How the splicing process changes with age

The average number of expressed isoforms per gene in Homo sapiens, Mus musculus, Danio rerio and Nothobranchius furzeri for every studied tissue and time point (YM – young mature, M – mature,
A -aged, OA – old-age). No significant difference in the number of expressed isoforms per gene can be observed between different ages within each investigated species and tissue. In addition, the variance between the samples of each time point and tissue remains stable, except for the old-age brain and skin sample of Nothobranchius furzeri, showing a manifold increased variance. The lower amount of expressed isoforms in the two fish as compared to both mammals might be biased due to the less complete isoform annotation.

We are happy to announce that our study on alternative splicing during aging is now available as a preprint on bioRxiv. Alternative splicing is an important co- and post-transcriptional process in eukaryotes that enables altered forms (also referred to as isoforms) of mRNA molecules of a gene, leading to multiple mature transcripts of a single gene with possible different or modified encoded functionality. In this descriptive RNA-Seq study, we investigated if and how the isoform usage during aging changes among different tissues (blood, brain, liver, skin) within one species and compare changes of alternative splicing among four evolutionarily distinct species: human, mouse, zebrafish and killifish.

Missplicing of certain genes has already been linked to several age-associated diseases, such as progeria, Alzheimer’s disease, Parkinson’s disease and cancer. Nevertheless, many studies focus only on transcriptional variations of single genes or the expression changes of spliceosomal genes, coding for the proteins that aggregate to the spliceosomal machinery. Little is known on the general change of present and switching isoforms in different tissues over time.

Although we identified a multitude of differentially spliced genes among different time points, we observed little to no general changes in the transcriptomic landscape of the investigated samples. Although there is undoubtedly considerable influence of specifically spliced genes on certain age-associated processes, this study shows that alternative splicing remains stable for the majority of genes with aging.

Nevertheless, further studies based on single cell RNA-sequencing could give deeper insights in the diversity of the transcriptome during aging and its implication in biological processes. We are looking forward to get our hands on such data to unveil more connections between splicing and aging.

[bibtex file= key=Sieber:19]

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