A neuron is like a city preparing for a long siege. First it reinforces the walls and stockpiles food, but meanwhile the archives where the blueprints are kept start falling into disarray. Scientists saw this in Drosophila flies whose nerve cells had the ERO1L gene switched on. This enzyme helps proteins fold, but along the way it generates extra oxidants.
On day 5 after hatching, the flies still moved normally, and there was no oxidative stress. But inside the cells a restructuring was already underway: stress-defense proteins increased, while the proteins that keep DNA in order decreased. DNA packaging became less dense, and some mobile regions of the genome switched on. The city reinforced its walls, but the librarians walked out, and the books began to be reshuffled by random hands.
Previously, scientists saw only the finale: damaged neurons and a sick fly. Now they have managed to catch the moment when the cell is still coping but is already losing order in its archives. For now this is just knowledge, but it could help find ways to slow brain aging at its very earliest stage.
In flies with elevated ERO1L only in their neurons, lifespan was cut in half: from 49.5 to 24 days. Yet the same enzyme in muscles or fat body had no effect on survival, and in glia the effect was weak.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.