Candidate for Senolitics
A group of researchers working under the leadership of Dr. James L. Kirkland from the Mayo Clinic has demonstrated that the introduction of even a small number of cells to young healthy mice that have entered the phase of physiological aging leads to a deterioration in animal health. However, as it turned out, therapy with a combination of two drugs – quercetin and dasatinib – can not only prevent the development of these changes, but also increase the life expectancy of normally aging animals.
Most normal cells continuously grow, die and divide. Physiological aging is a process as a result of which cells lose their functions, including the ability to divide, but remain resistant to cell death. Such cells influence their environment due to the proinflammatory and tissue remodeling molecules secreted by them. The number of cells that have entered the phase of physiological aging in many tissues increases with age, they also accumulate in organs associated with many chronic diseases, as well as after radio and chemotherapy.
Senolytics are a class of drugs that selectively destroy such cells. The authors suggested that the combination of two such drugs, dasatinib and quercetin, may slow down the development of physical dysfunction caused by cells that have entered the phase of physiological aging. Dasatinib is used to treat certain forms of leukemia, whereas quercetin is a flavonoid of plant origin used in dietary supplements and cosmetics.
To confirm that the cells that have entered the phase of physiological aging cause disorders of physical functions, the researchers injected these cells into 4-month-old mice. The animals of the control group received injections of normal cells. Already 2 weeks after transplantation, the experimental group of mice began to show signs of fading physical functions, determined by parameters such as movement speed, muscle strength, physical endurance, daily activity, amount of food consumed and body weight. In addition, an increase in the population of cells that entered the phase of physiological aging was observed in the body of animals, the number of which exceeded the number of injected cells, which indicates their detrimental effect on healthy cells of the body.
To test the possible effect of senolytic drugs on these changes, animals of both groups were administered a combined drug containing dasatinib and quercetin for three days. Subsequent observations demonstrated that this therapeutic cocktail provides selective destruction of cells that have entered the phase of physiological aging and slows down the extinction of the assessed physical functions.
As part of another series of experiments, a combination of senolytics was periodically administered for 4 months to healthy animals who had reached the age of 20 months. As a result, they experienced a slowdown in the normal age-related decline of physical functions, which was manifested by an increase in movement speed, endurance, grip strength and daytime activity.
At the final stage of the study, the authors administered a combination of dasatinib and quercetin once every 2 weeks to very old mice aged 24-27 months. This increased the life expectancy of the animals by an average of 36% after the start of therapy, and also reduced the risk of death compared to the control group mice.
The authors note that current and future preclinical studies may demonstrate the possibility of using senolytics to increase the life expectancy of not only elderly people, but also cancer-cured patients who have undergone chemo- and/or radiotherapy inducing physiological cell aging, as well as people with a whole spectrum of chronic diseases associated with physiological cell aging.
Article by Ming Xu et al. Senolytics improve physical function and increase lifespan in old age is published in the journal Nature Medicine.
Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the National Institute on Aging: Senolytic drugs reverse damage caused by senescent cells in mice.