Study Reveals Molecular Changes in Aging Brain

A new study on mice has provided insight into the cognitive decline associated with normal aging and its connection to neurodegenerative conditions like Alzheimer’s and Parkinson’s diseases. The study, conducted by researchers at Stanford University, found that the most significant changes occur in the white matter of the brain, which plays a crucial role in transmitting signals.

The researchers examined gene expression in different regions of the mouse brain as it matures to identify the molecular changes that occur with aging. They identified 82 genes that varied in concentration in 10 or more regions of the brain. The study revealed that the white matter showed the earliest and most pronounced changes in gene expression for mice aged 12 and 18 months, which is similar to humans in their 50s.

Past research has shown that aging disrupts a stable gene expression pattern in the brain, leading to inflammation and immune responses that affect the integrity of the myelin sheath, the insulation layer around nerves responsible for transmitting signals across the brain. Until now, white matter has been a neglected area in aging research, with most studies focusing on neuron-dense regions. The findings from this study highlight the vulnerability of white matter to aging and open up new possibilities for interventions to slow down age-related cognitive decline.

Interventions to Slow Aging

The researchers also explored two interventions to evaluate their effects on the gene expression shifts associated with aging. The first intervention was caloric restriction, which caused genes associated with circadian rhythms to turn on. The second intervention involved injections of plasma from young mice, which turned on genes involved in stem cell differentiation and neuronal maturation. Both interventions showed selective reversals of age-related gene expression in different regions of the brain.

The study suggests that there are multiple regions and pathways in the brain that have the potential to improve cognitive performance in old age. By understanding the gene expression changes associated with aging, researchers can identify cell populations that are vulnerable to aging and explore potential treatments and interventions.

Implications for Neurodegenerative Diseases

The study also examined age-related changes in genes associated with neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and multiple sclerosis. The expression distribution for these genes changed in older animals and occurred in regions of the brain that are not typically associated with specific neurodegenerative conditions.

This finding could provide insights into patients with neurodegenerative diseases who do not have a firm genetic link. The gene expression data could be used to target vulnerable cell populations and explore potential treatments for these diseases.

The researchers acknowledge that the gene changes observed in mice may not directly translate to humans, but they believe that the vulnerability of white matter to aging is likely similar in humans. The study opens up opportunities for future research to further understand the functional changes in neuronal activity and structure associated with gene expression in the aging brain.

Sources:

Cell Journal

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