Absolute Quantification of Aging-Associated Glycans in IgG for Biological Age Prediction: Insights from Glycomics and Transcriptomics

Immunoglobulin G (IgG) N-glycans are associated with aging. In this study, we introduce a novel strategy for discovering aging-associated IgG glycans and establish a prediction model on the basis of their absolute concentration alterations. We employed glycomic quantification technology to identify alterations in the amount of IgG glycan in natural aging and antiaging (caloric restriction (CR)) models and discovered aging-related glycans. The glycomic analysis revealed key features: downregulation of the bisected glycan GP3 (F(6)A2B) and upregulation of the digalactosylated glycan GP8 (F(6)A2G2). These glycan changes showed significant fold changes from an early stage. Using external standards of these two glycans, we subsequently measured their absolute concentrations, allowing for us to establish a predictive model, abGlycoAge, for biological aging. The abGlycoAge index suggested a younger state under CR, with an average age reduction of 3.9–14 weeks. Additionally, RNA sequencing of splenic B cells revealed that Derl3, Smarcb1, Ankrd55, Tbkbp1, and Slc38a10 may contribute to alterations in GP3 and GP8 during the aging process. In a preliminary therapeutic study, we tested IgG modified with young signature N-glycans (IgG-Ny). High-dose IgG-Ny showed promising results, alleviating aging-related physiological declines, including reductions in inflammatory markers and improvements in organ senescence, particularly in the brain, kidney, and lungs. This research provides new insights into glycan changes during aging and lays the groundwork for potential antiaging therapies. GP3 and GP8 may serve as biomarkers for aging, offering new perspectives on aging mechanisms and therapeutic approaches.