581 Spontaneous, Intrinsic Aging in Organ-Cultured Human Skin as Novel Ex Vivo Assay to Test Candidate Anti-Aging Actives

The document presents a new ex vivo assay for testing anti-aging compounds on healthy human skin. The study used skin biopsies from 2 males and 4 females aged 22-77 years, and treated them with known anti-aging compounds tretinoin, resveratrol, and caffeine. After 3 days, untreated skin showed significant aging-associated changes, including reduced keratinocyte proliferation, sirtuin-1, MTCO1, collagen 17A protein expression, and mitochondrial complex II/IV activity in the epidermis, and decreased collagen III protein and hyaluronic acid content in the dermis. Aging-associated DNA damage increased in epidermal keratinocytes, and mRNA levels of metalloproteinases and senescence-associated secretory phenotype cytokines also increased. The anti-aging compounds reduced DNA damage, increased collagen deposition, and reduced metalloproteinase protein expression. Caffeine also prevented the upregulation of certain cytokines and metalloproteinases. The study concludes that organ culture induces a spontaneous aging program in healthy human skin, which can be quantitatively assessed and manipulated with senolytics, providing a new assay system for preclinical testing of anti-aging compounds.