[Research Advances on Mechanisms and Interventions of DNA Methylation-Regulated Aging-Related Imbalance in Bone...

Aging can induce age-related bone diseases such as osteoporosis. DNA methylation, a core epigenetic regulatory mechanism, participate in the pathological process of aging-induced bone metabolism imbalance by modulating gene expression at the epigenetic level. Using S-adenosylmethionine as a methyl donor, it exhibits characteristics of hypomethylation in genomic repetitive regions and abnormal methylation in CpG islands of promoters of key bone metabolism genes with advancing age. The "epigenetic clock" constructed based on these features can accurately predict an individual's biological age. In bone metabolism, DNA methylation disrupts the osteoblast-osteoclast balance by targeting key factors. Such abnormalities are driven by aging-related inflammation and oxidative stress, while bone loss feedback exacerbates epigenetic disorders, forming a vicious cycle. Targeted intervention strategies have demonstrated significant potential in addressing bone metabolism-related issues. Low-dose DNA methyltransferase inhibitors can improve bone metabolism; nutrients such as folate and cobalamin maintain methylation homeostasis by optimizing one-carbon metabolism pathways; while CRISPR/dCas technology enables precise regulation in the cellular and animal levels, thereby affecting bone metabolism. However, existing strategies still face challenges such as off-target effects and low delivery efficiency. Future research needs to deepen mechanistic studies, optimize intervention methods, and promote their translation into clinical prevention and treatment of osteoporosis.