LB901 Inflammaging in Human Skin: Early Onset of Senescence and Imbalanced Epidermal Homeostasis Across the Decades

Inflammaging is a theory which purports that chronic inflammation leads to cellular dysfunction and premature aging of tissue. Skin is susceptible to inflammaging because it is the first line of defense from the environment and can be heightened in photoexposed skin. To better understand the impact of aging and photoexposure on epidermal biology we performed a systems biology-based analysis of photoexposed and protected sites from women between ages of 20’s to 70’s. Biopsies were analyzed by histology, transcriptomics, proteomics, and biomarkers from tape strips. We measured with age morphological changes including, thinning of the epidermis, loss of rete ridge pathlength, and thickening of stratum corneum. SASP components IL-8 and IL-1RA/IL1-a and photosensitive metabolite cis-urocanic acid were consistently elevated in photoexposed face across age. Staining for the DNA damage marker 53BP1 showed higher puncti numbers in the basal layer of older photoexposed arms. Expression of genes associated with differentiation and senescence show an increase starting in the 30’s and genes associated with hypoxia and glycolysis increase in the 50’s. Proteomics comparing 60’s vs 20’s arms confirmed elevated levels of differentiation and glycolytic proteins. Immunostaining for markers of differentiation, DNA damage, senescence, and hypoxia show similar relationships. This systems biology-based analysis provides a body of evidence that photoexposed skin is undergoing inflammaging. We propose the presence of chronic inflammation and SASP in young skin leads to an imbalance of epidermal homeostasis and prematurely aged appearance of skin.