Dr. Azra Frkatović-Hodžić from Genos Glycoscience Research Laboratory in Zagreb, Croatia, discusses a #research paper she co-authored that was #published by Aging (Aging-US) in Volume 15, Issue 24, entitled, “Mapping of the gene network that regulates glycan clock of ageing.”

DOI - https://doi.org/10.18632/aging.205106

Corresponding authors - Azra Frkatović-Hodžić - [email protected], and Gordan Lauc - [email protected]

Video - https://www.youtube.com/watch?v=5ExLCMDhpdE

Video transcription - https://aging-us.net/2024/03/13/behind-the-study-mapping-of-gene-network-that-regulates-glycan-clock-of-aging/

Abstract

Glycans are an essential structural component of immunoglobulin G (IgG) that modulate its structure and function. However, regulatory mechanisms behind this complex posttranslational modification are not well known. Previous genome-wide association studies (GWAS) identified 29 genomic regions involved in regulation of IgG glycosylation, but only a few were functionally validated. One of the key functional features of IgG glycosylation is the addition of galactose (galactosylation), a trait which was shown to be associated with ageing. We performed GWAS of IgG galactosylation (N=13,705) and identified 16 significantly associated loci, indicating that IgG galactosylation is regulated by a complex network of genes that extends beyond the galactosyltransferase enzyme that adds galactose to IgG glycans. Gene prioritization identified 37 candidate genes. Using a recently developed CRISPR/dCas9 system we manipulated gene expression of candidate genes in the in vitro IgG expression system. Upregulation of three genes, EEF1A1, MANBA and TNFRSF13B, changed the IgG glycome composition, which confirmed that these three genes are involved in IgG galactosylation in this in vitro expression system.

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Keywords - aging, genome-wide association study, glycosylation, glycan clock, immunoglobulin G, CRISPR/dCas9

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Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

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