The brain is like a city where every cell is a resident, and its fate depends on its neighbors. It used to be thought that the aging of each cell was its own private business: DNA damage accumulated, so the cell wore out on its own. But a new study shows that even a cell's ability to repair its DNA depends on who lives next door.
It turned out that neurons with low activity of DNA repair genes (such cells more often accumulate damage) are surrounded by immune cells and oligodendroglia, the cells that wrap neuronal processes in insulation. At the same time, vascular cells with high repair activity neighbor other vascular cells. That is, the same state of DNA repair has a different environment depending on the cell type. These patterns were reproduced in two independent analyses and were specific to individual brain regions.
This view could change intervention strategies: instead of targeting individual cells, it may be necessary to modulate entire cellular communities. But first we need to understand what signals cause immune cells to gather around neurons with low levels of DNA repair. Is this a protective response or a pathological process? Future studies with genetic manipulations will help test cause-and-effect relationships.
A city ages not one person at a time but block by block. And if we want to slow brain aging, perhaps we should look not at individual residents but at their neighbors.
MERFISH can simultaneously measure the expression of hundreds of genes in thousands of cells while preserving their exact location in the tissue. It's as if you could eavesdrop on the conversations of every resident of a city without evicting them from their homes.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.