title: Decreased levels of bisecting GlcNAc glycoforms of IgG are associated with human longevity.
abstract: BACKGROUND
  Markers for longevity that reflect the health condition and predict healthy aging are extremely scarce. Such markers are, however, valuable in aging research. It has been shown previously that the N-glycosylation pattern of human immunoglobulin G (IgG) is age-dependent. Here we investigate whether N-linked glycans reflect early features of human longevity.
  
  
  RESULTS
  The Leiden Longevity Study (LLS) consists of nonagenarian sibling pairs, their offspring, and partners of the offspring serving as control. IgG subclass specific glycosylation patterns were obtained from 1967 participants in the LLS by MALDI-TOF-MS analysis of tryptic IgG Fc glycopeptides. Several regression strategies were applied to evaluate the association of IgG glycosylation with age, sex, and longevity. The degree of galactosylation of IgG decreased with increasing age. For the galactosylated glycoforms the incidence of bisecting GlcNAc increased as a function of age. Sex-related differences were observed at ages below 60 years. Compared to males, younger females had higher galactosylation, which decreased stronger with increasing age, resulting in similar galactosylation for both sexes from 60 onwards. In younger participants (<60 years of age), but not in the older age group (>60 years), decreased levels of non-galactosylated glycoforms containing a bisecting GlcNAc reflected early features of longevity.
  
  
  CONCLUSIONS
  We here describe IgG glycoforms associated with calendar age at all ages and the propensity for longevity before middle age. As modulation of IgG effector functions has been described for various IgG glycosylation features, a modulatory effect may be expected for the longevity marker described in this study.
authors.affiliation: Biomolecular Mass Spectrometry Unit, Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: L Renee
authors.initials: LR
authors.lastname: Ruhaak
authors.forename: Hae-Won
authors.initials: HW
authors.lastname: Uh
authors.forename: Marian
authors.initials: M
authors.lastname: Beekman
authors.forename: Carolien A M
authors.initials: CA
authors.lastname: Koeleman
authors.forename: Cornelis H
authors.initials: CH
authors.lastname: Hokke
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp
authors.forename: Manfred
authors.initials: M
authors.lastname: Wuhrer
authors.forename: Jeanine J
authors.initials: JJ
authors.lastname: Houwing-Duistermaat
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.forename: André M
authors.initials: AM
authors.lastname: Deelder
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D005260:Female; D006031:Glycosylation; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism*; D008136:Longevity; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011134:Polysaccharides / Q000378:metabolism*
chemical_list: D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D011134:Polysaccharides