Shared circulation affected gene activity differently in brain immune cells from young and old mice

Shared circulation affected gene activity differently in brain immune cells from young and old mice

On August 28, Cell Reports published a reanalysis of single-cell data from the brains of male mice. The researchers examined how microglia, the brain’s immune cells, alter gene activity during normal aging and in animals that share circulation with a partner of a different age.

The authors used previously collected data from the cortex, hippocampus, cerebellum, and striatum. After quality control, 12 310 cells remained. For each cell, this analysis identifies which genes are active. The researchers could therefore compare the overall age-related shift with the response in each brain region.

The dataset included pairs of young and old mice whose circulatory systems had been surgically joined, a model known as heterochronic parabiosis. In 2022, Robert Palovics and colleagues produced a single-cell atlas of these pairs. Palovics was also part of the current research team. Pairs of mice of the same age served as surgical controls. The researchers therefore analyzed normal aging, young mice paired with old partners, and old mice paired with young partners as separate comparisons.

The authors identified eight microglial states, defined as groups of cells with different sets of active genes. Across six activated states, 75 genes changed similarly in at least five states. Forty of these 75 genes were part of the overall age-related shift in all four brain regions. This shared program appeared in every region, while each region also showed distinct changes.

In young mice paired with old partners, gene activity in the cerebellum and cortex changed in the same direction as during normal aging, although the changes were weaker. Under both conditions, the authors observed the largest number of changes in the cerebellum. In the cerebellum of old mice paired with young partners, 41 genes changed activity in the direction opposite to age-related changes. The corresponding numbers were 25 in both the cortex and hippocampus, and three in the striatum.