A University of Wisconsin-Madison review proposes that protein and amino acid restriction slows aging through several linked mechanisms, and questions whether sedentary adults benefit from today’s push to eat more protein.

Protein has become the nutrient of the moment. Supermarket shelves are crowded with protein bars, protein shakes and protein-fortified cereals, and dietary advice increasingly encourages people to eat more of it. A new review suggests that, for many people, more may not be better.

In a paper published in Cell Press Blue, researchers at the University of Wisconsin-Madison draw on more than 350 studies to argue that eating less protein, and in particular less of certain amino acids, may promote healthy aging. The authors outline what they call the hallmarks of protein and amino acid restriction, the biological changes through which lower protein intake may slow aging.

The researchers are careful not to dismiss protein’s benefits. “It’s absolutely crystal clear that there are benefits of protein to muscle growth and exercise response of active individuals,” said Dudley Lamming, the corresponding author. “But because most people are relatively sedentary, many people are likely consuming more protein than they actually need.”

Longer lives in the lab

Interest in the effects of diet on aging has long centered on calorie restriction, which extends lifespan in many laboratory animals. But eating less overall is difficult to sustain, and research over the past two decades has suggested that much of the benefit may come from what is eaten rather than how much.

Earlier studies found that reducing protein can extend lifespan in flies and rodents even without cutting calories. The new review pulls together that work and proposes that protein restriction acts through four broad routes: improving metabolism, changing how cells sense and respond to nutrients, reducing cellular damage and preserving healthy cell function.

Human evidence is more limited but growing. According to the review, recent trials found that people who ate less protein lost weight and fat mass and saw improvements in fasting blood sugar, even though they tended to eat more calories overall.

“These studies show that the amount of protein sedentary people are eating today may have negative health consequences,” Lamming said.

A hormone and three amino acids

One key player is fibroblast growth factor 21, or FGF21, a hormone that rises when protein intake is low. FGF21 can increase energy expenditure, improve blood sugar control and reduce inflammation. In mice, animals with higher levels of the hormone lived longer, with a stronger effect in males than in females.

FGF21 is produced mainly by the liver and acts as a signal of nutritional stress, telling the body to adjust its metabolism when certain nutrients are scarce. Because it can improve blood sugar control and promote weight loss in animals, drug developers have explored versions of the hormone as possible treatments for obesity, diabetes and fatty liver disease.

The review also highlights three amino acids that may drive many of the effects: methionine and the branched-chain amino acids isoleucine and valine. Excess amounts of these building blocks may promote growth-related processes in cells that are linked to obesity, inflammation and other age-related diseases.

That focus matters because proteins differ in their amino acid makeup. Animal proteins, such as meat, eggs and dairy, tend to be rich in methionine and branched-chain amino acids, while many plant proteins contain less of them. Lamming’s lab has previously studied diets that reduce specific amino acids rather than protein as a whole, an approach that might deliver some benefits without requiring people to cut protein sharply.

Branched-chain amino acids, a group that also includes leucine, are popular in sports supplements because they help stimulate muscle building. In people who are not exercising heavily, however, several studies have linked high blood levels of these amino acids to insulin resistance and type 2 diabetes, although whether they cause those problems is still debated.

Against the grain of new guidelines

The review arrives as official advice is moving in the opposite direction. U.S. dietary guidelines updated this year recommend 1.2 to 1.6 grams of protein per kilogram of body weight, or about 0.5 to 0.7 grams per pound, nearly double the previous recommendations.

The authors acknowledge that some groups need more protein, including pregnant women and some older adults, who are at risk of losing muscle mass. Regular exercise may also protect athletes who eat high-protein diets from potential downsides. But they argue that most sedentary adults may not gain the expected benefits from protein-fortified foods.

“Recent recommendations have encouraged people to eat more protein, but they’ve also encouraged people to exercise more,” Lamming said. “We probably need to personalize protein recommendations based not just on age, but also on how physically active people are.”

What the evidence can and cannot say

The review synthesizes existing research rather than presenting new experiments, and much of the strongest evidence for lifespan extension comes from animals. Lifespan studies in humans are not practical, so human research relies on shorter trials that measure markers such as weight, blood sugar and body composition, which may not fully capture effects on long-term health.

Protein needs also vary widely with age, health, body size and activity. For older adults in particular, too little protein can contribute to frailty and falls, and many nutrition researchers favor higher intakes in later life. Anyone considering a major change in diet, especially people with medical conditions, should discuss it with a doctor or dietitian.

The work was supported by the National Institute on Aging, the Wisconsin Partnership Program and the University of Wisconsin-Madison. Its message is not that protein is harmful, but that the right amount may depend more on how people live than on a single number on a label.

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Notes

1. Knopf et al. “The Hallmarks of Protein and Amino Acid Restriction in Aging and Longevity.” Cell Press Blue, 2026. DOI: 10.1016/j.cpblue.2026.100079.
2. Cell Press. “Reducing protein intake could promote healthy aging.” EurekAlert!, 31 July 2026. https://www.eurekalert.org/news-releases/1137190.

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