TY - JOUR
T1 - Alteration in N-glycomics during mouse aging
T2 - A role for FUT8
AU - Vanhooren, Valerie
AU - Dewaele, Sylviane
AU - Kuro-o, Makoto
AU - Taniguchi, Naoyuki
AU - Dollé, Laurent
AU - van Grunsven, Leo A.
AU - Makrantonaki, Evgenia
AU - Zouboulis, Christos C.
AU - Chen, Cuiying C.
AU - Libert, Claude
PY - 2011/12
Y1 - 2011/12
N2 - 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.
AB - 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.
KW - Aging
KW - Caloric restriction
KW - Glycosylation
KW - Klotho mouse
KW - N-glycan
KW - Snell Dwarf
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UR - http://www.scopus.com/inward/citedby.url?scp=81155138282&partnerID=8YFLogxK
U2 - 10.1111/j.1474-9726.2011.00749.x
DO - 10.1111/j.1474-9726.2011.00749.x
M3 - Article
C2 - 21951615
AN - SCOPUS:81155138282
SN - 1474-9718
VL - 10
SP - 1056
EP - 1066
JO - Aging Cell
JF - Aging Cell
IS - 6
ER -