DNA protection epigenetic marks: "Youth-associated genomic stabilization DNA gaps" (youth-DNA-gaps)

Global hypomethylation promotes genomic instability by increasing DNA damage.The accumulation of DNA damage contributes to cellular senescence(definition), which is implicated in the aging process and various age-associated diseases, including age-associated non-communicable diseases (NCDs).Methylated youth-DNA-gap epigenetic mark produced by the molecular scissoring activity of Box A of HMGB1 molecule or rejuvenating DNA by genomic stability molecule to strengthen DNA (REDGEM-S-DNA) protects DNA from damage by relieving the double helix torsion stress during replication or transcription.The activation through active or passive release of intranuclear HMGB1 causes youth-DNA-gaps depletion.The reduction of youth-DNA-gaps results in DNA damage accumulation and global hypomethylation.Restoring the function of the youth-DNA-gap epigenetic mark through treatment of Box A of HMGB1 leads to reduced cellular senescence, rejuvenation of aging cells, and improved organ function.Therefore, HMGB1-Box A or REDGEM-S-DNA gene therapy to produce DNA gaps could be a promising strategy for treating aging conditions and age-related diseases.