Fight Aging!

Researchers here report on a measure of brain aging constructed from expression levels of a variety of genes, noting that it appears to show the greatest changes in white matter rather than grey matter. They use this measure to assess the results of interventions shown to slow aging in old mice, calorie restriction and plasma transfer from young mice, finding that these two treatments have quite different mechanistic outcomes in the brain, slowing brain aging in quite different ways. This suggests that (a) there are multiple ways to intervene, and (b) there are ways to improve on present capabilities.

Researchers 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. These mice are about as old, in mouse years, as a person in their 50s.

Past work has shown that aging disrupts an otherwise stable gene expression pattern in the brain, turning on genes that regulate inflammation and the immune response, and turning off genes responsible for protein and collagen synthesis. The inflammation and immune response affect the integrity of the myelin sheath, the insulation layer around nerves responsible for transmitting signals across the brain. "White matter has been a rather neglected area in aging research, which usually focuses on the neuron-dense regions like the cortex or hippocampus. The fact that white matter is emerging in our data as an area of particular vulnerability to aging opens up new and intriguing hypotheses."

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 - caloric 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. "The interventions appeared to act on very different regions in the brain with strikingly different effects. This suggests that there are multiple regions and pathways in the brain that have the potential to improve cognitive performance at old age."

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