Major breakthrough could help slow aging of brain

By Stephen Beech

New treatments to slow the aging of the brain may be possible following a major breakthrough.

American scientists have identified specific cell types in the brain of mice that undergo major changes as they age, along with a "hot spot" where many of those changes occur.

They say their findings, published in the journal Nature, could pave the way for future therapies to slow or manage the aging process in the brain.

The research team discovered that dozens of specific cell types, mostly glial cells - known as brain support cells, underwent "significant" gene expression changes with age.

Those strongly affected included microglia and border-associated macrophages, oligodendrocytes, tanycytes, and ependymal cells.

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

They also identified a specific "hot spot" combining both the decrease in neuronal function and the increase in inflammationi 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.

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

Study lead author Dr. Kelly Jin, a scientist at the Allen Institute for Brain Science in Seattle, said: “Our hypothesis is that those cell types are getting less efficient at integrating signals from our environment or from things that we're consuming.

“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, the researchers used cutting-edge single-cell RNA sequencing and advanced brain-mapping tools to map more than 1.2 million brain cells from young (two 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.

Researchers say mouse brains share many similarities with human brains in terms of structure, function, genes, and cell types.

Dr. Richard Hodes, director of NIH’s National Institute on Aging, said: “Aging is the most important risk factor for Alzheimer’s disease and many other devastating brain disorders.

"These results provide a highly detailed map for which brain cells may be most affected by 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.”

The researchers say understanding the hot spot in the hypothalamus makes it a "focal point" for future study.

Along with knowing which cells to specifically target, the team believe it could lead to the development of age-related therapeutics, helping to preserve function and prevent neurodegenerative disease.

Dr. Hongkui Zeng, executive vice president and director of the Allen Institute for Brain Science, said: “We want to develop tools that can target those cell types.

“If we improve the function of those cells, will we be able to delay the aging process?”

The latest findings also align with previous studies that link aging to metabolic changes as well as research suggesting that intermittent fasting, balanced diet, or calorie restriction can influence or perhaps increase life span.

Dr. Jin said: “It’s not something we directly tested in this study.

“But to me, it points to the potential players involved in the process, which I think is a huge deal because this is a very specific, rare population of neurons that express very specific genes that people can develop tools for to target and further study.”

Dr. Zeng added: “The important thing about our study is that we found the key players - the real key players -and the biological substrates for this process.

“Putting 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, changes happening in specific cell types could be averaged out and undetected if you mix different types of cells together.”