Studies in mice have shown that limited intake of certain essential amino acids can slow the effects of aging and even extend lifespan.
Scientists are now wondering whether these discoveries could help people live longer and better lives.
Isoleucine is one of the three branched-chain amino acids that make up proteins in the body. Although it is essential for survival, cells cannot make isoleucine from scratch, so it must be obtained from foods such as eggs, dairy products, soy protein, and meat.
But too much of a good thing can be bad: A previous study using data from a 2016-2017 survey of Wisconsin residents found that dietary levels of isoleucine were linked to metabolic health, with people with higher BMIs generally consuming much higher amounts of this amino acid.
“Various components of the diet have value and impact beyond their role as calories, and we’ve looked closely at one component that many people may be eating too much of,” Dudley Lamming, a metabolic researcher at the University of Wisconsin in the US, who worked on both studies, explained when the new findings were published in November.
“It’s intriguing and encouraging to think that dietary changes, even as we approach middle age, could make such a big difference to our lifespan and what we call ‘healthspan.'”
In the latest study, genetically diverse groups of mice were fed a control diet that included 20 common amino acids, a diet that reduced all amino acids by about two-thirds, or a diet that reduced only isoleucine by the same amount.
The mice were about six months old at the start of the study, the human equivalent of 30 years old. They were allowed to eat as much as they wanted, but only the specific type of food that was given to their group.
Dietary isoleucine restriction increased lifespan and healthspan in mice, reduced frailty, and promoted leanness and blood sugar control. Male mice had a 33 percent longer lifespan than mice that did not have isoleucine restriction, and female mice had a 7 percent longer lifespan.
The mice also scored better in 26 health measures, including muscle strength, endurance, blood sugar levels, tail use and hair loss.
Male mice from this group suffered less age-related prostate enlargement and were less likely to develop cancerous tumors, a common condition in many mouse strains.
Interestingly, the mice on the low-isoleucine diet ate significantly more calories than the other mice, but rather than gaining weight, they burned more energy and maintained a leaner body weight, despite no difference in their activity levels.
The researchers believe that depriving people of isoleucine, either through dietary or pharmaceutical means, could have similar anti-aging effects, but as with any mouse study, it’s impossible to know for sure until it’s tested in humans.
This is easier said than done: Although the food given to the mice was controlled, the researchers noted that diet is an incredibly complex chemical process, and other dietary components may be involved in producing these results.
For example, restricting protein intake in general has negative effects on the body, mice, and humans. Applying these findings to real people is more complicated than simply reducing your intake of high-protein foods, but it’s also the simplest way to restrict isoleucine intake.
The amino acid restriction levels were constant across all experiments, and the researchers acknowledged that further tweaking may be necessary for optimal effects depending on the mouse strain and sex, since one size does not fit all when it comes to diet.
“You can’t switch everyone to a low-isoleucine diet,” Lamming says.
“But narrowing down these benefits to a single amino acid brings us closer to understanding the biological process and could lead to potential interventions in humans, such as isoleucine inhibitors.”
The research was published in the journal Cell Metabolism.
A previous version of this article was published in November 2023.
