Evidence so far has supported caloric restriction for its purported longevity benefits, but reducing protein intake has not been widely explored.
Now, a new review, published in the journal Cell Press Blue, suggests that restricting overall dietary protein intake or specific essential amino acids could help people achieve improved health span and increased longevity, similar to that achieved through calorie restriction.
The review, combing over 350 scientific papers on animal and human trials, outlines how restricting dietary protein and specific essential amino acids such as isoleucine and methionine helps promote healthy aging and extends life span.
The review examined the effects of protein restriction on several organisms, including microbes, mice, other animals, and humans, using observational studies, randomized controlled trials, and cell culture experiments.
Researchers found that eating less protein had many health benefits.
Consuming less protein helped the body burn more calories, reduced body fat, and better managed insulin levels by increasing levels of Fibroblast Growth Factor 21 (FGF21), a hormone that helps protect against aging.
A low protein diet also inhibited mTORC1 and activated GCN2, which are two key nutrient sensors that regulate cell growth and stress response, effectively telling the body’s cells to slow down aging and more efficiently clear cellular “trash” through autophagy.
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Eating less protein also reduced the number of senescent or aging cells. Senescent cells are often called “zombie” cells because they are damaged cells that stop dividing (mitosis) but refuse to die, driving inflammation in the background.
Another important effect scientists observed of a low protein diet was the improvements in mitochondria, the powerhouse of the cell, and decreased reactive oxygen species (ROS) damage to tissues. In animal studies, scientists also saw that lab animals lived longer and had lower age-related frailty when fed less protein.
However, the researchers emphasized that protein needs should be personalized according to physical activity and age.
Medical News Todaydiscussed the study findings with two experts — Kristin Kirkpatrick, MS, RDN, president of KAK Consulting and a dietitian at the Cleveland Clinic Department of Wellness & Preventive Medicine in Ohio, and Michelle Routhenstein, MS, RD, CDCES, CDN, a preventive cardiology dietitian at EntirelyNourished.
“This review suggests the benefit isn’t simply eating less protein — it’s how the body responds to lower levels of certain amino acids. Protein restriction appears to activate pathways involved in metabolic health and cellular repair, while reducing activity in pathways that may contribute to aging,” Kirkpatrick said.
“Eating less protein, especially certain amino acids, may help the body spend less time in a constant ‘build and grow’ state and more time in a ‘repair and clean up’ state. This may help improve how the body uses energy and reduce cellular stress, which may have longevity and metabolism-boosting effects,” Routhenstein explained.
The review specifically identifies three Essential Amino Acids (EAAs) — isoleucine, valine, and methionine — that may bring benefits when restricted in one’s diet. Reducing nonessential amino acids such as tyrosine and cysteine may also provide health benefits, according to the authors.
However, the review also stresses that reducing the intake of all amino acids may not be beneficial and lists three that may provide greater benefit when supplemented: glycine, serine, and proline.
“[T]he goal is not to avoid protein; it is about finding the right amount to support muscle strength while also promoting long-term metabolic health,” Routhenstein pointed out.
“First, this study is really examining protein intake beyond muscle health and focusing on the biology on longevity, health span, healthy aging, etc.,” said Kirkpatrick, speaking to MNT.
“This study is not saying not to consume protein, it is looking more at aging biology and metabolic pathways rather than muscle preservation,” Routhenstein clarified.
“What [the study is] examining is more about reducing certain amino acids (isoleucine and methionine) for healthy aging and the importance of balancing the message that ‘more is better’ without looking at other lifestyle changes and/or specific types of protein,” Kirkpatrick explained.
“I [w]ant to make sure that my patients don’t look at this study and just blindly eat less protein but to look at this to balance what type of protein they are consuming and their personalized needs based on age, activity level, chronic disease risk or existing conditions.”
— Kristin Kirkpatrick, MS, RDN
“Higher protein intake is still important for maintaining muscle mass, strength, and recovery, especially with aging and exercise. However, this review suggests that lower protein intake or restriction of specific amino acids may activate longevity pathways, reduce chronic growth signaling, and improve metabolic health,” Routhenstein told MNT.
“The findings do not mean everyone should eat less protein, but highlight that optimal protein intake depends on individual goals, age, activity level, and health status,” she said.
Kirkpatrick underscored that current calls for higher protein intake have largely been driven by research showing health benefits linked to muscle maintenance, improved muscle recovery, increased strength, and a reduced risk of sarcopenia (muscle wasting) associated with aging.
“These recommendations remain well supported by human research, so just having less is not the message, it’s to look deeper into types of protein as well as other factors associated with aging,” she explained.
Although the study does promote that low protein intake can support metabolic health in early and middle age, it makes an important point: age matters.
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The study notes that reduced protein intake may adversely affect certain groups. It states that adults older than age 65 can have protein insufficiency, be at risk of frailty, and experience sarcopenia, which means protein restriction could be contraindicated.
“If there is anything overlooked [in the study], perhaps it’s that this has the potential to underemphasize the well-studied role that protein plays in preserving muscle,” Kirkpatrick said.
“The study also does not fully account for the importance of maintaining muscle, resistance training, or the overall dietary pattern,” Routhenstein said.
This review also focuses on cellular longevity, which is the process of keeping individual cells in the body healthy and young at the molecular level.
The point of confusion and potential contention with previous research comes from the fact that most of them focus on functional longevity, which is about staying strong, mobile, and reducing frailty that comes with age.
And while functional longevity is important for operating independently and healthily throughout life, even in older age, cellular longevity is the driving factor.
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An important point the study makes is that it argues for restricting specific essential amino acids, rather than all proteins.
“The biggest surprise wasn’t that lower protein looked beneficial — it was that specific amino acids may matter more than total protein,” Kirkpatrick said, adding: “But we need more human studies to continue exploring this concept.”
The study also distinguishes between the type of protein consumed and its purported health benefits. The researchers emphasize that, compared with animal protein, plant protein has been associated with a lower risk of frailty.
“The biggest limitation is that much of the research comes from animal studies, and we still need more long-term human data,” Routhenstein said.
What all this research so far shows us is that our protein needs evolve and change over our life span:
“The takeaway I would discuss with my patients is that healthy aging has multiple goals—maintaining muscle, preserving metabolic health, reducing frailty, and supporting cognitive function. Protein is one piece of a larger puzzle related to health span but taking a step back and finding the best personalized approach for one’s individual needs is a key factor in living not only longer but better.”
— Kristin Kirkpatrick, MS, RDN
