Glycation metabolites predict incident age-related comorbidities and mortality in older people with HIV

• DOI: 10.1007/s11357-025-01652-3
• Publication Date: 2025-04-17T02:44:45Z
• Authors: Xi Qiao; Liangliang Zhang; Emely A. Hoffman; Grace E. Mastin; Corrilynn O. Hileman; Asha R. Kallianpur; Ming Wang; Ronald J. Ellis; Susan L. Koletar; Frank J. Palella; Katherine K. Tass...; Alan L. Landay; Pankaj Kapahi; James J. Galligan; Robert C. Kalayjian
• Keywords: Advanced glycation end-product

Abstract Glycation is a class of modifications arising from non-enzymatic reactions reducing sugars with proteins, lipids, and/or DNA, generating advanced glycation end-products (AGEs). AGEs are linked to many age-related comorbidities. In response HIV-1 infection, activated T-cells and macrophages shift their predominate metabolism oxidative phosphorylation glycolysis. Increased glycolytic flux enhances AGE formation, which may increase this prospective, multicenter cohort study antiretroviral therapy treated people HIV, we explored predictive associations by baseline plasma concentrations corresponding detoxification metabolites, incident comorbidities mortality. included dicarbonyl sugars: 3-deoxyglucosone, glyoxal, methylglyoxal. Methylglyoxal-derived metabolites carboxyethyl-arginine, carboxyethyl-lysine, methylglyoxal hydroimidazolone-1. Detoxification reduced oxidized glutathione, the glyoxalase cycle products lactoyl-glutathione lactoyl-Lysine modified proteins. Plasma was collected at entry, in fasting state, assayed liquid chromatography-mass spectroscopy. Incident clinical outcomes diabetes, chronic kidney disease, hypertension, neurocognitive impairment, peripheral neuropathy, frailty, fractures, recurrent falls, all-cause Among 376 participants, higher derived predicted increased risks while 3-deoxyglucosone an risk neuropathy. By contrast, or lactoyl-glutathione, proteins lower These findings support growing experimental evidence potential mitigate declines interventions that reduce glutathione.