Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Identification of novel plasma glycosylation-associated markers of aging

Mariangela Catera, Vincenzo Borelli, Nadia Malagolini, Mariella Chiricolo, Giulia Venturi, Celso A. Reis, Hugo Osorio, Provvidenza M. Abruzzo, Miriam Capri, Daniela Monti, Rita Ostan, Claudio Franceschi and Fabio Dall’Olio _

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Oncotarget. 2016; 7:7455-7468. https://doi.org/10.18632/oncotarget.7059

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Abstract

Mariangela Catera1,*, Vincenzo Borelli1,*, Nadia Malagolini1, Mariella Chiricolo1, Giulia Venturi1, Celso A. Reis2,3,4, Hugo Osorio2,4, Provvidenza M. Abruzzo1, Miriam Capri1, Daniela Monti5, Rita Ostan1, Claudio Franceschi1 and Fabio Dall’Olio1

1 Dipartimento di Medicina Specialistica Diagnostica e Sperimentale (DIMES) University of Bologna, Bologna, Italy

2 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

3 Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal

4 Faculty of Medicine of The University of Porto, Al. Prof. Hernâni Monteiro, Porto, Portugal

5 Dipartimento di Scienze Biomediche, Sperimentali e Cliniche “Mario Serio”, University of Florence, Florence, Italy

* Co-first authors

Correspondence to:

Fabio Dall’Olio, email:

Keywords: antibody glycosylation, inflammaging, plasma galactosyltransferases, plasma sialyltransferases, soluble glycosyltransferases, Gerotarget

Received: October 02, 2015 Accepted: January 23, 2016 Published: January 28, 2016

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.


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