The secret of a long and healthy life
The results obtained by specialists of the University of Texas Southwestern Medical Center over the past two decades have confirmed the theory that "recycling of secondary resources" inside the cell can increase both the life expectancy and the duration of a healthy life of mammals.
Twenty years ago, Dr. Levin and her colleagues established that the beclin 1 gene is key to the biological process of autophagy – a mechanism used by the cell to get rid of unnecessary or toxic compounds by recycling them and reusing them to synthesize the necessary molecules. Subsequent studies have demonstrated the importance of autophagy for many aspects of health, including the prevention of the development of neurodegenerative diseases, as well as for the fight against malignant tumors and infections.
In 2003, the authors established that the genetic mechanisms of autophagy are a necessary aspect of increasing life expectancy in long-lived nematode mutants. From that moment, it became obvious that autophagy is an important mechanism necessary to increase the life expectancy observed when exposed to model organisms with certain drugs or with mutations in the genes of certain signaling proteins. The natural ability of cells to autophagy fades with age, which most likely contributes to the aging process.
However, a very important question remained unanswered for a long time: is the increased activity of autophagy throughout the life of mammals safe and beneficial for the body? In other words, can autophagy increase life expectancy and help maintain health?
In search of an answer, the researchers created a line of genetically modified mice characterized by constantly increased autophagy activity. To do this, they introduced a mutation into the gene of the main autophagy protein Beclin 1, suppressing its binding to the Bcl-2 protein, which usually inhibits the function of Beclin 1 in the autophagy mechanism. As scientists expected, such animals from birth had increased autophagy activity in the cells of all organs.
In 2017, the authors showed that the mutation described above partially protects animals from the development of simulated mouse analogues of Alzheimer's disease. Later experiments also demonstrated that, compared with ordinary animals, mice with constantly increased autophagy activity live 10% longer and are less likely to suffer from oncological diseases, as well as pathological changes in the heart and kidneys. In addition, it turned out that increased autophagy protects against premature death of animals that do not have the anti-aging hormone klotho.
According to Professor Levin, all these data are extremely important for planning strategies to improve human health, as well as for the development of appropriate pharmacological drugs. They testify to the safety of chronic activation of autophagy and the possibility of its use to slow down the aging process and prevent the development of age-related diseases. Moreover, the conducted studies revealed a specific target for pharmacological intervention, namely violations of the interaction of Beclin 1 and Bcl-2 proteins. Currently, the authors, together with colleagues from the Faculty of Biochemistry, are already working on the synthesis of compounds capable of influencing this mechanism.
Article by Álvaro F. Fernández et al. Disruption of the beclin 1–BCL2 autophagy regulatory complex promotes longevity in mice published in the journal Nature.
Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru according to UT Southwestern Medical Center: Cellular recycling process is key to longer, healthier life.