Cellular senescence burden across chronic skin conditions

Summary: Abstract Body: Cellular senescence is a physiologic anti-proliferative defense mechanism in response to cellular damage and stress. Chronic accumulation of senescent cells is implicated in the pathogenesis of various skin diseases, such as psoriasis and skin cancer. The detrimental role of senescent cells can be largely attributed to the paracrine effect of secreted proinflammatory cytokines, growth factors, and proteases. In skin, this can cause chronic low grade inflammation, barrier dysfunction and immunosenescence. The distribution and the level of cellular senescence across skin conditions is poorly understood. We evaluated human skin biopsies from patients with psoriasis, dermatitis, radiation-induced dermatitis, bullous pemphigoid, prurigo nodularis, rosacea, alopecia areata, scleroderma, vitiligo, hidradenitis suppurativa, lichen planus, urticaria, actinic keratosis, seborrheic keratosis, and keloids. The skin samples were profiled by multiplexed immunostaining for markers of cellular senescence. In parallel we analyzed published single cell RNA sequencing data from the same diseases to identify cell populations enriched in senescence markers. Our findings indicated that a subset of chronic skin conditions present an elevated burden of senescent cells suggesting a therapeutic use of novel senolytics drugs to target senescent cells and trigger regulated cell death mechanisms. Heike Fuhrmann¹, Meagan Bodin¹, Akshay Pujari¹, Ben Kim¹, Allan Harell¹, Henry Ng¹, Cory Horton¹, Isaac Joshua¹, Julian Klein¹, Frederick Beddingfield¹, Marco Quarta¹, Ofir Moreno¹, Alex Laslavic¹, Alberto C. Vitari¹ 1. Rubedo Life Sciences Inc, Sunnyvale, CA, United States. Translational Studies: Cell and Molecular Biology