Two complementary research articles show that central and peripheral circadian clocks coordinate the daily activity of skin and muscles. Coordination between the two clocks (central and peripheral) ensures 50% of the circadian functions of tissues, including vital processes such as cell cycle, DNA repair, mitochondrial activity and metabolism. Synchronization between the brain’s central and peripheral clocks prevents premature muscle aging and improves muscle function, suggesting new strategies to combat age-related decline by modulating the 24-hour rhythm.

How Circadian Clocks Ensure the Maintenance of Optimal Muscle and Skin Functionality

Discovered in the 1970s, circadian clocks are essential for regulating biological time in most cells of the human body. These internal mechanisms adapt biological processes to a 24-hour cycle and enable the synchronization of cellular functions with daily fluctuations in the environment. The circadian rhythms, which are coordinated by a central clock in the brain that communicates with clocks in various peripheral tissues, influence many functions, from our sleep patterns to our ability to utilize food.

A team led by Dr. Salvador Aznar Benitah, ICREA researcher at IRB Barcelona, and Dr. Pura Muñoz-Cánoves, ICREA researcher at the Faculty of Medicine and Life Sciences of Pompeu Fabra University (UPF), has described how synchronization between the central clock and peripheral clocks in muscles and skin plays a key role in ensuring the correct functioning of these tissues, as well as in preventing degenerative processes associated with ageing. The results of this work have been published in two articles in high-ranking journals. Thus, the study on the synchronization between the central and peripheral clock appears in Science, while the work on the coordination between the central clock and the peripheral clock of the skin was published in Cell Stem Cell. Both studies highlight the common mechanisms that underline the importance of this coordination in maintaining optimal muscle and skin functionality.

The work also describes the remarkable degree of autonomy of peripheral clocks, which can maintain 24-hour cycles and control about 15% of circadian functions in the absence of the central clock. The study highlights that minimal interaction between just two tissue clocks (one central and one peripheral) is required to maintain optimal function of tissues such as muscle and skin and prevent their deterioration and aging. The next step is to identify the signaling factors involved in this interaction with a view to potential therapeutic applications.

Developing Therapies for Muscle Ageing and Improving Physical Performance in Old Age

The study on brain-muscle communication published in the journal Science confirms that coordination between the central and peripheral clocks is critical for maintaining daily muscle function and preventing premature aging of these tissues. Restoring the circadian rhythm reduces the loss of muscle mass and strength and thus improves deteriorated motor function in experimental mouse models.

Research findings have also shown that time-restricted feeding (TRF), which involves eating only during the active phase of the day, can partially replace the central clock and improve the autonomy of the muscle clock. More importantly, this restoration of the circadian rhythm through TRF can curb muscle wasting, deterioration of metabolic and motor functions and loss of muscle strength in aged mice.

These findings have significant implications for the development of therapies for muscle aging and improving physical performance in old age. Dr. Arun Kumar and Mireia Vaca Dempere, both from UPF, are the first authors of this study, to which Dr. Eusebio Perdiguero and Antonio Serrano, formerly at UPF and now at Altos Labs, also contributed.

In the study published in Cell Stem Cell, the team showed that the skin’s circadian clock plays a central role in coordinating the daily physiology of this tissue. By integrating and sometimes modifying brain signals, this coordination ensures the proper functioning of the skin.

A surprising discovery was that in the absence of the peripheral clock, the central body clock maintains the skin’s circadian rhythm but functions in the opposite way to normal (i.e. on an opposite schedule). For example, the researchers found that if DNA replication were controlled only by the central clock, it would occur during the day when the skin is exposed to ultraviolet light, which would increase the risk of mutation accumulation. This phenomenon underlines the importance of the peripheral clock, which not only receives signals from the central clock – which coordinates the rhythms of the whole organism – but also adapts these signals to the specific needs of the tissue in which they are located (in the case of skin stem cells, DNA replication peaks when they are exposed to ultraviolet light during the day).