Summary: New research shows that not all brain cells age in the same way, with some cells, such as those in the hypothalamus, undergoing more age-related genetic changes. These changes include reduced activity in neural circuit genes and increased activity in immunity-related genes.
The findings provide a detailed map of age-sensitive brain regions, offering insight into how aging may influence brain disorders like Alzheimer’s disease. This research could guide the development of treatments targeting aging-related brain changes and neurodegenerative diseases.
Key facts:
Source: NIH
Based on new brain mapping research funded by the National Institutes of Health (NIH), scientists have discovered that not all cell types in the brain age in the same way.
They found that some cells, such as a small group of cells controlling hormones, may undergo more age-related changes in genetic activity than others.
The results, published in Naturesupport the idea that some cells are more sensitive than others to the aging process and age-related brain disorders.
“Aging is the greatest 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 NIH National Institute on Aging.
“This new map could fundamentally change the way scientists think about how aging affects the brain and would also provide a guide for developing new treatments for aging-related brain diseases.”
Scientists used advanced genetic analysis tools to study individual cells in the brains of 2-month-old “young” mice and 18-month-old “old” mice.
For each age, the researchers analyzed the genetic activity of a variety of cell types located in 16 different large regions, making up 35% of a mouse’s total brain volume.
Like previous studies, initial results showed a decrease in the activity of genes associated with neuronal circuits.
These decreases were observed in neurons, primary circuit cells, as well as in “glial” cells called astrocytes and oligodendrocytes, which can support neuronal signaling by controlling neurotransmitter levels and electrically insulating nerve fibers.
In contrast, aging increased the activity of genes associated with immunity and inflammatory systems in the brain, as well as cells in the brain’s blood vessels.
Further analysis helped determine which cell types might be most susceptible to aging. For example, the findings suggest that aging reduces the development of newborn neurons present in at least three different parts of the brain.
Previous studies have shown that some of these newborn neurons might play a role in circuits that control certain forms of learning and memory, while others might help mice recognize different odors.
The cells that appear most susceptible to aging surround the third ventricle, a major pipeline that allows cerebrospinal fluid to pass through the hypothalamus.
Located at the base of the mouse brain, the hypothalamus produces hormones that can control the body’s basic needs, including temperature, heart rate, sleep, thirst and hunger.
The results showed that cells lining the third ventricle and neighboring neurons in the hypothalamus showed the greatest changes in their genetic activity with age, including an increase in immunity genes and a decrease in circuit-associated genes. neuronal.
The authors noted that these observations are consistent with previous studies in several different animals that showed links between aging and body metabolism, including those on how intermittent fasting and other low-calorie diets can increase lifespan.
Specifically, age-sensitive neurons in the hypothalamus are known to produce feeding and energy-controlling hormones, while cells lining the ventricles control the passage of hormones and nutrients between the brain and the body.
Further research is needed to examine the biological mechanisms behind these findings, as well as to investigate possible links to human health.
The project was led by Kelly Jin, Ph.D., Bosiljka Tasic, Ph.D., and Hongkui Zeng, Ph.D., of the Allen Institute for Brain Science in Seattle. The scientists used brain mapping tools developed as part of the NIH project. Brain Research Through the Advancement of Innovative Neurotechnologies® (BRAIN) Initiative – Cell Census Network (BICCN) – to study more than 1.2 million brain cells, or about 1% of total brain cells, from young and old mice.
“For years, scientists have studied the effects of aging on the brain, primarily one cell at a time. Now, thanks to innovative brain mapping tools – made possible by the NIH BRAIN Initiative – researchers can study how aging affects much of the brain as a whole,” said John Ngai, Ph.D., director of The BRAIN Initiative®.
“This study shows that looking at the brain more holistically can provide scientists with new insights into how the brain ages and how neurodegenerative diseases can disrupt the normal activity of aging.”
Funding: This study was supported by NIH grants R01AG066027 and U19MH114830.
Author: Christophe Thomas
Source: NIH
Contact: Christophe Thomas – NIH
Picture: Image is credited to Neuroscience News
Original research: Free access.
“Whole-Brain-Specific Transcriptomic Signatures of Healthy Aging in Mice” by Kelly Jin et al. Nature
Abstract
Whole-brain-specific transcriptomic signatures of healthy aging in mice
Biological aging can be defined as a progressive loss of homeostasis in various aspects of molecular and cellular function. The mammalian brain is made up of thousands of cell types, which may be differently sensitive or resilient to aging.
Here we present a comprehensive single-cell RNA-sequencing dataset containing approximately 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, brain middle and hindbrain.
High-resolution clustering of all cells results in 847 cell clusters and reveals at least 14 age-biased clusters, which are mostly glial types.
At the broader levels of cellular subclasses and supertypes, we find age-associated gene expression signatures and provide a list of 2,449 unique differentially expressed genes (age-DE genes) for many neuronal cell types. and not neuronal.
While most age-ED genes are unique to specific cell types, we observe common signatures with aging across cell types, including decreased expression of genes related to structure and neuronal function in many types of neurons, major types of mature astrocytes and oligodendrocytes, as well as increased expression of genes related to immune function, antigen presentation, inflammation and to the 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 aging are concentrated around the third ventricle in the hypothalamus, including tanycytes, ependymal cells, and certain types of neurons in the arcuate nucleus, dorsomedial nucleus, and nucleus paraventricular which express genes. canonically linked to energy homeostasis.
Many of these types demonstrate both a decrease in neuronal function and an increase in immune response.
These results suggest that the third ventricle of the hypothalamus may be a hub of aging in the mouse brain.
Overall, this study systematically delineates a dynamic landscape of cell type-specific transcriptomic changes in the brain associated with normal aging that will serve as a basis for studying aging-related functional changes and the interplay of aging and of the disease.
WASHINGTON — The fate of a law that would likely ban social media platform TikTok…
Look at their faces — formal, etched with experience, laden with the weight of momentous…
Topline Thousands of structures have been leveled by the wildfires that continue to burn across…
The National Football League announced Friday the Jets will play an international game in London…
The Browns are traveling across the pond in 2025 to London. The NFL announced the…
President-elect Donald Trump looks on during Turning Point USA's AmericaFest at the Phoenix Convention Center…