Glycans are a novel biomarker of chronological and biological ages

Jasminka Krištić, Frano Vučković, Cristina Menni, Lucija Klarić, Toma Keser, Ivona Beceheli, Maja Pučić-Baković, Mislav Novokmet, Massimo Mangino, Kujtim Thaqi, Pavao Rudan, Natalija Novokmet, Jelena Šarac, Saša Missoni, Ivana Kolčić, Ozren Polašek, Igor Rudan, Harry Campbell, Caroline Hayward, Yurii AulchenkoAna Valdes, James F. Wilson, Olga Gornik, Dragan Primorac, Vlatka Zoldoš, Tim Spector, Gordan Lauc

Research output: Contribution to journalArticle

101 Citations (Scopus)

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 Statement 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.

Original languageEnglish (US)
Pages (from-to)779-789
Number of pages11
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume69
Issue number7
DOIs
StatePublished - Jan 1 2014

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Glycosylation
Polysaccharides
Immunoglobulin G
Biomarkers
Telomere
Inflammation
Population
Immunoglobulins
Immune System

All Science Journal Classification (ASJC) codes

  • Aging
  • Geriatrics and Gerontology

Cite this

Krištić, J., Vučković, F., Menni, C., Klarić, L., Keser, T., Beceheli, I., ... Lauc, G. (2014). Glycans are a novel biomarker of chronological and biological ages. Journals of Gerontology - Series A Biological Sciences and Medical Sciences, 69(7), 779-789. https://doi.org/10.1093/gerona/glt190
Krištić, Jasminka ; Vučković, Frano ; Menni, Cristina ; Klarić, Lucija ; Keser, Toma ; Beceheli, Ivona ; Pučić-Baković, Maja ; Novokmet, Mislav ; Mangino, Massimo ; Thaqi, Kujtim ; Rudan, Pavao ; Novokmet, Natalija ; Šarac, Jelena ; Missoni, Saša ; Kolčić, Ivana ; Polašek, Ozren ; Rudan, Igor ; Campbell, Harry ; Hayward, Caroline ; Aulchenko, Yurii ; Valdes, Ana ; Wilson, James F. ; Gornik, Olga ; Primorac, Dragan ; Zoldoš, Vlatka ; Spector, Tim ; Lauc, Gordan. / Glycans are a novel biomarker of chronological and biological ages. In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences. 2014 ; Vol. 69, No. 7. pp. 779-789.
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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 Statement 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.",
author = "Jasminka Krištić and Frano Vučković and Cristina Menni and Lucija Klarić and Toma Keser and Ivona Beceheli and Maja Pučić-Baković and Mislav Novokmet and Massimo Mangino and Kujtim Thaqi and Pavao Rudan and Natalija Novokmet and Jelena Šarac and Saša Missoni and Ivana Kolčić and Ozren Polašek 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 Zoldoš and Tim Spector and Gordan Lauc",
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Krištić, J, Vučković, F, Menni, C, Klarić, L, Keser, T, Beceheli, I, Pučić-Baković, M, Novokmet, M, Mangino, M, Thaqi, K, Rudan, P, Novokmet, N, Šarac, J, Missoni, S, Kolčić, I, Polašek, O, Rudan, I, Campbell, H, Hayward, C, Aulchenko, Y, Valdes, A, Wilson, JF, Gornik, O, Primorac, D, Zoldoš, V, Spector, T & Lauc, G 2014, 'Glycans are a novel biomarker of chronological and biological ages', Journals of Gerontology - Series A Biological Sciences and Medical Sciences, vol. 69, no. 7, pp. 779-789. https://doi.org/10.1093/gerona/glt190

Glycans are a novel biomarker of chronological and biological ages. / Krištić, Jasminka; Vučković, Frano; Menni, Cristina; Klarić, Lucija; Keser, Toma; Beceheli, Ivona; Pučić-Baković, Maja; Novokmet, Mislav; Mangino, Massimo; Thaqi, Kujtim; Rudan, Pavao; Novokmet, Natalija; Šarac, Jelena; Missoni, Saša; Kolčić, Ivana; Polašek, Ozren; Rudan, Igor; Campbell, Harry; Hayward, Caroline; Aulchenko, Yurii; Valdes, Ana; Wilson, James F.; Gornik, Olga; Primorac, Dragan; Zoldoš, Vlatka; Spector, Tim; Lauc, Gordan.

In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences, Vol. 69, No. 7, 01.01.2014, p. 779-789.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Glycans are a novel biomarker of chronological and biological ages

AU - Krištić, Jasminka

AU - Vučković, Frano

AU - Menni, Cristina

AU - Klarić, Lucija

AU - Keser, Toma

AU - Beceheli, Ivona

AU - Pučić-Baković, Maja

AU - Novokmet, Mislav

AU - Mangino, Massimo

AU - Thaqi, Kujtim

AU - Rudan, Pavao

AU - Novokmet, Natalija

AU - Šarac, Jelena

AU - Missoni, Saša

AU - Kolčić, Ivana

AU - Polašek, 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 - Zoldoš, Vlatka

AU - Spector, Tim

AU - Lauc, Gordan

PY - 2014/1/1

Y1 - 2014/1/1

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 Statement 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.

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 Statement 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.

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