Circadian Rhythms, Chrononutrition, Physical Training, and Redox Homeostasis-Molecular Mechanisms in Human Health

Abstract

A multitude of physiological processes, human behavioral patterns, and social interactions are intricately governed by the complex interplay between external circumstances and endogenous circadian rhythms. This multidimensional regulatory framework is susceptible to disruptions, and in contemporary society, there is a prevalent occurrence of misalignments between the circadian system and environmental cues, a phenomenon frequently associated with adverse health consequences. The onset of most prevalent current chronic diseases is intimately connected with alterations in human lifestyle practices under various facets, including the following: reduced physical activity, the exposure to artificial light, also acknowledged as light pollution, sedentary behavior coupled with consuming energy-dense nutriments, irregular eating frameworks, disruptions in sleep patterns (inadequate quality and duration), engagement in shift work, and the phenomenon known as social jetlag. The rapid evolution of contemporary life and domestic routines has significantly outpaced the rate of genetic adaptation. Consequently, the underlying circadian rhythms are exposed to multiple shifts, thereby elevating the susceptibility to disease predisposition. This comprehensive review endeavors to synthesize existing empirical evidence that substantiates the conceptual integration of the circadian clock, biochemical molecular homeostasis, oxidative stress, and the stimuli imparted by physical exercise, sleep, and nutrition.

Keywords: chronobiology; chronotype; circadian rhythm; metabolism; oxidative stress; physical exercise; redox homeostasis; sleep; sport performance.

Figure 1

The increase in melatonin production can be achieved through various nutritional interventions that aim to enhance tryptophan (Trp) availability at the CNS level. Generally, this process can be realized by either increasing free Trp availability or reducing the relative plasma concentration of large neutral amino acids (LNAA). The passage of tryptophan through the blood–brain barrier constitutes a multifaceted process, as the active transport of amino acids to the brain, performed by a particular carrier protein, is accessible to all LNAA and is not exclusive to tryptophan. So, tryptophan must engage in competition with other LNAA, which are often more abundantly available in the food supply, to secure transport into the brain. To augment the availability of tryptophan for serotonin and melatonin synthesis, it is advantageous to redirect these competing amino acids toward peripheral tissues. This diversion can be facilitated through the release of insulin, which in turn fosters protein synthesis in muscle tissue. Notably, the process of insulin shunting effectively diminishes the pool of LNAA that reach the brain, thereby liberating transporters for tryptophan binding. In light of this mechanism, the co-consumption of carbohydrates in conjunction with tryptophan-rich foods holds the potential to enhance the entry of tryptophan into the brain. These objectives can also be accomplished by adopting a high-protein diet richer in tryptophan compared to LNAA, consuming carbohydrates to elevate the free Trp-to-branched-chain amino acid (BCAA) ratio and stimulate insulin release, which facilitates BCAA uptake into muscle. Additionally, melatonin production can be influenced by the consumption of high-fat meals, leading to increased free fatty acids and subsequently higher free Trp levels. Furthermore, engaging in physical exercise can impact both free fatty acids and insulin levels, contributing to the intensification of melatonin synthesis.

Figure 2

The human organism’s antioxidant defense mechanism involves a cooperative interaction between enzymatic and non-enzymatic antioxidant systems to collectively shield the cells and organ systems from harm caused by free radical damage. ROS—reactive oxygen species, SOD—Superoxide dismutase, GSH—reduced glutathione, GSSG—oxidized glutathione, GSH-Px—Glutathione peroxidase, GSH-R—Glutathione reductase.

Figure 3

The physiologic continuous process of reactive oxygen species (ROS) generation is counterbalanced by a plethora of antioxidant enzymatic and non-enzymatic mechanisms, whose modulation signals are finely orchestrated and intimately interconnected.

Figure 4

The generation of reactive species is at the same time a physiologic and a pathological process, dictated by the disequilibrium between the amount produced and the extent to which they are neutralized by active antioxidant mechanisms. The signaling processes involving reactive oxygen species (ROS) occupy a pivotal position in the control of proinflammatory mechanisms, protein redox adjustments, cellular proliferation, and apoptotic cell death. The safeguarding of cellular and tissue integrity against the detrimental effects of elevated ROS concentrations is effectively mediated by the actions of antioxidant defense enzymatic and non-enzymatic factors. ROS—reactive oxygen species, IL-6—interleukin 6, CRP-1—C reactive protein, TNF-α—Tumor necrosis factor-alpha, NOS—Nitric oxide synthase, NOX—NADPH oxidases, SOD—Superoxide dismutase, GSSG—oxidized glutathione, GSH—reduced glutathione, GSH—Px-Glutathione peroxidase, TrxR—Thioredoxin reductase, GSH-R—Glutathione reductase.