Maintaining a structured meal schedule, with prolonged fasting periods between meals, regulates the circadian rhythm of muscle cells, according to international research led by the Universitat Pompeu Fabra (UPF) and the Institut de Recerca Biomèdica (IRB) in Barcelona presented in the journal Science. This, in turn, prevents muscle deterioration with age and may potentially help delay the aging process of the entire organism.
The research is part of a project that began eight years ago to understand how the circadian rhythms of different organs and tissues in the body are regulated, as they must be active at different times of the day. The ultimate goal of the project is to apply this knowledge to improve people’s health.
Previous research had shown that the central clock of the human body is located in the suprachiasmatic nucleus of the brain, which receives information about ambient light directly from the retinas and signals the entire organism what time it is at all times. Research from the IRB and UPF now demonstrates that organs such as the skin and muscles also receive information from the environment that helps them adjust their individual clocks.
If the signal coming from the central clock in the brain deteriorates, as often happens in older people, peripheral clocks can compensate for this deterioration and restore a proper circadian rhythm. In experiments with mice whose central clock is damaged, regulating the times they are allowed to eat is sufficient for muscle cells to regain a correct circadian rhythm.
“As we grow older, it becomes more important for us to take care of the stimuli that synchronize the peripheral clocks,” states Salvador Aznar-Benitah, an ICREA researcher at the IRB and co-director of the project.
In addition to structured meal times, other habits that help maintain healthy circadian rhythms include exposing oneself to daylight, avoiding short-wavelength lights at night (such as those emitted by many screens), maintaining good sleep hygiene, and engaging in physical activity, stated Pura Muñoz-Cánoves, who co-directed the research at the UPF and currently works at Altos Labs in San Diego (USA).
A poorly regulated biological clock in the body leads to premature aging, as researchers have found. In the muscles, the proper production of proteins is altered, mitochondria that provide energy to the cells function poorly, and sarcopenia appears, which is the deterioration of muscle mass that occurs with age and is characterized by a loss of mass, strength, and tissue quality. In the overall organism, mice with a damaged central clock in the brain die at an age equivalent to 40 years in humans, indicating accelerated aging.
“Cells must oscillate between periods of activity and inactivity. If we are exposed to blue light and eat when it is already nighttime, they interpret it as still being daytime and function worse,” explains Aznar-Benitah, a specialist in chronobiology, who says, “Personally, I eat at the same time every day, at one o’clock, and at home we have dinner at eight, no later.”
Although the research has been based on experiments with mice, the results can be extrapolated to humans because the mechanisms that regulate the body’s biological clocks are the same in both species, the authors of the study point out.
Previous studies had already established that a structured meal schedule is beneficial for health. Research by the IRB and UPF reveals that it provides this benefit by acting on the peripheral clock of the muscles in a way that compensates for dysfunctions in the central clock.
As part of the project, researchers have also studied the relationship between the peripheral clock in the skin and the central clock in the brain. Similar to what happens in muscles, the skin modulates the timing signal it receives from the brain based on external stimuli. The results of the skin study are being published today in Cell Stem Cell, coinciding with those of the muscle study in Science.
“We have discovered that the body’s clocks function in a federated manner. From now on, we can explore how the different organs of the body synchronize with each other,” which can have important implications for health care, highlights Aznar-Benitah.
With the technology for studying biological clocks they have developed, researchers plan to investigate whether restoring proper circadian rhythms in peripheral organs can slow down aging. “It’s a question we’ve been asking ourselves since we started this project; now we have the tools to research it,” explains the scientist from IRB.
“Muscles represent 50% of the body’s volume and weight, and secrete a large amount of proteins that have effects on other tissues,” explains Muñoz-Cánoves. “It is possible that by improving muscle function, other organs may also improve.”
