Two new research studies show that the central and peripheral circadian clocks work together to control the daily functions of the skin and muscles. This coordination is responsible for regulating 50% of the circadian functions of tissues, including important processes like the cell cycle, DNA repair, mitochondrial activity, and metabolism. By synchronizing the central brain clock with peripheral clocks, it is possible to prevent premature muscle aging and enhance muscle function, offering new approaches to addressing age-related decline through modulation of circadian rhythms.
Discovered in the 1 rnrnIn the 1970s, circadian clocks play a crucial role in regulating biological time in most cells of the human body. These internal mechanisms adjust biological processes to a 24-hour cycle, allowing cellular functions to synchronize with daily environmental changes. Coordinated by a central clock in the brain, circadian rhythms communicate with clocks in different peripheral tissues, influencing functions such as sleep patterns and the metabolization of food. Dr. Salvador Aznar Benitah, an ICREA researcher at IRB Barcelona, and Dr. Pura Muñoz-Cánoves, an ICREA researcher, led a team working on this topic.Archer, a researcher at the Pompeu Fabra University, has explained the importance of the synchronization between the central clock and peripheral clocks in muscle and skin. This synchronization is crucial for the proper functioning of these tissues and for preventing age-related degenerative processes.
The findings of this research have been published in two high-impact journals. The study on the synchronization between the central and peripheral clocks is featured in Science, while the research on the coordination between the central clock and skin peripheral clock has also been released.Based on Cell Stem Cell, two studies have uncovered the shared mechanisms that emphasize the importance of this coordination to support the optimal functionality of muscle and skin.
The research also highlights the significant level of independence of the peripheral clocks, which are able to maintain 24-hour cycles and control approximately 15% of circadian functions even without the central clock.
“It is interesting to observe how synchronization between the brain and peripheral circadian clocks plays a crucial role in skin and muscle health, while peripheral clocks alone are self-sufficient in carrying out the most fundamental tissue functions,” says Dr.Aznar Benitah, who leads the Stem Cell and Cancer laboratory at IRB Barcelona, emphasized the importance of minimal interaction between two tissue clocks in maintaining optimal functioning of tissues like muscles and skin and preventing their deterioration and aging. Dr. Muñoz-Cánoves, a UPF Professor now working at Altos Labs in San Diego, US, highlighted the need to identify the signaling factors involved in this interaction for potential therapeutic applications. This coordination with the muscle peripheral clock plays a crucial role in maintaining muscle function.The research published in the journal “Science” about the interaction between the brain and muscles found that the synchronization of the central and peripheral clocks is essential for preserving daily muscle function and avoiding premature aging of the tissue. Reestablishing the circadian rhythm helps prevent the decline in muscle mass and strength, ultimately improving impaired motor functions in experimental mouse models. The study also showed that time-restricted feeding (TRF), which means eating only during the active phase of the day, plays a role in this process.During the day, time-restricted feeding (TRF) has the potential to partially substitute for the master clock and improve the muscle clock’s independence. Even more important is the fact that TRF’s ability to restore the circadian rhythm can help reduce muscle loss, metabolic and motor function deterioration, and loss of muscle strength in older mice.
These findings have important implications for the development of treatments for muscle aging and improving physical performance in old age. The study’s first authors, Drs. Arun Kumar and Mireia Vaca Dempere from UPF, received contributions from Drs. Eusebio Perdiguero and Antonio Serrano.Previously at the UPF and now at Altos Labs. The peripheral clock of the skin integrates and modulates brain signals. In a study published in Cell Stem Cell, the team showed that the skin’s circadian clock plays a crucial role in coordinating the daily physiology of this tissue. It integrates brain signals and sometimes even modifies them to ensure the skin functions correctly. A surprising finding was that, in the absence of the peripheral clock, the central body clock still maintains the skin’s circadian rhythm but in the opposite way than usual.In an opposing schedule). For instance, the scientists noticed that if DNA replication was solely regulated by the central clock, it would take place during the daytime when the skin is exposed to ultraviolet light. This would increase the likelihood of mutations accumulating. This illustrates the significance of the peripheral clock, which not only receives signals from the central clock (responsible for coordinating the organism’s rhythms) but also adjusts these signals to meet the specific needs of the tissue in which they are located (in the case of skin stem cells, DNA replication peaks after exposure to ultraviolet light during the day).
Dr. Thomas Mortimer, a postdoctoral fellow at IRB Barcelona, and Dr. Patrick-Simon Welz, from the Hospital del Mar Research Institute, have led this project, along with Drs. Aznar Benitah and Muñoz-Cánoves.
The results of the two studies come from international collaboration with researchers from the University of California and the University of Texas Health in San Antonio (both in the US), the University of Lübeck in Germany, the Karolinska Institute in Sweden, the Humanitas University in Italy, and Altos Labs San Diego Institute of Science in the US. The project received funding from the European Research Council, the EU H2020.The program is funded by the Ministry of Science, Innovation and Universities, the Government of Catalonia, the Lilliane Bettencourt Foundation, “la Caixa” Foundation, the Marató de TV3 Foundation, the BBVA Foundation, and the Novo Nordisk Foundation.
