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Activating a gene that slows brain aging and increases lifespan
Scientists are constantly looking for ways to keep humans young and healthy — especially ways that are inexpensive and easy for people to access.
You probably guessed that one of them has to do with diet. And you would be right…
Several studies have shown that restricting your calorie intake can slow the pace of aging in both animals and humans. One in particular, the CALERIE study conducted in early 2023, showed that reducing calories by about 12 percent slowed the pace of aging by 2 to 3 percent. This translates to a 10 to 15 percent reduction in mortality risk — about the same as the impact of quitting smoking!
These results have prompted investigators to continue to study the effects of calorie restriction, hoping to get to the bottom of exactly how it works in the body to slow aging. Along the way, they’ve discovered how calorie restriction works on the genetic level…
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The gene that delays aging
Researchers have previously shown mechanisms that improve health and lifespan through dietary restriction. However, there is so much variability in response to reduced calories across individuals and different tissues that they wanted to understand why different people respond to diets in different ways.
International researchers started by scanning about 200 strains of fruit flies with different genetic backgrounds. The flies were raised on two diets: one normal diet and one in which they were given 10 percent of normal nutrition.
The team identified five genes with specific variants significantly affecting longevity when put under calorie restriction. Of those five, two had counterparts in human genetics.
There was one gene in particular the researchers chose to explore more thoroughly. It was known as “mustard” (mtd) in fruit flies and “Oxidation Resistance 1” (OXR1) in humans and mice. This gene protects cells from oxidative damage.
In humans, losing OXR1 results in severe neurological defects and premature death. By contrast, extra OXR1 improves survival in a mouse model of amyotrophic lateral sclerosis (ALS).
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OXR1 could be linked to neurodegenerative disease
The researchers found that OXR1 affects a complex called the retromer, a set of proteins necessary for recycling cellular proteins and lipids.
“The retromer is an important mechanism in neurons because it determines the fate of all proteins that are brought into the cell,” says Dr. Kenneth Wilson, a postdoc at Buck Institute for Research on Aging and first author of the study. Retromer dysfunction has been associated with age-related neurodegenerative diseases, specifically Alzheimer’s and Parkinson’s diseases, both of which are protected by calorie restriction.
Calorie restriction slows brain aging through mtd/OXR1’s maintenance of the retromer. The study found that mtd/OXR1 preserves retromer function and is necessary for neuronal function, healthy brain aging and the lifespan extension seen with calorie restriction.
“Diet is influencing this gene,” Wilson says. “By eating less, you are actually enhancing this mechanism of proteins being sorted properly in your cells, because your cells are enhancing the expression of OXR1.”
The team also discovered that boosting mtd in fruit flies caused them to live longer. This could mean that more OXR1 might help extend lifespan in humans.
“Our next step is to identify specific compounds that increase the levels of OXR1 during aging to delay brain aging,” says Buck professor Dr. Lisa Ellerby, co-senior author of the study.
Researchers hope this work will help identify potential therapeutic targets to slow aging and age-related neurodegenerative diseases.
If you want to give calorie restriction a try but are intimidated by the idea of intermittent fasting, Virginia Tims-Lawson has some ideas to help you cut your calories by 15 percent. Since I like to eat out a lot, my favorite trick is to ask my server to bring a to-go box with my meal. I then put half the meal inside the box to ensure I don’t overeat.
And if you’re someone who can’t calorie restrict because of health issues or your life situation, check out nicotinamide riboside. This supplement could provide some of the benefits of calorie restriction without the hassle or hunger.
Other ways to slow brain aging include eating a daily serving of green leafy vegetables and exercise.
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Sources:
Scientists identify how dietary restriction slows brain aging and increases lifespan — Science Daily
OXR1 maintains the retromer to delay brain aging under dietary restriction — Nature Communications
By Carolyn Gretton
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