免疫球蛋白G（IgG）的N-聚糖与衰老相关。本研究提出了一种全新的策略来发现与衰老相关的IgG糖链，并基于其绝对浓度变化建立预测模型。利用糖组定量技术，分析了自然衰老和抗衰老（热量限制，CR）模型中IgG糖链的变化，发现了衰老相关糖链。糖组学分析揭示了两个关键特征：平分型糖链GP3（F(6)A2B）下调，双半乳糖基化糖链GP8（F(6)A2G2）上调。这些糖链从早期阶段就出现了显著的倍数变化。通过这两种糖链的标准品，进一步测定了其绝对浓度，并据此建立了生物学年龄预测模型 abGlycoAge。结果显示，在CR条件下，abGlycoAge指数提示个体处于更年轻状态，平均年龄降低了3.9-14周。此外，对脾脏B细胞的RNA测序表明，Derl3、Smarcb1、Ankrd55、Tbkbp1和 Slc38a10可能参与了衰老过程中GP3和GP8的变化。我们尝试使用“年轻型糖链修饰IgG”（IgG-Ny）进行了初步治疗研究。结果显示，高剂量IgG-Ny表现出良好效果，缓解了衰老相关的生理退化，包括炎症指标下降，以及大脑、肾脏和肺脏等器官老化的改善。本研究揭示了衰老过程中糖链变化的新见解，并为潜在抗衰老治疗奠定了基础。血清IgG GP3和GP8有望作为衰老生物标志物，为理解衰老机制和开发疗法提供新视角。

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 3.9-14.0 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.