Researchers at the Allen Institute have pinpointed distinct cell types in the mouse brain that undergo significant changes with age, along with a particular hotspot where many of these changes take place. These findings, published in Nature, could lead to future therapies aimed at slowing or managing the brain’s aging process.
The scientists identified numerous specific cell types, primarily glial cells, which are known as brain support cells, that experienced significant changes in gene expression as they aged. The cell types most notably affected included microglia, border-associated macrophages, oligodendrocytes, tanycytes, and ependymal cells.
They discovered that in aging brains, genes related to inflammation were more active, whereas those associated with neuronal structure and function were less active.
They also pinpointed a specific hotspot in the hypothalamus where a reduction in neuronal function coincides with an increase in inflammation. The most notable gene expression changes were found in cell types near the third ventricle of the hypothalamus, such as tanycytes, ependymal cells, and neurons that play key roles in regulating food intake, energy balance, metabolism, and nutrient utilization.
This suggests a potential link between diet, lifestyle factors, brain aging, and changes that may affect our vulnerability to age-related brain disorders.
“Our hypothesis is that these cell types are losing their ability to effectively process signals from both our environment and what we consume,” said Kelly Jin, Ph.D., a scientist at the Allen Institute for Brain Science and lead author of the study. “This decline in efficiency appears to play a role in the broader aging process we see in the body. I find that truly fascinating, and it’s remarkable that we’re able to identify such specific changes using our methods.”
Upcoming research on brain aging
Future research on brain aging will build on this study to develop new dietary and therapeutic strategies aimed at preserving brain health in old age, while also delving deeper into the complexities of aging in the brain. As scientists investigate these links further, their findings could lead to more precise dietary or drug interventions to slow or mitigate cellular aging.
“Our study’s key contribution is identifying the main players and the biological mechanisms behind this process,” said Zeng. “When piecing this puzzle together, it’s vital to focus on the right elements. This is a perfect example of why it’s crucial to study the brain and body at the cell type-specific level otherwise, changes in specific cell types could be overlooked if different cells are combined.”
