Epigenetic Modifications and Cellular Senescence: A Critical Review

Cellular senescence is a central hallmark of aging, functioning as a double-edged process that prevents malignant transformation while contributing to tissue dysfunction and chronic inflammation. Recent advances emphasize the critical role of epigenetic modifications—including DNA methylation, histone changes, chromatin remodeling, and regulation by non-coding RNAs—in both initiating and maintaining the senescent state. These mechanisms drive the senescence-associated secretory phenotype (SASP), promote inflammatory signaling, and shape the aging phenotype. The development of epigenetic clocks has provided powerful tools to estimate biological age and evaluate therapeutic interventions. Emerging strategies such as epigenetic drugs, partial reprogramming with Yamanaka factors, and the integration of senolytics with epigenetic modulators show promise in restoring youthful cellular function and delaying age-related decline. Future directions highlight the integration of multi-omics data, CRISPR-based epigenome editing, and next-generation clocks to refine biomarkers and therapeutic approaches. Collectively, targeting epigenetic regulation of senescence represents a promising pathway toward healthier aging and longevity.