MFN2 overexpression in skeletal muscles of young and old mice causes a mild hypertrophy without altering mitochondrial respiration and H2O2 emission.

AIM: Sarcopenia, the aging-related loss of muscle mass and function, is a debilitating process negatively impacting the quality of life of affected individuals. Although the mechanisms underlying sarcopenia are incompletely understood, impairments in mitochondrial dynamics, including mitochondrial fusion, have been proposed as a contributing factor. However, the potential of upregulating mitochondrial fusion proteins to alleviate the effects of aging on skeletal muscles remains unexplored. We therefore hypothesized that overexpressing Mitofusin 2 (MFN2) in skeletal muscle in vivo would mitigate the effects of aging on muscle mass and improve mitochondrial function. METHODS: MFN2 was overexpressed in young (7 mo) and old (24 mo) male mice for 4 months through intramuscular injections of an adeno-associated viruses. The impacts of MFN2 overexpression on muscle mass and fiber size (histology), mitochondrial respiration, and H2O2 emission (Oroboros fluororespirometry), and various signaling pathways (qPCR and western blotting) were investigated. RESULTS: MFN2 overexpression increased muscle mass and fiber size in both young and old mice. No sign of fibrosis, necrosis, or inflammation was found upon MFN2 overexpression, indicating that the hypertrophy triggered by MFN2 overexpression was not pathological. MFN2 overexpression even reduced the proportion of fibers with central nuclei in old muscles. Importantly, MFN2 overexpression had no impact on muscle mitochondrial respiration and H2O2 emission in both young and old mice. MFN2 overexpression attenuated the increase in markers of impaired autophagy in old muscles. CONCLUSION: MFN2 overexpression may be a viable approach to mitigate aging-related muscle atrophy and may have applications for other muscle disorders.

Cardiac Oxidative Stress and the Therapeutic Approaches to the Intake of Antioxidant Supplements and Physical Activity.

Reactive oxygen species (ROS) are strongly reactive chemical entities that include oxygen regulated by enzymatic and non-enzymatic antioxidant defense mechanisms. ROS contribute significantly to cell homeostasis in the heart by regulating cell proliferation, differentiation, and excitation-contraction coupling. When ROS generation surpasses the ability of the antioxidant defense mechanisms to buffer them, oxidative stress develops, resulting in cellular and molecular disorders and eventually in heart failure. Oxidative stress is a critical factor in developing hypoxia- and ischemia-reperfusion-related cardiovascular disorders. This article aimed to discuss the role of oxidative stress in the pathophysiology of cardiac diseases such as hypertension and endothelial dysfunction. This review focuses on the various clinical events and oxidative stress associated with cardiovascular pathophysiology, highlighting the benefits of new experimental treatments such as creatine supplementation, omega-3 fatty acids, microRNAs, and antioxidant supplements in addition to physical exercise.

An Overview of Physical Exercise and Antioxidant Supplementation Influences on Skeletal Muscle Oxidative Stress.

One of the essential injuries caused by moderate to high-intensity and short-duration physical activities is the overproduction of reactive oxygen species (ROS), damaging various body tissues such as skeletal muscle (SM). However, ROS is easily controlled by antioxidant defense systems during low to moderate intensity and long-term exercises. In stressful situations, antioxidant supplements are recommended to prevent ROS damage. We examined the response of SM to ROS generation during exercise using an antioxidant supplement treatment strategy in this study. The findings of this review research are paradoxical due to variances in antioxidant supplements dose and duration, intensity, length, frequency, types of exercise activities, and, in general, the lack of a regular exercise and nutrition strategy. As such, further research in this area is still being felt.

Adiponectin: Structure, Physiological Functions, Role in Diseases, and Effects of Nutrition.

Adiponectin (a protein consisting of 244 amino acids and characterized by a molecular weight of 28 kDa) is a cytokine that is secreted from adipose tissues (adipokine). Available evidence suggests that adiponectin is involved in a variety of physiological functions, molecular and cellular events, including lipid metabolism, energy regulation, immune response and inflammation, and insulin sensitivity. It has a protective effect on neurons and neural stem cells. Adiponectin levels have been reported to be negatively correlated with cancer, cardiovascular disease, and diabetes, and shown to be affected (i.e., significantly increased) by proper healthy nutrition. The present review comprehensively overviews the role of adiponectin in a range of diseases, showing that it can be used as a biomarker for diagnosing these disorders as well as a target for monitoring the effectiveness of preventive and treatment interventions.

A Brief Overview of Oxidative Stress in Adipose Tissue with a Therapeutic Approach to Taking Antioxidant Supplements.

One of the leading causes of obesity associated with oxidative stress (OS) is excessive consumption of nutrients, especially fast-foods, and a sedentary lifestyle, characterized by the ample accumulation of lipid in adipose tissue (AT). When the body needs energy, the lipid is broken down into glycerol (G) and free fatty acids (FFA) during the lipolysis process and transferred to various tissues in the body. Materials secreted from AT, especially adipocytokines (interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α)) and reactive oxygen species (ROS), are impressive in causing inflammation and OS of AT. There are several ways to improve obesity, but researchers have highly regarded the use of antioxidant supplements due to their neutralizing properties in removing ROS. In this review, we have examined the AT response to OS to antioxidant supplements focusing on animal studies. The results are inconsistent due to differences in the study duration and diversity in animals (strain, age, and sex). Therefore, there is a need for different studies, especially in humans.

A Short Overview of Changes in Inflammatory Cytokines and Oxidative Stress in Response to Physical Activity and Antioxidant Supplementation.

Excessive release of inflammatory cytokines and oxidative stress (OS) are triggering factors in the onset of chronic diseases. One of the factors that can ensure health in humans is regular physical activity. This type of activity can enhance immune function and dramatically prevent the spread of the cytokine response and OS. However, if physical activity is done intensely at irregular intervals, it is not only unhealthy but can also lead to muscle damage, OS, and inflammation. In this review, the response of cytokines and OS to exercise is described. In addition, it is focused predominantly on the role of reactive oxygen and nitrogen species (RONS) generated from muscle metabolism and damage during exercise and on the modulatory effects of antioxidant supplements. Furthermore, the influence of factors such as age, sex, and type of exercise protocol (volume, duration, and intensity of training) is analyzed. The effect of antioxidant supplements on improving OS and inflammatory cytokines is somewhat ambiguous. More research is needed to understand this issue, considering in greater detail factors such as level of training, health status, age, sex, disease, and type of exercise protocol.