A recent study in mice revealed that as animals age, the most profound changes occur in white matter, the tissue responsible for transmitting messages throughout the brain.
Many of us observe a decline in memory and cognitive abilities as we reach middle age. However, the exact molecular changes in the brain responsible for this are not fully understood by scientists.
But recent research in mice reveals that the most profound changes tend to occur in the white matter of the brain, a type of nervous system tissue essential for transmitting signals throughout the brain. became. The study also examined two of her treatments: caloric restriction and drug infusions. plasma Taken from young mice, it affects specific areas of the brain, and plasma appears to slow age-related decline.
The results provide insight into normal aging-induced cognitive decline and how aging contributes to neurodegenerative conditions such as: Alzheimer’s disease Parkinson’s disease and multiple sclerosis.
Scientists don’t know exactly why many neurodegenerative diseases make certain areas of the brain more susceptible to damage.
“We thought this study was a way to explain that somewhat puzzling local vulnerability,” says Neurology and Neuroscience, who led the study looking at gene expression in different regions of the mouse brain. said Dr. Tony Wys-Cawley, a professor at as you mature.
Wis Koray, Ph.D., Professor Cheng Nisei of Stanford Medicine and director of the Phil and Penny Nights Initiative for Brain Resilience at the Wu Tsai Neuroscience Institute at Stanford University, wrote a paper describing the study. Senior author of . Oliver Hahn, a former postdoctoral fellow in the Wis-Coley lab and now principal investigator at Calico Life Sciences, is the lead author of the paper.This paper was recently published in a journal cell.
Different genes found in different regions
The research team sampled 15 brain regions from both hemispheres of 59 male and female mice aged 3 to 27 months. They identified and ranked the top genes expressed by cells found in each region of the brain. They identified 82 genes that were frequently found and varied in concentration in more than 10 regions.
The researchers used these genes to create a common aging score to assess how gene activity in different regions of the brain changed with age.
The researchers found that white matter, located deep in the brain and containing nerve fibers protected by white myelin, showed the earliest and most pronounced changes in gene expression in 12- and 18-month-old mice. I discovered. According to Wyss-Coray, these mice are about the same age as humans in their 50s in terms of mouse age.
“We can’t say for sure how changes in gene expression in white matter affect memory and cognition. Mr Corey said. “But we do know that white matter is the wiring that connects different areas of the brain.”
Previous studies have shown that aging disrupts stable gene expression patterns in the brain, turning on genes that regulate inflammation and immune responses, and turning off genes involved in protein and collagen synthesis. It is shown. Inflammation and immune responses affect the integrity of the myelin sheath, the insulating layer around nerves that is responsible for transmitting signals throughout the brain.
“White matter is an area that has been largely neglected in aging studies, which usually focus on neuron-dense areas such as the cortex and hippocampus,” Hahn said. “The fact that white matter appears in the data as an area that is particularly vulnerable to aging raises new and interesting hypotheses.”
inspection intervention
Interventions that slow the genetic changes that lead to decline in specific areas of the brain may be beneficial in addressing not only the general decline associated with aging, but also neurodegenerative diseases.
During the study, the team examined two interventions, caloric restriction and plasma infusion from young mice, to assess whether they prevented region-specific changes in gene expression. Each intervention began when mice were 19 months old and lasted for 4 weeks.
The researchers found that the dietary intervention turned on genes associated with circadian rhythms, whereas the plasma intervention turned on genes involved in stem cell differentiation and neuromaturation, resulting in age-related gene expression selection. I have found that it leads to a reversal.
“These interventions appear to act on very different areas in the brain, [induce] It has a surprisingly different effect,” Hahn said. “This suggests that there are multiple areas and pathways in the brain that may improve cognitive performance in older adults.”
The researchers also looked at age-related changes in genes associated with three neurodegenerative diseases, Alzheimer’s, Parkinson’s and multiple sclerosis, which usually affect specific regions of the brain. The expression distribution of each gene was altered in aged animals, occurring in brain regions not normally associated with specific neurodegenerative conditions. This finding may provide insight into the vast number of patients with neurodegenerative diseases for whom there is no firm genetic link.
This study may also provide new opportunities to explore therapeutics and interventions by using gene expression data to focus on cell populations vulnerable to senescence. Future studies may investigate how gene expression leads to functional changes in neuronal activity and structure. Wyss-Coray of the Knight Initiative for Brain Resilience and colleagues aim to extend this research by building a similar genetic atlas for aging in the human brain.
“The individual gene changes observed in mice may not be directly reflected in humans,” Wis-Cawley said. “But we believe that white matter is probably vulnerable to aging.”
References: “An atlas of the aging mouse brain reveals white matter as a focal point of vulnerability.” Guldner, Christy Manson, Fabian Kahn, Robert Palovicz, Nannan Lu, Hui Zhang, Achint Kaur, Jacob Hull, John R. Huguenard, Sebastian Grönke, Benoit Lehallier, Linda Partridge, Andreas Keller, Tony Wyss-Coray, 2023 August 16th, cell.
DOI: 10.1016/j.cell.2023.07.027
researchers in new york university Langone Health, Saarland University, Helmholtz Research Center for Infectious Diseases, Max Planck Institute for Aging Biology, Alkahest and University College London contributed to the research.
This research was supported by the Phil and Penny Knight Brain Recovery Initiative, the European Research Council, the Max Planck Society, the Schaller Nikolich Foundation, the Wu Tsai Institute for Neuroscience and the Bertarelli Foundation, the Simons Foundation, the Alzheimer’s Disease Cure Fund, and the National Aging. Institute milky way Research Foundation, American Heart Association-Allen Initiative in Brain Health and Cognitive Impairment, Michael J. Fox Foundation for Parkinson’s Disease Research.