An article published in Frontiers in Physiology reviewed recent studies that examined the nuclear changes involved in muscle memory.
We often hear the phrase “use it or lose it”, indicating that if we do not use our muscles, we will lose them. For years, researchers thought muscle loss due to age also results in a loss of nuclei in muscle cells. These nuclei maintain muscle fibres.
Numerous factors influence whether muscles will grow, such as exercise, or shrink, such as starvation, cancer, denervation, and diabetes. Muscle loss is concerning as it is associated with morbidity and mortality, especially at an older age.
Unlike other cells of the body, skeletal muscle cells have many nuclei in order to produce adequate protein to supply the long muscle fibers. In 1893, Strassburger suggested that the maximum size of a muscle cell is limited because the nuclei can only support a certain amount of cytoplasm.
The myonuclear domain hypothesis
This lead to the creation of the “myonuclear domain hypothesis”, which states that when muscle cells grow or shrink, the number of nuclei in each cell changes. Specifically, with muscle growth, there is an increase in nuclei, and with muscle loss, there is a decrease in nuclei. This forms the foundation of the idea of muscle memory.
There is evidence to support that there is an increase in nuclei with muscle growth. However, it is not yet understood how, or if, a loss in nuclei occurs. It is known that enzymes known as proteases are involved in apoptosis, or programmed cell death, but researchers question how the enzymes affect some nuclei, but not others in the same cell.
A study by Bruusgaar induced muscle growth using muscles from the lower leg and saw an increase in muscle mass and the number of nuclei. When they induced muscle loss, the number of nuclei remained the same. They repeated the experiment with different stimuli to induce muscle loss and saw the same results.
Unfortunately, the study did not account for naturally occurring programmed cell death. Also, in mammalian cells, the nuclei are sometimes found outside of the muscle fibres making it difficult accurately count nuclei, so another model was studied.
Muscles can gain nuclei but not lose them
Researchers used the intersegmental muscle of the tobacco hawkmoth, which is involved in the mobility of larvae and in emerging from the pupal because they are not limited in the ways same ways as mammalian cells. In this study, researchers found that although the muscle cells decreased in volume and size, the number of nuclei did not change. They also measured the amount of DNA and found it did not change significantly. They published their results in Frontiers in Physiology.
The study found that exercise allows the muscle to gain nuclei, and these nuclei persist even when muscle cells shrink or start to break down. This suggests that individuals can “bank” their potential for muscle growth as early as their teenage years to prevent frailty in old age.
Study shows the importance of exercise in early life
Study author Lawrence Schwartz, Professor of Biology at the University of Massachusetts commented in a press release, “…the discovery that myonuclei are retained indefinitely emphasizes the importance of exercise in early life. During adolescence muscle growth is enhanced by hormones, nutrition and a robust pool of stem cells, making it an ideal period for individuals to “bank” myonuclei that could be drawn upon to remain active in old age.”
This new understanding of muscle memory has important implications for aging. It suggests that exercise at a younger age can not only increase muscle mass but the number of nuclei, which can be stored to possibly delay the large decrease in muscle loss that occurs after the age of 50.
Written by Monica Naatey-Ahumah, BSc
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Reference: Schwartz, L.M. (2019). Skeletal Muscles Do Not Undergo Apoptosis During Either Atrophy or Programmed Cell Death-Revisiting the Myonuclear Domain Hypothesis. Frontiers in Physiology. https://doi.org/10.3389/fphys.2018.01887