Effects of Aging on Brain Proteins – and How Diet Can Help Reverse Them

As we age, our brains undergo changes that increase susceptibility to diseases. A recent study offers new insights into these alterations and suggests potential strategies to prevent or reverse some of the damage.

Researchers at the Leibniz Institute on Aging Fritz Lipmann Institute in Germany examined the protein composition of young and old mouse brains using mass spectrometry. They discovered significant shifts in a process called ubiquitylation as the mice grew older. This process involves adding chemical tags to proteins, signaling which ones should be broken down and recycled by the brain.

In older mice, the study found that these ubiquitylation tags accumulated on certain proteins. "Our findings reveal that aging fundamentally changes how proteins are chemically labeled," explained molecular biologist Alessandro Ori. "Ubiquitylation functions as a molecular switch, deciding whether a protein stays active, changes role, or is degraded."

Further experiments with human neurons derived from stem cells showed that roughly one-third of the increased tagging was due to a slowdown in the proteasome, the brain's system for recycling proteins. While the decline in protein cleanup with age has been known, this research provides a detailed connection between ubiquitylation and the buildup of tags that the proteasome should remove.

"This system becomes imbalanced over time: many labels accumulate, while some disappear, regardless of the protein's quantity," Ori added.

The team also tested whether dietary interventions could influence ubiquitylation. Older mice were placed on a calorie-restricted diet for four weeks before returning to a normal diet. For some proteins, this approach restored the chemical tagging to levels observed in younger animals. Although the underlying mechanisms were not fully examined, the results suggest that brain protein tagging can be modified through diet even later in life.

While these findings have yet to be tested in living humans, they provide valuable insights into age-related changes in the brain. This could be important for improving treatments for conditions where protein balance is disrupted, such as Alzheimer's disease.

"Even in advanced age, diet can still significantly influence molecular processes in the brain," Ori noted. "However, its effects are selective: some aging processes slow down, while others remain unaffected or even intensify."

The full study is published in Nature Communications.

Author: Sophia Brooks