Brain cells reveal their past in chemical marks on DNA
Reading those lasting marks, plus how DNA is folded, showed aging microglia being replaced by more inflammatory outsiders.
Science Daily · Scientists discover a hidden brain shift that begins around age 50Researchers studying postmortem tissue from the hippocampus, a brain region tied to learning and memory, examined samples from 40 neurologically healthy adults ages 20 to 95. They found that microglia, the brain's resident immune cells, slowly become scarcer starting around age 50 and continuing to 75, while other immune cells that act more inflamed and resemble cells from blood outside the brain appear to become more common.
The pattern matters because microglia first form before birth, and scientists had long assumed they stayed in the brain and renewed themselves there for life. The new result suggests that, in the hippocampus, resident microglia decline and cells resembling blood-derived immune cells appear in their place.
The team could see the difference because it did not rely only on gene activity, the readout of which genes a cell has switched on. It also mapped the epigenome, chemical tags on DNA that help control genes, and the three dimensional folding of DNA inside cells, which helps decide which genes are within reach.
"Gene expression tells us what a cell is doing today, but epigenetic signatures preserve information about where a cell came from," said first author Nathan Zemke, who directs single-cell genomics work at UC San Diego's Center for Epigenomics.
The next studies are planned to look into why the resident microglia disappear with age and whether that change contributes to Alzheimer's disease. Judging cells only by what they are doing today can miss where they came from.
Questions people ask
What exactly is gene expression?
Gene expression means which genes a cell is actively using to make proteins at a given moment. Every cell carries nearly the same DNA, but different cell types turn different genes on or off. That is why measuring gene activity shows what a cell is doing right now, but not necessarily where it came from.
How can chemical marks on DNA remember a cell's past?
As cells develop and specialize, enzymes add or remove small chemical tags on DNA and on the proteins around it. Many of those tags are copied when a cell divides, so daughter cells inherit the pattern. Scientists can read those patterns to trace a cell's lineage, even after its current behavior has changed.
Why does the 3D folding of DNA matter?
Human DNA is about six feet long if stretched out, so it must be tightly folded to fit inside a cell nucleus. How it folds determines which genes are exposed and can be switched on. Mapping that folding helps researchers understand cell identity, because different cell types fold their DNA in characteristic ways.