Chronological age is an imperfect tool for assessing healthspan and risk for diseases. As a result, biological markers of age become important components of personalized medicine. One of such markers, the plasma glycome, and especially Immunoglobulin G (IgG) $N$-glycosylation, is gaining attention due to its dynamic nature and involvement of genetics, environment, and lifestyle. In this review, we summarize current knowledge about the role of glycomic biological age markers (“Glycan Age”) in health and disease. Aging causes the progressive reduction in the levels of IgG galactosylation and sialylation with changes in fucosylation and bisection. Moreover, these structural changes do not only reflect the physiological decline, but also impact immune cell activity by changing the affinity for activating and inhibitory $Fc\gamma$ receptors and cause the shift from anti-inflammatory towards pro-inflammatory status resulting in sterile systemic low-level inflammation, called “inflammaging.” As a marker clinically, premature glycan aging becomes a strong predictor of disease outcomes in various disease categories. Glycan aging tends to occur several years prior to the onset of clinical symptoms in autoimmunity, heart diseases, metabolic syndromes, neurodegenerative conditions, and cancers, and works as an independent predictor of overall mortality. Importantly, glycan aging is a very manipulable clock; changes in endocrine status (perimenopause), lifestyle modifications, and therapies of longevity have been shown to effectively reverse this biological clock. Finally, it would be necessary to overcome the technical issues related to standardization and integrate glycomics into multi-omics clocks using machine learning approaches.
Review Article
English
P. 27-32