Singularity reports on a new study charting the pathway that stress takes from brain to your body — literally going into the center of your bones:
A new study offers one of clearest answers yet. In mice modeling chronic stress, activity dropped in two brain regions governing emotional resilience. By way of a large nerve to the digestive track, the change wiped out a beneficial bacterial strain key to a healthy microbiome.
Without those microbes, the gut produced less of a crucial molecule that helps cells clear damaged proteins and other molecular junk. These effects impacted the bone marrow, where stem cells generate oxygen-carrying blood cells and components of the immune system. Over time, these stem cells dwindled, leaving signs of premature immune aging in stressed mice.
“One surprising finding of our study was that suppression of only two specific brain regions was sufficient to produce many of the hematopoietic [blood stem cell] defects caused by psychological stress,” study author Linjia Jiang at Sun Yat-sen University said in a press release.
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To trace how chronic stress ages the body, the team tested four mouse models. Some experienced mild nerve injury. Others faced subtle disruptions to their daily routines, such as lights switching on earlier than expected or their home cages gently rocking at unpredictable times.
The changes put the mice on edge based on established behavioral tests. Mapping brain activity, the team zeroed in on two regions that consistently quieted. One, the medial prefrontal cortex, orchestrates executive control, or the ability to keep ideas in mind while reaching towards a goal. The other, the periaqueductal grey, coordinates attention to potential threats.
As activity decreased in both regions, blood stem cells struggled to divide and replenish immune cells. Inflammation and other toxic pathways flared up, and the cells developed molecular signatures similar to those seen in much older animals. Silencing either brain region with genetic tools reproduced many of the same symptoms, suggesting neural changes are a cause, not just a correlation.
But how was the brain communicating with the bone marrow? The answer lay in the gut microbiome.
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Spermidine levels plummeted in stressed mice due to the loss of Lactobacillus reuteri, a beneficial strain of bacteria in the gut ecosystem that supports spermidine production. Stress-related nerve signals from the brain depleted these microbes, which caused spermidine levels to collapse and leaves blood stem cells unable to maintain themselves.
In another test, transplanting gut microbes from a stressed mouse into a happy-go-lucky mouse triggered early blood stem cell aging in the recipient—even though it didn’t experience stress itself.