In the orchestra of an aging brain, the instruments go out of tune one after another. The vessels that deliver oxygen thin out. The insulation around nerve fibers, like the sheathing on old wires, loses its density. The workshop for making new neurons, tucked away in the hippocampus, slows its assembly line. The conductor of this orchestra, it turns out, sits not in the head but in the belly.
Once the microbial choir fell silent, the old animals' brains began to sound cleaner. Vessel density increased in the cortex, and the tight-junction protein claudin-5 reinforced the filter between blood and brain. New oligodendrocytes appeared in the corpus callosum, rewrapping nerve fibers in myelin. In the dentate gyrus of the hippocampus, stem cells woke up and produced new neurons. The brain's immune cells, the microglia, calmed down: the area of their activation and the phagocytosis marker CD68 both shrank.
Mice that received the eotaxin-1 blockade were less anxious in the open field and remembered new objects better. This means the signal from gut to brain travels through the blood, not through nerves, and that a single protein can conduct an entire orchestra of cellular changes.
It was previously unclear whether stripping the microbiome from an old animal could reverse several hallmarks of brain aging at once, and which molecules do the work. Now it is clear: it can, and the key mediator has been found. Blocking eotaxin-1 or modulating the microbiome could become the basis for treating age-related memory decline and, possibly, the early stages of neurodegeneration. What remains is to find out which bacteria trigger production of this protein, and whether the same effect can be achieved with diet or probiotics, without resorting to antibiotics.
Eotaxin-1 was first tied to brain aging in 2011, when its blood level correlated with memory decline in people, and giving the protein to young mice impaired their neurogenesis. Now it turns out its source may be not only the brain but also the gut, where eosinophils accumulate with age.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.