Suchergebnisse

The search and testing of drugs with senolytic activity is one of the new directions in gerontology. The number of "senescent" cells that increases with age contributes to the development of age-related diseases and chronic non-infectious inflammation. Removing "senescent" cells or suppressing their influence on surrounding tissues seems a logical step to improve the quality of life and, possibly, prolong lifespan. However, drugs that have senolytic and senomorphic activity in model systems cause the development of a number of side effects in clinical trials. In this review, we consider the main advances in the field of senotherapy, the prospects for the use of senotherapy drugs, and the limitations that researchers and clinicians may encounter.

The study of the functioning of various body systems in diff erent vertebrates is one of the key tasks of comparative physiology. Teleost fi sh are a large group of vertebrates, however, the mechanisms of functioning of their digestive tract have been studied little and mainly only for such a model object as Danio rerio. The aim of this work was to characterize the participation of various subtypes of M-cholinergic receptors and the enzyme Rho-kinase in the cholinergic contraction of the intestinal smooth muscles of the White Sea cod Gadus morhua marisalbi (Gadidae). A longitudinal strip was excised from the proximal cod intestine and placed in an apparatus for recording contractile responses in the isometric mode. Contractile responses to acetylcholine were
ompletely blocked by atropine. Blockade of M3 cholinergic receptors with 4-DAMP resulted in a decrease in acetylcholine-induced contraction compared with the control response. Blockade of M1 receptors with pirenzepine led to a weakening of contraction, less pronounced than with blockade of M3 cholinergic receptors. Blockade of M2-cholinergic receptors with methoctramine did not affect the magnitude of the contractile response. Incubation of preparations with the Rho-kinase inhibitor fasudil was accompanied by a significant decrease in contractile responses compared with the control, as well as a faster decrease in the contraction force after reaching the "peak" of the reaction. Thus, acetylcholine causes contraction of cod intestinal smooth muscle by activating M3- and M1- but not M2-cholinergic receptors. The activity of the Rho-kinase enzyme contributes to the development and maintenance of cod intestinal smooth muscle contraction under the action of acetylcholine. The results obtained are of interest for comparative physiology, may be important for understanding the mechanisms of the damaging effect of environmental factors on the bony fish' body, as well as for the use of fish as objects of preclinical studies of drugs.