title: Alteration in N-glycomics during mouse aging: a role for FUT8.
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.
authors.affiliation: Department for Molecular Biomedical Research, VIB, Technologiepark 927, Ghent, Belgium.
authors.forename: Valerie
authors.initials: V
authors.lastname: Vanhooren
authors.forename: Sylviane
authors.initials: S
authors.lastname: Dewaele
authors.forename: Makoto
authors.initials: M
authors.lastname: Kuro-O
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
authors.forename: Laurent
authors.initials: L
authors.lastname: Dollé
authors.forename: Leo A
authors.initials: LA
authors.lastname: van Grunsven
authors.forename: Evgenia
authors.initials: E
authors.lastname: Makrantonaki
authors.forename: Christos C
authors.initials: CC
authors.lastname: Zouboulis
authors.forename: Cuiying C
authors.initials: CC
authors.lastname: Chen
authors.forename: Claude
authors.initials: C
authors.lastname: Libert
mesh_terms: D000375:Aging; D000818:Animals; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism*; D031204:Caloric Restriction; D005643:Fucose / Q000378:metabolism; D005647:Fucosyltransferases / Q000097:blood* / Q000235:genetics; D015870:Gene Expression; D005966:Glucuronidase / Q000172:deficiency* / Q000235:genetics; D054794:Glycomics / Q000379:methods*; D006023:Glycoproteins / Q000097:blood / Q000235:genetics; D006031:Glycosylation; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D000090265:Klotho Proteins; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011134:Polysaccharides / Q000097:blood* / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D001798:Blood Proteins; D006023:Glycoproteins; D011134:Polysaccharides; C519530:insulin-like growth factor-1, mouse; D005643:Fucose; D007334:Insulin-Like Growth Factor I; D005647:Fucosyltransferases; C020559:Glycoprotein 6-alpha-L-fucosyltransferase; D017526:Receptor, IGF Type 1; D005966:Glucuronidase; D000090265:Klotho Proteins