The Combination of Physical Exercise with Muscle-Directed Antioxidants to Counteract Sarcopenia: A Biomedical Rationale for Pleiotropic Treatment with Creatine and Coenzyme Q10

Abstract

Sarcopenia represents an increasing public health risk due to the rapid aging of the world's population. It is characterized by both low muscle mass and function and is associated with mobility disorders, increased risk of falls and fractures, loss of independence, disabilities, and increased risk of death. Despite the urgency of the problem, the development of treatments for sarcopenia has lagged. Increased reactive oxygen species (ROS) production and decreased antioxidant (AO) defences seem to be important factors contributing to muscle impairment. Studies have been conducted to verify whether physical exercise and/or AOs could prevent and/or delay sarcopenia through a normalization of the etiologically relevant ROS imbalance. Despite the strong rationale, the results obtained were contradictory, particularly with regard to the effects of the tested AOs. A possible explanation might be that not all the agents included in the general heading of "AOs" could fulfill the requisites to counteract the complex series of events causing/accelerating sarcopenia: the combination of the muscle-directed antioxidants creatine and coenzyme Q10 with physical exercise as a biomedical rationale for pleiotropic prevention and/or treatment of sarcopenia is discussed.

Figure 1

The role of ROS in the pathogenesis of sarcopenia and the multiple positive and converging effects promoted by Cr, CoQ10, or physical training. The sequences of relevant ROS-related pathogenetic events leading to sarcopenia are summarized in the flow chart, where the effects promoted by Cr, CoQ10, or physical exercise (corresponding to the labels “Cr,” “Q10,” and “EX” in the figure, resp.) are also illustrated. The types of the modulations caused by Cr, CoQ10, and EX are symbolized according to the following scheme: labels with the arrow pointing down = decrease, arrow pointing up = increase, and arrow pointing right = hormetic effect. The inset in the upper rightmost of the figure emphasizes the high accumulation of Cr and CoQ10 in skeletal muscles.