Brain aging accelerates dramatically around age 44 — could ketone supplements help?

The human brain suddenly starts aging much faster around age 44, and that aging reaches a maximum speed at age 67, a new study finds.

The research, published March 3 in the journal PNAS, seems to align with the results of a different study that Live Science recently reported on, which looked at aging using blood samples and found that periods of accelerated aging take place around ages 44 and 60.

The new neuroscience study also found that brain aging was linked to insulin resistance, in which cells need more insulin than usual to keep blood sugar in check. Furthermore, it uncovered early hints that ketone supplements may offer some protection against certain measures of brain aging.

Ketones are compounds in the body that act as an alternative fuel source, standing in for sugars. So if the brain is aging because it's not getting enough sugars, ketones could help fill the gap, the team theorized.

However, much more research is needed to back this idea.

Related: 13 proteins tied to brain aging seem to spike at ages 57, 70 and 78

Early warning signs of brain aging

The researchers used four existing datasets of brain scans that together included scans from 19,300 people ages 18 to 90. To study how different brain regions are linked in networks, the team looked at two types of brain scans: functional magnetic resonance imaging (fMRI), which measures blood flow in the brain, and electroencephalograms (EEGs), which measure electrical firing between neurons in the outermost layer of the brain.

In these scans, the scientists looked for signs that blood flow and electric firing between brain regions either disappeared or became inconsistent, suggesting there was a breakdown in communication between nodes in the network. They had considered this network disintegration a hallmark of aging in previous research wherein they assessed the impact of diet on the brain. Such disruptions are also seen in age-related neurodegenerative diseases, and the degree of disruption typically reflects the person's overall degree of aging.

Through their analysis, the researchers found that the brain starts to age more quickly around age 44 and that the aging accelerates to a maximum rate around age 67. After that, brain aging starts slowing down, until the rate stabilizes around age 90.

"What we did not anticipate was that the effects might be occurring as early as the 40s," study senior author Lilianne Mujica-Parodi, a neuroscientist at Stony Brook University, told Live Science.

Sugars versus ketones

The network disruptions the researchers observed resembled changes previously documented in the brains of people ages 50 to 80 with type 2 diabetes. Mujica-Parodi and her team wondered if the changes arose because neurons were not responding well to insulin, the hormone responsible for shuttling sugar from the blood into cells.

This effect wouldn't affect only people with diabetes. About "88% of North Americans have at least one detectable sign of insulin resistance," said Dr. Luis Adrian Soto-Mota, a metabolism researcher at the Monterrey Institute of Technology in Mexico who was not involved with the study but previously worked with the team.

Looking at all the brain scans, which included scans from people with and without insulin resistance, the team found that people in their 40s with high blood sugar levels experienced faster brain aging than people of the same age with no signs of insulin resistance.

In addition, across all of the scans, certain parts of the brain aged more quickly than others, so the researchers wondered if those brain regions might be more insulin dependent. It's known that a protein named GLUT4 relies on insulin to move sugar into cells. So the team turned to the Allen Brain Atlas, which includes data on the activity of the GLUT4 gene, and found that the fast-aging regions did depend more on GLUT4.

The slow-aging brain regions, on the other hand, had higher levels of a protein that moves ketones into cells, suggesting that those regions use ketones as an alternative energy source.

Related: Biological aging may not be driven by what we thought

Ketone supplements?

That raised the question of whether ketone supplements might be able to slow brain aging. To test this idea, the team recruited 53 men and 48 women, ages 20 to 79, who got fMRI scans after fasting overnight to deprive the brain of sugar.

Half an hour after the scan, the participants received either a ketone-filled drink or a sugary drink with the same number of calories. The researchers then waited 30 minutes for the energy source to reach the participants' brains, before repeating the fMRI scans.

Even over this short time frame, the ketone drink appeared to reduce brain network disruptions tied to aging, while the glucose beverage didn't, the team found.

The ketone drink had the greatest effect on people ages 40 to 59, where its impact was over 80% higher than in younger adults ages 20 to 39. The ketone drink had the smallest effect in the 60-to-79 age group. That might hint that, if ketone supplements prove to be effective for slowing brain aging, early intervention could be necessary.

This part of the study was limited in that the researchers tested the effects of ketone and glucose drinks only at a single time point; they didn't monitor brain aging over time or conduct any cognitive tests. They also considered only specific fMRI data, which may not reflect all aspects of brain aging, so we don't know if ketone supplements would help across the board.

Mujica-Parodi said future studies could track brain aging in people taking these supplements over time and thus provide more insight into its long-term potential. In addition, if the ketone supplements are making up for insulin resistance, the best measure people could take might be to avoid developing insulin resistance in the first place, she suggested, which could be achieved through dietary changes.

Soto-Mota added that when glucose levels are low enough, the body can make more ketones on its own than it can obtain from supplements. That's the goal of the "keto diet," although maintaining the diet for a long time comes with downsides.

Mujica-Parodi said that ketone supplements could be helpful in people with extreme insulin resistance who are incapable of making their own ketones, due to metabolic changes in the body.

Editor's note: Some of the authors on the new paper have patented the ketone supplement tested in the research, and one is the director of a company aimed at developing products based on the science of ketone bodies in human nutrition.

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