Senolytics – a new class of geroprotectors?

Scientists from the Scripps Research Institute, the Mayo Clinic and several other institutions, working under the leadership of Professor James Kirkland, have identified a new class of drugs that significantly slow down the aging process in animal models. The effect of these drugs, called senolytics ("solvents of old age", from Lat. senesco – aging and Greek lysis – dissolution, decay), is manifested by softening the manifestations of senility, improving cardiac function and increasing the duration of a healthy life.

The aging process is accompanied and aggravated by the accumulation of cells in the body that have entered the phase of physiological aging, which is manifested by the loss of their ability to divide. Based on previously obtained data (see, for example, the note "To rejuvenate the body, it is enough to remove old cells"), according to which the duration of a healthy (disease-free) life of mice increases with the elimination of such cells from the body, the researchers suggested that the introduction of such an approach into clinical practice may have huge potential.

However, they faced the problem of finding a target that would allow them to selectively affect cells that have entered the phase of physiological aging without damaging the rest of the body's cells. The resistance of such cells to death under stress and damage was chosen as a potential key to identifying the necessary target. Indeed, the analysis of gene transcripts showed that, like cancer cells, cells that have entered the phase of physiological aging have an increased expression of gene complexes that ensure their resistance to programmed cell death (apoptosis).

Using the data obtained, the researchers selected two compounds available on the market: the antitumor drug dasatinib, sold under the brand name Sprycel (sprycel), and quercetin, a natural compound sold as a dietary supplement that has antihistamine and anti–inflammatory effects.

Experiments on cell cultures have shown that these drugs do selectively induce the death of cells that have entered the phase of physiological aging. At the same time, each of them has its own strengths. Dasatinib destroys human adipocyte progenitor cells in the physiological aging phase, whereas quercitin is more effective against human endothelial cells and mouse bone marrow stem cells in the physiological aging phase. The combination of these two drugs had the greatest effectiveness.

Further experiments on numerous mouse models demonstrated the ability of the studied drugs to improve the functioning of the cardiovascular system and physical endurance, reduce the severity of symptoms of osteoporosis and senility, as well as increase the duration of a healthy life.

In particular, within five days after a single administration of a combination of drugs, a significant improvement in the functioning of the cardiovascular system was observed in old animals. At the same time, a single administration of drugs improved the ability to tolerate physical activity of animals weakened by radioactive irradiation, similar to antitumor radiotherapy. The observed effect persisted for at least seven months after therapy.

Periodic administration of drugs to mice with accelerated aging syndrome increased their healthy life expectancy, delayed the manifestation of aging-associated symptoms, as well as the development of degenerative spinal changes and osteoporosis.

Graph from additional materials to the article in Aging Cell

Manifestation of symptoms of senility in the placebo group consisting of siblings (left)
and in therapy with a combination of dasatinib (D) and quercitin (Q)
lines of rapidly aging mice.

The authors warn that before using these drugs to slow down human aging, it is necessary to conduct a lot more research. Moreover, it should be borne in mind that both drugs can have side effects, at least with prolonged use. At the same time, they note that therapy with senolytic drugs aimed at destroying damaged cells will be carried out infrequently, which will reduce the likelihood of side effects.

Article by Yi Zhu et al. The Achilles’ Heel of Senescent Cells: From Transcriptome to Senolytic Drugs is published in the journal Aging Cell.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the Scripps Research Institute:
Scripps Research, Mayo Clinic Scientists Find New Class of Drugs that Dramatically Increases Healthy Lifespan.

11.03.2015