Region-Specific Lipid Alterations Around the 28-Year Transition as Early Indicators of Skin Aging

Background: Early molecular changes on the facial skin surface during early adulthood remain insufficiently characterized. We integrated biophysical readouts with untargeted skin surface lipid (SSL) profiling to identify region-dependent, age-associated features in women with combination skin. Methods: Eighty healthy Chinese women were stratified into 22–28 years (n = 40) and 29–35 years (n = 40). Sebum was measured on the cheek and forehead; cheek elasticity, hydration (CM), transepidermal water loss (TEWL), pH, and tone indices were assessed under standardized conditions. SSLs from both regions were profiled by UPLC–QTOF–MS. Differential features were prioritized using OPLS-DA (VIP > 1) with univariate screening (p < 0.05; fold change > 2 or <0.5). Results: TEWL, CM, and pH were comparable between age groups, whereas the older group showed lower cheek elasticity and reduced sebum. Lipidomics revealed clearer remodeling on the cheek than the forehead: 30 and 59 differential SSL features were identified in the cheek and forehead, respectively. Cheek changes in the older group were characterized by lower ceramides (including acylceramides), TG/DG and long-chain fatty acids, alongside relatively higher cholesteryl esters. Conclusions: Conventional barrier indices remained largely stable across this age window, while cheek SSL profiles captured earlier molecular shifts, providing candidates for targeted validation and longitudinal follow-up.