Abstract
BackgroundAging human skin undergoes significant morphological and functional changes such as wrinkle formation, reduced wound healing capacity, and altered epidermal barrier function. Besides known age-related alterations like DNA-methylation changes, metabolic adaptations have been recently linked to impaired skin function in elder humans. Understanding of these metabolic adaptations in aged skin is of special interest to devise topical treatments that potentially reverse or alleviate age-dependent skin deterioration and the occurrence of skin disorders.ResultsWe investigated the global metabolic adaptions in human skin during aging with a combined transcriptomic and metabolomic approach applied to epidermal tissue samples of young and old human volunteers. Our analysis confirmed known age-dependent metabolic alterations, e.g. reduction of coenzyme Q10 levels, and also revealed novel age effects that are seemingly important for skin maintenance. Integration of donor-matched transcriptome and metabolome data highlighted transcriptionally-driven alterations of metabolism during aging such as altered activity in upper glycolysis and glycerolipid biosynthesis or decreased protein and polyamine biosynthesis. Together, we identified several age-dependent metabolic alterations that might affect cellular signaling, epidermal barrier function, and skin structure and morphology.ConclusionsOur study provides a global resource on the metabolic adaptations and its transcriptional regulation during aging of human skin. Thus, it represents a first step towards an understanding of the impact of metabolism on impaired skin function in aged humans and therefore will potentially lead to improved treatments of age related skin disorders.
Highlights
Aging human skin undergoes significant morphological and functional changes such as wrinkle formation, reduced wound healing capacity, and altered epidermal barrier function
The analysis revealed agedependent metabolic adaptations of metabolites already reported to be involved in skin aging and metabolites with potential impact on skin function, such as osmolytes
Differences in the epidermal skin metabolome of young and old human volunteers To chart metabolic adaptations in human skin during aging in vivo, we performed non-targeted metabolomics analysis of epidermal skin tissue samples obtained from the inner side of the forearm of 28 young (20 to 25 years) and 54 old (55 to 66 years) female human donors
Summary
Aging human skin undergoes significant morphological and functional changes such as wrinkle formation, reduced wound healing capacity, and altered epidermal barrier function. The main molecular adaptations occurring during aging are loss of Kuehne et al BMC Genomics (2017) 18:169 amino acids [13, 14], can significantly increase lifespan [15] This suggests that metabolic activity as well as nutrient sensing pathways are highly relevant for cellular aging processes (reviewed in [10]). While the underlying molecular mechanisms that cause cellular aging and influence lifespan of model organisms are well described, the mechanistic details of age-related alterations in human tissues in vivo are barely explored. Metabolic studies suggested that aged epidermal keratinocytes shift their energy generation from aerobic respiration in mitochondria to anaerobic glycolysis This was attributed to a reduction of coenzyme Q10 levels in the respiratory chain [25,26,27]. These examples highlight the relevance of metabolic changes in human skin aging, both as drivers of functional deterioration as well as a target for anti-aging treatments
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