Alteration in N-glycomics during mouse aging: a role for FUT8

Autor: Laurent Dollé, Claude Libert, Evgenia Makrantonaki, Naoyuki Taniguchi, Sylviane Dewaele, Valerie Vanhooren, Christos C. Zouboulis, Cuiying Chitty Chen, Makoto Kuro-o, Leo A. van Grunsven
Rok vydání: 2011
Předmět:
Zdroj: Aging Cell. 10:1056-1066
ISSN: 1474-9718
DOI: 10.1111/j.1474-9726.2011.00749.x
Popis: 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 alpha-1,6-fucosylated-beta-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 alpha-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.
Databáze: OpenAIRE