As the brain ages, the delicate balance of its proteins begins to shift, increasing vulnerability to cognitive decline and neurodegenerative diseases. A new study from the Leibniz Institute on Aging – Fritz Lipmann Institute in Germany reveals how aging alters brain protein regulation and suggests that certain dietary interventions may help reverse some of this damage.
Aging Disrupts the Brain’s Protein Tagging System
Using advanced mass spectrometry, researchers compared brain tissue from young and old mice. They discovered major age-related disturbances in ubiquitylation—a biochemical process that tags proteins to determine whether they should keep functioning or be broken down.
In older mice, these ubiquitylation tags were found in excess on many proteins.
“Aging leads to fundamental changes in how proteins in the brain are chemically labeled,” explained molecular biologist Alessandro Ori.
Ubiquitylation serves as a molecular “traffic controller,” deciding whether a protein stays active, changes its function, or is flagged for recycling. But when the balance is disrupted, the brain’s ability to maintain healthy protein turnover begins to falter.
The Proteasome Slows Down With Age
Further experiments using lab-grown human neurons showed that roughly one-third of the tag buildup in older brains could be traced to a slowdown in the proteasome, the cell’s protein-recycling machinery. Although scientists knew the proteasome becomes less efficient over time, this study provides a clearer picture of how this bottleneck contributes to protein imbalance in aging neurons.
Calorie Restriction Showed Signs of Reversing Damage
To test whether lifestyle interventions might influence this process, older mice were placed on a calorie-restricted diet for four weeks before returning to a normal diet.
The results were promising:
For several proteins, the ubiquitylation patterns returned to those seen in younger animals once normal feeding resumed. This suggests that diet—even late in life—can partially reset the chemical signals that guide protein maintenance in the brain.
Not every protein responded to the dietary change, however, underscoring the complexity of brain aging.
Implications for Alzheimer’s and Other Brain Disorders
While the findings have not yet been tested in humans, they offer new insight into how aging disrupts brain chemistry and point toward potential strategies for protecting brain health later in life.
Since protein mismanagement is a hallmark of conditions like Alzheimer’s disease, understanding how to restore stability in the brain’s protein-tagging system may open the door to new treatments.
“Our results show that even in old age, diet can still have an important influence on molecular processes in the brain,” Ori said. “However, diet does not affect all aging processes equally—some slow down, others barely change, and some even increase.”
