Aging is a gradual, irreversible, and physiological process. It results in a decline in cellular function greatly increasing the risk of age-related diseases. These include cardiovascular diseases, neurodegenerative diseases, and muscle diseases. You have seen aging from a different perspective in a previous blog post. Research has been done globally to study the mechanism of aging at a molecular level. Among the different causes of endogenous and exogenous stress, is an altered intercellular communication. Let’s have a look at one such study. Here, the miscommunication between RNA molecules of cells greatly enhances the chance of aging.
Work at UNICAMP
Cells from different tissues communicate with each other by exchanging RNA molecules. Researchers at the State University of Campinas (UNICAMP), Brazil experimented this on C.elegans and the results were surprising. According to them, stopping the communication between the cells ( if they are dysregulated) reduces the life span of C.Elegans. This work was published in the Journal of Gene. This study helps us understand the process of aging and its associated diseases better.
What information did we previously possess?
It was previously shown that just like proteins and metabolites, RNA molecules were exchanged between cells of different tissues. This acts as a means of communication. It is a signaling mechanism responsible for communication between organs. This mechanism is crucial for human health and malfunctioning of this mechanism manifests itself as age-related diseases.
What did they just uncover?
While we knew that RNA molecules are exchanged between cells as a means of communication, what we did not know is that disturbing this communication could affect aging. This communication is very crucial in maintaining the lifespan of a person. If a particular tissue gets an increased capacity to absorb a specific type of RNA molecule from the extracellular medium, it could significantly impact the lifespan of that person. So, it is not just a disturbance in the communication between cells of a given molecule but also the enhanced absorption of these molecules from the environment. This especially happens in bacteria.
The phenomenon of imbalance in miscommunication is known as Intercellular/Extracellular Systemic RNA imbalance (InExS), as termed by the researchers of this team.
What served as the inspiration for this project?
The research on intracellular RNA transport was inspired by RNA interference. This Nobel prize-winning technique was developed by two American scientists Andrew Fire and Craig Mello in 2006. In this technique, they injected double- stranded RNA into their model organism: C.elegans to precisely silence genes. What they also found was that the silencing affected other tissues and it was also passed on to the next generation. This paved the way for studying the mechanism of RNA transfer between cells of organisms as well as between the organism and the environment.
RNA plays a regulatory role
During an RNA interference, the mRNA of an organism is destroyed and hence the gene is silenced without altering the DNA sequence. This shows they can also play a regulatory function in our cells.
Work on C.elegans
As mentioned before, the above work was done on the model organism C.elegans. The team wanted to check how RNA communication can affect physiological processes specifically aging. C.elegans has specific genes for RNA transfer between cells. They are the systemic RNA interference defective (SID) gene.
A specific pattern of gene expression of SID was observed and this pathway changed in certain tissues during aging. A messenger RNA encodes the protein SID-1 (necessary for RNA’s absorption) increased in some tissues while decreased in others.
Upon manipulating the protein expression of SID1 in specific tissues like neuronal, intestinal, and muscle cells, they found that over-expression of SID1 shortened their lifespans. This does not just include SID-1, but also other proteins involved in the transport including SID-2 and SID-5. They have noticed that an imbalance in RNA transfer resulted in an inability to produce miRNA. This eventually leads to a reduction in lifespan.
Conclusion
Excessive RNA transfer interferes with homeostasis and RNA production. This enhances the rate of aging in the organism. The findings of this study give us a better understanding of aging and its associated diseases.
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