NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200062, China.
Exp Gerontol. 2020 Nov;141:111098. doi: 10.1016/j.exger.2020.111098. Epub 2020 Sep 30.
Studying the changes of serum N-glycome during mouse aging is beneficial to explore the molecular basis behind the alterations reported in human. However, such studies remainscarce and lack some information such as sialylation due to the method limitation. Here, we introduced Bionic Glycome method to quantify the serum N-glycome changes during C57BL/6 mouse aging (from the pubertal period to the old age stage). This technique enabled reliable and comprehensive quantitation of the expression level changes of more than 20 N-glycans in mouse serum at 12 time points in both genders for the first time, involving the analysis of sialic acid and its different linkages. The results demonstrated that the expression level of total glycans increased from middle age to old age. Interestingly, sex-specific N-glycome profiles and alterations were observed. Female mice showed higher level of serum fucosylation and lower level of serum afucosylation than male mice (fucosylation: p < 1.0E-6; afucosylation: p < 1.0E-6). Obviously, higher increase of serum fucosylation level was found in female mice than in male mice from middle age to old age. In addition, the opposite alterations of the afucosylated glycans with α2,3-linked sialic acid and those only with α2,6-linked sialic acid were observed at old age in male mice. These findings suggested that N-glycome could be a valuable target for investigating aging and possible contributors to aging.
研究小鼠衰老过程中血清 N-糖组的变化有助于探索人类报道的变化背后的分子基础。然而，由于方法的限制，此类研究仍然很少，并且缺乏一些信息，如唾液酸化。在这里，我们引入仿生糖组学方法来定量 C57BL/6 小鼠衰老过程中（从青春期到老年阶段）血清 N-糖组的变化。这项技术首次能够可靠和全面地定量分析 12 个性别时间点的 20 多种血清 N-聚糖的表达水平变化，包括分析唾液酸及其不同的连接。结果表明，总糖的表达水平从中年到老年增加。有趣的是，观察到了性别特异性的 N-糖组谱和变化。与雄性小鼠相比，雌性小鼠的血清岩藻糖基化水平更高，而血清去岩藻糖基化水平更低（岩藻糖基化：p<1.0E-6；去岩藻糖基化：p<1.0E-6）。显然，从中年到老年，雌性小鼠血清岩藻糖基化水平的升高更为明显。此外，在雄性小鼠老年时，α2,3 连接唾液酸化的去岩藻糖基化聚糖和仅含有α2,6 连接唾液酸化的去岩藻糖基化聚糖发生了相反的变化。这些发现表明，N-糖组可能是研究衰老和可能导致衰老的因素的一个有价值的靶点。
