The role of mitochondria in the myocardium of senescent Meriones unguiculates

Abstract

According to the mitochondrial theory of aging, changes in the functional state of mitochondria, which lead to excessive formation of active forms of oxygen, are the main factor in the development of age changes in organs and tissues of the whole organism. The assessment of the mitochondria state of the heart of senescent gerbils (Mongolian Gerbilia, Meriones unguiculates Milne-Edwards, 1867). It is proved that the aging of the heart is preceded by the appearance of dysfunction in mitochondria. The disturbance of metabolic processes in the myocardium of gerbils over the age of two years was established, which was accompanied by activation of oxidative stress by increasing the concentration of TBK-active compounds. An increase in the concentration of cytochrome C in cytosol has been shown due to the destructive effects of oxidized products on the outer membrane of mitochondria and enhancement of its permeability. The violation of bioenergetic processes, increase of the anaerobic respiration and the accumulation of lactate and unoxidative metabolites, which increases oxidative stress and cell damage, are determined. We established that for gerbils the critical age for senescence is 24 months. Major metabolic changes in the heart occur mostly at this age. This is marked by activation of prooxidants formation, proteolytic processes (decrease in total protein concentration) and inhibition of aminotransferase activity in cytosol. The switching of metabolic processes in the mitochondria of the heart with the participation of aminotransferases has been registered: increased activity of the mitochondrial isoenzyme alanine aminotransferase and reciprocal reduction of aspartate aminotransferase. After two years of age in the experimental gerbils the intensification of adaptive processes was established: activation of catalase, γ-glutamyltransferase, relative restoration of the activity of alanine and aspartate aminotransferase, thus maintaining the processes of the vital activity of the whole organism, but at a new metabolic level. With age, irreversible damage to cardiomyocytes occurs, which gradually lose the ability to convert lactate, resulting in its increase, and the processes of its utilization are inhibited. The results confirm the key role of mitochondria in the process of aging of the myocardium. However, when gerbils reach the 36 months of age the metabolic disturbances in the myocardium reach their peak, resulting in large-scale cell damage.