Myc is the only one of the four factors that can be generated by working out skeletal muscle. It’s possible that Myc acts as a naturally produced reprogramming stimulus in muscle, which makes it a suitable point of comparison between cells that have been reprogrammed by the overexpression of Yamanaka factors and cells that haven’t been reprogrammed.
Building on previous work done with laboratory mice that were getting close to the end of their natural lifespan and had access to a weighted exercise wheel, a recent paper was published in the Journal of Physiology that provided further evidence that exercise can promote a more youthful appearance in organisms that are aging. This paper added to the growing body of evidence that exercise can have a rejuvenating effect on older organisms.
There are a staggering 16 authors listed in the study titled “A molecular signature defining exercise adaptation with aging and in vivo partial reprogramming in skeletal muscle.” Of these authors, six are associated with the University of Arkansas. Ronald G. Jones III, who is currently pursuing his doctorate in Kevin Murach’s Molecular Muscle Mass Regulation Laboratory, is listed as the paper’s first author. Kevin Murach, who is an assistant professor in the university’s Department of Health, Human Performance, and Recreation, is the corresponding author of the paper.
In this study, the researchers compared older mice that had access to a weighted exercise wheel with mice that had undergone epigenetic reprogramming through the expression of Yamanaka factors. The researchers found that the older mice with access to the exercise wheel had a significantly longer lifespan.
The Yamanaka factors are four protein transcription factors (identified as Oct3/4, Sox2, Klf4, and c-Myc, often abbreviated to OKSM) that have the ability to convert highly specified cells (such as a skin cell) back into a stem cell, which is a younger and more adaptable state. This process can be used to treat a variety of diseases. In recognition of his work in this field, Dr. Shinya Yamanaka was given the Nobel Prize in Physiology or Medicine in 2012. Inducing the Yamanaka factors throughout the bodies of mice in the appropriate dosages has the potential to delay the onset of the telltale signs of aging by imitating the adaptability that is typical of cells in their more youthful states.
that have been reprogrammed as a result of engaging in physical activity, where “reprogramming” in this latter case refers to the way in which an external stimulus can modify the accessibility of genes and how they are expressed.
The researchers examined the skeletal muscles of mice that were genetically modified to overexpress OKSM in their muscles, genetically modified mice that were limited to overexpressing just Myc in their muscles, and genetically modified mice that had been allowed to exercise late in life. All of these mice were compared to the skeletal muscles of mice that had been allowed to exercise late in life.
In the end, the group came to the conclusion that physical activity encourages a chemical profile that is congruent with epigenetic partial programming. That is to say, muscle fibers that have been subjected to Yamanaka factors and then subjected to exercise have molecular profiles that are quite similar (thus displaying the molecular characteristics of more youthful cells). It’s possible that the unique actions of Myc in muscles are responsible for this advantageous effect of exercise, at least in part.
Murach warns against jumping to the conclusion that we will one day be able to manipulate Myc in muscle to achieve the effects of exercise, thus sparing us the actual hard work. Despite the fact that it would be simple to hypothesize that one day we may be able to do so and that this would be the case, he emphasizes that this would be the incorrect conclusion to draw.
To begin, Myc could never be capable of duplicating all of the impacts that exercise produces on a cascading level throughout the body. As a consequence of the fact that it is also the root cause of tumors and malignancies, there are inherent risks involved with modifying its expression. Murach believes that a better use for altering Myc would be as an experimental method to learn how to restore exercise adaptation to older muscles that are displaying decreased responsiveness. It is also possible that it could be used to boost the exercise response of astronauts in zero gravity, as well as people who are confined to bed rest and have a limited capacity for exercise. Determining which of Myc’s various effects are beneficial could, in the future, pave the way for the development of a treatment that is not only risk-free but also has the potential to be of use to humans.
According to Murach, their findings provide further validity for the use of exercise as a polypill. According to him, physical activity is “the most powerful drug we have,” and it should be seen as a treatment that not only improves one’s health but also has the ability to lengthen one’s life in addition to the use of pharmaceuticals and a nutritious diet.
At the University of Arkansas, Francielly Morena Da Silva, Seongkyun Lim, and Sabin Khadgi were among the researchers who contributed to the study that Murach and Jones authored. Nicholas Greene, an exercise science professor at the University of Arkansas, was also a co-author.