Protein Restriction May Slow Aging and Extend Lifespan, Comprehensive Review of 350+ Papers Suggests
核心洞察
A review of over 350 papers published in Cell Press Blue finds that consuming less protein may improve metabolism, reduce cellular damage, and extend lifespan, particularly in sedentary individuals.
The hormone FGF21 (搜索), which rises when protein intake is low, appears to increase energy expenditure, improve blood sugar control, and reduce inflammation (搜索).
Restricting specific amino acids such as methionine, isoleucine, and valine may drive many of the observed anti-aging benefits.
A sweeping review of more than 350 scientific papers, published July 31 in the Cell Press journal Cell Press Blue, challenges the prevailing enthusiasm for high-protein diets by presenting evidence that consuming less protein could improve metabolic health and, in some cases, extend lifespan. The analysis, led by aging biologist Dudley Lamming of the University of Wisconsin–Madison and colleague Bailey Knopf, outlines how protein restriction slows aging by improving metabolism, changing how cells respond to nutrients, reducing cellular damage, and preserving healthy cell function.
"It's absolutely crystal clear that there are benefits of protein to muscle growth and exercise response of active individuals," Lamming said. "But because most people are relatively sedentary, many people are likely consuming more protein than they actually need, which probably has negative health consequences."
The review arrives at a moment when protein-fortified foods have proliferated across grocery shelves—from cereals and coffee to protein-infused water—and U.S. dietary guidelines have nearly doubled previous recommendations for daily protein intake to 1.2–1.6 grams per kilogram of body weight.
The FGF21 Connection
One of the central mechanisms identified in the review involves fibroblast growth factor 21 (FGF21 (搜索)), a hormone that rises when protein intake is low. FGF21 can increase the body's energy expenditure, improve blood sugar control, and reduce inflammation (搜索). Studies in mice have shown that animals with higher FGF21 levels lived longer than normal mice, with the benefit more pronounced in male mice than female mice. Eating less protein raises FGF21 levels in humans as well.
In one recent study cited in the analysis, researchers placed 22 healthy, lean men in their 20s on low-protein diets for five weeks. As with mouse studies, the men needed to eat more to maintain body weight, and their FGF21 (搜索) levels increased. The findings were reported in March 2025 in Nature Metabolism.
Key Amino Acids Driving the Effect
The review highlights several amino acids that appear to drive many of the observed effects, including methionine, isoleucine, and valine. Studies show that consuming too much of these amino acids could trigger biological processes that promote growth, increasing the risk of obesity (搜索), inflammation (搜索), and other age-related diseases.
Cristal Hill, a molecular biologist of aging at the University of Southern California's Leonard Davis School of Gerontology who was not involved with the study, explained the underlying mechanism: when someone exercises, the body uses amino acids to help build muscle. Without exercise, however, extraneous amino acids accelerate cell turnover, resulting in more molecular and cellular damage that accumulates across one's lifetime.
The Exercise Factor
Lamming notes that athletes often consume large amounts of protein without developing metabolic diseases. He suspects that regular exercise, perhaps by using protein to build strong healthy muscles, helps protect them from the negative health effects associated with a protein-rich diet.
"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."
This view is echoed by behavioral scientist Chris Macdonald of the University of Cambridge's Lucy Cavendish College, who argues that dietary guidance typically starts with protein and treats exercise as an afterthought. "We need to start from exercise," Macdonald said.
A Divided Field and Open Questions
The protein research landscape remains a paradox. Depending on the study, eating less or more protein helps with weight loss and disease prevention, as Hill and colleagues noted in a 2025 Annual Review of Nutrition. Proponents of high-protein diets point to considerable evidence showing that eating more protein can benefit health by bolstering physical performance and reducing or preventing obesity (搜索)—work largely conducted in humans. Studies suggesting the opposite have been done mainly using other animals.
No long-term studies of low-protein diets in humans exist yet, Lamming acknowledges. Nutritionist Joseph Matthews of the University of Arkansas for Medical Sciences in Little Rock said, "What we need is a handful of high-quality human studies." Matthews added that the review offers "sufficient evidence to warrant trialing [low-protein diets] in humans."
Both high- and low-protein diet camps agree that protein recommendations should be personalized based on individual sex, age, genetics, and exercise levels. What those amounts should be, however, remains an open question. Lamming and most experts do not recommend a low-protein diet for pregnant women, children, the elderly, and certain other groups who have higher protein needs.