Sestrin protein is a natural retarder of aging processes
Scientists at the University of California at San Diego, working under the guidance of Professor of Pharmacology Michael Karin, identified the protein Sestrin, which is an inhibitor of aging processes and the development of age-related pathologies in fruit flies. They also demonstrated that sestrin, whose human counterpart has a similar structure and biochemical function, is necessary for the functioning of a signaling mechanism that plays a key role in the regulation of aging processes and metabolism in general.
The proteins of the sestrin family are small proteins synthesized in large quantities by the cells of many organisms during periods of stress. The functions of these proteins remained a mystery until Professor Karin's group established that they are activators of adenosine monophosphate-dependent protein kinase (AMPK) and inhibitors of another protein kinase, the so-called "Target of Rapamycin" (Target of Rapamycin, TOR). These two enzymes are key components of the signaling mechanism that performs the function of a central regulator of aging and metabolism in various model organisms, including roundworms Caenorhabditis elegans and fruit flies-Drosophila melanogaster, as well as in mammals.
AMP-dependent protein kinase is activated under conditions of caloric restriction of the diet – a condition that slows down the aging process – whereas the activity of the rapamycin target is characteristic, on the contrary, of the overeating state that accelerates the aging process. Activation of the first enzyme suppresses the functioning of the second, and the ability of drugs that appropriately affect their work to slow down the aging process has been demonstrated in a number of model organisms, including mammals. For a long time, scientists could not answer the question of how the body manages to maintain a balance of activity of these two enzymes, the failure of which is fraught with premature aging. In addition, the presence of three separate genes encoding proteins of the sestrin family in mammals made it difficult to study their physiological functions.
In their latest work, the authors took advantage of the fact that in drosophila flies, with only one Sestrin gene, the AMPK-TOR signaling mechanism mediated by its protein functions in the same way as a similar mechanism in mammals. Using a set of genetic methods, they inactivated the studied gene in drosophila and found that, despite the absence of developmental abnormalities, such insects had reduced activity of AMP-dependent protein kinase and hyperactivity of the rapamycin target, which confirmed the key role of sestrin in the regulation of the studied signaling mechanism. And, more importantly, the biochemical imbalance caused by the lack of expression of the Sestrin gene caused a number of typical age-related pathologies in relatively young insects, including fat accumulation, cardiac arrhythmia and degeneration of muscle tissue.
After that, the researchers demonstrated that the addition of genetically modified drosophila drugs to the feed that activate the activity of AMP-dependent protein kinase or inhibit the target of rapamycin prevents the development of most symptoms of early aging. They also found that excessive activation of the rapamycin target disrupts the autophagy mechanism by which cells dispose of damaged organelles, including mitochondria. As we age, the efficiency of mitochondria decreases, and they begin to produce a large amount of reactive oxygen species (free radicals), which leads to tissue damage and premature aging. These processes were most noticeable in cardiac and skeletal muscles, whose cells consume a lot of energy and, accordingly, contain a huge amount of mitochondria.
The addition of vitamin E to insect food, which has antioxidant properties and neutralizes free radicals, prevented premature degeneration of the heart and skeletal muscles of insects.
In the future, scientists plan to study the participation of proteins of the sestrin family in the regulation of aging processes and mammalian metabolism. They also plan to test whether defects in the expression of genes encoding these proteins can shed light on the currently incomprehensible mechanisms of development of a number of age-associated degenerative diseases.
According to Professor Karin, perhaps someday analogues of sestrins can be used not only for the prevention of age-related tissue degeneration, but also for the treatment of certain diseases, such as Alzheimer's disease and sarcopenia.
The results of the work were published in the journal Science on March 5 in the article Jun Hee Lee et al. «Sestrin as a Feedback Inhibitor of TOR That Prevents Age-Related Pathologies».
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru according to ScienceDaily: Protein Shown to Be a Natural Inhibitor of Aging in Fruit Fly Model.
09.03.2010