A new study describes the molecular mechanism involved in the link between calorie restriction and longevity
The answers of scientists on the issue of extending life expectancy are not always unequivocal, but one direction of research that is gaining strength points to a link between a low-calorie diet and longevity. Already in 1930, Clive McKay, a nutritionist from Cornell University in the United States, found that rats fed a low-calorie diet lived 48 months, compared to rats fed a normal diet, whose lifespan was 30 months. Since then, hundreds of studies have been published, in which the phenomenon was tested in yeast, worms, flies, mice, rats and dogs. According to these studies, reducing the number of calories consumed by about a third extends the animals' lives by about 30%. Moreover, mammals whose caloric intake was restricted developed fewer tumors, had less diabetes, and had delayed signs of aging. To date, calorie restriction is the only treatment found to be effective in prolonging life.
Despite the 70 years that have passed since McKay's research, not much knowledge has been accumulated about the molecular mechanism involved in the phenomenon. In the last decade, many studies were conducted in model animals, such as yeast and the worm C. elegans, and mutations were discovered in dozens of genes that were found to be involved in the connection between calorie restriction and life span and which managed to extend the life span of the animals sometimes up to 70%.
One of the genes that has attracted a lot of interest is SIR2, which is found in yeast and its activity increases when the yeast is grown under conditions of calorie restriction. Researchers found that yeast with a defective SIR2 gene lived an average of 40% less than those with the normal gene. On the other hand, yeast that carry an extra copy of SIR2 live an average of 30% longer than those that carry one copy of the gene. The protein SIR2 - the product of the gene - affects the extension of the life of the yeast. Proteins from the SIR2 family are found in all organisms, from bacteria to humans, but the question of how they are involved in the aging process remains unanswered.
Since the discovery of the role of SIR2 in aging and extending life span in a regime of calorie restriction, a race has begun between research laboratories in the world to discover its role in humans. It turned out that mammals, including humans, are equipped with seven genes that correspond to the SIR2 gene found in yeast. They are called SIRT1-7. Now, for the first time, it has become clear that one of these genes is involved in the connection between a low-calorie diet and the extension of life expectancy, and an article about this will be published tomorrow in the journal "Science".
The article presents a study carried out at Harvard University Medical School by the Israeli researcher Dr. Haim Cohen and Prof. David Sinclair's research group. The researchers found that in rats that ate a low-calorie diet, the level of one of the seven proteins (SIRT1 protein) increased four times compared to its level in rats that were fed a normal diet.
So what is the connection between the increase in the level of this protein and the extension of the rats' lifespan? In a previous study, Cohen found that the SIRT1 protein is involved in the mechanisms of cell death. Today it is known that the central mechanism that directs life and death in cells is carried out by means of "suicide software" found in each and every cell. The end of cell life due to old age, disease, injury, etc. occurs through special proteins that activate the suicide program. Since the aging processes in the body are the result of cell death, any way to prevent cell death will slow down these processes.
Cohen found in a previous study that the SIRT1 protein found in mammalian cells mediates the molecular mechanism involved in cell suicide, in which three proteins participate. The key protein, Bax, causes cells to die in a process of suicide. Bax is normally attached to the Ku70 protein, preventing it from functioning, but in certain situations Ku70 is neutralized and Bax is released and causes cell suicide. Such a situation occurs when an acetyl group is attached to Ku70. Its attachment to the Ku70 protein is done in a well-controlled process, and that's it
which determines the fate of the cell to life or death.
In the current study, Cohen, along with the group of researchers, showed that SIRT1 can remove the acetyl group from Ku70 and thus prevent cell death. Later, the researchers showed that the connection between calorie restriction and the aging process can also be shown in human cell cultures.
They grew a group of cells in a nutrient medium containing the serum (blood fluid) of rats, which were fed
on a calorie restricted diet. A second group of cells were grown in food soil containing serum from rats that ate a normal diet. "It became clear to us that the cells from the first group lived longer," says Cohen. "We later proved that the prevention of cell death from the first group depended on the activity of the SIRT1 protein, which was present in the serum. Without this protein, cells that we grew on a low-calorie diet behaved like cells that were on a normal diet. Without SIRT1, the Ku70 protein no longer held Bax, and this protein was free to cause cell death."
In the study, the researchers come up with ideas for developing drugs that may delay aging. "We discovered some molecules that are found in a smaller amount in rats that were fed a calorie-restricted diet, compared to rats that consumed a normal diet," says Cohen. "We also found that these molecules affect the SIRT1 protein level in the cells. We hope that it will be possible to develop drugs that will regulate the level of these molecules and thus maybe manage to regulate the rate of aging in humans as well."
