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The Basic Science of Exercise Fatigue


Medicine & Science in Sports & Exercise: November 2016 - Volume 48 - Issue 11 - p 2222–2223
doi: 10.1249/MSS.0000000000001103
SPECIAL COMMUNICATIONS: The Basic Science of Exercise Fatigue


Fatigue—this word certainly evokes strong images in the minds of researchers and laypersons alike. A common representation would be that of an athlete collapsing at the finish line of a race or breathing heavily with hands on his/her knees. Others may envision a wan appearance accompanied by the “sensations of tiredness and weakness that accompany some clinical conditions” (2) or perhaps an exhausted worker at the end of a long day of hard labor. But, what exactly is fatigue and what are the underlying mechanisms that cause it? In May 2015, the American College of Sports Medicine’s Annual Meeting in San Diego, California included the World Congress on The Basic Science of Exercise Fatigue. A special section of the same name in this month’s journal is derived from that meeting.

Previous reference starting points for researchers interested in exercise fatigue were the Ciba Foundation symposium published in 1981 (13) and the volume on fatigue in Advances in Experimental Medicine and Biology published in 1995 (4). Now, more than 20 years later, our special section will in my opinion, become the present-day reference landmark for those interested in the underlying mechanisms of exercise fatigue. Although there was some discussion of so-called central fatigue in the Ciba symposium, there was a particular emphasis on skeletal muscle contractile function and metabolism. The lack of attention to enhanced sense of effort as a key component of fatigue prompted a concluding general discussion that focused on the perception of fatigue. In our special section, both Joyner (8) and particularly Enoka and Duchateau (2) attempt to capture the expansive nature of fatigue with revised definitions.

Reid (15) provides an historical overview and up-to-date summary of the probable role of reactive oxygen species in the overall fatigue process whereas Hunter (6) assesses the relevance of sex differences in performance fatigability. Jones (7) provides a comparative physiology perspective on fatigue and quoting Krogh (10) reminds us that revealing insights are often available from detailed observations of animal performance: “For a large number of problems there will be some animal of choice or a few such animals on which it can be most conveniently studied.” Debold et al. (1) delve deeply into the basic mechanisms of muscle contraction and provide a molecular perspective on fatigue as exemplified by the effects of metabolite accumulation on myosin, and its interactions with actin, troponin, and tropomyosin. Kent and coauthors (9) report on fatigue from an integrative perspective with most of the emphasis being on the nervous, vascular, and energy systems. Their review concludes with a discussion of the importance of interweaving human and animal research, particularly as these investigations relate to fatigue. Next, Taylor et al. (17) approach the fatigue process from the neural perspective, noting that exercise induces numerous neural perturbations that contribute to the overall fatigue process and at the same time compensate for reduced muscle function. Powers and colleagues (14) direct attention to the underlying mechanisms of skeletal muscle weakness and fatigue in patients, including intensive care-induced, cancer cachexia-induced, chronic inflammatory-induced, and neurological disorder-induced skeletal muscle weaknesses. Poole et al. (12) use the concept of critical power to combine the basic and applied sciences of fatigue. They note that critical power is an important fatigue threshold that offers a path into the loci of fatigue development and the mechanisms of cardiovascular and metabolic control, and O2 delivery.

Our special fatigue section concludes with an insightful pro/con debate on the role of acidosis in fatigue. Despite claims to the contrary, lactate accumulation, along with increased weak acid concentration, elevated partial pressure of carbon dioxide and other metabolic and electrolyte changes are associated with increased hydrogen ion concentration; that is, decreased pH (5,16). Such an acidosis is a hallmark of maximal, all-out effort exercise, but is acidosis a cause of the exercise/muscle fatigue? For most of the 20th century, skeletal muscle acidosis was considered to be a key causative factor in the fatigue resulting from severe-intensity exercise. However, in the past 15 years or so, acidosis has been relegated to a nonfactor status, or even viewed as a protective agent against fatigue (11). There is no doubt that some of the major deleterious effects of low pH on muscle function are much smaller at more physiological temperatures (≈30°C) than at lower, nonphysiological temperatures (≤ ≈15°C), at least nonphysiological for homeotherms. Fitts (3) argues that acidosis induces fatigue at the level of cross-bridges, particularly affecting velocity and thereby the power of muscle contraction. In opposition, Westerblad (18) contends that evidence from human muscle in situ and isolated intact muscle fibers lead to the conclusion that acidosis is not a major player in muscle fatigue.

In summary, this special section encompasses the range of fatigue from neural to muscular, animal to human, health to disease, and molecular to whole organism. It concludes with a debate that originates in some of the very earliest studies of fatigue. Enjoy.

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1. Debold EP, Fitts RH, Sundberg CW, Nosek TM. Muscle fatigue from the perspective of a single crossbridge. Med Sci Sports Exerc. 2016;48(11):2270–80.
2. Enoka RM, Duchateau J. Translating fatigue to human performance. Med Sci Sports Exerc. 2016;48(11):2228–38.
3. Fitts RH. The role of acidosis in fatigue: pro perspective. Med Sci Sports Exerc. 2016;48(11):2335–8.
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© 2016 American College of Sports Medicine