Glycans Are a Novel Biomarker of Chronological and Biological Ages

Jasminka Kristic; Frano Vuckovic; Cristina Menni; Lucija Klaric; Toma Keser; Ivona Beceheli; Maja Pucic-Bakovic; Mislav Novokmet; Massimo Mangino; Kujtim Thaqi; Pavao Rudan; Natalija Novokmet; Jelena Sarac; Sasa Missoni; Ivana Kolcic; Ozren Polasek; Igor Rudan; Harry Campbell; Caroline Hayward; Yurii Aulchenko; Ana Valdes; James F Wilson; Olga Gornik; Dragan Primorac; Vlatka Zoldos; Tim Spector; Gordan Lauc

doi:10.1093/gerona/glt190

Glycans Are a Novel Biomarker of Chronological and Biological Ages

Jasminka Kristic, Frano Vuckovic, Cristina Menni, Lucija Klaric, Toma Keser, Ivona Beceheli, Maja Pucic-Bakovic, Mislav Novokmet, Massimo Mangino, Kujtim Thaqi, Pavao Rudan, Natalija Novokmet, Jelena Sarac, Sasa Missoni, Ivana Kolcic, Ozren Polasek, Igor Rudan, Harry Campbell, Caroline Hayward, Yurii AulchenkoAna Valdes, James F Wilson, Olga Gornik, Dragan Primorac, Vlatka Zoldos, Tim Spector, Gordan Lauc

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Abstract

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.Significance StatementGlycosylation 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.

Original language	English
Pages (from-to)	779-789
Number of pages	11
Journal	The journals of gerontology. Series A, Biological sciences and medical sciences
Volume	69
Issue number	7
DOIs	https://doi.org/10.1093/gerona/glt190
Publication status	Published - Jul 2014

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Kristic, J., Vuckovic, F., Menni, C., Klaric, L., Keser, T., Beceheli, I., Pucic-Bakovic, M., Novokmet, M., Mangino, M., Thaqi, K., Rudan, P., Novokmet, N., Sarac, J., Missoni, S., Kolcic, I., Polasek, O., Rudan, I., Campbell, H., Hayward, C., ... Lauc, G. (2014). Glycans Are a Novel Biomarker of Chronological and Biological Ages. The journals of gerontology. Series A, Biological sciences and medical sciences, 69(7), 779-789. https://doi.org/10.1093/gerona/glt190

@article{39eb15f2dbe04c649dca0ffbcfd222b6,

title = "Glycans Are a Novel Biomarker of Chronological and Biological Ages",

abstract = "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.Significance StatementGlycosylation 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.",

author = "Jasminka Kristic and Frano Vuckovic and Cristina Menni and Lucija Klaric and Toma Keser and Ivona Beceheli and Maja Pucic-Bakovic and Mislav Novokmet and Massimo Mangino and Kujtim Thaqi and Pavao Rudan and Natalija Novokmet and Jelena Sarac and Sasa Missoni and Ivana Kolcic and Ozren Polasek and Igor Rudan and Harry Campbell and Caroline Hayward and Yurii Aulchenko and Ana Valdes and Wilson, {James F} and Olga Gornik and Dragan Primorac and Vlatka Zoldos and Tim Spector and Gordan Lauc",

year = "2014",

month = jul,

doi = "10.1093/gerona/glt190",

language = "English",

volume = "69",

pages = "779--789",

journal = "The journals of gerontology. Series A, Biological sciences and medical sciences",

publisher = "Gerontological Society of America",

number = "7",

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Kristic, J, Vuckovic, F, Menni, C, Klaric, L, Keser, T, Beceheli, I, Pucic-Bakovic, M, Novokmet, M, Mangino, M, Thaqi, K, Rudan, P, Novokmet, N, Sarac, J, Missoni, S, Kolcic, I, Polasek, O, Rudan, I, Campbell, H, Hayward, C, Aulchenko, Y, Valdes, A , Wilson, JF, Gornik, O, Primorac, D, Zoldos, V, Spector, T & Lauc, G 2014, 'Glycans Are a Novel Biomarker of Chronological and Biological Ages', The journals of gerontology. Series A, Biological sciences and medical sciences, vol. 69, no. 7, pp. 779-789. https://doi.org/10.1093/gerona/glt190

TY - JOUR

T1 - Glycans Are a Novel Biomarker of Chronological and Biological Ages

AU - Kristic, Jasminka

AU - Vuckovic, Frano

AU - Menni, Cristina

AU - Klaric, Lucija

AU - Keser, Toma

AU - Beceheli, Ivona

AU - Pucic-Bakovic, Maja

AU - Novokmet, Mislav

AU - Mangino, Massimo

AU - Thaqi, Kujtim

AU - Rudan, Pavao

AU - Novokmet, Natalija

AU - Sarac, Jelena

AU - Missoni, Sasa

AU - Kolcic, Ivana

AU - Polasek, Ozren

AU - Rudan, Igor

AU - Campbell, Harry

AU - Hayward, Caroline

AU - Aulchenko, Yurii

AU - Valdes, Ana

AU - Wilson, James F

AU - Gornik, Olga

AU - Primorac, Dragan

AU - Zoldos, Vlatka

AU - Spector, Tim

AU - Lauc, Gordan

PY - 2014/7

Y1 - 2014/7

N2 - 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.Significance StatementGlycosylation 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.

AB - 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.Significance StatementGlycosylation 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.

U2 - 10.1093/gerona/glt190

DO - 10.1093/gerona/glt190

M3 - Article

C2 - 24325898

VL - 69

SP - 779

EP - 789

JO - The journals of gerontology. Series A, Biological sciences and medical sciences

JF - The journals of gerontology. Series A, Biological sciences and medical sciences

IS - 7

ER -

Glycans Are a Novel Biomarker of Chronological and Biological Ages

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