Is RNA Splicing Linked To Aging?

Getting your Trinity Audio player ready...

A phenomenon called RNA splicing allows one sequence of DNA to code for multiple different proteins. Research on C. elegans has revealed that deregulation of this process may contribute to the aging process

In order to make the abundant variety of proteins that exists in our bodies, DNA is translated into RNA in sequences which are meshed together to form proteins. Each gene can be spliced together in a number of different ways – allowing one sequence to produce multiple different results. This not only allows for fine tuning of cellular responses, but also massively increases structural variety in the protein world. 

“What kills neurons in Alzheimer’s is certainly different from what causes cardiovascular disease, but the shared underlying risk factor for these illnesses is really age itself. So one of the big questions is: Is there a unifying theme that unfolds molecularly within various organ systems and allows these diseases to take hold?”

Looking to the roundworm In a new study using the common model organism, the roundworm C. elegans, scientists used fluorescent tagging to visualise gene splicing in real time. In 5 days a distinct variety in the population emerged, with some displaying signs of altered splicing and some sticking to youthful patterns. C. elegans typically lives a maximum of 3 weeks. Interestingly, this changed splicing behaviour corresponded with premature aging onset and even emerged as a good way of predicting lifespan. 

“This is a really interesting result, and suggests that we might someday be able to use splicing as a kind of biomarker or early signature of aging”

When the researchers put a group of worms through dietary restriction, which is known to extend C. elegans healthspan and lifespan, they found a youthful RNA splicing pattern stuck around for longer; indicating that RNA splicing may either be a good biomarker of the aging process, or perhaps involved in some way in the growing dysregulation that aging brings with it. On closer observation they discovered that splicing factor 1 (SFA-1), an important protein also present in humans, appeared to play a longevity enhancing effect in the worms. Increasing levels of this protein is actually able to increase lifespan. 

“These are fascinating results, and suggest that variability in RNA splicing might be one of the smoking guns of the aging process. Of course, we have much more to learn, but this study opens up an entirely new avenue of investigation that could help us understand how to not only live longer, but also healthier”

Read more at MedicalXpress