A new study has revealed that brain aging doesn’t follow a smooth, gradual decline but instead happens in distinct phases, with critical transition points.
Researchers from Stony Brook University found that brain network function starts to become unstable around age 44, with the fastest decline occurring at age 67 before slowing down around age 90.
This discovery, published in Proceedings of the National Academy of Sciences, suggests that there are ideal time periodswhen interventions might be most effective at slowing cognitive decline and preventing diseases like Alzheimer’s.
The research team, led by Dr. Lilianne R. Mujica-Parodi, analyzed brain scans from over 19,300 people across multiple large datasets.
Their findings suggest that the main cause of brain aging is insulin resistance in neurons, meaning that brain cells struggle to use glucose for energy as people get older. This lack of fuel leads to stress in the brain, which accelerates its decline.
By comparing various biological markers, the researchers found that metabolic problems occur first, followed by blood vessel damage and inflammation. Specific genes linked to glucose and fat metabolism—like GLUT4 and APOE (a gene associated with Alzheimer’s)—were identified as key players in this aging process.
However, there was also a potential solution. The study found that neurons can use ketones as an alternative fuel, which could help stabilize brain function when glucose metabolism starts failing. The key transporter for this process, MCT2, was identified as a protective factor in brain aging.
To test the impact of alternative fuels, researchers conducted an experiment on 101 participants at different stages of brain aging. Some were given glucose (the brain’s normal energy source), while others received ketones (an alternative fuel the brain can use without insulin).
The results were striking:
- Ketones helped stabilize brain function, while glucose did not.
- The biggest benefits were seen in middle-aged adults (40-59 years old), when neurons are stressed but still functional.
- The effects were weaker in younger adults (20-39 years old) and diminished in older adults (60-79 years old), when brain decline was already accelerating due to compounding vascular damage.
These findings suggest a major shift in how we approach brain aging. Instead of waiting for memory problems to appear, interventions should start in midlife (around the 40s), when the brain is still responsive to metabolic support.
Dr. Mujica-Parodi emphasized that current treatments focus on symptoms that appear too late. This study suggests that early metabolic intervention—such as a ketogenic diet or supplements—might significantly slow down cognitive decline.
Dr. Botond Antal, the study’s first author, highlighted the potential for new screening guidelines: Instead of relying on late-stage symptoms, doctors could test for early signs of insulin resistance in the brain and recommend personalized metabolic interventions before damage becomes irreversible.
With dementia cases expected to triple by 2050, finding ways to slow brain aging is more important than ever. This research suggests that targeting brain metabolism early in life could help millions of people maintain cognitive health as they age.
By identifying key transition points in brain aging, scientists now have a roadmap for when and how to intervene—offering new hope for preventing cognitive decline long before it begins.
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The research findings can be found in PNAS.
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