How Do Cells Age?
Ask five biologists for a mechanism of cellular aging, and you’ll get five different answers. Numerous cellular processes have been implicated in the aging process, proposed as both causative and collateral factors. Telomere shortening, failure of DNA repair machinery, downregulation of tissue-specific enzymes, and more have all been studied in the aging process.
What about transcription? Surprisingly, studying the effects of aging on transcription has been less of a focus, in spite of transcription being the central regulatory process for gene expression. In an article published yesterday in Nature, a research group from the University of Cologne in Germany studied the effects of transcription on aging across five different animals. Their findings were remarkably consistent across humans, fruit flies, rats, mice, and worms, suggesting a universality of the mechanisms they discovered.
The Role of RNA Polymerase II
The authors’ first observation when studying genome-wide changes to transcription with age was an increase in the speed of transcription with age, specifically an increase in the speed of the RNA polymerase II enzyme (RNA pol II). However, as the speed of RNA pol II increased, it became less accurate and more error-prone across all five groups, as measured by the incidence of mutations compared to reference genomes.
Is this change in the rate of RNA pol II related to lifespan? The authors measured the lifespan of fruit flies and worms with mutations that slowed down RNA pol II and found that the animals lived between 10 and 20% longer than non-mutated animals. When the researchers used gene editing in worms to reverse the mutation and speed the enzyme up again, the lifespan shortened, establishing a convincing link.
Histone Expression Decreases with Age
What could be driving this increase in RNA pol II speed? The authors found that in aging human lung cells and human umbilical vein cells, there were fewer nucleosomes, the structures of tightly compacted DNA and histones that allows DNA to be packaged in the cell and moderates its accessibility to enzymes like RNA pol II. When the authors increased the expression of histones in the cells, RNA pol II moved more slowly, and when repeated in fruit flies, seemed to extend their lifespan.
The potential applications of this research are immediately apparent in designing therapeutic strategies to mitigate some of the effects of cellular aging. The authors found that changes in diet and insulin signaling affected the rate of RNA pol II. This study also opens up avenues for targeting RNA pol II in conditions of accelerated aging, or even in cancer.
Outsourcing Bioinformatics Analysis: How Bridge Informatics Can Help
Groundbreaking studies like these are made possible by technologies like RNA-seq, and advances that have made whole genome sequencing, sample processing, and data analysis faster, cheaper, and more accessible than ever before. From pipeline development and software engineering to deploying existing bioinformatics tools, Bridge Informatics can help you on every step of your research journey.
As experts across data types from leading sequencing platforms, we can help you tackle the challenging computational tasks of storing, analyzing, and interpreting genomic and transcriptomic data. Bridge Informatics’ bioinformaticians are trained bench biologists, so they understand the biological questions driving your computational analysis. Click here to schedule a free introductory call with a member of our team.
Jane Cook, Biochemist & Content Writer, Bridge Informatics
Jane Cook, the leading Content Writer for Bridge Informatics, has written over 100 articles on the latest topics and trends for the bioinformatics community. Jane’s broad and deep interdisciplinary molecular biology experience spans developing biochemistry assays to genomics. Prior to joining Bridge, Jane held research assistant roles in biochemistry research labs across a variety of therapeutic areas.
While obtaining her B.A. in Biochemistry from Trinity College in Dublin, Ireland, Jane also studied journalism at New York University’s Arthur L. Carter Journalism Institute. As a native Texan, she embraces any challenge that comes her way. Jane hails from Dallas but returns to Ireland any and every chance she gets. If you’re interested in reaching out, please email [email protected] or [email protected].