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Glycobiology of Aging

  • Fabio Dall’OlioEmail author
Chapter
Part of the Subcellular Biochemistry book series (SCBI, volume 90)

Abstract

Glycosylation is one of the most frequent post-translational modification of proteins. Many membrane and secreted proteins are decorated by sugar chains mainly linked to asparagine (N-linked) or to serine or threonine (O-linked). The biosynthesis of the sugar chains is mainly controlled by the activity of their biosynthetic enzymes: the glycosyltransferases. Glycosylation plays multiple roles, including the fine regulation of the biological activity of glycoproteins. Inflammaging is a chronic low grade inflammatory status associated with aging, probably caused by the continuous exposure of the immune system to inflammatory stimuli of endogenous and exogenous origin. The aging-associated glycosylation changes often resemble those observed in inflammatory conditions. One of the most reproducible markers of calendar and biological aging is the presence of N-glycans lacking terminal galactose residues linked to Asn297 of IgG heavy chains (IgG-G0). Although the mechanism(s) generating IgG-G0 remain unclear, their presence in a variety of inflammatory conditions suggests a link with inflammaging. In addition, these aberrantly glycosylated IgG can exert a pro-inflammatory effect through different mechanisms, triggering a self-fueling inflammatory loop. A strong association with aging has been documented also for the plasmatic forms of glycosyltrasferases B4GALT1 and ST6GAL1, although their role in the extracellular glycosylation of antibodies does not appear likely. Siglecs, are a group of sialic acid binding mammalian lectins which mainly act as inhibitory receptors on the surface of immune cells. In general activity of Siglecs appears to be associated with long life, probably because of their ability to restrain aging-associated inflammation.

Keywords

Glycosylation in aging Inflammaging Hypogalactosylated antibodies Siglecs Plasmatic glycosyltransferases 

Abbreviations

DAMPS

danger-associated molecular patterns

DC-SIGN

dendritic cell-specific ICAM-grabbing non-integrin

Fuc

fucose

Gal

galactose

GalNAc

N-acetylgalactosamine

Glc

glucose

GlcNAc

N-acetylglucosamine

ITIM

immunoreceptor tyrosine-based inhibition motif

Man

mannose

MBL

mannose binding lectin

PAMPS

pathogen-associated molecular patterns

RA

rheumatoid arthritis

ROS

reactive oxygen species

SASP

senescence-associated secretory phenotype

SHP

Src-homology 2 domain (SH2)-containing phosphatese

TLR

toll-like receptor

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© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Department of Experimental, Diagnostic and Specialty Medicine (DIMES)University of BolognaBolognaItaly

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