A Mismatch Between Central versus Peripheral Circadian Regulation in Aging
Researchers here present an interesting view of age-related circadian dysfunction, focusing on mismatched regulation between the central circadian clock and somewhat independent peripheral clocks. The regulation of circadian rhythm in tissues results from the activities of these complex systems of multiple parts - and like all complex systems they begin to exhibit dysfunction with advancing age. The novel aspect of this research is the concept of multiple mismatched circadian regulators as a cause of further dysfunction in tissues.
Discovered in the 1970s, circadian clocks are essential for the regulation of biological time in most cells in the human body. These internal mechanisms adjust biological processes to a 24-hour cycle, allowing the synchronisation of cellular functions with daily variations in the environment. Circadian rhythms, which are coordinated by a central clock in the brain that communicates with clocks in different peripheral tissues, influence many functions, from our sleep patterns to our ability to metabolise food.
A study on the communication between the brain and muscle confirmed that the coordination between the central and peripheral clocks is crucial for maintaining daily muscle function and preventing the premature ageing of this tissue. Restoration of the circadian rhythm reduces the loss of muscle mass and strength, thereby improving deteriorated motor functions in experimental mouse models.
The results of the study have also demonstrated that time-restricted feeding (TRF), which involves eating only in the active phase of the day, can partially replace the central clock and enhance the autonomy of the muscle clock. More relevant still is that this restoration of the circadian rhythm through TRF can mitigate muscle loss, the deterioration of metabolic and motor functions, and the loss of muscle strength in aged mice.
"It is fascinating to see how synchronisation between the brain and peripheral circadian clocks plays a critical role in skin and muscle health, while peripheral clocks alone are autonomous in carrying out the most basic tissue functions. Our study reveals that minimal interaction between only two tissue clocks (one central and the other peripheral) is needed to maintain optimal functioning of tissues like muscles and skin and to avoid their deterioration and ageing. Now, the next step is to identify the signalling factors involved in this interaction, with potential therapeutic applications in mind."