Point:Counterpoint: Skeletal muscle mechanical efficiency does/does not increase with age POINT: SKELETAL MUSCLE MECHANICAL EFFICIENCY DOES INCREASE WITH AGE

We thank Dr. Ortega for the opportunity to debate the concept that aging affects exercise efficiency. From the outset we must acknowledge that, indeed, some studies report an age-related reduction task efficiency during walking and other rather complex tasks (2, 12, 20, 21). However, in contrast, our recent study of leg cycling in centenarians (28), as well as other work focused more specifically on skeletal muscle function (17, 27), suggests that healthy aging is actually associated with increased mechanical efficiency, likely caused primarily by the age-dependent shift toward an aerobic muscle phenotype (5, 15). Systems energy conservation and efficiency. Important in terms of background, the law of the conservation of energy, first formulated in the nineteenth century, states that total energy in an isolated system remains constant over time. Energy can change its characteristics within the system; for instance, chemical energy can become kinetic energy but that energy can be neither created nor destroyed. Additionally, in terms of energy conversion, the first law of thermodynamics indicates that energy output cannot exceed the input, and the ratio of these two forms of energy describes the efficiency of a system (24): efficiency output energy/input energy. Muscle energy demand, supply, and efficiency. Although, the well accepted energy-related laws of physics are clearly applicable to isolated systems, human energy supply, demand, and efficiency during exercise, each a consequence of numerous biological systems, are significantly more complex. All the energy required for cellular function, including contractile activity, is provided by the hydrolysis of ATP to ADP and Pi. To balance the significant consumption of ATP during physical activity, efficient pathways of ATP resynthesis are needed. Three main mechanisms facilitate ATP resynthesis in skeletal muscle fibers: creatine kinase activity, glycolysis, and mitochondrial oxidative phosphorylation. Finally, to ensure that all metabolic processes continue to work during sustained exercise, energetic substrates and oxygen must be readily available at the cellular level or supplied via the circulation (23). Previous physiological studies have defined mechanical efficiency as the ratio of the work performed and the amount of oxygen consumed during sustained exercise (8, 22). With this approach, there are convincing data that both in vitro (29) and in vivo (6) the energetic cost of force production is fiber type dependent, with type I or slow-twitch fibers being more efficient than type II or fast-twitch fibers. The mechanisms responsible for the lower cost of developing tension with slow-twitch fibers include higher chemical-to-mechanical coupling efficiency and lower energy cost of the adenosine triphosphatase (ATPase) driven calcium pump whose activity is 5 to 10 times slower in the type I compared with type II fibers (29). The heterogeneity of skeletal muscle metabolic efficiency is also influenced by muscle mitochondrial volume, which varies from 6% in type I fibers to 4% in type II fibers, and the wide-ranging mitochondrial enzymatic activity in slowand fast-twitch fibers (14). Thus slowtwitch muscle fibers are designed to generate ATP by oxidative mitochondrial processes, and their relatively low ATP consumption during contraction contributes to their high efficiency. In contrast, fast-twitch muscle fibers that depend more upon glycolytic processes to generate ATP are less efficient during contractile activity (13). Effect of aging on muscle structure, function, and metabolic efficiency. Typically, the percentage of type I fibers is higher in old compared with young muscle, as aging is associated with selective sarcopenia of type II fibers (18, 19). Indeed, this pronounced atrophy of the type II fibers typically results in a greater type I fiber fraction of the total contractile volume in the elderly, which, as already indicated, likely alters metabolic efficiency. Again, due to differences in myosin ATPase and the cost of calcium handling, metabolic efficiency is significantly higher in type I fibers with respect to type II fibers, (7, 9, 25, 26). By using an animal model (10), this concept was translated to reveal increased skeletal muscle metabolic efficiency in senescent rats that had a significant decrease in type II myosin heavy chain content, which was not evident in the middle-aged animals. In humans there are also data that support this phenomenon, with age-dependent changes in fiber-type composition playing a key role in the reduced contractile cost in older men and subsequent increases mechanical efficiency (27). The age-related shift toward a slow-twitch muscle fiber phenotype contributes to an overall slowing of skeletal muscle contractile properties, causing a change in the force frequency relationship (1). Consequently, it is possible that attenuated kinetics may reduce the ATPase rate of type I muscle fibers, contributing to an increase in metabolic efficiency. Thus, the higher relative force at lower stimulation frequencies in older skeletal muscle likely reduces the energy required for ion transport and lessens the motor drive needed to maintain a given relative workload. Indeed, the recent literature indicates that type I myosin kinetics are, indeed, slowed in older humans, primarily driven by modifications of the myosin molecule (11). Certainly, some aspects of muscle performance decline with age; however, recent research indicates that muscular endurance is actually enhanced in older subjects (4, 16). Moreover, it is evident that fiber type differences in healthy long-lived subjects, such as centenarians, may explain the difference in mechanical efficiency observed during exercise (28). It is highly likely that age-related changes in skeletal muscle phenotype can work synergistically with changes in activation pattern, increasing muscle metabolic efficiency in older muscle. Influence of age range and exercise task on mechanical efficiency. Again, it must be recognized that, although an age-related increase in mechanical efficiency has been documented in an animal model (10), in humans, utilizing an MRI approach to interrogate the muscle itself (27), and during cycling exercise in extremely longevous subjects (28), there are certainly other investigations that have failed to reveal this phenomenon (2, 20, 21). However, there are two main differences between these studies that may explain these contrasting results. First, the differing age range of the subjects studied: Bell et al. (2) revealed that in 70-year-old women, net and mechanical efficiency during cycling was significantly reduced. However, recent studies have revealed that the greatest J Appl Physiol 114: 1108–1113, 2013; doi:10.1152/japplphysiol.01438.2012. Point:Counterpoint