A carefully balanced diet of plant- and fish-based, low-protein, amino acid foods found in foods such as eggs, meat and dairy products can help mice stay healthy as they age, according to a new study from the University of Southern California. This diet increased the healthy lifespan, reduced body fat, and decreased frailty in older mice.
The survey results are cell metabolismbacked by an analysis of dietary and health data from more than 200,000 people conducted by researchers at USC, the University of Toronto, and Harvard University. People who followed a more plant-based dietary pattern were also shown to have lower rates of obesity and type 2 diabetes.
Together, the findings in mice and humans suggest that a Mediterranean-style “longevity diet” centered on vegan or vegetarian foods, including primarily fish, may provide important health benefits. According to senior author Valter Longo, this diet provides a small but sufficient amount of methionine and other essential amino acids.
A Mediterranean-inspired longevity diet
Longo has spent years researching how nutrition affects aging and disease. His previous research focused on the traditional low-protein, plant-based Mediterranean diet commonly found in parts of southern Europe, where people often live very long lives.
Although these people tend to have the highest life expectancies in the world, they also experience relatively high levels of frailty in old age. Because plant foods naturally contain lower levels of essential amino acids than animal foods, Longo developed a modified longevity diet that added small amounts of methionine to determine whether he could reduce frailty while maintaining the benefits of a plant-based eating pattern.
To test this idea, the researchers fed 20-month-old mice one of four diets. Western diet high in fat and sugar. Low carbohydrate ketogenic diet. or a low-protein, methionine-added longevity diet (LDMM).
Mice fed LDMM consistently performed best. Mice on other diets had longer health spans (the portion of their lives spent in good health), had less body fat, and showed fewer signs of frailty.
“We expected that different diets would produce different results, but what really impressed us was that modulating just one amino acid, methionine, in the longevity diet could cause such dramatic metabolic changes,” said USC Leonard Davis Research Fellow Maura Fanti, lead author of the new study. “This points to the idea that not only the overall protein amount, but also the amino acid composition may be a target for strategic metabolic intervention.”
Metabolic health improved despite higher food intake
The researchers also discovered several biological markers associated with improved cardiometabolic health in mice fed LDMM. Among them were increased levels of GLP-1 and other signaling molecules involved in regulating metabolism and aging across many species.
“Of course, there are differences in how these pathways are regulated between mice and humans, but it’s really encouraging to see such coordinated changes across multiple metabolic hormones, and we’re very interested to see if similar magnitude effects are seen in human studies,” Fanti said.
Longo highlighted another surprising result. Mice that ate LDMM ate more food than any other group and took in as many calories as any other diet, yet still lost body fat while maintaining lean muscle mass. These benefits appeared only when low methionine levels were sufficient.
Human data shows similar benefits
An analysis of more than 200,000 people revealed a similar pattern. Participants who ate the highest amount of animal protein, i.e. those who had the highest intakes of methionine and other essential amino acids, had higher rates of obesity and were twice as likely to develop type 2 diabetes than those who ate little or no animal protein.
These differences remained even though those who ate the highest amounts of animal protein generally ate fewer calories and otherwise had healthier diets, Longo said.
“This challenges the conventional wisdom that you need to reduce calories to lose weight, but it also tells us that we need a clear understanding of the mechanisms,” he says. “Too little methionine causes frailty, but too much methionine eliminated the benefits of this diet based on diets of long-lived populations, such as traditional Italian and Okinawan diets. … These results indicate that overall protein intake may be less important than specific amino acid intakes.”
The next step, the researchers say, is to test LDMM in controlled clinical trials in humans to determine whether the same health benefits can be achieved in humans.
Research details and disclosures
The study was led by researchers at the University of Southern California Leonard Davis School of Gerontology in collaboration with scientists at the University of Toronto, Harvard University, University of Campinas, Keck School of Medicine at the University of Southern California, and Children’s Hospital Los Angeles.
Funding was provided by National Institute on Aging grant AG084485, National Institutes of Health grant GR1045540, and the USC Edna Jones Chair Fund.
Valter Longo owns shares in L-Nutra, a company that develops medical foods. Longo, Todd Morgan and Sebastian Brandhorst have filed a patent on the fasting-mimicking diet through the University of Southern California, which has licensed related intellectual property to L-Nutra and may receive royalty payments. Longo and Maura Fanti are also inventors on a U.S. provisional patent application covering aspects of the method and discovery described in the study.
