Less methionine – longer life: details

Life expectancy depends on the balance of amino acids in foodAlexander Markov, Elements
A restrictive diet prolongs the life of many animals, while reducing their fertility.

This was usually explained by the redistribution of the body's resources between the functions of reproduction and maintaining bodily health. However, experiments on fruit flies have not confirmed this hypothesis. As it turned out, fertility depends on the content of methionine in food, and longevity depends on the quantitative ratio of methionine and other essential amino acids. This allows you to choose a diet in which life is prolonged without reducing fertility.

The positive effect of a restrictive diet on longevity has been revealed in many living creatures – from yeast to primates. However, an increase in life expectancy in dieting animals (in particular, in C. elegans roundworms, fruit flies and rodents) is usually accompanied by a decrease in fertility. Many experts assumed that this was due to the redistribution of the body's resources: when there is a lack of food, the body throws all its efforts to preserve health and reduces the cost of reproduction. The strategic meaning of such a reaction may be to wait for more abundant times, when there will be plenty of food again and the offspring will have a better chance of survival.

Richard Grandison, Matthew Piper and Linda Partridge of the Institute of Healthy Aging (London) tested the "hypothesis of resource redistribution" in a series of experiments on fruit flies. The results clearly showed that the hypothesis is incorrect – at least for fruit flies.

In nature, fruit flies feed on yeasts that develop on a variety of rotting substrates – from fermented fruits to old fruit bodies of forest mushrooms. In experiments to study the effect of a restrictive diet on life expectancy, two types of feed are usually used – "standard" and "dietary". In the first case, 200 g of dry yeast powder is used in the manufacture of 1 liter of feed, in the second – 100 g. In principle, flies put on a diet have the opportunity to "deceive" researchers by eating twice as much food, but in practice they do not do this.

The fruit flies used in the experiments live about the same number of days as humans live for years. On a standard feed, half of the flies live up to 50-60 days, on a diet – up to about 70. At the same time, females lay significantly more eggs on standard feed during their short life than during a long life on a diet.

The authors divided the nutrients contained in yeast into four groups (carbohydrates, fats, vitamins, amino acids) and began to add them to dietary food separately. It turned out that increasing the concentration of carbohydrates, fats and vitamins to a standard level does not affect either the longevity or fertility of flies on a diet. Flies that receive a standard amount of any of these components still live a long time, and lay few eggs. But if you add a full set of amino acids to a dietary feed, the effect is the same as with a "standard" diet: life is shortened, and fertility increases. Therefore, it's all about amino acids.

The survival rate of flies depending on the diet. A drawing from the discussed article in Nature.
On the horizontal axis – the age of the fly in days, on the vertical – the proportion of flies that have survived to this age.
On the left: the lifespan of flies on a diet (DR, blue circles) does not decrease from the addition of carbohydrates (carbohydrates, gray triangles), lipids (lipids, gray diamonds) or vitamins (vitamins, gray squares), however, flies live significantly less on a "standard" (full) diet (Fully fed, red circles).
On the right: adding a complete set of amino acids (all AAs, gray triangles) to dietary food dramatically reduces life expectancy.

In the next series of experiments, the authors divided amino acids into two groups: interchangeable and irreplaceable (10 amino acids in each group; the set of essential amino acids in flies and mammals is almost the same). The addition of interchangeable amino acids to dietary food did not affect anything, the irreplaceable ones gave the same effect as the transfer to standard food.

After that, the authors focused on 10 essential amino acids (NA), adding them to the diet feed one at a time or in different combinations. The results were very unexpected. It turned out that the fertility of flies depends only on one NA – methionine. With a "standard" amount of methionine, fertility is high, with a "dietary" one, it is low, regardless of other factors.

With life expectancy, everything turned out to be somewhat more complicated. Life is shortened only if the flies receive a "standard" amount of both methionine and other NA at the same time. All other combinations: (1) there is a lot of methionine, there are few others; (2) methionine is not enough, there are many others; (3) both are not enough – they guarantee a long life (see the table).

The most interesting thing is that one of these combinations (there is a lot of methionine, the others are few) provides both a long life and high fertility. This result actually puts an end to the "resource redistribution hypothesis", at least for fruit flies. This hypothesis suggested that the functions of reproduction and slowing down aging "compete" with each other for some food resources. But it turned out that in reality fertility and life expectancy do not compete for anything, because they depend on different parameters of the diet: the first – on the amount of methionine, the second – on the balance of NA, that is, on the ratio of methionine and other NA. Which of the essential amino acids interact with methionine in such a way that with a large amount of both, life is shortened – the authors could not find out. Apparently, the relationship between these components of nutrition is quite complex.

It should be assumed that in the near future these results will be tested on other animals. It is possible that mammals will find something similar. At least, it has previously been shown in mice that reducing the amount of methionine in food can prolong life. However, in mice, another NA – tryptophan has similar effects, and in drosophila, tryptophan itself does not affect longevity.

From the point of view of the fruit flies themselves, the results obtained suggest that the balance of amino acids in their natural food – yeast – is not optimal for fly longevity. Natural selection, as expected, optimized the drosophila organism not by longevity (which it does not care about), but by fertility, that is, by the efficiency of converting feed (yeast) into viable eggs laid. But we humans, unlike natural selection, highly value our longevity. We, too, are most likely optimized by evolution not at all according to the parameters by which we would like to be optimized at this stage of cultural and social development. Almost certainly, like flies, our "standard food" does not have the best balance of components for our longevity. And this is very good, because such an imbalance is not difficult to correct – and then people will get extra years of life without much effort, almost for nothing.

Source: Richard C. Grandison, Matthew D. W. Piper, Linda Partridge. Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila // Nature. Advance online publication 2 December 2009.

Portal "Eternal youth" http://vechnayamolodost.ru10.12.2009