Andersson, K. | bioRxiv Science

bioRxiv2026

Neurostructural and molecular evidence of advanced brain aging in rheumatoid arthritis

Chronic systemic inflammation has been implicated in age-related neurodegeneration, but whether rheumatoid arthritis (RA) is associated with accelerated brain aging remains unclear. We combined structural magnetic resonance imaging (MRI), circulating neurodegeneration biomarkers, and peripheral monocyte transcriptomics to investigate brain aging in RA across two independent cohorts. A brain-age prediction model trained in healthy controls from the IXI imaging dataset was applied to RA patient cohorts from Gothenburg (n = 71) and Glasgow (n = 50). RA was associated with significantly elevated corrected brain-age gap relative to healthy controls (+6.5 years, 95% CI 4.2-8.8 years, p = 1.2 x 10-7), with substantially stronger effects in patients [≥]60 years. Older RA patients demonstrated a significant ventricular enlargement together with reduced frontal and parietal lobe volumes. Serum brain-derived tau and glial fibrillary acidic protein levels were elevated in RA. The increased brain-age gap was associated with altered myeloid transcriptional signatures. These findings demonstrate that RA is associated with age-related neurostructural alterations consistent with accelerated brain aging.

neuroscience↗

bioRxiv2022

Survivin prevents the Polycomb Repressor Complex 2 from methylating Histone 3 lysine 27

Survivin is a small protein that belongs to the inhibitor of apoptosis protein family and participates in cell division and apoptosis. It was actively studied in human cancers, inflammatory diseases and in autoimmune diseases. Here, we reveal that survivin takes part in epigenetic gene silencing by interaction with the polycomb repressive complex 2 (PRC2). PRC2 silences gene expression through tri-methylation of lysine 27 on histone 3 (H3K27). We detected differential expression of PRC2 core subunits in CD4+T cells with different survivin expression. ChIP-seq experiments indicated that survivin binds chromatin that overlap with the regions occupied by PRC2. ChIP-seq of H3K27 in CD4+T cells indicate that inhibition of survivin leads to a substantial increase in H3K27 tri-methylation by PRC2 in contrast to other histone modifications, which lends support to that survivin prevents PRC2 from functioning. Survivin binds peptides derived from PRC2 subunits EZH2, EED, SUZ12 and JARID2 in a peptide microarray that cover intersubunit interfaces, catalytic residues, and present binding sites for substrates, DNA, and regulatory proteins. Amino acid composition of the peptides has substantial predictive power for survivin interaction in the peptide microarray as determined by multilayer perceptron classification analysis. NMR experiments with 15N labelled survivin indicate that peptide colocalization does not entirely depend on binding mediated by short range interactions. These results indicate that survivin interacts with PRC2, preventing the methylation of H3K27 and specific gene silencing. This has transcriptional consequences and specific gene silencing.

molecular biology↗