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

Aging Cell

Valerie Vanhooren²  Sylviane Dewaele²  Makoto Kuro-o⁴  Naoyuki Taniguchi¹  Laurent Dollé⁵  Leo A. van Grunsven⁵  Evgenia Makrantonaki³  Christos C. Zouboulis³  Cuiying C. Chen² 

[1] Systems Glycobiology Research Group, Department of Chemical Biology, RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako, Saitama, Japan;Department for Molecular Biomedical Research, VIB, Technologiepark 927, 9000, Ghent, Belgium;Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, 38 Auenweg, 06847, Dessau, Germany;Department of Pathology, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390-9072, USA;Liver Cell Biology Lab, Department of Cell Biology, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090, Brussels, Belgium

关键词: N‐glycan;    glycosylation;    aging;    Snell Dwarf;    klotho mouse;    caloric restriction;   

DOI  :  10.1111/j.1474-9726.2011.00749.x

来源: Wiley

【 摘 要 】

Summary

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.

【 授权许可】

Unknown   
© 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland