A transcriptomic analysis of primary fibroblasts isolated from young donors identifies a subset of donors displaying features of early senescence

Even though its development starts early in utero, neonatal skin is still immature at birth relative to adult and undergoes a maturation process extending to the first years of life. It is now established that stratum corneum is thinner and dryer, and that skin contains less natural moisturizing factors and lipids in newborns compared to children and adults. Moreover, it has been shown that skin surface area expansion is not linear throughout life and is peaking perinatally, suggesting that baby skin has a higher epidermal cellular turnover. 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 revealed a major shift in the global energetic metabolism in baby keratinocytes compared to adults, highlighting increased amino acid metabolism and mitochondrial oxidative phosphorylation in baby cells to fuel TCA cycle, while showing glycolysis as the major cell energy source in adult cells. The proliferation potential of fibroblasts isolated from young donors was measured and compared to the one of cells isolated from the older group. Two subsets of donors were evidenced in the younger group: the first one with high proliferative (HP) capacities, the second one with significantly lower proliferative (LP) capacities, similar to the one of the older group. To further investigate the differences between the two subsets of young donors, a transcriptomic profiling was performed on fibroblasts from both young subgroups.