Skin aging: Mechanistic insights and targeted therapeutic strategies

Aging exerts broad effects on human physiology, leading to reduced organ function and increased susceptibility to chronic diseases. Cutaneous aging provides a visible and accessible model of systemic aging, driven by both intrinsic biological processes and extrinsic environmental factors, leading to progressive structural and functional deterioration of the skin. A key hallmark of aging is cellular senescence, which links molecular damage and inflammation through the senescence-associated secretory phenotype, altering matrix composition, impairing epidermal renewal, and promoting chronic inflammation. In parallel, inflammaging, a low-grade, persistent inflammatory state, sustains immune activation and hinders regeneration, accelerating cutaneous deterioration. In advanced stages, skin aging is characterized by marked atrophy and manifests clinically as chronic cutaneous fragility, impaired wound healing, and diminished immunosurveillance, ultimately increasing susceptibility to infection and injury. Thus, targeting skin aging now extends beyond a merely aesthetic pursuit, addressing tissue homeostasis, counteracting cumulative molecular damage, and preserving the equilibrium between regeneration and inflammation. This review summarizes recent advances in the understanding of skin aging, focusing on its mechanistic drivers, phenotypic expression, and evolving treatment approaches. It also explores the bidirectional crosstalk between skin and systemic inflammation, highlighting key knowledge gaps and future directions for clinical and translational research.