Stress Turns Microglia Into Two Different Kinds of Old People ✎ bioRxiv

In the brain of an elderly person there are cells whose job is to clear out the trash and protect neurons. But with age they become a source of trouble themselves: they stop dividing and start constantly releasing inflammatory molecules. It's a bit like two old men who arrive at the same nursing home by different roads. One ends up there after an accident that wrecked his body, the other after long years of overeating sweets. Both wind up in the same place, but they look and behave differently.

Scientists took human immune cells from the brain and subjected them to two kinds of stress. The first was DNA damage, as if the cell had been hit by radiation or a toxic drug. The second was excess glucose, as if the cell had been forced to live in sugar syrup. Both stresses made the cells enlarge, stop dividing and begin releasing inflammatory substances. But past that point the paths diverged.

The difference also shows up in the cell's power plants, the mitochondria. Under DNA damage their number fell, while under excess glucose it rose, but to no avail: the cell couldn't use that energy efficiently. In both cases the cells didn't die; they stayed alive in a damaged state. That explains why dysfunctional immune cells accumulate in the brains of elderly people.

Back to the image of the two old men: now it's clear that in the nursing home they aren't just different people, they are people with different medical histories. One needs treatment for the aftermath of an injury, the other for the aftermath of diabetes. The same goes for cells: therapy has to take into account which particular stress drove them into aging. For now scientists are only feeling out these differences, but the road is already in sight.