Effect of clock genes over the immunometabolism and monocyte/macrophage differentiation in immunosenescence: the role of exercise training throughout life

Abstract

Aging is enhanced by a gradual decline in numerous physiological processes, including changes in the immune system, which are collectively called immunosenescence, and circadian rhythms, which show age-related changes. The relationships between clock genes, aging and immunosenescence are not well understood. Monocytes and macrophages show high rhythmicity with a high amplitude of expression of clock genes. Consequently, different functions of macrophages and monocytes exhibit circadian rhythms, such as the pattern recognition receptors (PRRs) response, an expression of cytokines in response to an endotoxin challenge, tissue recruitment and phagocytosis. The elucidation of the process by which immunosenescence impairs the activity of innate immunity, favoring the installation of low-grade chronic inflammation, in addition to decreasing the response against invaders, especially viruses, in addition to the greater susceptibility to septic shock, can help in the development of new ways to delay and decrease the amplitude of immunosenescence. Regular physical exercise throughout life slows down the aging processes, providing better quality and prolongation of life. Given the anti-inflammatory nature of aerobic exercise training, the hypothesis of the present study is that the systems differentiation of monocytes may be related to genes that control the circadian rhythm in immunosenescence, which are positively regulated by physical training. Thus, the aim of the study will be to evaluate the role of exercise training during life in immunosenescence and the relationship of this protective effect with the modulation of clock genes. (AU)