N(6)-Carboxymethyllysine Explained

N(6)-Carboxymethyllysine (CML), also known as N^ε-(carboxymethyl)lysine, is an advanced glycation endproduct (AGE). CML has been the most used marker for AGEs in food analysis.^[1]

Recently, it has been demonstrated that gut microbiota mediates an aging-associated decline in gut barrier function, allowing AGEs to leak into the bloodstream from the gut and impairing microglial function in the brain. It is suggested that the amount of CML in human blood samples may correlated with age.^[2]

A humanized monoclonal antibody which binds to N6 – carboxymethyl lysine shows considerable promise as a possible therapeutic agent for treating pancreatic cancer.^[3]

Notes and References

1. Semba RD, Nicklett EJ, Ferrucci L . Does accumulation of advanced glycation end products contribute to the aging phenotype? . The Journals of Gerontology . 65A . 9 . 2010 . 963–975 . 20478906 . 10.1093/gerona/glq074 . 2920582.
2. O. Mossad, B. Batut, B. Yilmaz, N. Dokalis, C. Mezö, E. Nent, L. S. Nabavi, M. Mayer, F. J. M. Maron, J. M. Buescher, M. G. de Agüero, A. Szalay, T. Lämmermann, A. J. Macpherson, S. C. Ganal-Vonarburg, R. Backofen, D. Erny, M. Prinz, T. Blank . Gut microbiota drives age-related oxidative stress and mitochondrial damage in microglia via the metabolite N6-carboxymethyllysine . Nat. Neurosci. . 2022. 25 . 3. 295–305 . 10.1038/s41593-022-01027-3 . 35241804 . 247228807.
3. Rossi . Gabriela R. . Jensen . Ashley . Ng . Serina . Yin . Zhirong . Li . Aimin . Misra . Anjan . Von Hoff . Daniel D. . Gruber . Lewis . Gruber . Misty . Han . Haiyong . Advanced glycation end product (AGE) targeting antibody SIWA318H is efficacious in preclinical models for pancreatic cancer . Scientific Reports . 7 October 2023 . 13 . 1 . 16953 . 10.1038/s41598-023-44211-6 . 37805542 . 10560265 . 2023NatSR..1316953R .