New research published in the journal Aging cell highlights the potential of exercise to prevent or slow cognitive decline associated with aging. This study found that exercise can significantly change the gene expression of aged microglia, a type of brain cell, returning them to a more youthful state.
As people age, their physical health and cognitive abilities often decline. This decline can lead to conditions such as dementia, for which there are currently few effective treatments.
Previous observational studies have suggested that exercise may help alleviate some age-related brain deficits, but the exact mechanisms behind these benefits were not well understood. The researchers aimed to explore how exercise affects the brain at the 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, but to date it is not known how it exercise orchestrates these changes. It would be surprising to discover the key components of exercise that induce beneficial effects on the brain and its functions,” said study author Jana Vukovic, associate professor at the University of Queensland.
The researchers conducted their study in 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) and old (18 months). The mice were divided into two groups: those with access to a wheel (exercise group) and those without (sedentary group). The exercise program consisted of 21 days of voluntary running on wheels followed by a 14-day rest period.
To study the effects of exercise on the brain, researchers used a technique called single-cell RNA sequencing. This method allows gene expression to be analyzed in individual cells, providing a detailed view of cellular activity. The researchers specifically studied the hippocampus, a brain region critical to 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 may contribute to cognitive decline. In this study, aged sedentary mice exhibited a gene expression profile in their microglia indicative of this harmful aging state. These microglia showed increased expression of inflammatory genes, consistent with an increased 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 of microglia, restoring their gene expression to a more youthful, anti-inflammatory state.
Another important 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. Researchers have discovered that aging naturally causes a buildup of T cells in the brain.
However, exercise significantly reduced the number of T cells in aged mice. This reduction was observed not only 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.
“Of all the different cell types in the brain, it was surprising that it was immune cells that responded the most to exercise,” Vukovic told PsyPost. “It was also surprising to see the dramatic effect of exercise on the T cell population in the brain. T cells are not normally present in the adult brain, but with aging their numbers appear to increase. Exercise led to a drop in T-cell counts.”
Although the most dramatic effects of exercise were seen 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, although these changes were less pronounced than those observed in microglia.
Astrocytes, which support neuronal function and health, and oligodendrocytes, which produce the myelin sheath that insulates nerve fibers, both showed signs of improving function and reducing inflammation in mice elderly people who were exercising. This suggests that exercise has a broad beneficial effect on various types of brain cells, contributing to overall brain health.
The cognitive benefits of exercise have been demonstrated by a behavioral test known as the active location avoidance task, which measures spatial learning and memory. Aged mice with access to a wheel performed significantly better in 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 cellular and molecular changes observed, including rejuvenation of microglia and reduction of brain inflammation.
“Our study provides additional evidence and demonstrates that exercise changes the brain at the cellular level,” Vukovic said. “Exercise shifts the immune landscape of the aging brain to a more youthful state and these changes are associated with improved learning and memory.”
The study offers promising evidence that exercise can counteract age-related brain changes, including by rejuvenating microglia. The findings contribute to our understanding of how physical activity can benefit cognitive health and open new avenues for developing interventions to prevent or slow cognitive decline during aging.
“One of the goals is to encourage older people to exercise, because we have demonstrated that it is possible to reverse some of the negative aspects of aging on the brain and thus improve cognitive performance” , said Vukovic. “The other long-term goal is to find ways and treatments to help bring out the beneficial aspect of exercise on the brain in individuals who are unable to exercise or are bedridden.”
The study, “Exercise rejuvenates microglia and reverses T cell accumulation in the brains of aged female mice,” was authored by Solal Chauquet, Emily F. Willis, Laura Grice, Samuel BR Harley, Joseph E. Powell, Naomi R. Wray, Quan Nguyen. , Marc J. Ruitenberg, Sonia Shah and Jana Vukovic.