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641 Age-specific changes in normal skin barrier and immunity

      Aging alters immunity through a process termed “immunosenescence”. While cytokine changes have been observed with aging, age-specific changes in skin immunity are unknown. We sought to characterize age-specific gene and protein expression changes in healthy participants (n=72) using immunohistochemistry and qRT-PCR. Participants were compared using age-groups (18-40, 41-60, and >60 yo). We found age-specific changes in both skin barrier measures and immunity. Epidermal hyperplasia (thickness, Ki67) significantly decreased and negatively correlated with age (r=-0.52; r=-0.52, P<0.01). Epidermal differentiation markers (LOR, FLG) also decreased with age (P<0.05 for FLG). Dendritic cell markers (CD1a+, FcεRI+) increased in the older population (P<0.01), and positively correlated with age (r=0.67; r=0.47, P<0.01). General inflammation marker MMP12 significantly increased with age (P<0.01). Older skin showed greater inflammation across multiple T-helper axes. TH2 (IL-5, IL-13, CCL13, CCL18, TLSPR; P<0.05), TH22 (IL-22, S100A8; P<0.05), and TH1 (IFN-γ, IL-12/23p40, STAT1, CXCL9; P<0.05 for CXCL9) measures increased with age in a stepwise fashion. TH17-associated measured also showed increases with age (IL-20; P<0.05), and IL-17A upregulation strongly correlated with age (r=0.63, P<0.001). Negative regulator IL-37 decreased in older participants (P<0.05) and negatively correlated with age (r=-0.59, P<0.001). Thus, older skin demonstrated decreased hyperplasia, worsening barrier measures, and increased inflammation across all T-helper axes. These data shed light on how the aging process affects skin immunity, providing context for changes in dermatological diseases in the elderly.