The Immunoglobulin G Glycome: A Modifiable Biomarker and Functional Effector of Aging, Disease, and Mortality

Mijakovac, A., Butz, E., Vuckovic, F., Frkatovic Hodzic, A., Rapcan, B., Kifer, D., Deris, H., Radovani Trbojevic, B., Luksic, F., Cindric, A., Gudelj, I., simunic Briski, N., Josipovic, G., Stara Yuksel, Z., catic, J., saler, F., Szavits-Nossan, J., Hedin, C. R. H., simunovic, J., Borosak, I., Kristic, J., Monteiro-Martins, S., Pribic, T., Hanic, M., Pucic-Bakovic, M., Trbojevic-Akmacic, I., stambuk, T., stambuk, J., Martinic Kavur, M., Fancovic, M., Cvetko, A., Pezer, M., Polasek, O., Gornik, O., Kiprov, D., Verdin, E., Younggren, B., Newson, L., Menni, C., Steves, C. J., Spector, T. D., Hal

Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia · medrxiv

Paper

Abstract

Glycosylation is a key structural modification of immunoglobulin G (IgG) that modulates its effector functions and has multiple roles in balancing inflammation. Altered IgG glycosylation has been reported in many diseases, often years before clinical manifestation, suggesting its causal role and biomarker potential. Here, we analyzed IgG glycome composition in 20,405 individuals from 42 different studies processed at the Genos Glycoscience Research Laboratory between 2008 and 2025. Across nearly all diseases, specific IgG glycome profiles reflected accelerated biological aging. Accelerated glycan aging was strongly associated with increased risk of all-cause mortality, independent of established clinical risk factors and potential confounders. Moreover, interventions known to reduce mortality risk, including hormone replacement therapy, therapeutic plasma exchange and caloric restriction, were associated with reversal of glycan aging. Given their role in modulating low-grade systemic inflammation, IgG glycans may represent a functional link between chronic inflammation, aging, disease susceptibility and all-cause mortality.

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Research summary

Altered IgG glycosylation profiles are associated with accelerated biological aging and increased mortality risk. The paper addresses the role of IgG glycosylation in aging and its potential as a modifiable biomarker, linking chronic inflammation to aging and disease susceptibility, which is central to longevity research.

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