A mostly plant and fish based diet with low protein and carefully balanced levels of an amino acid found in foods like eggs, meat, and dairy helped mice stay healthier as they aged, according to new research from the University of Southern California. The diet increased healthspan, reduced body fat, and lowered frailty in older mice.
The findings, published in Cell Metabolism, were supported by an analysis of dietary and health data from more than 200,000 people conducted by researchers from USC, the University of Toronto, and Harvard University. People who followed more plant focused eating patterns also showed lower rates of obesity and Type 2 diabetes.
Together, the mouse and human findings suggest that a Mediterranean inspired “longevity diet” centered on mostly vegan or vegetarian foods with fish may offer important health benefits. According to senior author Valter Longo, the diet provides low but adequate amounts of methionine and other essential amino acids.
A longevity diet inspired by the Mediterranean
Longo has spent years studying how nutrition influences aging and disease. His previous work has focused on the traditional low protein, plant centered Mediterranean diets commonly found in parts of southern Europe, where people often live exceptionally long lives.
Although these populations tend to have some of the world’s longest life expectancies, they also experience relatively high levels of frailty in old age. Because plant foods naturally contain lower levels of essential amino acids than animal products, Longo developed a modified longevity diet that adds a small amount of methionine to determine whether it could reduce frailty while preserving the advantages of a plant focused eating pattern.
To test the idea, researchers fed 20 month old mice one of four diets: a standard diet; a Western diet high in fats and sugars; a low carbohydrate ketogenic diet; or a low protein, methionine supplemented longevity diet (LDMM).
The mice eating the LDMM consistently performed best. They experienced a longer healthspan (the portion of life spent in good health), carried less body fat, and showed fewer signs of frailty than mice on the other diets.
“We expected different diets to produce different outcomes, but what really impressed us was how modulating just a single amino acid, methionine, in the longevity diet could produce such dramatic metabolic changes,” said USC Leonard Davis Research Associate Maura Fanti, first author of the new study. “It points to the idea that amino acid composition, not just overall protein quantity, may be the target of strategic metabolic interventions.”
Metabolic health improved despite higher food intake
The researchers also found several biological markers associated with improved cardiometabolic health in mice fed the LDMM. Among them were increased levels of GLP-1 and other signaling molecules involved in regulating metabolism and aging across many species.
“There are, of course, differences in how these pathways are regulated between mice and humans, but seeing such coordinated changes across multiple metabolic hormones is genuinely encouraging, and we’re very curious to know whether effects of similar magnitude would be seen in human studies,” Fanti said.
Longo highlighted another surprising result. Mice eating the LDMM consumed more food than any of the other groups and took in as many calories as the other diets, yet still lost body fat while maintaining lean muscle mass. Those benefits appeared only when methionine levels remained low but sufficient.
Human data point to similar benefits
The analysis of more than 200,000 people revealed a similar pattern. Participants who consumed the most animal protein, and therefore the highest levels of methionine and other essential amino acids, had higher rates of obesity and were twice as likely to have Type 2 diabetes compared with people who ate little or no animal protein.
According to Longo, these differences remained even though people with the highest animal protein intake generally consumed fewer calories and otherwise had healthier diets.
“This challenges the dogma that calorie reduction is necessary to lose weight, but it also tells us that we need to have clear understanding of the mechanisms,” he said. “Too little methionine caused frailty, but too much methionine abolished the benefits of this diet, which was otherwise based on the diet of long-lived populations like the traditional Italian and Okinawa diets. … These results indicate that overall protein intake may be less important than specific amino acid intake.”
The research team says the next step is to test the LDMM in a controlled clinical trial involving people to determine whether the same health benefits can be achieved in humans.
Study details and disclosures
The study was led by researchers from the USC Leonard Davis School of Gerontology in collaboration with scientists from the University of Toronto, Harvard University, the University of Campinas, the Keck School of Medicine of USC, and Children’s Hospital Los Angeles.
Funding was provided by National Institute on Aging grant AG084485, National Institute of Health grant GR1045540, and the USC Edna Jones Chair Fund.
Valter Longo has an equity interest in L-Nutra, a company that develops medical foods. Longo, Todd Morgan, and Sebastian Brandhorst have filed patents related to 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 methods and findings described in the study.