Decreased levels of bisecting GlcNAc glycoforms of IgG are associated with human longevity.

<h4>Background</h4>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...

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Main Authors: L Renee Ruhaak, Hae-Won Uh, Marian Beekman, Carolien A M Koeleman, Cornelis H Hokke, Rudi G J Westendorp, Manfred Wuhrer, Jeanine J Houwing-Duistermaat, P Eline Slagboom, André M Deelder
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2010-09-01
Series:PLoS ONE
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20830288/?tool=EBI
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author L Renee Ruhaak
Hae-Won Uh
Marian Beekman
Carolien A M Koeleman
Cornelis H Hokke
Rudi G J Westendorp
Manfred Wuhrer
Jeanine J Houwing-Duistermaat
P Eline Slagboom
André M Deelder
author_facet L Renee Ruhaak
Hae-Won Uh
Marian Beekman
Carolien A M Koeleman
Cornelis H Hokke
Rudi G J Westendorp
Manfred Wuhrer
Jeanine J Houwing-Duistermaat
P Eline Slagboom
André M Deelder
author_sort L Renee Ruhaak
collection DOAJ
description <h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.
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spelling doaj.art-254679fc5da44461af61d94e662aee7f2022-12-21T22:58:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-09-0159e1256610.1371/journal.pone.0012566Decreased levels of bisecting GlcNAc glycoforms of IgG are associated with human longevity.L Renee RuhaakHae-Won UhMarian BeekmanCarolien A M KoelemanCornelis H HokkeRudi G J WestendorpManfred WuhrerJeanine J Houwing-DuistermaatP Eline SlagboomAndré M Deelder<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20830288/?tool=EBI
spellingShingle L Renee Ruhaak
Hae-Won Uh
Marian Beekman
Carolien A M Koeleman
Cornelis H Hokke
Rudi G J Westendorp
Manfred Wuhrer
Jeanine J Houwing-Duistermaat
P Eline Slagboom
André M Deelder
Decreased levels of bisecting GlcNAc glycoforms of IgG are associated with human longevity.
PLoS ONE
title Decreased levels of bisecting GlcNAc glycoforms of IgG are associated with human longevity.
title_full Decreased levels of bisecting GlcNAc glycoforms of IgG are associated with human longevity.
title_fullStr Decreased levels of bisecting GlcNAc glycoforms of IgG are associated with human longevity.
title_full_unstemmed Decreased levels of bisecting GlcNAc glycoforms of IgG are associated with human longevity.
title_short Decreased levels of bisecting GlcNAc glycoforms of IgG are associated with human longevity.
title_sort decreased levels of bisecting glcnac glycoforms of igg are associated with human longevity
url https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20830288/?tool=EBI
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