Most of us who’ve reached middle age have noticed a slowing in memory and cognition, but scientists don’t have a clear picture of the molecular changes that take place in the brain to cause it.
Now, a study in mice has determined that the most pronounced changes occur in the white matter, a type of nervous system tissue that’s integral to transmitting signals across the brain. The study also examined two treatments — caloric restriction and infusions of plasma from young mice — that affect certain regions of the brain, with the plasma appearing to slow the age-related decline.
The results offer insight into the cognitive decline of normal aging, as well as the way aging contributes to neurodegenerative conditions such as Alzheimer’s and Parkinson’s diseases and multiple sclerosis.
In many neurodegenerative diseases, certain areas of the brain are more vulnerable to damage, but scientists don’t know exactly why.

Different genes found in different regions:

The research team sampled 15 regions in both hemispheres of the brains of 59 female and male 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 are frequently found and vary in concentration in 10 or more regions.
The team used these genes to develop a common aging score, assessing how gene activity in different regions of the brain change with age.
The researchers found that the white matter, which is found deep in the brain and contains nerve fibers protected by white-colored myelin, showed the earliest and most pronounced changes in gene expression for mice 12 and 18 months old. According to Wyss-Coray, these mice are about as old, in mouse years, as a person in their 50s.

Testing interventions:

Interventions to slow the genetic shift that leads to the decline in specific regions of the brain could be beneficial in addressing neurodegenerative disease as well as the general decline associated with aging.
During the study, the team explored two interventions — carloric restriction and injections of plasma from young mice — to evaluate whether they protected against the region-specific shifts in gene expression. Each intervention began when the mice were 19 months old and lasted four weeks.
The researchers found that the dietary intervention caused genes associated with circadian rhythms to turn on, while the plasma intervention turned on genes involved in stem cell differentiation and neuronal maturation that led to selective reversal of age-related gene expression.

Source: https://med.stanford.edu/news/all-news/2023/08/brain-aging-genes.html