Reducing the activity of the gene increases the duration of a healthy life
Researchers from several scientific institutions in the United States, working under the leadership of Professor John Sedivy from Brown University, have found that reducing the expression of the Myc gene significantly increases the healthy life expectancy of laboratory mice.
The Myc gene is present in the genomes of all animals, from the simplest unicellular organisms to humans. It is one of the actively studied objects of biomedical research and is known as an important regulator of cell division, growth and death. Its functions in the body are so fundamental and widespread that animals cannot live without this gene (its protein product regulates the expression of up to 15% of all known genes). However, in mice and humans, overexpression of this protein is closely associated with the development of cancer, which makes Myc a well-known but difficult target for drug developers.
As part of their study, the authors created a line of mice with only one copy of the Myc gene instead of the usual two. This reduced the expression of the corresponding protein and increased the life expectancy of animals by 15% (20% for females and 10% for males). Moreover, the experimental animals maintained a good state of health until old age.
The only reported undesirable side effect was the small body size of experimental animals (about 15% less than normal). In the wild, this factor is potentially unfavorable for survival.
A detailed study of the physiological parameters of animals and the functioning of their organs and systems revealed no differences from normal indicators. At the same time, they did not experience many problems associated with aging. They did not develop osteoporosis, the functions of the immune system were not impaired, and fibrosis of the heart muscle practically did not develop. Compared to normal mice, they were more active, their metabolism did not slow down as they aged, less cholesterol was synthesized in the body, and the ability to coordinate movements was preserved better.
Young mice have high bone density regardless of the number of Myc copies in their genomes
(2 copies – top row, Myc+/+, 1 copy – bottom row, Myc+/–). However, aging Myc+ mice/–
they retain high bone density and better overall health for longer.
Molecular analysis of a number of mechanisms involved in the regulation of life expectancy revealed in experimental animals changes in the signaling mechanism mediated by insulin-like growth factor-1 (IGF-1), as well as several mechanisms that provide sensitivity to nutrients and registration of energy levels in the cell. However, it is still unclear how the Myc gene is involved in these mechanisms. The most interesting was the fact that the activity of protein synthesis was reduced in some tissues of experimental animals. It is known that this process is directly regulated by the Myc gene and that its suppression by various methods increases the life expectancy of representatives of different species, ranging from yeast to mammals.
Genome-wide analysis of gene expression revealed pronounced features in the mechanisms involved in the metabolism and functioning of the immune system in experimental mice. However, these features only slightly coincided with the gene expression profiles characteristic of other interventions that increase life expectancy.
Based on the data obtained, the authors came to the conclusion that the longevity model recognized by many experts is invalid, according to which an increase in the activity of various mechanisms of stress resistance increases life expectancy. The long-lived animals created by them react to stresses and suffer from their consequences no less than ordinary mice.
The authors hope that the results of their work will find their application in clinical practice. Identification of the key components of Myc-mediated metabolic or immune mechanisms and their use as therapeutic targets will not necessarily increase people's life expectancy. However, it can improve their health in old age. Professor Sedivy believes that a particularly promising target is the mechanism of protein synthesis, a decrease in the activity of which has a positive effect on many organ systems.
Currently, pharmacological companies are already developing antitumor drugs that block the overexpression of Myc. Apparently, the scope of application of such drugs will not be limited to oncology.
Article by Jeffrey W. Hofmann et al. Reduced Expression of MYC Increases Longevity and Enhances Healthspan is published in the journal Cell.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Brown University:
Reducing Myc gene activity extends healthy lifespan in mice.
26.01.2015