August 31st, 2026
One might think that an alteration to the machinery of gene expression that systemically changes the amino acid components of proteins, in effect giving all proteins the possibility of multiple single nucleotide polymorphisms, would be quite harmful. But some forms of mistranslation of RNA into protein actually extend life span, as demonstrated in flies. The reason why this happens is unknown at the present time. It is suspected that this is a hormetic effect of some sort, mistranslation triggering stress responses that clean up the cell for an overall benefit. The evidence presented here argues against a meaningful role for stress and stress response in mistranslation induced longevity, however.
Accurate translation of genes into proteins is critical to organism fitness, and errors in this process are usually detrimental and cause proteotoxic stress. Mistranslation occurs when the amino acid that is incorporated into the nascent polypeptide chain does not match what is dictated by the genetic code. Valine-to-serine (V→S) and threonine-to-serine (T→S) mistranslating models of the fruit fly Drosophila melanogaster have demonstrated a surprising, sex-specific increase in virgin female longevity. We predict that the added stressor of reproduction would eliminate this mistranslation-induced lifespan increase since females prioritize reproductive tissues over somatic tissues, and proteotoxic stress would therefore lead to higher protein damage and cell death in the somatic tissues of mated females.
