Thursday, January 02, 2025

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

Good news! Closing in on the fountain of youth!

"Largest study on brain aging points to possible connections between diet, inflammation, and brain health.

Scientists ... 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. ...

Aging hot spot: Scientists 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.  ..."

From the abstract:
"Biological ageing can be defined as a gradual loss of homeostasis across various aspects of molecular and cellular function. Mammalian brains consist of thousands of cell types, which may be differentially susceptible or resilient to ageing.

Here we present a comprehensive single-cell RNA sequencing dataset containing roughly 1.2 million high-quality single-cell transcriptomes of brain cells from young adult and aged mice of both sexes, from regions spanning the forebrain, midbrain and hindbrain. High-resolution clustering of all cells results in 847 cell clusters and reveals at least 14 age-biased clusters that are mostly glial types.

At the broader cell subclass and supertype levels, we find age-associated gene expression signatures and provide a list of 2,449 unique differentially expressed genes (age-DE genes) for many neuronal and non-neuronal cell types. Whereas most age-DE genes are unique to specific cell types, we observe common signatures with ageing across cell types, including a decrease in expression of genes related to neuronal structure and function in many neuron types, major astrocyte types and mature oligodendrocytes, and an increase in expression of genes related to immune function, antigen presentation, inflammation, and cell motility in immune cell types and some vascular cell types.

Finally, we observe that some of the cell types that demonstrate the greatest sensitivity to ageing are concentrated around the third ventricle in the hypothalamus, including tanycytes, ependymal cells, and certain neuron types in the arcuate nucleus, dorsomedial nucleus and paraventricular nucleus that express genes canonically related to energy homeostasis. Many of these types demonstrate both a decrease in neuronal function and an increase in immune response. These findings suggest that the third ventricle in the hypothalamus may be a hub for ageing in the mouse brain. Overall, this study systematically delineates a dynamic landscape of cell-type-specific transcriptomic changes in the brain associated with normal ageing that will serve as a foundation for the investigation of functional changes in ageing and the interaction of ageing and disease."

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

Key players in brain aging (original news release) "New research identifies age-related damage on a cellular level"



Fig. 1: Transcriptomic cell types in young adult and aged mouse brains.


Fig. 6: Decreased neuronal function and increased immune activity as common signatures of ageing across brain cell types.


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