In the orchestra of the cell, every RNA has its own part. Some molecules deliver instructions from genes to ribosomes, while others help snip out the extra bits from those instructions. The conductor of this orchestra is a protein complex called Integrator. It gives the signal when it's time to stop making small RNAs. Scientists decided to see what would happen if the conductor got tired.
The experiment was done on the nematode Caenorhabditis elegans, a tiny worm that lives just three weeks and is therefore convenient for studying aging. The researchers switched off the genes for Integrator subunits in adult animals using RNA interference. Worms with INTS-11 turned off lived 20% longer than normal ones, moved better, and tolerated heat. The effect didn't depend on reproduction: even sterile worms, and those whose gene was switched off after the reproductive period, lived longer.
Then came the really interesting part. When the conductor stopped giving its final signal, small RNAs weren't finished on time. Fragments of instructions piled up in the cells. Trans-splicing suffered especially badly: this is the process in which a short leader fragment from a separate RNA is stitched onto the start of an mRNA. In the worm, 85% of all genes are processed this way. Without that seam, the instruction keeps an extra piece that gets in the way of reading it.
The cell took this chaos as a danger signal and launched a protective response. Small RNAs 22 nucleotides long entered the game: they find faulty instructions and destroy them. The templates for mitochondrial proteins came under attack. Mitochondria, the cell's power plants, began to work a little worse. And paradoxically, this worked in the worm's favor: mild mitochondrial dysfunction is a known longevity pathway that switches on cellular repair mechanisms.
When the scientists bred worms lacking these small RNAs, the lifespan extension from switching off INTS-11 disappeared. The health of these worms even got worse. So it was the small RNAs that were the key link between the conductor's breakdown and longevity. The orchestra that lost its conductor didn't just play more quietly: it rearranged itself and struck up a new, more careful tune.
In the worm C. elegans, about 85% of genes undergo trans-splicing, in which a short leader exon from a separate RNA is stitched onto the start of the mRNA. Humans have no such mechanism, so directly transferring the results to people is difficult.
The idea that mild damage to cellular systems can extend life echoes the concept of hormesis, played with in Kim Stanley Robinson's novel Aurora: there, the crew of a starship faces the consequences of artificially slowing aging by manipulating cellular stress pathways.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.