Nucleosides, Nucleotides & Nucleic Acids · Nov 3, 2026
The role of methionine-driven epigenetic modulation in the regulation of health and disease: a comprehensive review
By Nath SK, Rahman N, Roy TK et al.
Methionine, a sulfur-containing essential amino acid, plays a pivotal role in epigenetic regulation through its involvement in one-carbon metabolism and as a precursor to S-adenosylmethionine (SAM), the universal methyl donor. This review explores how methionine availability dynamically influences DNA and histone methylation, non-coding RNA expression, and RNA modifications, ultimately shaping gene expression, cellular identity, and developmental outcomes. Emerging evidence suggests that balanced methionine intake is critical for maintaining epigenetic homeostasis. At the same time, both deficiency and excess can disrupt this equilibrium, contributing to diseases such as cancer, metabolic disorders, neurodevelopmental abnormalities, and cardiovascular dysfunction. Methionine deficiency is shown to impair DNA and histone methylation, alter non-coding RNA profiles, and compromise stem cell pluripotency and neurogenesis. Conversely, excess methionine can trigger aberrant hypermethylation, genomic instability, and metabolic imbalances, with links to oncogenic transformation and accelerated aging. Notably, methionine restriction (MR) enhances stress resilience, promotes healthy aging, and reduces tumor progression by reprogramming the epigenetic landscape. This review highlights methionine’s dualistic nature, both as a crucial epigenetic regulator and a potential contributor to disease when imbalanced. It also underscores the need for context-specific dietary strategies and further research into the intricate interplay between methionine metabolism, gene regulation, and long-term health outcomes. Understanding these molecular mechanisms may unlock novel nutritional and therapeutic approaches for disease prevention and epigenetic reprogramming.