Recent research has found that Caenorhabditis elegans can grow old faster due to imbalances in RNA communication, which can also reduce the organism's lifespan.
Cells in multiple tissues communicate using RNA molecules to share them. Researchers from the State University of Campinas (UNICAMP) in Brazil have recently conducted a study that has been published in Gene. They discovered that disruptions in this communication method can lead to a reduced lifespan.
Research conducted earlier indicated that RNA transfer from one cell to another can facilitate intertissue communication, similar to proteins and metabolites, which are now considered essential for disease diagnosis and normal functioning. However, it was not immediately clear that changes in this pattern between RNA molecules could affect aging, as Marcelo Mori has discovered.
FAPESP has granted a grant to OCRC, an RIDC, and Mori is the principal investigator for the research, which was conducted at the OCRC.
To ensure a suitable lifespan, the communication channel must be well-adapted. Mori stated that the study revealed that if certain RNAs are more readily absorbed by tissue from the extracellular environment, it can have an impact on the organism's lifespan.
The study revealed that the decrease in lifespan was caused by both the disruption of RNA-based communication between tissues in the same organism and an increase in the ability of the environment, including microbiota bacteria.
Mori mentioned that the discovery of RNA interference, which led Andrew Fire and Craig Mello to win the 2006 Nobel Prize in Physiology and Medicine, motivated him to investigate the intercellular RNA transport mechanism. They injected double-stranded RNA into C. elegans to "silence" genes with great precision, and the silencing mechanism was found to have an effect on genes in other tissues and was passed on to subsequent generations.
This "interference" elucidates the mechanisms by which RNA is carried to another cell in the organism, or between the organism and the environment; it also relativizes the "presence" of molecular biology that information contained within the genetic code (back in the 1950s, for instance) was assumed to flow only from DNA to RNA and then through proteins; Fire and Craig found that double-spaced RNA "intercepts RNA, which then act as a bridge between information transporters and proteins, and ultimately silence all genes in the human genome, showing that messenger
We searched for clues as to how the process of aging compromising key physiological functions (such as RNA interference defective (SID) genes) plays a role in RNA transfer between cells in C. elegans, and in particular tissues showed an altered gene expression pattern as the organism reputation and absorption of RNA changed, Mori said.
The researchers conducted experiments aimed at examining the function of SID-1 protein in certain tissues of C. elegans, including neurons, intestinal and muscle cells, using RNA manipulation to gain insight into its intertissue signaling contribution.
Despite the fact that mutants lacking SID-1 were found to be as healthy as wild-type worms, overexpression of SID-1 in the gut, muscles, or neurons resulted in a shorter lifespan.
Dysregulation of RNA distribution to tissues may be the reason. "We increased SID-1 expression in certain tissues and found that channeling it to a specific organ could decrease RNA distribution in worms and potentially decrease lifespan," he explained.
The pathway that produces microRNAs suffered from loss of function due to an imbalance in RNA transfer, leading to a competition among different groups. Previous research had shown that this was the reason behind the decrease in lifespan due to loss of function in microRNA production.
Exogenous RNA transfer between an organism's external environment and its own internal environment was studied by the UNICAMP group. As previously shown, a reduction in lifespan is linked to overexpression of SID-2, which mediates RNA uptake from the gut and to excessive RNA production by bacteria that feed on worms, which ultimately binds to its gut microbiota.
According to Mori, worms may rely on exogenous RNA to track microorganisms in their environment, but if too much is absorbed by their tissue, it may have detrimental effects. Compressing bacterial RNA was shown to decrease worm lifespan because it disrupts homeostasis and accelerates aging by increasing exogenous RNA transfer.
The authors of a study on 2023 using Gene. DOI: 10.1016/j.gene.2023.148014 suggest that C. elegans' lifespan may be reduced due to tissue-specific overexpression of systemic RNA interference components.
Funding for the study came from the So Paulo Research Foundation.