Researchers have made significant progress in understanding the intricate regulatory mechanisms behind the glycan clock of aging. Glycans, which are a crucial structural component of immunoglobulin G (IgG), play a major role in modulating its structure and function. However, the precise mechanisms that regulate this complex posttranslational modification have remained largely unknown.
Previous genome-wide association studies (GWAS) have identified 29 genomic regions that are involved in the regulation of IgG glycosylation. However, only a few of these regions have been functionally validated. One particularly important feature of IgG glycosylation is the addition of galactose, a process known as galactosylation, which has been associated with the aging process.
In a recent study, researchers conducted a GWAS of IgG galactosylation using a significantly larger sample size (N=13,705) compared to previous studies on IgG N-glycome. The study identified 16 loci that were significantly associated with IgG galactosylation. These findings suggest that the regulation of IgG galactosylation involves a complex network of genes that extends beyond the galactosyltransferase enzyme responsible for adding galactose to IgG glycans.
The researchers also prioritized 37 candidate genes based on in silico evidence suggesting their involvement in the IgG galactosylation process. To further investigate their roles, the researchers manipulated the expression of these candidate genes in an in vitro IgG expression system using a CRISPR/dCas9 system. The upregulation of three genes, namely EEF1A1, MANBA, and TNFRSF13B, resulted in noticeable changes in the composition of the IgG glycome. This confirmed the involvement of these three genes in IgG galactosylation in the in vitro expression system.
While this study provides valuable insights into the gene network underlying the regulation of IgG galactosylation, additional research is needed to fully understand the functional mechanisms behind the identified genes’ role in the aging process. Additionally, further investigation is required to uncover the complete network of gene interactions that regulate the intricate process of IgG glycosylation.
This research lays the groundwork for future studies aiming to determine the precise mechanisms by which glycans and IgG glycosylation impact the aging process. A better understanding of these mechanisms could potentially lead to the development of interventions or therapies that target the glycan clock of aging, offering the possibility of promoting healthier aging and preventing age-related diseases.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
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