Scientists suggest restricting “essential” amino acid may be key to extending lifespan

29 Nov 2023 --- Researchers suggest that reducing the intake of the amino acid isoleucine extends the lifespan of mice, making them leaner and less frail as they age and reducing cancer and prostate problems. They are optimistic that these results can be translated to humans, but further research is required.

Mice consuming a reduced isoleucine diet lived longer, by an average of 33% for males and 7% for females. Based on 26 health measurements, these mice were in much better shape during their extended lives. 

Moreover, they explain that isoleucine restriction is geroprotective because it extends the mice’s lifespan and decreases frailty in those that were six months old — equivalent to a 30-year-old human. 

“We have identified isoleucine as a key amino acid — one of the building blocks of protein — as a crucial regulator of lifespan and healthy aging in adult mice of both sexes,” lead author Dudley Lamming, a professor and metabolism researcher at the University of Wisconsin, US, tells Nutrition Insight.

“Overall, this research adds to accumulating evidence that consuming lower than typical levels of isoleucine can promote metabolic health and reduce adiposity. We need to prove that our results in mice translate into humans. If they do, isoleucine-restricted diets or drugs to mimic these effects could be a way to promote healthy aging in people.”  

Previous data indicates that overweight and obese US citizens may be eating more isoleucine than needed.Isoleucine can be found in eggs, dairy, soy protein and several types of meat. Previous data from the research team indicates that overweight and obese US citizens may be eating significantly more isoleucine than needed. 

Low-isoleucine diet 
The researchers highlight that low-protein diets promote health and longevity. Moreover, they explain that previous research demonstrated that restricting the branched-chain amino acids (BCAAs) leucine, isoleucine and valine, drive many of these benefits in young mice. 

In the study, published in Cell Metabolism, the researchers fed genetically diverse mice either a balanced control diet, a diet low in 20 amino acids or a diet that restricted isoleucine intake by 67%. 

Isoleucine restriction had “dramatic effects on weight, fat mass, glycemic control and energy expenditure,” reveals the study. Moreover, the authors note that these effects were more significant in mice with a low-isoleucine diet than those with a reduced intake of 20 amino acids. Moreover, the low-amino acid diet did not extend lifespan in mice. 

“Previous research has shown lifespan increase with low-calorie and low-protein or low-amino-acid diets starting in very young mice,” says Lamming. “We started with mice that were already getting older. It’s interesting and encouraging to think a dietary change could still make such a big difference in lifespan and what we call ‘healthspan,’ even when it started closer to mid-life.”

He adds that mice on the low-isoleucine diet consumed significantly more calories than mice on other diets, which he attributes to the mice trying to make up for obtaining less isoleucine. However, these mice also burned more calories, maintaining a leaner body weight through adjustments in metabolism, not by getting more exercise. 

At the same time, Lamming says mice on the low-isoleucine diet maintained steadier blood sugar levels, while male mice experienced less age-related prostate enlargement. Male mice on this diet were also less likely to develop a tumor. 

Importance of protein quality   
The researchers note that isoleucine restriction improves metabolic health without inducing ‘‘binge eating’’ behavior and improves median lifespan in female mice, which is not seen by restricting intake of branched-chain amino acids. 

Moreover, the study provides “new evidence that protein quality — the specific amino acid composition of dietary protein — is as important, or even more important, than the amount of protein or calories consumed.”

Lamming highlights that different components of people’s diet have value and impact beyond their function as a calorie, adding that “a calorie is not just a calorie.” 

While the study has promising results, the researchers note that the precise biological mechanism by which isoleucine restriction extends healthspan and lifespan is unclear. Lamming expects that the study’s results may help future research. 

“That we see less benefits for female mice than male mice is something we may be able to use to get to that mechanism,” he says.

The researchers are optimistic that isoleucine restriction may have similar benefits in humans.Health implications for humans 
The researchers are optimistic about the benefits of isoleucine restriction. The fact that this works in a “genetically heterogeneous population suggests that such an intervention may apply to humans.” 

At the same time, Lamming cautions not everyone can switch to a low-isoleucine diet. “Isoleucine is an essential amino acid in our diet — we need it to live.” 

“However, many people may be eating a harmful amount. We previously showed that dietary isoleucine consumption is associated with body mass index — and thus obesity — in humans, while other groups have found that blood levels of isoleucine are associated with insulin resistance and mortality risk.”  

Meanwhile, he notes that it may be challenging for people to reduce their isoleucine intake as it is prevalent in various foods. He suggests: “It could be that by choosing healthier foods and eating in general, we might be able to lower isoleucine enough to make a difference.” 

The authors add that additional research is required to determine if there are any potentially harmful effects of restricting isoleucine intake and to determine optimal levels of the amino acid for different ages and genders. 

“These studies were not performed in people, and testing the effects of dietary isoleucine restriction in people remains to be done,” says Lamming. 

“We would also like to find pharmaceutical methods to restrict isoleucine or mimic the effects of these diets, as many people find long-term dietary modifications very difficult.”

By Jolanda van Hal