Splicing factor 3B1 hypomethylation is associated with altered SF3B1 transcript expression in older humans

Area of Science:

• Molecular Biology
• Genetics
• Aging Research

Background:

• Aging is associated with alterations in splicing factor pools.
• The Ataxia Telangiectasia Mutated (ATM) gene regulates some age-related splicing factors.
• Mechanisms controlling other age-associated splicing factor changes remain unclear.

Purpose of the Study:

• To investigate age-associated DNA methylation and expression levels of 27 splicing factor genes.
• To determine the role of DNA methylation in regulating splicing factors during aging.
• To examine splicing patterns in relation to age-associated molecular changes.

Main Methods:

• Analysis of DNA methylation and gene expression in peripheral blood samples from the InCHIANTI cohort.
• Assessment of splicing patterns in a second cohort (Exeter 10000 study).
• Correlation analysis between methylation, expression, and splicing patterns.

Main Results:

• Age-associated methylation changes were observed in 17 out of 27 splicing factor genes.
• Most methylation changes did not correlate with transcript expression or splicing patterns.
• Hypomethylation of the SF3B1 promoter significantly mediated the relationship between age and SF3B1 expression.

Conclusions:

• DNA methylation plays a limited role in the age-associated regulation of most splicing factors.
• SF3B1 expression changes in aging may be attributed to promoter hypomethylation.
• Altered SF3B1 expression could contribute to age-related dysregulation of mRNA splicing.