Glycans Are a Novel Biomarker of Chronological and Biological Ages
Open accessAbstract
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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Recent mass spectrometry studies examining the concentrations of just a few well-studied glycans have been able to accurately predict chronological age and ageing phenotypes.
“Although it is not yet possible to comprehensively survey the glycome, recent mass spectrometry studies examining the concentrations of just a few well-studied glycans have been able to accurately predict chronological age and ageing phenotypes.”
From Measuring biological age using omics data (2022) · cites this paper as [129]
Krištić et al. observed changes in the N-glycosylation pattern of serum IgG protein, which predicted age in multiple European cohorts.
“Krištić et al.129 observed changes in the N-glycosylation pattern of serum IgG protein, which predicted age in multiple European cohorts.”
From Measuring biological age using omics data (2022) · cites this paper as [129]
IgG glycan age correlated with clinical markers of metabolic health.
“Moreover, IgG glycan age correlated with clinical markers of metabolic health129.”
From Measuring biological age using omics data (2022) · cites this paper as [129]
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Self-citation
- Authors
- 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, J. F., Gornik, O., Primorac, D., Zoldoš, V., Spector, T., & Lauc, G.
- Affiliations
- King's College London (GB)
- University of Zagreb (HR)
- Institute for Anthropological Research (HR)
- University of Split (HR)
- University of Edinburgh (GB)
- Institute of Genetics and Cancer (GB)
- Institute of Cytology and Genetics (RU)
- University of Osijek (HR)
- Corresponding author
- Krištić, Jasminka
- Vučković, Frano
- ORCID
- Krištić, Jasminka
- Vučković, Frano
- Menni, Cristina
- Klarić, Lucija
- Keser, Toma
- Novokmet, Mislav
- Mangino, Massimo
- Novokmet, Natalija
- Šarac, Jelena
- Missoni, Saša
- Kolčić, Ivana
- Polašek, Ozren
- Rudan, Igor
- Hayward, Caroline
- Aulchenko, Yurii
- Valdes, Ana
- Wilson, James F.
- Gornik, Olga
- Primorac, Dragan
- Zoldoš, Vlatka
- Spector, Tim
- Lauc, Gordan
- Venue
- The Journals of Gerontology: Series A
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-12-10
- Volume
- 69
- Issue
- 7
- Pages
- 779-789
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- PMC
- PMC4049143
- OpenAlex
- W2136722035
- Cited by
- 400
- References
- 52
- Citations by year
- 2026: 33 · 2025: 41 · 2024: 50 · 2023: 41 · 2022: 40 · 2021: 37 · 2020: 44 · 2019: 25 · 2018: 28 · 2017: 18 · 2016: 25 · 2015: 13 · 2014: 2 · 2013: 1
- FWCI
- 6.12
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- The Journals of Gerontology Series A (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, other-oa)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by-nc)
- Funders
- Wellcome Trust
- National Institute for Health and Care Research
- European Commission (305479)
- Russian Foundation for Basic Research
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Keywords
- IgG glycosylation, glycans, biological age, chronological age, aging biomarkers, N-glycosylation, telomere length, inflammation, post-translational modification, IgG
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Female, Glycosylation, United Kingdom, Humans, Immunoglobulin G, Longevity, Male, Middle Aged, Models, Biological, Polysaccharides, Protein Processing, Post-Translational, Scotland, Cohort Studies, Biomarkers, Croatia, Inflammation Mediators, Young Adult
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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