BG04 (P063) Marked changes in the skin lipidome as we age are associated with reduced skin barrier function and can be rescued by topical therapy with physiologic lipids

Abstract As we age the integrity of our skin declines and it becomes increasingly prone to xerosis, especially in people with a history of atopic dermatitis (AD). We set out to investigate whether changes in the stratum corneum (SC) lipidome contribute to this decline, and subsequently establish whether topical lipid supplementation can mitigate this process. We undertook a double-blind bilateral-controlled interventional study in adults with dry eczema-prone skin stratified into three age groups: 18–39, 40–59 and ≥ 60 years (the BRaCE study). Each participant underwent 28 days of treatment (twice-daily application) with a ceramide-containing cream on one forearm and leg and a control cream without ceramides on the other (randomized allocation). The appearance and biophysical properties of the skin were assessed at baseline and after treatment. Shotgun lipidomic analysis of SC samples was performed to determine the composition of skin lipids. Group 1 comprised 24 adults (mean age 27 years, SD 7), with 16 in group 2 (mean 47 years, SD 5) and 18 in group 3 (mean 73 years, SD 8). All participants exhibited visibly dry skin on the shins. On a five-point scale of 0–4 the mean (SD) dryness values were group 1, 1.59 (0.86), group 2, 2.36 (0.93) and group 3, 2.78 (0.96). In total, 1633 lipid species were identified, of which 98 displayed significant differences between age groups. The most significant change was a broad increase in nonhydroxy (N) dihydroceramide (dS) subspecies; NdS 24:0;2/16:0;0 increased from a mean (SD) 67 (24) pmol g−1 protein in the youngest group to 166 (84) in the oldest (P < 0.001). Relative to total N ceramides (including NP, NH, NS and NdS), high NdS levels were associated with weakened skin barrier integrity [measured as transepidermal water loss (TEWL) after 20 tape strips: r = 0.50, P < 0.001]. In contrast to the control, treatment with the ceramide cream significantly increased the absolute levels of ceramide NP(18C) in the SC by 38% compared with baseline, altering the relative levels of N ceramides in the lamellar matrices. This was accompanied by an improvement in skin barrier integrity by 22% [mean (SD) TEWL 38.0 (18.6) g m−2 h−1 before vs. 29.8 (13.5) after, P = 0.002], whereas no significant change was observed at control-treated sites. The improvement in integrity was associated with the increase in ceramide NP(18C) relative to NdS ceramides (r = −0.44, P < 0.001). In adults predisposed to AD, age-associated changes in the SC lipidome are associated with the integrity of the skin barrier. Unlike with standard emollient creams, treatment with a ceramide-containing cream helped rebalance the SC lamellar lipids and improve barrier integrity, offering a promising intervention to protect against the increase in xerosis and AD associated with advancing age. This study was supported by a grant from L’Oréal.