Fatigue is a crucial concept for exercisers because it represents the point where they fail to complete a set or feel too exhausted to continue a long-distance run or other endeavor. Fatigue fascinates researchers because it reflects mental, chemical and mechanical processes that affect muscle performance. Indeed, the physiology of fatigue recently inspired the journal Medicine & Science in Sports & Exercise to devote a special section to the topic.

I'll review highlights from the journal's special section in a question-and-answer format:

What Is Fatigue?

World-renowned muscle fatigue researchers Roger Enoka and Douglas Stuart (1992) described fatigue as an acute performance impairment with two distinct outcomes: an increase in perceived effort required to exert a desired force and, eventually, an inability to produce this force. Citing early work by Mosso (further developed by Kluger and colleagues), Enoka and Duchateau (2016) explain the idea of performance fatigability, meaning an activity's tendency to produce fatigue. Fatigability measures factors like contractile function or muscle activation that decline during exercise over a distinct period of time.

Two categories of physiological processes contribute to fatigue:

  • central—muscle activation signaling from the brain
  • peripheral—physiological mechanisms at the neuromuscular junction and within the contracting muscle

Enoka and Duchateau also describe perceived fatigability, which measures factors like the psychological state and homeostasis of sensations that regulate an exerciser's integrity.

What Causes Muscle Fatigue?

Reid (2016) summarizes 30 years of research by muscle biologists, who have developed a clear picture of how strenuous exercise generates reactive oxygen species (ROS)—reactive molecules and free radicals derived from molecular oxygen—that can impair or damage muscle proteins (and other molecules). According to Reid, a large body of research provides conclusive evidence that ROS are influential in loss of muscle function during fatigue.

The evidence says ROS have a causal effect on fatigue in small muscles, at the neuromuscular junction and in whole-body exercise (like running) by elite athletes (Reid 2016). Reid expects future research to look for ways to enhance the body's acute ability to make antioxidants, the specialized molecules that neutralize ROS in muscle. If and when this occurs, we'll likely see elite athletes setting new cardiovascular and anaerobic world records.

What Are the Sex Differences in Fatigability?

Sandra Hunter (2016) explains that every human cell has a sex (defined by the chromosome complement of XX in men and XY in women) that influences fatigue in women and men differently. Hunter recaps research indicating that women are less fatigable then men in many isometric tasks and some dynamic tasks when women and men are performing similar-intensity contractions. Note that much of the research comparing fatigue in sexes uses isometric contractions because of the ability to quantify a decline in force production so accurately.

Hunter says women are less fatigable then men during isometric fatiguing tasks for several muscle groups. It is interesting to note that sex fatigue differences actually vary between muscle groups. For instance, sex differences in fatigability are less in ankle dorsiflexor muscles than they are in elbow flexor muscles (Hunter 2016). In addition, Hunter notes, sex fatigue differences are less pronounced in high-intensity isometric muscle contractions than they are in low-intensity isometric contractions.

In regard to dynamic muscle functions, the emerging evidence indicates that sex differences in fatigue are task specific (Hunter 2016). For instance, Hunter describes evidence that women are less fatigable then men when dynamic tasks contract the elbow flexor muscles slowly, but not when tasks contract the muscles quickly.

Interestingly, Hunter cites studies showing that after long-duration running and cycling, women have smaller reductions in lower-body maximal strength than men do. More research in this area will eventually point to new and different recovery strategies for men and women after fatiguing endurance exercise (Hunter 2016).

What Are the Mechanisms for Sex Differences in Fatigue?

Contractile mechanisms of muscle are largely responsible for muscle fatigue differences in men and women (Hunter 2016). In addition, there are differences in the delivery of blood to capillary beds in muscle—called muscle perfusion—between men and women. And the voluntary activation of muscle groups varies between the sexes (Hunter 2016).

Hunter (2016) spotlights evidence of sex differences in whole-body foodstuff use during endurance exercise. Women break down less carbohydrate and more fat than men during similar-intensity endurance exercise. These differences in muscle energy metabolism are largely attributable to differences in muscle fiber proportions between the sexes. To briefly review muscle fiber types, type I (slow-twitch) fibers are highly involved in activities requiring sustained muscle contractions, like endurance events. Type II (fast-twitch) muscle fibers are engaged mainly in shorter-length activities with greater force production, such as sprinting and burst-type exercise

Hunter explains that the relative number of muscle fibers may not differ between men and women, but women have smaller fast-twitch fibers than men and a greater relative area of slow-twitch fibers. This proportional difference in fiber-type areas leads to more fatigue-resistant muscle, says Hunter. She suggests that the mechanism for recovery after a strength event may differ between the sexes, but more research is needed. This may eventually suggest different recovery strategies for men and women after resistance training.

How Does the Brain Influence Fatigue?

Central fatigue—the activation signal from the brain—is one of the key factors that generate a fatigue reaction. Taylor et al. (2016) explain that a chain of processes in the nervous system before muscle contraction may also impair the force generated by the muscle. The brain's signal to muscle, known as neural drive, determines when and to what degree muscle fibers are activated (Taylor et al. 2016). However, feedback mechanisms such as pain, discomfort and perception of effort may directly affect neural drive.

In addition, Taylor and colleagues explain that the disturbance of homeostasis with fatiguing exercise leads to multiple neural alterations contributing to central fatigue. However, the brain tries to compensate by recruiting other motor units (a motor unit is a single nerve plus the many muscle fibers innervated by that nerve). Thus, during fatiguing exercise the brain is evaluating all of the sensory input and determining whether to reduce the signals to muscle or compensate to attempt to continue the specific muscle task performance.

What Is the Future of Fatigue Research?

There's more to the story of fatigue than its effects on exercisers and athletes. Fatigue is also implicated in neuromuscular disease, cancer, chronic inflammatory disease, acute critical illness and other health problems (Powers et al. 2016). Powers and colleagues underscore that muscle wasting and fatigue are clinical concerns, as they are associated with decreased quality of life and increased morbidity and mortality. Therefore, future research on fatigue has the potential not only to improve exercise performance, but also to introduce health-promoting strategies for combating diseases.