The role of cellular senescence in wound healing of diabetic skin

Diabetic foot ulcers (DFUs) are a severe complication of diabetes mellitus, characterized by impaired wound healing due to complex pathophysiological mechanisms. Cellular senescence, particularly the senescence-associated secretory phenotype (SASP), contributes to delayed healing by inducing persistent inflammation and dysfunction in dermal fibroblasts, macrophages, and adipose tissue cells. Here we review the molecular pathways leading to senescence in these cell types, including p53/p21 activation and apoptosis resistance, and how their SASP perpetuates chronic inflammation and impairs tissue regeneration. We also discuss emerging therapeutic approaches targeting senescent cells with senolytic and senomorphic agents to improve healing outcomes. These insights suggest that modulating cellular senescence may offer promising avenues for treating diabetic wounds, warranting further investigation into senescence-targeted therapies in clinical settings.