title: Identification of novel plasma glycosylation-associated markers of aging.
abstract: The pro- or anti-inflammatory activities of immunoglobulins G (IgGs) are controlled by the structure of the glycan N-linked to Asn297 of their heavy chain. The age-associated low grade inflammation (inflammaging) is associated with increased plasmatic levels of agalactosylated IgGs terminating with N-acetylglucosamine (IgG-G0) whose biogenesis has not been fully explained. Although the biosynthesis of glycans is in general mediated by glycosyltransferases associated with internal cell membranes, the extracellular glycosylation of circulating glycoproteins mediated by plasmatic glycosyltransferases has been recently demonstrated. In this study we have investigated the relationship between plasmatic glycosyltransferases, IgG glycosylation and inflammatory and aging markers. In cohorts of individuals ranging from infancy to centenarians we determined the activity of plasmatic β4 galactosyltransferase(s) (B4GALTs) and of α2,6-sialyltransferase ST6GAL1, the glycosylation of IgG, the GlycoAge test (a glycosylation-based marker of aging) and the plasma level of inflammatory and liver damage markers. Our results show that: 1) plasmatic B4GALTs activity is a new marker of aging, showing a linear increase throughout the whole age range. 2) plasmatic ST6GAL1 was high only in children and in people above 80, showing a quadratic relationship with age. 3) Neither plasmatic glycosyltransferase correlated with markers of liver damage. 4) plasmatic ST6GAL1 showed a positive association with acute phase proteins in offspring of short lived parents, but not in centenarians or in their offspring. 5) Although the glycosylation of IgGs was not correlated with the level of the two plasmatic glycosyltransferases, it showed progressive age-associated changes consistent with a shift toward a pro-inflammatory glycotype.
authors: Dipartimento di Medicina Specialistica Diagnostica e Sperimentale (DIMES) University of Bologna, Bologna, Italy.
authors: Mariangela
authors: M
authors: Catera
authors: Dipartimento di Medicina Specialistica Diagnostica e Sperimentale (DIMES) University of Bologna, Bologna, Italy.
authors: Vincenzo
authors: V
authors: Borelli
authors: Dipartimento di Medicina Specialistica Diagnostica e Sperimentale (DIMES) University of Bologna, Bologna, Italy.
authors: Nadia
authors: N
authors: Malagolini
authors: Dipartimento di Medicina Specialistica Diagnostica e Sperimentale (DIMES) University of Bologna, Bologna, Italy.
authors: Mariella
authors: M
authors: Chiricolo
authors: Dipartimento di Medicina Specialistica Diagnostica e Sperimentale (DIMES) University of Bologna, Bologna, Italy.
authors: Giulia
authors: G
authors: Venturi
authors: Instituto de Investigação e Inovação em Saúde (Institute for Research and Innovation in Health), University of Porto, and Institute of Molecular Pathology and Immunology of The University of Porto IPATIMUP), Porto, Portugal.|Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.|Faculty of Medicine of The University of Porto, Al. Prof. Hernâni Monteiro, Porto, Portugal.
authors: Celso A
authors: CA
authors: Reis
authors: Instituto de Investigação e Inovação em Saúde (Institute for Research and Innovation in Health), University of Porto, and Institute of Molecular Pathology and Immunology of The University of Porto IPATIMUP), Porto, Portugal.|Faculty of Medicine of The University of Porto, Al. Prof. Hernâni Monteiro, Porto, Portugal.
authors: Hugo
authors: H
authors: Osorio
authors: Dipartimento di Medicina Specialistica Diagnostica e Sperimentale (DIMES) University of Bologna, Bologna, Italy.
authors: Provvidenza M
authors: PM
authors: Abruzzo
authors: Dipartimento di Medicina Specialistica Diagnostica e Sperimentale (DIMES) University of Bologna, Bologna, Italy.
authors: Miriam
authors: M
authors: Capri
authors: Dipartimento di Scienze Biomediche, Sperimentali e Cliniche "Mario Serio", University of Florence, Florence, Italy.
authors: Daniela
authors: D
authors: Monti
authors: Dipartimento di Medicina Specialistica Diagnostica e Sperimentale (DIMES) University of Bologna, Bologna, Italy.
authors: Rita
authors: R
authors: Ostan
authors: Dipartimento di Medicina Specialistica Diagnostica e Sperimentale (DIMES) University of Bologna, Bologna, Italy.
authors: Claudio
authors: C
authors: Franceschi
authors: Dipartimento di Medicina Specialistica Diagnostica e Sperimentale (DIMES) University of Bologna, Bologna, Italy.
authors: Fabio
authors: F
authors: Dall'Olio
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D015703:Antigens, CD / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005700:Galactosyltransferases / Q000097:blood*; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007223:Infant; D007231:Infant, Newborn; D007249:Inflammation / Q000097:blood / Q000175:diagnosis*; D008107:Liver Diseases / Q000097:blood / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012799:Sialyltransferases / Q000097:blood*; D055815:Young Adult; D006023:Glycoproteins; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D005700:Galactosyltransferases; D007074:Immunoglobulin G; D012799:Sialyltransferases; C046179:glycosylated IgG; D006023:Glycoproteins; C119701:beta-1,4-galactosyltransferase I; C093493:ST6GAL1 protein, human; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
keywords: Gerotarget; antibody glycosylation; inflammaging; plasma galactosyltransferases; plasma sialyltransferases; soluble glycosyltransferases