Farmatsevtychnyi Zhurnal · Feb 27, 2026
The role of high mobility group Box 1 (HMGB1) in the formation of senescence-associated secretory phenotype and age-related changes (Review)
By Сенюк І, Кравченко ВМ, Galuzinska LV et al.
The biology of aging is one of the most intensively studied areas of modern biomedicine, since age-related changes underlie the development of most chronic non-infectious diseases. High Mobility Group Box 1 (HMGB1) protein, a non-histone nuclear protein with pronounced pleiotropic activity, plays an important role in the regulation of cellular homeostasis, response to damage, and inflammatory processes. The aims of this review is to summarize and systematize current scientific data on the molecular mechanisms of HMGB1 involvement in biological aging and the development of age-related pathological conditions. Materials and methods. We analyzed and summarized the results of experimental and clinical studies presented in professional scientific publications using the Web of Science, Scopus, and PubMed bibliographic databases. Particular attention was paid to studies devoted to the role of HMGB1 in cellular senescence, aging, and intercellular signaling. It has been shown that HMGB1 participates in the realization of key signs of aging, in particular genomic instability, epigenetic changes, cellular senescence, chronic sterile inflammation, mitochondrial dysfunction, loss of proteostasis, disruption of intercellular communication, and extracellular matrix remodeling. The dual biological activity of HMGB1 determines its protective role in the cell nucleus and pro-inflammatory effect in the extracellular environment. The accumulation of extracellular HMGB1 is associated with the progression of age-related diseases and the formation of a senescence-associated secretory phenotype. HMGB1 is a key molecular regulator of aging processes, combining intracellular mechanisms for maintaining genomic stability with intercellular pro-inflammatory signaling. Further study of this protein opens up prospects for the use of HMGB1 as a biomarker of biological age and a pharmacological target for slowing age-related changes.