Identification of novel plasma glycosylation-associated markers of aging.
Identification of novel plasma glycosylation-associated markers of aging.
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DOI：
10.18632/oncotarget.7059
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发表时间：
2016-02-16
期刊：
影响因子：
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通讯作者：
Dall'Olio F
中科院分区：
文献类型：
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作者：
Catera M;Borelli V;Malagolini N;Chiricolo M;Venturi G;Reis CA;Osorio H;Abruzzo PM;Capri M;Monti D;Ostan R;Franceschi C;Dall'Olio F
免疫球蛋白G（IgG）的促炎或抗炎活性受其重链Asn 297 N-连接聚糖结构控制。年龄相关的低度炎症（炎症）与血浆中以N-乙酰葡糖胺（IgG-G 0）终止的无半乳糖基化IgG水平升高相关，其生物起源尚未得到充分解释。虽然聚糖的生物合成通常由与细胞内膜相关的糖基转移酶介导，但最近已证实由血浆糖基转移酶介导的循环糖蛋白的细胞外糖基化。在这项研究中，我们研究了血浆糖基转移酶，IgG糖基化和炎症和衰老标志物之间的关系。在从婴儿到百岁老人的人群中，我们测定了血浆β4半乳糖基转移酶（B4 GALTs）和α 2，6-唾液酸转移酶ST 6 GAL 1的活性、IgG的糖基化、GlycoAge试验（一种基于糖基化的衰老标志物）以及炎症和肝损伤标志物的血浆水平。我们的研究结果表明：1）血浆B4 GALTs活性是一个新的衰老标志，在整个年龄范围内呈线性增加。2)血浆ST 6 GAL 1仅在儿童和80岁以上的人中高，显示与年龄的二次关系。3)血浆糖基转移酶与肝损伤标志物均不相关。4)血浆ST 6 GAL 1在短寿父母的后代中显示出与急性时相蛋白的正相关，但在百岁老人或其后代中没有。5)尽管IgG的糖基化与两种血浆糖基转移酶的水平不相关，但其显示与促炎糖型转变一致的进行性年龄相关变化。
The pro- or anti-inflammatory activities of immunoglobulins G (IgGs) are controlled by the structure of the glycan N-linked to Asn297 of their heavy chain. The age-associated low grade inflammation (inflammaging) is associated with increased plasmatic levels of agalactosylated IgGs terminating with N-acetylglucosamine (IgG-G0) whose biogenesis has not been fully explained. Although the biosynthesis of glycans is in general mediated by glycosyltransferases associated with internal cell membranes, the extracellular glycosylation of circulating glycoproteins mediated by plasmatic glycosyltransferases has been recently demonstrated. In this study we have investigated the relationship between plasmatic glycosyltransferases, IgG glycosylation and inflammatory and aging markers. In cohorts of individuals ranging from infancy to centenarians we determined the activity of plasmatic β4 galactosyltransferase(s) (B4GALTs) and of α2,6-sialyltransferase ST6GAL1, the glycosylation of IgG, the GlycoAge test (a glycosylation-based marker of aging) and the plasma level of inflammatory and liver damage markers. Our results show that: 1) plasmatic B4GALTs activity is a new marker of aging, showing a linear increase throughout the whole age range. 2) plasmatic ST6GAL1 was high only in children and in people above 80, showing a quadratic relationship with age. 3) Neither plasmatic glycosyltransferase correlated with markers of liver damage. 4) plasmatic ST6GAL1 showed a positive association with acute phase proteins in offspring of short lived parents, but not in centenarians or in their offspring. 5) Although the glycosylation of IgGs was not correlated with the level of the two plasmatic glycosyltransferases, it showed progressive age-associated changes consistent with a shift toward a pro-inflammatory glycotype.