Universität zu Köln

Nkuipou-Kenfack, Esther, Bhat, Akshay, Klein, Julie ORCID: 0000-0002-3279-0559, Jankowski, Vera, Mullen, William, Vlahou, Antonia ORCID: 0000-0003-3284-5713, Dakna, Mohammed, Koeck, Thomas, Schanstra, Joost P., Zuerbig, Petra, Rudolph, Karl L., Schumacher, Bjoern, Pich, Andreas and Mischak, Harald ORCID: 0000-0003-0323-0306 (2015). Identification of ageing-associated naturally occurring peptides in human urine. Oncotarget, 6 (33). S. 34106 - 34118. ORCHARD PARK: IMPACT JOURNALS LLC. ISSN 1949-2553

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Abstract

To assess normal and pathological peptidomic changes that may lead to an improved understanding of molecular mechanisms underlying ageing, urinary peptidomes 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; vertical bar rho vertical bar >= 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Nkuipou-Kenfack, Esther UNSPECIFIED UNSPECIFIED UNSPECIFIED Bhat, Akshay UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, Julie UNSPECIFIED orcid.org/0000-0002-3279-0559 UNSPECIFIED Jankowski, Vera UNSPECIFIED UNSPECIFIED UNSPECIFIED Mullen, William UNSPECIFIED UNSPECIFIED UNSPECIFIED Vlahou, Antonia UNSPECIFIED orcid.org/0000-0003-3284-5713 UNSPECIFIED Dakna, Mohammed UNSPECIFIED UNSPECIFIED UNSPECIFIED Koeck, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Schanstra, Joost P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zuerbig, Petra UNSPECIFIED UNSPECIFIED UNSPECIFIED Rudolph, Karl L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schumacher, Bjoern UNSPECIFIED UNSPECIFIED UNSPECIFIED Pich, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Mischak, Harald UNSPECIFIED orcid.org/0000-0003-0323-0306 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-389369
DOI:	10.18632/oncotarget.5896
Journal or Publication Title:	Oncotarget
Volume:	6
Number:	33
Page Range:	S. 34106 - 34118
Date:	2015
Publisher:	IMPACT JOURNALS LLC
Place of Publication:	ORCHARD PARK
ISSN:	1949-2553
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROTEOME ANALYSIS; EXTRACELLULAR-MATRIX; MASS-SPECTROMETRY; RENAL-FUNCTION; PREDICTION; DISCOVERY; DISEASE; PROGRESSION; BIOMARKERS; COLLAGEN Multiple languages Oncology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/38936