The Impact of Age on the Lipidomic Profile of the Stratum Corneum and Associated Effects on Structure, Function and Overall Skin Health in Adults Predisposed to Atopic Dermatitis

Abstract

Advancing age is associated with an increasing prevalence of dry skin conditions such as xerosis, asteatotic eczema and atopic dermatitis (AD). Although broad changes in stratum corneum (SC) lipids and AD history have been implicated, age-related alterations in the SC lipidome within at-risk populations remain unclear. We characterised SC structure and lipidomic profiles in 58 adults with dry, eczema-prone skin across a wide age range. Assessments included visual dryness, biophysical properties (TEWL, capacitance, skin-surface-pH), irritant sensitivity, ATR-FTIR spectroscopy and lipidomic analysis through quantification of extracted SC lipids via mass spectrometry. Age correlated significantly with increased dryness (r = 0.46, p ≤ 0.0001) and reduced hydration (r = −0.42, p ≤ 0.0001). Spectroscopy revealed declines in total lipids (p < 0.0026), water (p < 0.0009), lipid esters (p < 0.0001) and carboxylates (p < 0.0004) with age. Among 1385 quantified lipid species, triacylglycerol (TAG) was most abundant; TAG 46:1;0 associated with dryness (r = −0.42, p ≤ 0.0001). Ceramides CER[AH] (p < 0.0001), CER[AP] (p < 0.0001), CER[AdS] (p = 0.042), CER[NP] (p = 0.031) and CER[NdS] (p < 0.0001) all significantly increased with age relative to protein. Notably, CER[NdS] species shifted towards shorter (16ºC) acyl chains (+2.23%, p = 0.01) and away from longer (24ºC) chains (−3.9%, p < 0.0001). The CER[NdS]/CER[NH] ratio correlated with age (r = 0.59, p < 0.0001), dryness (r = 0.36, p = 0.0006), and barrier integrity (r = 0.59, p < 0.0001) (all p ≤ 0.0006). Within an at-risk population, SC lipid levels change as the skin ages. These changes, especially an increase in short acyl chain NdS ceramides, were associated with the decline in skin barrier function and may help explain the increased prevalence of xerosis and the (re)emergence of eczema in later life.