Even though its development starts early in utero, neonatal skin remains immature at birth relative to adult and undergoes a maturation process during the first years of life. It is now established that in newborns compared to children and adults, skin has a thinner stratum corneum, less natural moisturizing factors and lipids, a higher cellular turnover, and a higher permeability. Epidermal renewal relies on the balance between proliferation and differentiation of epidermal basal cells as well as removal of corneocytes by desquamation to maintain skin homeostasis or to restore epidermal structure and functions. Skin uses energy metabolism through a dynamic and adaptative process to support its development and to maintain homeostasis. Despite growing resources showing differences between adult and infant skin physiology, molecular and metabolic specificities of baby skin are still poorly understood. To address this critical knowledge gap, we performed an integrative transcriptomic and metabolomic study comparing human primary keratinocytes from babies and adults. Based on state-of-the-art integrative frameworks, our analyses highlighted a major shift in the global energetic metabolism in baby keratinocytes compared to adults. Baby cells mainly use mitochondrial oxidative phosphorylation through upregulation of (i) nicotinate and nicotinamide metabolism and (ii) amino acid metabolism (upregulation of lysine degradation, increased metabolism of glycine, threonine, and serine) implicated in pyruvate production that fuels the TCA cycle. Conversely, the glycolysis pathway is preferred in adult cells correlated with an increased activity of nucleotide-related pathways (purine, pyrimidine, nitrogen metabolism) to produce energy and to promote cell proliferation. These new findings allow a better understanding of the physiology and metabolism of baby skin cells, improving our knowledge on the development of healthy baby skin.

ESDR108 - An integrative multi-omic analysis reveals a major metabolic rewiring between keratinocytes from babies and adults

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING