title: An integrative metabolomics and transcriptomics study to identify metabolic alterations in aged skin of humans in vivo.
abstract: Aging 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.
  
  
  
  We 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.
  
  
  
  Our 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.
authors.affiliation: Institute of Molecular Systems Biology, ETH Zurich, Auguste-Piccard-Hof 1, 8093, Zürich, Switzerland.|PhD Program Systems Biology, Life Science Zurich Graduate School, Zurich, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kuehne
authors.affiliation: Coburg University of Applied Sciences and Arts, Friedrich-Streib-Straße 2, Coburg, 96450, Germany.
authors.forename: Janosch
authors.initials: J
authors.lastname: Hildebrand
authors.affiliation: Beiersdorf AG, R&D, Skin Research Center, Unnastrasse 48, Hamburg, 20253, Germany.
authors.forename: Joern
authors.initials: J
authors.lastname: Soehle
authors.affiliation: Beiersdorf AG, R&D, Skin Research Center, Unnastrasse 48, Hamburg, 20253, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Wenck
authors.affiliation: Beiersdorf AG, R&D, Skin Research Center, Unnastrasse 48, Hamburg, 20253, Germany.
authors.forename: Lara
authors.initials: L
authors.lastname: Terstegen
authors.affiliation: Beiersdorf AG, R&D, Skin Research Center, Unnastrasse 48, Hamburg, 20253, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Gallinat
authors.affiliation: Beiersdorf AG, R&D, Skin Research Center, Unnastrasse 48, Hamburg, 20253, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Knott
authors.affiliation: Beiersdorf AG, R&D, Skin Research Center, Unnastrasse 48, Hamburg, 20253, Germany. Marc.Winnefeld@Beiersdorf.com.
authors.forename: Marc
authors.initials: M
authors.lastname: Winnefeld
authors.affiliation: Institute of Molecular Systems Biology, ETH Zurich, Auguste-Piccard-Hof 1, 8093, Zürich, Switzerland. nzamboni@ethz.ch.
authors.forename: Nicola
authors.initials: N
authors.lastname: Zamboni
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics* / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism* / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D006017:Glycolipids / Q000096:biosynthesis; D006019:Glycolysis / Q000235:genetics; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D011073:Polyamines / Q000378:metabolism; D055815:Young Adult
chemical_list: D006017:Glycolipids; D011073:Polyamines
keywords: Aging; Metabolism; Metabolomics; Skin; Systems biology; Transcriptomics