights the potential of lactylation and methylation as early epigenetic biomarkers and therapeutic targets for myocardial aging, suggesting that interventions targeting these pathways could provide new strategies for delaying age-related cardiac diseases.

Future research should concentrate on the regulatory networks involving lactylation and methylation to develop more effective interventions aimed at addressing myocardial aging.

Cardiomyocyte senescence plays a crucial role in heart dysfunction, leading to irreversible cell cycle arrest, functional decline, and the development of a senescence-associated secretory phenotype (SASP).

Lactylation and methylation have emerged as two important metabolically regulated epigenetic modifications that significantly influence gene expression and metabolic regulation in the context of myocardial aging.