8 hours Ago By Zena le Roux
Our brain’s neurons are like a bustling city, where each building relies on a steady flow of electricity to function. In the event of a brief power outage, systems are in place to bring it back to life—no harm done. But what if a power failure were to last for months? Emergency generators may keep essential services running, but eventually, they would fail.
Water systems might freeze and burst, buildings would deteriorate, and infrastructures would start to crumble. When the power finally returned, the damage would be done—the city in ruins. The study showed that aging follows a specific progression, with the first stage occurring in middle age and coinciding with higher insulin resistance.
One key factor in brain aging is reduced glucose metabolism—in which the brain struggles to use carbohydrates for energy, impairing its function. These metabolic changes begin decades before symptoms appear but often go unnoticed until later stages of aging when intervention is far less effective. However, functional magnetic resonance imaging (fMRI) and electroencephalogram—tools used to study brain activity—can detect early age-related brain changes, providing an opportunity for prevention rather than late-stage treatment.
Understanding disease mechanisms is the first step toward effective treatment, Mujica-Parodi said. For example, Alzheimer’s disease has long been attributed to the buildup of beta-amyloid, a protein that forms sticky plaques between brain cells, and tau proteins that form twisted tangles inside brain cells, leading to drug development aimed at clearing these proteins. However, these treatments have largely failed.
One reason for this failure is that by the time Alzheimer’s disease is diagnosed, irreversible neuronal damage has already occurred. Protein accumulation is a consequence of insulin resistance in the brain—in other words, by targeting the beta-amyloid and tau proteins, the drug is failing to address the root cause. Unlike many other cells, adult neurons have very limited regenerative capacity.
If cognitive decline stems from neurons effectively starving, as the study suggests, waiting until they are incapacitated or dead is unlikely to be effective, she added. Physiological systems are designed to maintain homeostasis—a balance between energy supply and demand. When that balance is disrupted, the resulting stress can drive further dysregulation, worsening the problem over time, Mujica-Parodi said.
Neurons rely on two primary energy sources: glucose and ketones. While some neurons require insulin to access glucose, those that become resistant to insulin struggle to utilize this fuel, a condition known as “insulin resistance,” Mujica-Parodi said. As the cells lose their ability to effectively use glucose—their primary energy source—metabolic stress increases, slowing how messages are sent between nerve cells and contributing to cognitive decline.
When neurons become insulin-resistant, they lose their ability to access glucose but can still utilize ketones—which don’t require insulin for metabolism and provide an alternative energy source, Mujica-Parodi said. Even in older adults with mild cognitive impairment or Alzheimer’s, it has been shown that brain cells can still take in ketones, though, by this stage, irreversible damage may limit their effectiveness. Brain aging follows a predictable trajectory.
Unlike a gradual, linear decline, these changes occur in an “S-shaped” curve, suggesting specific windows during which interventions could be most effective. The period between 40 and 60 is the most critical window for intervention. During this time, brain networks are most unstable but still adaptable, making it an optimal period for interventions.
Mujica-Parodi was surprised by how quickly these interventions took effect—brain networks stabilized within just 30 minutes of consuming a ketone drink in her studies. Ketones can be produced in the body through low-carbohydrate, high-fat diets or fasting—or taken as a supplement—but brain health doesn’t need to wait until your 40s. Early lifestyle changes, such as adopting lower-carbohydrate, higher-fiber diets and engaging in regular exercise, can help prevent or delay insulin resistance in the brain, Mujica-Parodi said.
Once you hit your 40s, screenings for brain insulin resistance—beyond the standard HbA1c measures—could help identify risk early enough to implement ketogenic diets or supplements to support glucose access. “Not everyone needs a strict keto diet,” Planells said. “But reducing processed carbs and improving insulin sensitivity generally benefits brain health.
” In addition to ketogenic diets and supplements, cognitive resilience—the brain’s ability to adapt to stress and maintain its function—can also be built through activities such as mentally stimulating tasks, learning new skills, and maintaining social connections, said Planells. Chronic stress and elevated cortisol levels can speed up brain aging—which is why mindfulness practices, like meditation, are beneficial, he said. “The window of opportunity may be narrow, but knowing it exists gives us the power to act.
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