Cellular senescence in skin inflammation: molecular mechanisms and potential clinical implications

Cellular senescence is increasingly regarded as a mechanism linking chronic tissue stress to persistent skin inflammation. Senescent cells are defined by stable cell-cycle arrest with remodeling of morphology, metabolism, and secretory phenotype, of which the senescence-associated secretory phenotype (SASP) is central. Because no single marker is sufficient, senescence in skin requires multiparameter, cell-type-resolved criteria. This Review addresses stress sensing, SASP induction, paracrine propagation, immune evasion, cellular heterogeneity, and therapeutic targeting, stratifying evidence by disease: chronic and diabetic wounds are best supported, whereas in psoriasis, atopic dermatitis, cutaneous lupus erythematosus, systemic sclerosis, and vitiligo the evidence remains largely associative, as SASP-like mediators overlap with cytokine programs from activated keratinocytes, stromal cells, and immune cells. Senescence-targeted interventions are classified as senolytics, senomorphics, or senopreventive/geroprotective strategies, and assessed at marker, SASP, senescent-cell-burden, and disease-outcome levels. It further notes that clinical translation depends on defining senescence-maintained lesion subtypes, establishing combinatorial biomarkers and spatial maps, and validating the efficacy and safety window of local therapies in suitable models and human tissues.