A new neuroimaging study has found some good news and bad news about brain aging.
First the bad news: Neurobiological changes associated with aging can be seen at a much younger age than would be expected, in the late 40s.
Now the good news: The new study also found that this aging may be prevented or reversed based on dietary changes that involve minimizing the consumption of simple carbohydrates.
To better understand how diet influences brain aging, a research team led by Stony Brook University professor and lead author Lilianne R. Mujica-Parodi, Ph.D., focused on the presymptomatic period during which prevention may be most effective.
Using large-scale life span neuroimaging datasets, the researchers found that functional communication between brain regions destabilizes with age, typically in the late 40s. This destabilization correlates with poorer cognition and accelerates with insulin resistance.
Targeted experiments then showed this biomarker for brain aging to be reliably modulated with changes in eating, including decreasing glucose and increasing ketones, both factors in the popular Keto diet.
This effect was replicated across both changes to diet, as well as after drinking a fuel-specific calorie-matched supplement, according to the study’s findings.
“What we found with these experiments involves both bad and good news,” said Mujica-Parodi, a professor in the Department of Biomedical Engineering with joint appointments in the College of Engineering & Applied Sciences and Renaissance School of Medicine at Stony Brook University, and a faculty member in the Laufer Center for Physical and Quantitative Biology.
“The bad news is that we see the first signs of brain aging much earlier than was previously thought. However, the good news is that we may be able to prevent or reverse these effects with diet, mitigating the impact of encroaching hypometabolism by exchanging glucose for ketones as fuel for neurons.”
Using neuroimaging of the brain, the researchers discovered that there is breakdown of communication between brain regions — known as network stability — much earlier than expected.
“We think that, as people get older, their brains start to lose the ability to metabolize glucose efficiently, causing neurons to slowly starve, and brain networks to destabilize,” said Mujica-Parodi. “Thus, we tested whether giving the brain a more efficient fuel source, in the form of ketones, either by following a low-carb diet or drinking ketone supplements, could provide the brain with greater energy. Even in younger individuals, this added energy further stabilized brain networks.”
To conduct their experiments, brain network stability was established as a biomarker for aging by using two large-scale brain neuroimaging (fMRI) datasets totaling nearly 1,000 individuals, between the ages of 18 and 88.
The researchers found that destabilization of brain networks was associated with impaired cognition and was accelerated with Type 2 diabetes, an illness that blocks the neurons’ ability to effectively metabolize glucose.
To identify the mechanism as being specific to energy availability, the researchers then held age constant and scanned an additional 42 adults under the age of 50 years old with fMRI. This allowed them to directly observe the impact of glucose and ketones on each individual’s brain, they explained.
The brain’s response to diet was tested in two ways. The first was holistic, comparing brain network stability after study participants had spent one week on a standard (unrestricted) diet vs. a low carb diet (for example, meat or fish with salad, but no sugar, grains, rice, or starchy vegetables).
In a standard diet, the primary fuel metabolized is glucose, whereas in a low-carb diet, the primary fuel metabolized is ketones, the researchers noted.
However, the researchers also realized there might have been other differences between the diets driving the observed effects. That led to another experiment. To isolate glucose vs. ketones as the crucial difference between the diets, an independent set of participants was scanned before and after drinking a small dose of glucose on one day, and ketones on the other, where the two fuels were individually weight-dosed and calorically matched.
The results were the same, showing that the differences between the diets could be attributed to the type of fuel they provide to the brain, the researchers reported.
Additional findings from the study included:
- effects of brain aging emerged at age 47, with most rapid degeneration occurring at age 60;
- even in adults under the age of 50, dietary ketosis (whether achieved after one week of dietary change or 30 minutes after drinking ketones) increased overall brain activity and stabilized functional networks.
This is thought to be due to the fact that ketones provide greater energy to cells than glucose, even when the fuels are calorically matched. This benefit has previously been shown for the heart, but the current set of experiments provides the first evidence for equivalent effects in the brain, according to the researchers.
“This effect matters because brain aging, and especially dementia, are associated with ‘hypometabolism,’ in which neurons gradually lose the ability to effectively use glucose as fuel. Therefore, if we can increase the amount of energy available to the brain by using a different fuel, the hope is that we can restore the brain to more youthful functioning,” said Mujica-Parodi.
The study was published in PNAS.
Source: Stony Brook University