It is not always the case that genetic alterations that shorten life span are interesting. There are many ways to disrupt a complex system, and only some of those disruptions are relevant to aging. Researchers are exploring the transfer of RNA between cells in nematode worms, showing that excessive RNA uptake can lead to a reduced life span. However, this may only be relevant to aging if these regulatory processes become maladaptively changed later in life. Otherwise, it is just another way to disrupt the complex regulatory systems of a living organism.
Intertissue RNA transport has recently been identified as a novel signaling mechanism. In mammals, there is growing evidence that small RNA transfer between cells is widespread and utilized in various physiological contexts. In the nematode C. elegans, a similar mechanism is facilitated by the systemic RNAi pathway. Members of the SID protein family are involved in different stages of cellular RNA uptake and export.
The key step in systemic RNA interference (RNAi) is the import of extracellular RNAs through the conserved double-stranded RNA (dsRNA)-gated channel SID-1. To understand the role of RNAs as intertissue signaling molecules, researchers modified the function of SID-1 in specific tissues of C. elegans. They found that overexpression of sid-1 in the worm’s intestine, muscle, or neurons resulted in a shortened life span. This reduction in lifespan was linked to systemic RNA signaling, as silencing components of the SID family attenuated the effects of overexpression. Further research on non-coding RNA pathways also supported the idea that disrupting systemic RNA signaling can lead to a decrease in lifespan.
