Splicing ourselves to a longer life
As we age, we move more slowly and think less clearly. This slow decline stems from reduced efficiency and precision in our cells. Today, research collaboration between the United States and Denmark reveals that the ageing process can be slowed by ensuring that the splicing within cells functions optimally. The results have just been published in Nature.
Researchers from Harvard University and the University of Southern Denmark investigated the ageing process in the 1-mm-long roundworm Caenorhabditis elegans, which is often used as a model organism for humans. This research examined whether influencing the natural metabolism of C. elegans could affect its longevity.
One essential part of cellular metabolism is the splicing process that occurs when genes synthesize proteins through gene expression. During this process, the genes transcribe into messenger RNA (mRNA) molecules that serve as a template for protein synthesis. However, the splicing must be totally accurate for the mRNA template to be correct. The research suggests that this process becomes less precise as people get older.
The researchers began by restricting the food intake of C. elegans, which significantly prolongs their life according to other studies. However, when the researchers removed splicing factor 1 (SFA-1), longevity fell to normal. Conversely, on an unrestricted diet, life expectancy increased when the splicing factor was overexpressed.
This research is especially significant because many of the genes of C. elegans are similar to those of humans and can actually be replaced by human genes. Experiments using C. elegans thereby normally simulate human metabolism well, and the splicing factors can therefore be expected to be equally significant for the human ageing process.
Today, inefficient splicing can be corrected by inserting small fragments of modified RNA into cells (splice-switching oligonucleotides), and the Danish research group is working on many projects to use these to correct the poor functioning of the splicing process. This new study may also suggest new candidate genes for this type of therapy.
“Splicing factor 1 modulates dietary restriction and TORC1 pathway longevity in C. elegans” was published in Nature. The Novo Nordisk Foundation awarded Brage Storstein Andresen of the University of Southern Denmark a grant for the project Pseudoexon Activation: an Underreported Disease Mechanism with a Unique Potential for Targeted Intervention.