Glycans Are a Novel Biomarker of Chronological and Biological Ages

被引：282

作者：

Kristic, Jasminka ^{[1
]}

Vuckovic, Frano ^{[1
]}

Menni, Cristina ^{[2
]}

Klaric, Lucija ^{[1
]}

Keser, Toma ^{[3
]}

Beceheli, Ivona ^{[1
]}

Pucic-Bakovic, Maja ^{[1
]}

Novokmet, Mislav ^{[1
]}

Mangino, Massimo ^{[2
]}

Thaqi, Kujtim ^{[1
]}

Rudan, Pavao ^{[4
]}

Novokmet, Natalija ^{[4
]}

Sarac, Jelena ^{[4
]}

Missoni, Sasa ^{[4
]}

Kolcic, Ivana ^{[5
]}

Polasek, Ozren ^{[5
]}

Rudan, Igor ^{[6
]}

Campbell, Harry ^{[6
]}

Hayward, Caroline ^{[7
]}

Aulchenko, Yurii ^{[8
]}

Valdes, Ana ^{[2
]}

Wilson, James F. ^{[6
]}

Gornik, Olga ^{[3
]}

Primorac, Dragan ^{[9
]}

Zoldos, Vlatka ^{[10
]}

Spector, Tim ^{[2
]}

Lauc, Gordan ^{[1
,3
]}

机构：

[1] Genos Glycobiol Lab, Zagreb, Croatia

[2] Kings Coll London, Dept Twins Res & Genet Epidemiol, London WC2R 2LS, England

[3] Univ Zagreb, Fac Pharm & Biochem, Zagreb 10000, Croatia

[4] Inst Anthropol Res, Zagreb, Croatia

[5] Univ Split, Fac Med, Split, Croatia

[6] Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, Edinburgh EH8 9YL, Midlothian, Scotland

[7] Univ Edinburgh, Inst Genet & Mol Med, MRCHGU, Edinburgh EH4 2XU, Midlothian, Scotland

[8] Inst Cytol & Genet SD RAS, Novosibirsk, Russia

[9] Univ Osijek, Sch Med, Osijek, Croatia

[10] Univ Zagreb, Fac Sci, Zagreb 41000, Croatia

来源：

JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES | 2014年 / 69卷 / 07期

基金：

俄罗斯基础研究基金会; 英国惠康基金; 英国医学研究理事会;

关键词：

Aging; Glycome; Glycosylation; Immunoglobulin G; Inflammation; IGG GLYCOSYLATION; SERUM-PROTEINS; PROFILES; PLASMA; OLIGOSACCHARIDES; GALACTOSYLATION; MODULATION; INDEX;

D O I：

10.1093/gerona/glt190

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

Fine structural details of glycans attached to the conserved N-glycosylation site significantly not only affect function of individual immunoglobulin G (IgG) molecules but also mediate inflammation at the systemic level. By analyzing IgG glycosylation in 5,117 individuals from four European populations, we have revealed very complex patterns of changes in IgG glycosylation with age. Several IgG glycans (including FA2B, FA2G2, and FA2BG2) changed considerably with age and the combination of these three glycans can explain up to 58% of variance in chronological age, significantly more than other markers of biological age like telomere lengths. The remaining variance in these glycans strongly correlated with physiological parameters associated with biological age. Thus, IgG glycosylation appears to be closely linked with both chronological and biological ages. Considering the important role of IgG glycans in inflammation, and because the observed changes with age promote inflammation, changes in IgG glycosylation also seem to represent a factor contributing to aging. Glycosylation is the key posttranslational mechanism that regulates function of immunoglobulins, with multiple systemic repercussions to the immune system. Our study of IgG glycosylation in 5,117 individuals from four European populations has revealed very extensive and complex changes in IgG glycosylation with age. The combined index composed of only three glycans explained up to 58% of variance in age, considerably more than other biomarkers of age like telomere lengths. The remaining variance in these glycans strongly correlated with physiological parameters associated with biological age; thus, IgG glycosylation appears to be closely linked with both chronological and biological ages. The ability to measure human biological aging using molecular profiling has practical applications for diverse fields such as disease prevention and treatment, or forensics.

引用

页码：779 / 789

页数：11

共 49 条

[1] NEW LOOK AT STATISTICAL-MODEL IDENTIFICATION [J].