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.
  
  
  CONCLUSIONS
  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.
authors: Genos Glycobiology Laboratory, Zagreb, Croatia.
authors: Jasminka
authors: J
authors: Krištić
authors: Genos Glycobiology Laboratory, Zagreb, Croatia.
authors: Frano
authors: F
authors: Vučković
authors: Department of Twins Research and Genetic Epidemiology, Kings College London, UK.
authors: Cristina
authors: C
authors: Menni
authors: Genos Glycobiology Laboratory, Zagreb, Croatia.
authors: Lucija
authors: L
authors: Klarić
authors: Faculty of Pharmacy and Biochemistry, University of Zagreb, Croatia.
authors: Toma
authors: T
authors: Keser
authors: Genos Glycobiology Laboratory, Zagreb, Croatia.
authors: Ivona
authors: I
authors: Beceheli
authors: Genos Glycobiology Laboratory, Zagreb, Croatia.
authors: Maja
authors: M
authors: Pučić-Baković
authors: Genos Glycobiology Laboratory, Zagreb, Croatia.
authors: Mislav
authors: M
authors: Novokmet
authors: Department of Twins Research and Genetic Epidemiology, Kings College London, UK.
authors: Massimo
authors: M
authors: Mangino
authors: Genos Glycobiology Laboratory, Zagreb, Croatia.
authors: Kujtim
authors: K
authors: Thaqi
authors: Institute for Anthropological Research, Zagreb, Croatia.
authors: Pavao
authors: P
authors: Rudan
authors: Institute for Anthropological Research, Zagreb, Croatia.
authors: Natalija
authors: N
authors: Novokmet
authors: Institute for Anthropological Research, Zagreb, Croatia.
authors: Jelena
authors: J
authors: Sarac
authors: Institute for Anthropological Research, Zagreb, Croatia.
authors: Saša
authors: S
authors: Missoni
authors: Faculty of Medicine, University of Split, Croatia.
authors: Ivana
authors: I
authors: Kolčić
authors: Faculty of Medicine, University of Split, Croatia.
authors: Ozren
authors: O
authors: Polašek
authors: Centre for Population Health Sciences, The University of Edinburgh Medical School, UK.
authors: Igor
authors: I
authors: Rudan
authors: Centre for Population Health Sciences, The University of Edinburgh Medical School, UK.
authors: Harry
authors: H
authors: Campbell
authors: MRCHGU, Institute of Genetics and Molecular Medicine, University of Edinburgh, EH4 2XU, UK.
authors: Caroline
authors: C
authors: Hayward
authors: Institute of Cytology and Genetics SD RAS, Novosibirsk, Russia.
authors: Yurii
authors: Y
authors: Aulchenko
authors: Department of Twins Research and Genetic Epidemiology, Kings College London, UK.
authors: Ana
authors: A
authors: Valdes
authors: Centre for Population Health Sciences, The University of Edinburgh Medical School, UK.
authors: James F
authors: JF
authors: Wilson
authors: Faculty of Pharmacy and Biochemistry, University of Zagreb, Croatia.
authors: Olga
authors: O
authors: Gornik
authors: University of Osijek School of Medicine, Croatia.
authors: Dragan
authors: D
authors: Primorac
authors: Faculty of Science, University of Zagreb, Croatia.
authors: Vlatka
authors: V
authors: Zoldoš
authors: Department of Twins Research and Genetic Epidemiology, Kings College London, UK.
authors: Tim
authors: T
authors: Spector
authors: Genos Glycobiology Laboratory, Zagreb, Croatia. Faculty of Pharmacy and Biochemistry, University of Zagreb, Croatia. glauc@pharma.hr.
authors: Gordan
authors: G
authors: Lauc
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D015331:Cohort Studies; D017523:Croatia; D005260:Female; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry* / Q000378:metabolism*; D018836:Inflammation Mediators / Q000737:chemistry / Q000378:metabolism; D008136:Longevity / Q000502:physiology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011134:Polysaccharides / Q000737:chemistry* / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012606:Scotland; D006113:United Kingdom; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007074:Immunoglobulin G; D018836:Inflammation Mediators; D011134:Polysaccharides
keywords: Aging; Glycome; Glycosylation; Immunoglobulin G; Inflammation.