ArticleProceedings of the National Academy of Sciences of the United States of America2016
Protein carbamylation is a hallmark of aging.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 186 citations in OpenAlex.
- Anti-carbamylated protein antibodies and skin involvement in patients with systemic sclerosis: An intriguing association.PloS one · 2018Trial
- Discovery of Post-Translationally Modified Epitopes in Autoimmunity: Someone Has to Fish so Everyone Can Eat.Immunological reviews · 2026Review
- Complement Activation by Post-Translationally Modified Proteins: Links to Chronic Inflammation and Autoimmunity.Immunological reviews · 2026Review
- Metabolic exhaustion and immune ageing in rheumatoid arthritis.Nature reviews. Rheumatology · 2026Review
- Bis-hydroxylation of Homocitrulline Catalyzed by a Multinuclear Nonheme Iron Oxidative Enzyme during RiPP Biosynthesis.Journal of the American Chemical Society · 2026Article
- Beyond Genes: Metabolomic Evidence Indicates Potential Species-Level Differentiation in European Wild Rabbits.Journal of experimental zoology. Part A, Ecological and integrative physiology · 2026Article
- Review
- Spontaneous Non-Catalyzed Molecular Reactions and Interactions in the Human Body: Biomedical Implications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Comprehensive profiling of the competitive interplay among carbamylation, glycation, and enzymatic cross-links in human bone.JBMR plus · 2026Article
- Bis-hydroxylation of Homocitrulline Catalyzed by a Multinuclear Nonheme Iron-Dependent Oxidative Enzyme during RiPP Biosynthesis.bioRxiv : the preprint server for biology · 2026Article
- The Impact of Ageing on Fibrillar Collagens.Sub-cellular biochemistry · 2026Review
- Age-associated accumulation of carbamylation-derived products in tissues is independent from the myeloperoxidase pathway in mice.PloS one · 2026Article
- Protein carbamylation is associated with increased mortality and CKD progression in patients with CKD: results from the EQUAL study.Clinical kidney journal · 2025Article
- Proteomic Characterization of the Rhesus Macaque Lens Nucleus: Similarity to Human Lens, Age Effects on Protein Solubility, and Trends in Post-Translational Modifications.Investigative ophthalmology & visual science · 2025Article
- Sustained immune youth risks autoimmune disease in the aging host.Nature aging · 2025Review
- Collagen formation, function and role in kidney disease.Nature reviews. Nephrology · 2025Review
- Non-enzymatic posttranslational protein modifications in protein aggregation and neurodegenerative diseases.RSC chemical biology · 2025Review
- Article
- High-resolution mass spectrometry measurement of N-terminal carbamylated hemoglobin as a potential marker for chronic diseases with elevated blood urea levels.Journal of mass spectrometry and advances in the clinical lab · 2025Article
- Proteomic analysis of infiltrating neutrophils from rheumatoid arthritis synovial fluid and their contribution to protein carbamylation.Frontiers in immunology · 2025Article
33 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aging is a progressive process determined by genetic and acquired factors. Among the latter are the chemical reactions referred to as nonenzymatic posttranslational modifications (NEPTMs), such as glycoxidation, which are responsible for protein molecular aging. Carbamylation is a more recently described NEPTM that is caused by the nonenzymatic binding of isocyanate derived from urea dissociation or myeloperoxidase-mediated catabolism of thiocyanate to free amino groups of proteins. This modification is considered an adverse reaction, because it induces alterations of protein and cell properties. It has been shown that carbamylated proteins increase in plasma and tissues during chronic kidney disease and are associated with deleterious clinical outcomes, but nothing is known to date about tissue protein carbamylation during aging. To address this issue, we evaluated homocitrulline rate, the most characteristic carbamylation-derived product (CDP), over time in skin of mammalian species with different life expectancies. Our results show that carbamylation occurs throughout the whole lifespan and leads to tissue accumulation of carbamylated proteins. Because of their remarkably long half-life, matrix proteins, like type I collagen and elastin, are preferential targets. Interestingly, the accumulation rate of CDPs is inversely correlated with longevity, suggesting the occurrence of still unidentified protective mechanisms. In addition, homocitrulline accumulates more intensely than carboxymethyl-lysine, one of the major advanced glycation end products, suggesting the prominent role of carbamylation over glycoxidation reactions in age-related tissue alterations. Thus, protein carbamylation may be considered a hallmark of aging in mammalian species that may significantly contribute in the structural and functional tissue damages encountered during aging.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.