Box A of HMGB1 plasmid reverses the age-related changes in the plasma proteomic profile of perimenopausal monkeys

Aging, a complex biological process, is intrinsically linked to the pathogenesis of numerous age-related diseases. A key factor in the aging process is the accumulation of DNA damage and the subsequent activation or failure of the DNA damage response. To mitigate this damage, DNA repair mechanisms often involve the formation of DNA gaps. This study investigates the potential role of the Box A domain of High Mobility Group Box 1 (HMGB1) in modulating age-related changes. We utilized a label-free quantitative proteomic technique to analyze the plasma proteome of three female adult and eight female perimenopausal cynomolgus macaques (Macaca fascicularis), with the perimenopausal group receiving an intravenous administration of the Box A plasmid. Proteomic analysis revealed differential expressions in proteins primarily associated with stress response, immune regulation, lipid transport, and cellular homeostasis following Box A plasmid intervention. Notably, the expression levels of key proteins, such as apolipoprotein E (APOE) and sex hormone-binding globulin (SHBG), showed a reversal effect, restoring levels closer to those observed in the younger, adult monkeys. These findings highlight the potential of the Box A of HMGB1 plasmid as a therapeutic candidate to mitigate age-related proteomic alterations, offering a novel avenue for targeted interventions in aging and associated diseases.