Biomolecular Mass Spectrometry Unit, Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
PLoS One. 2010 Sep 7;5(9):e12566. doi: 10.1371/journal.pone.0012566.
Markers for longevity that reflect the health condition and predict healthy aging are extremely scarce. Such markers are, however, valuable in aging research. It has been shown previously that the N-glycosylation pattern of human immunoglobulin G (IgG) is age-dependent. Here we investigate whether N-linked glycans reflect early features of human longevity.
METHODOLOGY/PRINCIPAL FINDINGS: The Leiden Longevity Study (LLS) consists of nonagenarian sibling pairs, their offspring, and partners of the offspring serving as control. IgG subclass specific glycosylation patterns were obtained from 1967 participants in the LLS by MALDI-TOF-MS analysis of tryptic IgG Fc glycopeptides. Several regression strategies were applied to evaluate the association of IgG glycosylation with age, sex, and longevity. The degree of galactosylation of IgG decreased with increasing age. For the galactosylated glycoforms the incidence of bisecting GlcNAc increased as a function of age. Sex-related differences were observed at ages below 60 years. Compared to males, younger females had higher galactosylation, which decreased stronger with increasing age, resulting in similar galactosylation for both sexes from 60 onwards. In younger participants (<60 years of age), but not in the older age group (>60 years), decreased levels of non-galactosylated glycoforms containing a bisecting GlcNAc reflected early features of longevity.
CONCLUSIONS/SIGNIFICANCE: We here describe IgG glycoforms associated with calendar age at all ages and the propensity for longevity before middle age. As modulation of IgG effector functions has been described for various IgG glycosylation features, a modulatory effect may be expected for the longevity marker described in this study.
反映健康状况并预测健康衰老的长寿标志物极为稀缺。然而，此类标志物在衰老研究中具有重要价值。先前已经表明，人类免疫球蛋白 G (IgG) 的 N-糖基化模式具有年龄依赖性。在这里，我们研究了 N-连接糖基是否反映了人类长寿的早期特征。
方法/主要发现：莱顿长寿研究 (LLS) 由 90 岁以上的兄弟姐妹对、他们的后代以及后代的配偶作为对照组成。通过 MALDI-TOF-MS 分析胰蛋白酶 IgG Fc 糖肽，从 LLS 的 1967 名参与者中获得 IgG 亚类特异性糖基化模式。应用几种回归策略来评估 IgG 糖基化与年龄、性别和长寿的关联。IgG 的半乳糖基化程度随年龄增长而降低。对于半乳糖基化的糖型，双分支 GlcNAc 的发生率随年龄增加而增加。在 60 岁以下的年龄观察到性别相关差异。与男性相比，年轻女性的半乳糖基化程度更高，随着年龄的增长下降幅度更大，导致 60 岁以后两性的半乳糖基化程度相似。在较年轻的参与者（<60 岁）中，但在较年长的年龄组（>60 岁）中，双分支 GlcNAc 含量非半乳糖基化的糖型水平降低反映了长寿的早期特征。
结论/意义：我们在这里描述了与所有年龄段的年龄相关的 IgG 糖型以及中年前长寿的倾向。由于各种 IgG 糖基化特征的 IgG 效应功能的调节已被描述，因此预计本研究中描述的长寿标志物会产生调节作用。
