1139 Identification and quantification of senescent cell types in chronologically aged skin and UV-induced skin pathologies

Skin aging is an inevitable consequence of human life and accelerated by environmental factors including exposure to ultraviolet radiation and pollution. Senescent cells are irreversibly growth arrested and accumulate in aging tissues including human skin, in pre-neoplastic lesions such as naevi and at sites of age-related pathologies. Actinic keratosis is a common skin condition associated with prolonged sun exposure and age. If untreated, actinic keratosis can progress towards squamous cell carcinoma (SCC). Despite its prevalence, current diagnostic tools are limited to visual and histological examination of lesions and frequently fail to distinguish benign actinic keratosis from cancerous SCC lesions. To detect senescent cells within specific compartments of the skin, we multiplexed novel senescence biomarkers HMGB1 and lamin B1, with proliferation and cell type specific markers. Collectively, we found that senescent cells accumulate in chronologically aged human skin and upon UVB exposure. Moreover, senescent cells are present within the epidermis of pre-neoplastic actinic keratosis lesions as compared to non-affected isogenic control skin, while the dermis remained unaffected. In contrast, SCC lesions contained a heterogenous mixture of senescent and proliferative cells. The characterization of senescence biomarkers and tools developed in this study lay the foundation to investigate how different environmental factors impact skin aging and regeneration, and shed light on how senescence changes the function of skin cell types, ultimately resulting in age-related skin pathologies, including pigmentation disorders, skin wrinkling, skin cancer and chronic wounds.