SIRT3 is a potential source of longevity
Researchers at the University of California at Berkeley managed to "set back" the molecular clock by embedding the "longevity gene" SIRT3 into the blood stem cells of old mice. The result of this manipulation was the restoration of the regenerative potential of aging stem cells.
The head of the study, Associate Professor Danica Chen, notes that over the past 10-20 years, many breakthroughs have been made in the study of the mechanisms of aging, which is now considered not a spontaneous uncontrolled process, but a process whose regulation is no less complex than the regulation of the development process. Understanding this opens up the possibility of controlling the course of the inevitable process of extinction of the body that worries many.
As one of the "sources of longevity", experts consider proteins of the sirtuin family, whose important role in the aging process is no longer in doubt. In particular, there is evidence that the activation of the gene encoding the SIRT3 protein occurs when a low-calorie diet is observed, which significantly prolongs the life of representatives of many animal species. The SIRT3 protein is part of the energy centers of the cell – mitochondria – whose functioning is closely related to the processes of growth and death of the organism.
As an object for studying the effects of aging, the authors chose adult hematopoietic stem cells that provide the production of all types of blood cells. These cells have the ability to completely restore the hematopoiesis system, destroyed, for example, as a result of chemotherapy or radiotherapy of oncological diseases.
At the first stage of the work, scientists observed the functioning of the hematopoietic system of mice that do not have a functional SIRT3 gene. Unexpectedly, it turned out that at a young age, the absence of this gene did not affect the health of the animals in any way. However, the situation radically changed by the age of two, when mice had a significant decrease in the number of hematopoietic stem cells and the extinction of their ability to form new blood cells compared to normal animals of the same age.
What is the reason? It turned out that the hematopoietic stem cells of a young organism are characterized by relatively low levels of oxidative stress caused by metabolic byproducts. At this stage of development, the body's antioxidant defense systems easily cope with oxidative stress and the absence of the SIRT3 gene has almost no significance.
As we age, the effectiveness of protective systems decreases simultaneously with an increase in the level of oxidative stress, which leads to the accumulation of toxic by-products of metabolism. At this stage, the body needs SIRT3, which can stimulate the protective antioxidant system. However, the level of activity of this gene also decreases with age and gradually the vital activity of the body fades.
To test how an increase in the level of SIRT3 activity will affect the state of the hematopoietic system, the authors increased the expression of this gene in hematopoietic stem cells of aging mice. The result was an increase in the efficiency of blood cell production.
The authors have yet to find out whether overexpression of the SIRT3 gene can actually prolong life. However, they state that increasing life expectancy is not the sole purpose of their work. An extremely important task set by specialists working in the field of studying the mechanisms of aging is the application of knowledge about regulatory genetic mechanisms in the treatment of age-related diseases.
They also note that other groups of researchers have demonstrated that SIRT3 acts as a suppressor of tumor growth. This makes it an ideal candidate for the role of a "rejuvenating" agent, since an increase in its expression is not associated with an increase in the risk of developing malignant neoplasms.
Article by Katharine Brown et al. SIRT3 Reverses Aging-Associated Degeneration is published in the journal Cell Reports.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the University of California – Berkeley:
Discovery opens the door to a potential ‘molecular fountain of youth’.
01.02.2013