This is an excerpt from Timing Resistance Training by Amy Ashmore.
Muscle Clocks: Description and Functions
Muscle clocks are transcription factors or genes inside each muscle that regulate physiological cycles according to environmental changes and physical activity. The primary function of muscle clocks is to monitor what happens outside and inside the body during a 24 h period. To help muscles function optimally, muscle clocks pay careful attention to things such as day-night phases, activity-rest cycles, hormone levels, body temperature, and eating and exercise habits.
The discovery of these internal, autonomous regulating clocks in muscle is significant because it shifts how we think about muscles. Muscles are not simply responding to central nervous system commands; instead, the muscles themselves are able to cause action.
Muscle clocks play a role in regulating muscle function. They also communicate with each other, the musculoskeletal system, the brain, and the entire body. Muscle clocks synchronize muscles to the master biological clock in the brain. They also connect muscles to other periphery clocks located in tissues inside and outside the musculoskeletal system.
Muscle clocks are like internal pacemakers. At the cellular level, a molecular clock provides an essential timekeeping method to prepare the muscle for daily changes in the environment. The capacity to synchronize the molecular clock and intracellular activity with outside events, such as day-night cycles, indicates an ability to adapt to environmental conditions. In that way, muscles are smart and show the ability to adapt to their surroundings. An example of another musculoskeletal system clock is a bone clock; an example of a periphery clock is one located in the liver.
Relationship to Muscle Tissue
Muscles make up an estimated 40% to 45% of the body's total mass. Muscle is the single most abundant tissue in the human body. It would make sense, due to its volume alone, that muscle is not simply an effector, a structure under control of the central nervous system that acts only in response to commands. Instead, muscle is an important regulator that causes action in other body systems and has capabilities beyond only responding.
Whatever muscles do affects the entire body. The finding that muscles have clocks that control their functions and communicate with other body systems is revolutionary. It shows that muscles, through a variety of cues, including strategically planned exercise, play a critical role in regulating whole body functioning. For example, with the help of muscle clocks, muscle communicates with the liver and plays an important role in maintaining metabolic homeostasis of the body.
The idea that muscles are more than effectors is not new. Because muscle mass makes up a huge percentage of the human body, it has seemed illogical to many people that muscle's only function would be to act under central nervous system command and execute movements. Although the hypothesis is not new, the evidence to support the idea is new and is explored in detail later in the chapter.
There are more than 600 skeletal muscles in the human body. Each one has its own muscle clock composed of many different types of genetic material (20, 26). Because humans have more than 600 muscles and each one has its own clock, there are more than 600 individual skeletal muscle clocks working 24 h days to synchronize muscle activity to the master clock in the brain, the other musculoskeletal system clocks, the other body systems, and the environment. Muscle clocks are not one size fits all. Different muscle clocks exist in different muscles made up of different fiber types. The significance of the various types of muscle clocks is discussed later in the chapter.
Muscle clocks are located inside muscles. They are made up of transcription factors, a sequence-specific binding factor that controls the rate of transcriptionof genetic information (transcription is the process by which genetic information from a thread of DNA is used to produce a thread of complementary RNA) and is involved in the conversion of DNA into RNA (figure 1.1). Once DNA is converted to RNA, the RNA is used to regulate and express genes important to muscle clock function. Transcription factors include essential proteins that initiate and regulate gene activity inside muscle. Each internal clock is made up of numerous transcriptional factors, each with a different role in controlling the clock. Among these transcription factors, some are exclusive to the core molecular clock and some are found across different types of clocks; the muscle clocks also contain genes important for skeletal muscle-specific functions, such as the proteins myosin and troponin, and others important for metabolism and ATP synthesis.
All biological clocks are on a 24 h schedule. The 24 h cycle is reflected in daily changes of the whole body, global gene expression pattern, and metabolism. In other words, the transcription factors within the muscle and other clocks behave differently at different times of the day and in response to different stimuli.
The local activity of specific peripheral tissues such as muscles reflect the 24 h cycle of their clocks. Muscle clocks learn a schedule by paying attention to cues outside of the body such as the light-dark cycle, which is associated with the time of day relative to the position of the earth's orbit and is a universal entrainment cue to all biological clocks. (Entrainment refers to the matching of rhythmic biological events, such as the circadian rhythm, to changes in the outside or local tissue environment.) Time-of-day cues set and reset all internal clocks, including muscle clocks. The time of day is the most obvious and well understood clock cue, but as discussed in later chapters, cues are numerous and tissue specific. In the case of muscle, additional cues include hormone levels, activity-rest patterns, and exercise programming (such as the timing of resistance training), all of which are discussed at length in chapter 3.
Figure 1.1 DNA is converted to RNA, which is used to code, decode, regulate, and express genes important to muscle clock function.