Generalized low levels of serum N‐glycans associate with better health status

Abstract Caloric restriction (CR) can prolong life and ameliorate age‐related diseases; thus, its molecular basis might provide new insights for finding biomarker and intervention for aging and age‐related disease. Glycosylation is an important post‐translational modification, which can timely reflect the changes of intracellular state. Serum N‐glycosylation was found changed with aging in humans and mice. CR is widely accepted as an effective anti‐aging intervention in mice and could affect mouse serum fucosylated N‐glycans. However, the effect of CR on the level of global N‐glycans remains unknown. In order to explore whether CR affect the level of global N‐glycans, we performed a comprehensive serum glycome profiling in mice of 30% calorie restriction group and ad libitum group at 7 time points across 60 weeks by MALDI‐TOF‐MS. At each time point, the majority of glycans, including galactosylated and high mannose glycans, showed a consistent low level in CR group. Interestingly, O‐acetylated sialoglycans presented an upward change different from other derived traits, which is mainly reflected in two biantennary α2,6‐linked sialoglycans (H5N4Ge2Ac1, H5N4Ge2Ac2). Liver transcriptome analysis further revealed a decreased transcriptional level of genes involved in N‐glycan biosynthesis while increased level of acetyl‐CoA production. This finding is consistent with changes in serum N‐glycans and O‐acetylated sialic acids. Therefore, we provided one possible molecular basis for the beneficial effect of CR from N‐glycosylation perspective.