Fatigue mechanisms determining exercise performance: integrative physiology is systems biology.

FOR MORE THAN A CENTURY, applied physiologists have investigated the complex nature of fatigue and its implications for exercise performance. Long before the term “systems biology” entered the biomedical lexicon, physiologists appreciated the need to understand fatigue at various levels of integration and across multiple organ systems, a point eloquently highlighted in a recent editorial (13). In his early 20th century text Physiology of Muscular Exercise, Bainbridge (1a) noted the following: