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

• Published in: Proteomics. Clinical applications Vol. 13; no. 2; pp. e1800135 - n/a
• Main Authors: Lucas‐Herald, Angela K, Zürbig, Petra, Mason, Avril, Kinning, Esther, Brown, Catriona E, Mansoorian, Bahareh, Mullen, William, Ahmed, Syed Faisal, Delles, Christian
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.03.2019; John Wiley and Sons Inc
• Subjects: Age; Aging; Aging - genetics; biomarkers; Bone Diseases, Developmental - genetics; Capillary electrophoresis; capillary electrophoresis‐mass spectroscopy; Cardiovascular disease; Cardiovascular diseases; Child; Child, Preschool; Children; Classifiers; Coronary artery; Coronary artery disease; Coronary vessels; Craniofacial Abnormalities - genetics; Dataset Brief; Dysplasia; Electrophoresis; Heart diseases; Heterozygote; Humans; Kidney diseases; Mass spectroscopy; Membrane Proteins - genetics; Metalloendopeptidases - genetics; Mutation; Peptides; Progeria; Proteomes; Proteomics; progeria; capillary electrophoresis-mass spectroscopy; biomarkers
• ISSN: 1862-8346; 1862-8354
• DOI: 10.1002/prca.201800135

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.