New research published in the journal Aging Cell sheds light on the potential of exercise to prevent or slow down cognitive decline associated with aging. This study found that exercise can significantly alter the gene expression of aged microglia, a type of brain cell, reverting them to a more youthful state.
As people age, they often experience a decline in both physical health and cognitive abilities. This decline can lead to conditions like dementia, for which there are currently few effective treatments.
Previous observational studies have suggested that exercise can help alleviate some age-related deficits in the brain, but the exact mechanisms behind these benefits were not well understood. The researchers aimed to explore how exercise affects the brain at a cellular level, particularly focusing on microglia, to uncover potential therapeutic targets for cognitive decline.
“I have experienced myself and seen in others that regular exercise has many beneficial effects, including on brain health, however to this date it is unknown how exercise orchestrates these changes. It would be amazing to find out the key components of exercise that the mediate the beneficial effects on the brain and its function,” said study author Jana Vukovic, an associate professor at the University of Queensland.
The researchers conducted their study using mice, a common model for understanding human biology due to their genetic and physiological similarities. They used female mice from two age groups: young (3 months old) and aged (18 months old). The mice were divided into two groups: those with access to a running wheel (exercise group) and those without (sedentary group). The exercise regimen consisted of 21 days of voluntary wheel running followed by a 14-day rest period.
To study the effects of exercise on the brain, the researchers used a technique called single-cell RNA sequencing. This method allows for the analysis of gene expression in individual cells, providing a detailed view of cellular activity. The researchers specifically looked at the hippocampus, a brain region critical for learning and memory, to assess changes in various cell types, including microglia.
Microglia play a critical role in maintaining brain health by responding to injury and infection. However, as the brain ages, microglia tend to adopt a pro-inflammatory state, which can contribute to cognitive decline. In this study, aged sedentary mice exhibited a gene expression profile in their microglia indicative of this harmful, aged state. These microglia showed increased expression of inflammatory genes, which is consistent with a heightened immune response that can damage neurons and other brain cells.
Remarkably, when aged mice engaged in regular voluntary exercise, their microglia showed a gene expression profile similar to that of young mice. This indicates that exercise can effectively reverse the aging process in microglia, restoring their gene expression to a more youthful, anti-inflammatory state.
Another significant finding of the study was the effect of exercise on T cells in the brain. T cells are a type of immune cell that, when present in large numbers in the brain, can contribute to inflammation and cognitive decline. The researchers found that aging naturally leads to an accumulation of T cells in the brain.
However, exercise significantly reduced the number of T cells in aged mice. This reduction was not only observed in the brain but also in peripheral organs such as the liver, suggesting that exercise has a systemic anti-inflammatory effect that extends beyond the brain.
“Amongst all the different cell types in the brain, it was surprising that it was the immune cells that responded to exercise the most,” Vukovic told PsyPost. “It was also surprising to see the dramatic effect of exercise on the T-cell population in the brain. T-cell are not normally there in the adult brains, however with ageing their numbers appear to increase. Exercise resulted in T-cell numbers dropping.”
While the most dramatic effects of exercise were observed in microglia, the study also noted changes in other types of brain cells. Astrocytes, endothelial cells, and oligodendrocytes also showed altered gene expression profiles in response to exercise, though these changes were less pronounced than those seen in microglia.
Astrocytes, which support neuronal function and health, and oligodendrocytes, which produce the myelin sheath that insulates nerve fibers, both showed signs of improved function and reduced inflammation in exercising aged mice. This suggests that exercise has a broad beneficial effect on various cell types within the brain, contributing to overall brain health.
The cognitive benefits of exercise were demonstrated through a behavioral test known as the active place avoidance task, which measures spatial learning and memory. Aged mice that had access to a running wheel performed significantly better on this task than their sedentary counterparts, indicating that exercise can improve cognitive function even in an aging brain. This improvement in cognitive performance was likely linked to the observed cellular and molecular changes, particularly the rejuvenation of microglia and the reduction in brain inflammation.
“Our study provides further evidence and demonstrates that exercise changes the brain at the cellular level,” Vukovic said. “Exercise changes the immune landscape in the ageing brain to the more youthful state and these changes are associated with improvement in learning and memory.”
The study offers promising evidence that exercise can counteract age-related changes in the brain, particularly by rejuvenating microglia. The findings contribute to our understanding of how physical activity can benefit cognitive health and open up new avenues for developing interventions to prevent or slow cognitive decline during aging.
“One of the goals is it to encourage elderly to exercise as we have demonstrated that it is possible to reverse some of the negative aspect of ageing on the brain and thereby improve cognitive performance,” Vukovic said. “The other long-term goals is to find ways and treatments to help elicit the beneficial aspect of exercise on the brain in those individual that are unable to exercise or bed-bound.”
The study, “Exercise rejuvenates microglia and reverses T cell accumulation in the aged female mouse brain,” was authored by Solal Chauquet, Emily F. Willis, Laura Grice, Samuel B. R. Harley, Joseph E. Powell, Naomi R. Wray, Quan Nguyen, Marc J. Ruitenberg, Sonia Shah, and Jana Vukovic.