Generalized low levels of serum N-glycans associates with young biological age and good physical condition

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, the minority of glycans which have O-acetylated sialic acid modification primarily on a2,6-linked sialic acid showed a consistent high level in CR group. Liver transcriptome analysis further revealed a decreased transcripts 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. Overall design: The calorie restriction was initiated at 12 weeks of age and liver tissues were collected from male mice at 30 weeks of age. There were 3 control-fed mice and 4 calorie restricted mice in the analysis.