Allen Institute scientists have identified specific cell types in the brains of mice that undergo major changes as they age, along with a hot spot where many of those changes occur. The discoveries, published in the journal Naturecould pave the way for future therapies to slow or control the aging process in the brain.
Key findings
- Sensitive cells: The scientists discovered dozens of specific cell types, mostly glial cells, known as brain supporting cells, that underwent significant changes in gene expression with age. Those strongly affected included microglia and border-associated macrophages, oligodendrocytes, tanycytes, and ependymal cells.
- Inflammation and neuronal protection: In aging brains, genes associated with inflammation increased in activity, while those related to neuronal structure and function decreased.
- Aging hot spot: The scientists discovered a specific hot spot that combines both decreased neuronal function and increased inflammation in the hypothalamus. The most significant changes in gene expression were found in cell types close to the third ventricle of the hypothalamus, including tanycytes, ependymal cells, and neurons known for their role in food intake, energy homeostasis, metabolism, and shape. how our body uses nutrients. This points to a possible connection between diet, lifestyle factors, brain aging and changes that may influence our susceptibility to age-related brain disorders.
“Our hypothesis is that these types of cells are becoming less efficient at integrating signals from our environment or from the things we consume,” said Kelly Jin, Ph.D., a scientist at the Allen Institute for Brain and Brain Science. 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.” . wearing.”
To conduct the study, funded by the National Institutes of Health (NIH), researchers used cutting-edge single-cell RNA sequencing and advanced brain mapping tools developed through NIH’s The BRAIN Initiative® to map more than 1.2 million of brain cells from young (two months old) and aged (18 months old) mice in 16 broad brain regions. Elderly mice are what scientists consider the equivalent of a middle-aged human. Mouse brains share many similarities with human brains in terms of structure, function, genes, and cell types.
“Aging is the most important risk factor for Alzheimer’s disease and many other devastating brain disorders. These results provide a very detailed map of which brain cells may be most affected by aging,” said Richard J. Hodes, MD, director of the National Institute of the NIH. about aging. “This new map may fundamentally alter the way scientists think about how aging affects the brain and also provides a guide for developing new treatments for aging-related brain diseases.”
A path towards new therapies
Understanding this hot spot in the hypothalamus makes it a focal point for future studies. In addition to knowing which cells to target specifically, this could lead to the development of age-related therapies that help preserve function and prevent neurodegenerative diseases.
“We want to develop tools that can target those cell types,” said Hongkui Zeng, Ph.D., executive vice president and director of the Allen Institute for Brain Science. “If we improve the function of those cells, can we slow the aging process?”
The latest findings also align with previous studies linking aging to metabolic changes, as well as research suggesting that intermittent fasting, a balanced diet or calorie restriction can influence or perhaps increase life expectancy.
“It’s not something we tested directly in this study,” Jin said. “But to me, it points to the potential players involved in the process, which I think is very important because this is a very specific and rare population of neurons that express very specific genes for which people can develop tools to identify and study them further.” “.
Future research on brain aging
This study lays the foundation for new dietary strategies and therapeutic approaches aimed at maintaining brain health in old age, along with further research into the complexities of advanced aging in the brain. As scientists further explore these connections, research may unlock more targeted dietary or pharmacological interventions to combat or slow aging at the cellular level.
“The important thing about our study is that we found the key players, the real key players, and the biological substrates for this process,” Zeng said. “As you put the pieces of this puzzle together, you have to find the right players. It’s a beautiful example of why you need to study the brain and the body at this kind of cell type-specific level. Otherwise, the changes that occur in specific cell types could be averaged out and not detected if different cell types are mixed.”
This study was funded by NIH grants R01AG066027 and U19MH114830. The content is the sole responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.