Lucknow: A recent research sheds light on the cognitive loss that comes with aging and how it affects neurodegenerative disorders like Alzheimer’s and Parkinson’s disease. Most of us in our middle age must have noticed a decline in memory and cognition. Scientists did not have a strong understanding of the chemical changes that occur in the brain to create it until recently.
The most noticeable alterations, according to a recent mouse research, are seen in the white matter, a kind of nervous system tissue that is crucial for signal transmission throughout the brain.
Infusions of young mouse plasma and caloric restriction, which influence specific areas of the brain, were also studied in the research that discovered a gene “fingerprint” for brain aging. The plasma seemed to delay the age-related memory impairment.
There was uncertainty over the precise cause of why specific parts of the brain are more susceptible to injury in various neurodegenerative illnesses.
The research, which looked at gene expression in several parts of the maturing mouse brain, was conducted by neurology professor Tony Wyss-Coray. “I saw this study as a way to explain that somewhat mysterious regional vulnerability,” he said.
Scientists from Stanford University published their findings on August 16 in the journal Cell.
The 59 male and female mice, ranging in age from 3 to 27 months, had 15 different brain areas from both hemispheres sampled by the study team. They determined the top genes expressed by cells in each area of the brain, classified them, and discovered 82 genes that are often detected and have different concentrations in at least ten different regions of the brain.
With the use of these genes, the researchers created a score that measures how the gene activity in various brain areas changes with aging.
White matter, which is located deep inside the brain and comprises nerve fibers shielded by white myelin, was discovered to exhibit the earliest and most significant alterations in gene expression in 12 and 18-month-old mice. Wyss-Coray estimates that these mice are around 50 years old in human years.
Previous studies have shown that aging alters a normally stable pattern of gene expression in the brain, activating genes that control immune response and inflammation while silencing genes involved in protein and collagen formation. The integrity of the myelin sheath, the insulating layer surrounding neurons important for transporting information throughout the brain, is impacted by inflammation and the immune response.
White matter has received little attention in ageing research, which often focuses on areas with plenty of neurons, such the cortex or hippocampus, according to Hahn. The discovery that white matter is more vulnerable to aging in our data “opens up new and intriguing hypotheses.” Neurodegenerative diseases and the overall decline brought on by aging may both benefit from interventions to halt the genetic shift that causes the loss in certain brain areas.
In order to determine if they offered protection against the region-specific changes in gene expression, the research team looked at two interventions throughout the study: caloric restriction and injections of young mouse plasma. Each intervention lasted four weeks and started when the mice were 19 months old.
The scientists discovered that the plasma intervention activated genes involved in stem cell differentiation and brain development, leading to a selective reversal of age-related gene expression, while the food intervention activated genes linked to circadian rhythms.
According to Hahn, “the interventions seemed to act on very different brain regions and [induce] strikingly different effects.” This “indicates that there are numerous brain regions and pathways that have the potential to enhance cognitive function in old age.” The scientists also looked at age-related alterations in the genes linked to three neurodegenerative illnesses that often affect certain parts of the brain: Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. In older animals, the pattern of each gene’s expression had altered, and this shift had happened in parts of the brain that are not generally linked to a specific neurodegenerative disease. This discovery may shed light on the enormous number of people who suffer from neurodegenerative illnesses without a clear hereditary cause.
By focusing on the cell types susceptible to aging utilizing the gene expression data, the research may also provide fresh chances to investigate therapies and interventions. Future research might examine how changes in gene expression affect the shape and function of neurons.
By creating comparable genetic atlases of ageing in the human brain, Wyss-Coray and colleagues at the Knight Initiative for Brain Resilience want to build on this research.
According to Wyss-Coray, “the specific gene changes observed in the mouse may not directly translate to humans.” However, we think that the white matter’s susceptibility to aging undoubtedly does.