title: Identification of ageing-associated naturally occurring peptides in human urine.
abstract: To assess normal and pathological peptidomic changes that may lead to an improved understanding of molecular mechanisms underlying ageing, urinarypeptidomes of 1227 healthy and 10333 diseased individuals between 20 and 86 years of age were investigated. The diseases thereby comprised diabetes mellitus, renal and cardiovascular diseases. Using age as a continuous variable, 116 peptides were identified that significantly (p < 0.05; |ρ|≥0.2) correlated with age in the healthy cohort. The same approach was applied to the diseased cohort. Upon comparison of the peptide patterns of the two cohorts 112 common age-correlated peptides were identified. These 112 peptides predominantly originated from collagen, uromodulin and fibrinogen. While most fibrillar and basement membrane collagen fragments showed a decreased age-related excretion, uromodulin, beta-2-microglobulin and fibrinogen fragments showed an increase. Peptide-based in silico protease analysis was performed and 32 proteases, including matrix metalloproteinases and cathepsins, were predicted to be involved in ageing. Identified peptides, predicted proteases and patient information were combined in a systems biology pathway analysis to identify molecular pathways associated with normal and/or pathological ageing. While perturbations in collagen homeostasis, trafficking of toll-like receptors and endosomal pathways were commonly identified, degradation of insulin-like growth factor-binding proteins was uniquely identified in pathological ageing.
authors.affiliation: Mosaiques Diagnostics GmbH, Hannover, Germany.|Hannover Medical School, Core Facility Proteomics, Hannover, Germany.
authors.forename: Esther
authors.initials: E
authors.lastname: Nkuipou-Kenfack
authors.affiliation: Mosaiques Diagnostics GmbH, Hannover, Germany.|Charité-Universitätsmedizin Berlin, Med. Klinik IV, Berlin, Germany.
authors.forename: Akshay
authors.initials: A
authors.lastname: Bhat
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Institut of Cardiovascular and Metabolic Disease, Toulouse, France.|Université Toulouse III Paul-Sabatier, Toulouse, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Klein
authors.affiliation: University Hospital RWTH Aachen, Institute for Molecular Cardiovascular Research (IMCAR), Aachen, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Jankowski
authors.affiliation: BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
authors.forename: William
authors.initials: W
authors.lastname: Mullen
authors.affiliation: Biotechnology Division, Biomedical Research Foundation Academy of Athens, Athens, Greece.|School of Biomedical and Healthcare Sciences, Plymouth University, Plymouth, United Kingdom.
authors.forename: Antonia
authors.initials: A
authors.lastname: Vlahou
authors.affiliation: Mosaiques Diagnostics GmbH, Hannover, Germany.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Dakna
authors.affiliation: Mosaiques Diagnostics GmbH, Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Koeck
authors.affiliation: Université Toulouse III Paul-Sabatier, Toulouse, France.|University Hospital RWTH Aachen, Institute for Molecular Cardiovascular Research (IMCAR), Aachen, Germany.
authors.forename: Joost P
authors.initials: JP
authors.lastname: Schanstra
authors.affiliation: Mosaiques Diagnostics GmbH, Hannover, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Zürbig
authors.affiliation: Leibniz Institute of Age Research, Fritz Lipmann Institute, Jena, Germany.
authors.forename: Karl L
authors.initials: KL
authors.lastname: Rudolph
authors.affiliation: Institute for Genome Stability in Ageing and Disease and Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD) Research Center, University of Cologne, Cologne, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Schumacher
authors.affiliation: Hannover Medical School, Core Facility Proteomics, Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Pich
authors.affiliation: Mosaiques Diagnostics GmbH, Hannover, Germany.|BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Harald
authors.initials: H
authors.lastname: Mischak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology / Q000652:urine*; D002318:Cardiovascular Diseases / Q000652:urine*; D003094:Collagen / Q000378:metabolism; D003920:Diabetes Mellitus / Q000652:urine*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007674:Kidney Diseases / Q000652:urine*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000032:analysis / Q000652:urine*; D020543:Proteome / Q000032:analysis*; D058949:Uromodulin / Q000378:metabolism; D055815:Young Adult
chemical_list: D010455:Peptides; D020543:Proteome; D058949:Uromodulin; D005340:Fibrinogen; D003094:Collagen
keywords: Gerotarget; ageing; collagen; peptidomics; proteases; systems biology; urine