Protein advice often sounds simple: Eat more of it. But a new USC-led study suggests the relationship between protein, aging and metabolic health may be more complicated, especially when researchers look at the type of protein and the mix of amino acids in the diet.
The study, published in Cell Metabolism, found that older mice fed a low-protein, Mediterranean-inspired diet supplemented with a small amount of the amino acid methionine had lower fat mass, less frailty and better markers of cardiometabolic health than mice fed several other diets. Researchers also analyzed existing human diet data from more than 200,000 people and found that higher animal protein intake was associated with higher prevalence of obesity and type 2 diabetes. The findings are intriguing, but they do not prove that this diet would extend healthy lifespan in people.
The study also comes with important commercial context: Lead researcher Valter Longo has equity interest in L-Nutra, a company that develops medical foods, and several authors or USC have patent or licensing interests related to fasting-mimicking diet research or aspects of the new findings.
The main experiment was conducted in 20-month-old mice, an age meant to model later life. Researchers compared four diets: a standard diet, a Western diet high in fats and sugars, a low-carbohydrate ketogenic diet and a low-protein, methionine-supplemented longevity diet.
Methionine is an essential amino acid, meaning the body needs it but cannot make it on its own. It is found in foods including eggs, meat and dairy, as well as fish and some plant foods. The diet tested in the study was largely plant- and fish-based, with a small but sufficient amount of methionine and other essential amino acids.
Mice fed the methionine-supplemented longevity diet had better health span, meaning the portion of life spent in good health. They also had reduced fat mass and less frailty. Researchers reported improvements in several metabolic signals, including higher levels of GLP-1 and FGF21, hormones involved in metabolism and energy balance.
“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 Maura Fanti, first author of the study and a research associate at the USC Leonard Davis School of Gerontology.
That does not mean methionine supplementation is ready for everyday use. The release notes that too little methionine caused frailty in the animal experiments, while too much appeared to cancel out the benefits of the diet. That narrow balance is one reason the findings should not be treated as a do-it-yourself supplement strategy.
The human data also require caution. Researchers analyzed existing information on diet and health, which can show patterns but cannot prove cause and effect. People who eat more or less animal protein may differ in many other ways, including overall diet quality, income, health history, physical activity and access to care. The study found associations with obesity and type 2 diabetes, not proof that animal protein caused those conditions.
Still, the study raises a timely question. Protein has become one of the dominant themes in wellness marketing, with many products and diet plans emphasizing higher intake. For some people, especially older adults at risk of muscle loss, adequate protein matters. But the new findings add to a more nuanced conversation: More is not always the only question. Protein source, amino acid composition, life stage and overall dietary pattern may matter too.
“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,” Longo said.
The study does not overturn existing nutrition advice. It does not show that people should avoid animal protein entirely, follow a very low-protein diet or start taking methionine. It also does not prove that a low-protein diet is safe or beneficial for everyone. Protein needs can vary by age, health status, activity level and medical conditions.
What it does offer is a reason to look beyond protein totals alone. A plant-forward eating pattern that includes fish, legumes, whole grains, vegetables, nuts and healthy fats already aligns with many long-standing recommendations for metabolic and heart health. Whether a carefully designed amino acid-supplemented version of that pattern can improve healthy aging in humans remains a question for future clinical trials.
The study was funded by the National Institute on Aging, the National Institutes of Health and the USC Edna Jones Chair Fund. Valter Longo has 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 at the University of Southern California, and USC has licensed related intellectual property to L-Nutra. Under that agreement, USC may receive royalty payments from L-Nutra. Longo and Maura Fanti are also inventors on a U.S. provisional patent application filed by USC covering aspects of the methods and findings described in the study.