1. Alteration in N-glycomics during mouse aging: a role for FUT8.
- Author
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Vanhooren V, Dewaele S, Kuro-O M, Taniguchi N, Dollé L, van Grunsven LA, Makrantonaki E, Zouboulis CC, Chen CC, and Libert C
- Subjects
- Animals, Blood Proteins genetics, Caloric Restriction, Fucose metabolism, Fucosyltransferases genetics, Gene Expression, Glucuronidase genetics, Glycoproteins blood, Glycoproteins genetics, Glycosylation, Insulin-Like Growth Factor I genetics, Insulin-Like Growth Factor I metabolism, Klotho Proteins, Liver metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Polysaccharides genetics, Receptor, IGF Type 1 genetics, Receptor, IGF Type 1 metabolism, Aging, Blood Proteins metabolism, Fucosyltransferases blood, Glucuronidase deficiency, Glycomics methods, Polysaccharides blood, Signal Transduction
- Abstract
We recently reported that N-glycosylation changes during human aging. To further investigate the molecular basis determining these alterations, the aging process in mice was studied. N-glycan profiling of mouse serum glycoproteins in different age groups of healthy C57BL/6 mice showed substantial age-related changes in three major N-glycan structures: under-galactosylated biantennary (NGA2F), biantennary (NA2), and core α-1,6-fucosylated -β-galactosylated biantennary structures (NA2F). Mice defective in klotho gene expression (kl/kl), which have a shortened lifespan, displayed a similar but accelerated trend. Interestingly, the opposite trend was observed in slow-aging Snell Dwarf mice (dw/dw) and in mice fed a calorically restricted diet. We also discovered that increased expression and activity of α-1,6-fucosyltransferase (FUT8) in the liver are strongly linked to the age-related changes in glycosylation and that this increased FUT8 and fucosylation influence IGF-1 signaling. These data demonstrate that the glycosylation machinery in liver cells is significantly affected during aging and that age-related increased FUT8 activity could influence the aging process by altering the sensitivity of the IGF-1R signaling pathway., (© 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.)
- Published
- 2011
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