Regulatory role of m
6A (N
6-methyladenosine) in cellular senescence-related processes
Telomere shortening, increased SASP secretion, DNA damage, and oxidative stress are important factors contributing to cellular senescence.Overall, m 6A plays an important regulatory role in these senescence-related processes. During telomere shortening, alterations in m 6A levels regulate the cell cycle; ultimately, this regulates cellular senescence by affecting telomere length and integrity, thereby causing DNA damage and promoting p53/p21 expression. During SASP secretion, m 6A affects the degree of inflammation primarily by regulating the expressions of pro- and anti-inflammatory cytokines; these cytokines, in turn, affect the progression of cellular senescence by regulating p53/p21 and p16 expression to influence the cell cycle. During DNA damage, m 6A regulates p53/p21 expression by influencing the recruitment of DNA polymerase at the site of damage and regulating DNA break repair, thereby regulating cellular senescence. During oxidative stress, m 6A predominantly acts on oxidative and antioxidant systems to regulate the balance of oxidation and antioxidation in vivo; overall, this further influences the degree of DNA damage and inflammation levels and ultimately regulates the process of cellular senescence via cell cycle regulation.