Yoshitaka Kondo, Theme Leader, Molecular Regulation of Aging
● What kind of diet leads to a long and healthy life?
In Japan, which has entered a super-aged society, the average lifespan continues to increase. However, the considerable gap between life expectancy and healthy life expectancy (the period during which one can live without limitations in daily life) has become a societal issue. In this context, what can we do in our daily lives to live long and stay healthy?
For a long time, the saying "Hara hachibunme" (eating until 80% full) has been regarded essential for health and longevity. Studies on monkeys and mice have shown that dietary or calorie restriction by limiting the amount of food intake and calories can suppress the onset of age-related diseases and extend lifespan. However, reducing food intake or calories over a long period requires enduring hunger, which makes it quite difficult to maintain.
On the other hand, "a well-balanced diet" is also considered important. Many people probably try to eat a variety of foods, combining staple foods, main dishes, side dishes, and soups, including rice, meat, fish, and vegetables. But how much of each nutrient should we actually consume in order to live a long and healthy life?
● The Balance of the Three Major Nutrients in the Japanese Diet
Nutrients can be categorized into three major nutrients that provide energy (proteins, fats, and carbohydrates) as well as micronutrients (vitamins and minerals) (Figure 1). According to the 2022 National Health and Nutrition Survey (Reference 1), the average daily energy intake per person in Japan is 1,888 kcal, and the ratio of energy derived from the three major nutrients against the total energy is 15% for proteins, 29% for fats, and 56% for carbohydrates (Figure 1). Meanwhile, the 2025 edition of the Dietary Reference Intakes for Japanese (Reference 2) sets the target ratios for the three major nutrients against the total energy intake as follows: (1) proteins: 13-20% (for individuals younger than 50 years of age), 14-20% (for individuals aged 50-64 years), 15-20% (for individuals aged 65 years and older); (2) fat: 20-30%; and (3) carbohydrates: 50-65%. Therefore, on average, most people in Japan can be considered to have a good balance of the three major nutrients. However, given that the target ratios for the three major nutrients were established to prevent the onset and progression of lifestyle-related diseases, there is still a lack of scientific evidence regarding the optimal intake ratios for achieving longevity and maintaining health.
Figure 1: The Balance of the Three Major Nutrients in the Japanese Diet
Proportions of the Three Major Nutrients in Total Energy Intake (Ministry of Health,
Labour and Welfare, 2022 National Health and Nutrition Survey, 2024)
● The Ratio of Protein in the Diet Affects the Amount of Food Intake
In recent years, studies in mice have revealed that the balance of the three major nutrients in the diet, especially the proportion of protein intake, has a marked impact on lifespan and health. However, the optimal balance of these nutrients for a healthy and long life across different life stages, such as childhood, young adulthood, middle age, and old age, has not yet been clearly determined.
To investigate the appropriate protein intake ratio for maintaining health in older adults, we conducted an experiment using young (6 months old) and middle-aged (16 months old) male mice. We fed them five different diets for 2 months, each with a different protein ratio (5%, 15%, 25%, 35%, 45%), and examined how protein intake ratios and age affected the body (Figure 2). All diets had equal caloric content, with the fat ratio fixed at 25%, which is similar to that of the Japanese population, and only the protein and carbohydrate ratios were varied. Specifically, the composition of the five diets was as follows: (1) 5% proteins, 25% fats, and 70% carbohydrates; (2) 15% proteins, 25% fats, and 60% carbohydrates; (3) 25% proteins, 25% fats, and 50% carbohydrates; (4) 35% proteins, 25% fats, and 40% carbohydrates; and (5) 45% proteins, 25% fats, and 30% carbohydrates. The nutrient balance in the 15% protein diet closely resembles the average balance of the three nutrients in a typical Japanese diet and can thus be considered the standard diet.
Results showed that the body weight of middle-aged mice was higher than that of the younger mice, and mice in the 5% protein group had lower body weight than those in the other groups (Figure 3) (Reference 3). Furthermore, the amount of food consumed by middle-aged mice was greater than that by the younger mice. Among the groups, the 5% protein group consumed more food than the others, while the 45% protein group consumed the least (Figure 3). This phenomenon, where insufficient protein intake leads to increased food consumption, and adequate protein intake leads to decreased consumption, is known as the "protein leverage" hypothesis. It suggests that appetite is regulated in order to maintain a consistent internal level of protein. Therefore, we can say that with a diet containing 5% protein, the intake of protein is insufficient, causing an increase in the quantity of food consumed (and thus an increase in calorie intake). Conversely, with a diet containing 45% protein, protein is consumed in excess, leading to a reduction in food intake (and therefore a decrease in calorie intake).
Figure 2: The Relationship Between Dietary Protein Intake and Health by Age
Young and middle-aged mice were fed five types of diets with varying protein and
carbohydrate ratios, and changes in their bodies were examined after 2 months.
● A Healthy "Well-Balanced Diet" Has a Protein Ratio of 25-35%
Next, we investigated how the proportion of protein intake affects fat accumulation in mouse liver. In the livers of the mice in the 5% protein group, numerous fat droplets were observed, and the livers contained high levels of triglycerides and total cholesterol, indicating the presence of mild fatty liver (Figure 3) (Reference 3). Fatty liver caused by protein deficiency is known in humans as one of the symptoms of kwashiorkor, a form of malnutrition due to insufficient protein intake. Additionally, in the livers of the middle-aged mice in the 5% and 15% protein groups, triglyceride levels were higher than those in younger mice (Figure 3). In contrast, both young and middle-aged mice in the 35% protein group had low levels of triglycerides in their livers (Figure 3). These findings suggest that increasing the dietary protein ratio to around 35% may help prevent or alleviate fatty liver.
We also examined how the dietary protein ratio affects blood test values. Blood glucose levels were lower in both young and middle-aged mice in the 25% and 35% protein groups (Figure 3). There was no significant difference in blood triglyceride levels across the different protein intake groups (Figure 3). However, total cholesterol levels in the blood were highest in the 15% protein group for both age groups, while the 5%, 35%, and 45% protein groups showed lower levels (Figure 3). Our findings suggest that a dietary protein ratio of 25-35% is the most beneficial for the health of both young and middle-aged individuals (Figure 3).
● Conclusion
It has become clear that the balance of the three major nutrients in the diet, particularly the proportion of protein intake, has a marked impact on health during young and middle age. Going forward, we plan to further investigate the effects during growth and old age and differences between sexes, and to conduct studies in humans, with the aim of establishing scientific evidence for a "well-balanced diet" that promotes health and longevity. Adjusting the balance of the three major nutrients in one's diet is something we can all work on in our daily lives. Nowadays, there are mobile apps that, by recording your meals, can tell you your intake of the three major nutrients. Why not start paying attention to the balance of the three major nutrients in your diet starting tomorrow?
Figure 3: Effects of Different Dietary Protein Ratios on the Bodies of Young and Middle-Aged Mice
In both young and middle-aged mice, diets with a protein ratio of 25-35% were found to be healthier than the 15% protein diet,
which reflects the average intake in the Japanese population (Reference 3).
References
