Key players in brain aging: New research identifies age-related damage on a cellular level

 


Scientists at the Allen Institute have identified specific cell types in the brain of mice that undergo major changes as they age, along with a specific hot spot where many of those changes occur. The discoveries, published in the journal Nature, could pave the way for future therapies to slow or manage the aging process in the brain.


The scientists discovered dozens of specific cell types, mostly , known as brain support cells, that underwent significant gene expression changes with age. Those strongly affected included microglia and border-associated macrophages, oligodendrocytes, tanycytes, and ependymal cells.

They found that in aging brains, genes associated with inflammation increased in activity while those related to neuronal structure and function decreased.

They also discovered a specific hot spot combining both the decrease in neuronal function and the increase in inflammation in the hypothalamus. The most significant gene expression changes were found in cell types near the third ventricle of the hypothalamus, including tanycytes, ependymal cells, and neurons known for their role in food intake, energy homeostasis, metabolism, and how our bodies use nutrients.

This points to a possible connection between diet, lifestyle factors, brain aging, and changes that can influence our susceptibility to age-related brain disorders.

"Our hypothesis is that those cell types are getting less efficient at integrating signals from our environment or from things that we're consuming," said Kelly Jin, Ph.D., a scientist at the Allen Institute for Brain Science and lead author of the study. "And that loss of efficiency somehow contributes to what we know as aging in the rest of our body. I think that's pretty amazing, and I think it's remarkable that we're able to find those very specific changes with the methods that we're using."

To conduct the study, researchers used cutting-edge single-cell RNA sequencing and advanced brain-mapping tools developed through NIH's BRAIN Initiative to map over 1.2 million brain cells from young (2 months old) and aged (18 months old) mice across 16 broad brain regions. The aged mice are what scientists consider to be the equivalent of a late middle-aged human. Mouse brains share many similarities with human brains in terms of structure, function, genes, and cell types.

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