Proteomic Evidence of Biological Aging in a Child with a Compound Heterozygous ZMPSTE24 Mutation.
biomarkers
capillary electrophoresis-mass spectroscopy
progeria
Journal
Proteomics. Clinical applications
ISSN: 1862-8354
Titre abrégé: Proteomics Clin Appl
Pays: Germany
ID NLM: 101298608
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
16
08
2018
revised:
03
12
2018
pubmed:
15
12
2018
medline:
3
5
2019
entrez:
15
12
2018
Statut:
ppublish
Résumé
Progeria-like syndromes offer a unique insight into aging. Here the case of a boy affected with mandibuloacral dysplasia and compound heterozygous mutations in ZMPSTE24 is presented. Capillary electrophoresis-mass spectroscopy is used for proteome analysis to analyze peptides previously found to be differentially regulated in chronic kidney disease (273 peptides defining the CKD273 classifier), coronary artery disease (238 peptides defining the CAD238 classifier), and aging (116 peptides defining the AGE116 classifier). No evidence of renal disease is identified. Although the boy has no overt cardiovascular disease other than a raised carotid intima media thickness relative to his age, a proteomic classifier for the diagnosis of coronary artery disease is mildly raised. The biological age based on the proteomic AGE116 classifier is 24 years compared to the chronological ages of 5 and 10 years. In contrast, a control group of healthy children has a significantly lower (p < 0.0001) calculated mean age of 13. Urinary proteomic analysis is effective in confirming advanced biological age and to identify early evidence of renal or cardiovascular damage. This case highlights the value of proteomic approaches in aging research and may represent a method for non-invasive monitoring of the effects of early aging.
Sections du résumé
BACKGROUND
Progeria-like syndromes offer a unique insight into aging. Here the case of a boy affected with mandibuloacral dysplasia and compound heterozygous mutations in ZMPSTE24 is presented.
METHODS
Capillary electrophoresis-mass spectroscopy is used for proteome analysis to analyze peptides previously found to be differentially regulated in chronic kidney disease (273 peptides defining the CKD273 classifier), coronary artery disease (238 peptides defining the CAD238 classifier), and aging (116 peptides defining the AGE116 classifier).
RESULTS
No evidence of renal disease is identified. Although the boy has no overt cardiovascular disease other than a raised carotid intima media thickness relative to his age, a proteomic classifier for the diagnosis of coronary artery disease is mildly raised. The biological age based on the proteomic AGE116 classifier is 24 years compared to the chronological ages of 5 and 10 years. In contrast, a control group of healthy children has a significantly lower (p < 0.0001) calculated mean age of 13.
CONCLUSION
Urinary proteomic analysis is effective in confirming advanced biological age and to identify early evidence of renal or cardiovascular damage. This case highlights the value of proteomic approaches in aging research and may represent a method for non-invasive monitoring of the effects of early aging.
Identifiants
pubmed: 30548811
doi: 10.1002/prca.201800135
pmc: PMC6492098
doi:
Substances chimiques
Membrane Proteins
0
Metalloendopeptidases
EC 3.4.24.-
ZMPSTE24 protein, human
EC 3.4.24.84
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1800135Subventions
Organisme : Medical Research Council
ID : MR/N003403/1
Pays : United Kingdom
Organisme : European Commission
ID : 603288
Pays : International
Organisme : British Heart Foundation
ID : RE/13/5/30177
Pays : United Kingdom
Informations de copyright
© 2018 The Authors. Proteomics - Clinical Application published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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