Nuclear Changes in Muscle Memory: Insights from Recent Research

Understanding Muscle Loss and Retention

An article published in *Frontiers in Physiology* reviews recent studies focusing on the nuclear changes associated with muscle memory. The common adage “use it or lose it” suggests that inactivity can lead to muscle loss. Historically, researchers believed that muscle degeneration due to aging also resulted in a reduction of nuclei within muscle cells, which are essential for maintaining muscle fibers.

Various factors can influence muscle growth or shrinkage, including exercise, starvation, cancer, denervation, and diabetes. Muscle loss is alarming as it often correlates with increased morbidity and mortality, particularly among older individuals. Skeletal muscle cells are unique as they contain multiple nuclei, which are necessary for producing sufficient protein to support long muscle fibers.

The Myonuclear Domain Hypothesis

In 1893, Strassburger proposed that the maximum size of a muscle cell is constrained since nuclei can only support a limited amount of cytoplasm. This concept led to the development of the “myonuclear domain hypothesis,” which posits that the number of nuclei in muscle cells varies with changes in muscle size. Specifically, muscle growth is associated with an increase in nuclei, while muscle loss results in a decrease. This hypothesis underpins the concept of muscle memory.

Although evidence supports the idea that muscle growth leads to an increase in nuclei, the mechanisms behind the potential loss of nuclei remain unclear. It is known that proteases, enzymes involved in apoptosis (programmed cell death), play a role in this process. However, researchers are still investigating why some nuclei are affected while others remain intact within the same cell.

Research Findings on Muscle Growth and Loss

A study conducted by Bruusgaar examined muscle growth in the lower leg, observing increases in both muscle mass and the number of nuclei. However, when muscle loss was induced, the number of nuclei did not decrease. This experiment was replicated using various stimuli to induce muscle loss, consistently yielding the same results. Unfortunately, the study did not account for naturally occurring programmed cell death, and the presence of nuclei outside muscle fibers in mammalian cells complicates accurate counting.

Insights from Tobacco Hawkmoth Muscles

To further investigate, researchers turned to the intersegmental muscle of the tobacco hawkmoth, which plays a role in larval mobility and emergence from the pupal stage. This model is advantageous as it does not face the same limitations as mammalian cells. The study revealed that despite a decrease in muscle cell volume and size, the number of nuclei remained unchanged. Additionally, measurements of DNA did not show significant variation. The findings were published in *Frontiers in Physiology*.

The study concluded that exercise facilitates the gain of nuclei in muscle cells, and these nuclei remain even when muscle cells undergo shrinkage or breakdown. This suggests that individuals may “bank” their muscle growth potential during their teenage years, potentially mitigating frailty in older age.

The Importance of Early Exercise

Lawrence Schwartz, a Professor of Biology at the University of Massachusetts and author of the study, emphasized in a press release the significance of retaining myonuclei. He stated, “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 holds important implications for aging, suggesting that engaging in exercise at a young age can not only enhance muscle mass but also increase the number of nuclei, potentially delaying the substantial muscle loss typically observed after the age of 50.

Written by Monica Naatey-Ahumah, BSc
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