Scientists have pointed to a possible link between protein deficiency and longevity.
Limiting protein in the diet can trigger a coordinated body response that affects metabolism, hormonal signals, brain function, and dietary preferences. Scientists suggest that it is precisely this adaptation that helps explain the increase in life expectancy previously found in experiments on model organisms. The new concept was presented by researchers at the Pennington Biomedical Research Center at Louisiana State University in an article for Cell Metabolism. What is known about the protein's connection with aging and why the experimental results cannot yet be turned into a universal diet is in the "Izvestia" material.
What did the authors of the new publication suggest?
The authors of the article are Sora Kim, Sanho Yu and Christopher Morrison. Their work is a theoretical publication that combines previous research and offers an explanation of the discovered patterns. It does not present the results of a new human trial of the diet.
The researchers draw attention to the fact that a decrease in protein availability causes several changes at once. The body regulates metabolism and glucose levels differently, changes energy consumption, growth rate and food choice. According to the authors, these effects should be studied in conjunction.
The proposed concept is based on the body's ability to recognize the lack of a certain nutrient and adapt the work of different systems to it. Cells respond to the availability of amino acids, hormones transmit information between organs, and the brain participates in coordinating physiological and behavioral changes.
"The question that underlies our work is deceptively simple: how does an animal know that it's not getting enough protein?" said Christopher Morrison, professor of nutrition neuroscience.
According to him, years of research have led scientists to assume that the brain plays a key role in organizing this reaction. The same adaptive changes, as shown by animal experiments, can be associated with an increase in life expectancy.
How does protein restriction differ from calorie reduction?
Calorie restriction involves reducing the overall energy value of food. When protein is limited, the composition of the diet changes first of all: the amount of energy may remain the same. For researchers, this difference is fundamental. It allows you to find out which changes are associated with a general lack of energy, and which are related to the availability of protein and its constituent amino acids.
In experiments, an increase in life expectancy with a decrease in protein load was observed in different species. The authors of the new publication consider these results as a basis for searching for common mechanisms of adaptation to the composition of food.
However, the concept of "protein restriction" does not describe a single standard diet. To evaluate the results, the degree of reduction, the initial diet, the duration of the intervention and the characteristics of the body are important. The mere presence of a positive effect in a particular experiment does not establish the optimal amount of protein for humans.
How nutrition is related to the signs of aging
In research on aging, the concept of its key features is widely used — biological processes that are involved in age-related changes. The updated model, published in Cell in 2023, identifies 12 such features.
These include genome instability, mitochondrial dysfunction, cellular aging, and changes in nutrient recognition systems. These processes help to describe how cells and tissues change over time and why their functional capabilities decrease.
Previous work has shown that protein restriction can affect several signs of aging simultaneously. However, many studies look at individual cellular mechanisms, whereas changes in appetite, hormonal signals, and metabolism occur at the level of the entire body.
The authors of the new concept propose to combine these levels of analysis. In their opinion, it is important to find out how the cellular response to the composition of food is consistent with the work of the brain and other organs.
"Considering protein restriction as a consistent physiological state shifts attention to how cellular nutrient recognition systems, endocrine signals, neural circuits, and tissue physiology work together," the publication says.
What role does the hormone FGF21 play?
Researchers consider FGF21, fibroblast growth factor 21, which performs the function of a hormonal signal, to be one of the central elements of this reaction.
FGF21 helps transmit information about protein availability beyond individual cells. According to the research discussed by the authors of the new article, its effect in the brain is involved in changing metabolism and food preferences.
The significance of this signal for longevity was studied in a paper published in 2022 in Nature Communications. Researchers have shown that FGF21 is necessary to increase life expectancy and improve metabolic health while limiting protein in male mice.
This result indicates the importance of the body's response to dietary changes. In the studied model, protein reduction alone was not enough to obtain the expected benefits without the involvement of the corresponding hormonal signal. In the new concept, FGF21 is considered as part of a broader system. The authors seek to understand how its action is related to cellular mechanisms, neural circuits, and changes in various tissues.
Why scientists are interested in food preferences
As the availability of protein decreases, the desire to choose foods that contain it may also change. The authors believe that such behavioral changes deserve attention when studying the mechanisms of longevity.
Food preferences reflect the interaction of the body's needs and the functioning of the nervous system. If the brain is involved in coordinating the response to protein deficiency, changes in food choice can provide information about how pronounced this reaction is.
Similar principles of the connection between nutrition and the brain have been studied in fruit flies. According to the authors, signals from the intestine transmit information about the nutritional status of the body and can affect both food preferences and life expectancy.
However, an increased desire for protein foods does not in itself mean that the body has benefited or will live longer. The researchers suggest studying it as a possible indicator of activation of a broader adaptive response.
"The desire for protein—rich foods does not necessarily cause the positive health effects of protein restriction itself, but its severity can serve as an observable indicator of how effectively a broader adaptive program has been activated," the authors write.
Is it possible to measure the body's response to a diet
The proposed concept poses a question for scientists: which link of the adaptive response is associated with an increase in life expectancy? This may be the effect of individual mechanisms or the result of their coordinated work. The answer is important for understanding the differences between organisms. The same diet can cause different hormonal, metabolic, and behavioral changes.
The authors propose to investigate the potential indicators of this reaction. These include sensitivity to FGF21, metabolic changes, and cravings for foods containing protein or essential amino acids. In the long run, such indicators may help explain how the response is influenced by gender, genetic characteristics, age, and metabolic health.
What is already known about people's reactions
Some elements of the response to protein restriction have also been observed in humans. In a 2014 study, researchers analyzed blood samples from participants in a randomized trial of diets with different protein contents.
After 28 days, participants in the low-protein group had increased FGF21 levels. At the same time, the study was conducted in conditions of excessive nutrition: the energy value of the diets exceeded the needs of the participants by about 40%. Therefore, its results cannot be directly transferred to a normal diet.
The work confirmed that a hormonal response to a decrease in protein load exists in humans. However, an increase in FGF21 does not prove an increase in life expectancy and does not establish the safety of prolonged protein restriction.
It is also necessary to distinguish between intermediate indicators and real health outcomes when evaluating a new concept. Changes in hormones, glucose levels, or energy expenditure can help understand the mechanisms, but additional data is needed to draw conclusions about longevity.
Why Protein Reduction can have a Downside
Protein is necessary for the maintenance of tissues, including muscle mass. Therefore, when evaluating dietary interventions, it is important to take into account not only metabolic parameters, but also physical function.
In a review published in 2025 in the Annual Review of Nutrition, researchers noted that the benefits of protein restriction for metabolism and longevity may be accompanied by a loss of fat-free mass and a decrease in physical stability. This is one of the reasons why the results of experiments on model organisms are difficult to turn into universal recommendations.
The issue is of particular importance for the elderly. The practical guidelines of the European Society for Clinical Nutrition and Metabolism ESPEN, published in 2022, recommend the consumption of at least one gram of protein per kilogram of body weight per day. The amount should be adjusted individually, taking into account the state of nutrition, physical activity, diseases and tolerance.
The authors propose to study how the body recognizes a change in nutrition and what consequences its adaptation has. Further research should show which links of this reaction really determine the long-term benefits and whether the knowledge gained can be used to maintain health with age.
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