Diet supplemented with methionine extended the healthy life span of mice

The study was based on a diet inspired by the traditional diet of the long-lived people of Southern Europe, which is predominantly plant-based, with the addition of fish, and contains low levels of protein. The experimental version (LDMM) was designed to include a small but sufficient amount of methionine (an amino acid found in eggs, meat, and dairy products). The goal was to test whether this approach could reduce the risk of frailty, as plant-based diets tend to have lower levels of essential amino acids compared to animal-based diets.

The experiment involved 20-month-old mice, which were divided into four groups and fed according to different schemes:

• standard diet;
• Western diet with high fat and sugar content;
• low-carbohydrate ketogenic diet;
• low-protein longevity diet with added methionine (LDMM).

The LDMM diet performed the best. They increased the healthy period of life, reduced fat mass and manifestations of senility. At the same time, they could eat the same amount of calories as the other groups, and even more in terms of food volume, but they lost fat without losing muscle mass. An important condition was that the level of methionine should be low but sufficient.

Additionally, mice on the LDMM diet showed more favorable biomarkers of cardiometabolic health. In particular, they had higher levels of signaling molecules that affect metabolism and aging processes (such as GLP-1). According to the authors of the work, the fact that the changes affected several metabolic hormones at once looks promising, although the mechanisms of regulation of these pathways differ in mice and humans.

The key conclusion of the researchers is that it is not only the total amount of protein in the diet that matters, but also the composition of amino acids. Too little methionine led to senility, while too much negated the benefits of a diet based on the principles of nutrition of long-lived populations (such as the traditional diets of the inhabitants of Italy and Okinawa).

An analysis of the participants’ data showed that those who consumed the most animal protein (and therefore more methionine) were more likely to be obese and twice as likely to have diabetes compared to those who consumed little animal protein. This was true even when they had lower overall calorie intake and a healthier diet in general.

These findings challenge the assumption that reducing calorie intake is the only way to lose weight. They also highlight the importance of understanding specific mechanisms. Strategically, it is more important to manage not just the amount of protein, but the level of specific amino acids.

The next step that scientists are planning is a controlled clinical trial of the LDMM diet in humans. If the effects are comparable, this approach could become a tool for extending the period of healthy life.