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, 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; |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.

Urinary Glycopeptide Analysis for the Investigation of Novel Biomarkers

“…Considering that the group of normal subjects was much younger (mean of age 30) than the cancer groups (means of age ranging between 61 to 68 years), we investigated further if the differences in O‐glycopeptide and N‐glycopeptide abundance may be related to age. Investigation of previous data on the association of urinary peptides with age in over 10 000 subjects revealed no significant association of any of the O‐glycopeptides and N‐glycopeptides with age. We further extracted data from an additional group of older, apparently healthy subjects ( n = 226, mean of age 60, similar to the age range of the cancer groups).…”

Coupling of CE‐MS for protein and peptide analysis

“…A top‐down CE‐MS to discover disease biomarkers in biofluids has also been described . The arrangement of the equipment is simple.…”

Proteomic Evidence of Biological Aging in a Child with a Compound Heterozygous ZMPSTE24 Mutation

“…More recently, urinary proteomes of 1227 healthy and 10 333 diseased individuals between 20–86 years of age were investigated . A total of 116 peptide biomarkers were identified that significantly correlated with age in the healthy cohort.…”