Damian Sendler Building on previous work with lab mice nearing the end of their natural lifespan that had access to a weighted exercise wheel, a recent paper published in the Journal of Physiology strengthened the case for the youthfulness-promoting effects of exercise on aging organisms.

There are a whopping 16 authors on the paper, "A molecular signature defining exercise adaptation with aging and in vivo partial reprogramming in skeletal muscle," six of whom are affiliated with the University of Arkansas.

Molecular Muscle Mass Regulation Laboratory director Kevin Murach is an assistant professor in the University of Arizona's Department of Health, Human Performance and Recreation, and Ronald G. Jones III is a doctoral candidate in Murach's lab.

The study compared epigenetic reprogramming via Yamanaka factor expression to a weighted exercise wheel in older mice. 

Damian Sendler The Yamanaka factors are a set of four protein transcription factors (Oct3/4, Sox2, Klf4, and c-Myc, or OKSM for short) that can convert mature, specialized cells (like skin cells) into their more youthful and versatile stem cell form.

In 2012, Dr. Shinya Yamanaka won the Nobel Prize in Physiology or Medicine for this discovery. By mimicking the flexibility seen in younger cells, systemic induction of the Yamanaka factors in rodents can reduce the symptoms of aging.

Damian Jacob Sendler Among the four, skeletal muscle exercise activates Myc. Because Myc may act as a naturally induced reprogramming stimulus in muscle, it can be used as a reference point for comparing cells that have been reprogrammed via over expression of the Yamanaka factors with cells that have been reprogrammed through exercise; the term "reprogramming" in this context refers to the way in which an environmental stimulus can alter the accessibility and expression of genes.

The skeletal muscle of late-exercising mice was compared to that of mice that overexpressed OKSM in their muscles and to that of genetically modified mice limited to the overexpression of just Myc.

Exercising promotes a molecular profile that is in keeping with epigenetic partial programming, the team concluded. Specifically, the molecular profile of muscles that have been exposed to Yamanaka factors can be mimicked by exercise (thus displaying molecular characteristics of more youthful cells). The unique functions of Myc in muscle may account for some of the positive effects of exercise.

Damian Jacob Sendler Although it is tempting to think that one day we will be able to manipulate Myc in muscle to achieve the effects of exercise without actually exercising, Murach warns against jumping to such a conclusion.

An elderly couple out for a bike ride.

This paper contrasts mice that had undergone epigenetic reprogramming through the expression of Yamanaka factors with aging mice that had access to a weighted exercise wheel. This image can be used freely by anyone.

To start, the domino effect of exercise on the body is too great for Myc to ever hope to replicate. Since it also causes tumors and cancers, there is a clear risk in trying to control its expression.

Instead, Murach suggests experimenting with Myc manipulation to learn how to rehabilitate aged muscles with diminished responsiveness to exercise.

It is also possible that this could be used to help people whose physical activity is restricted, such as astronauts in zero gravity or those on bed rest, respond better to exercise. Since myc has both positive and negative effects, isolating the former could one day lead to a safe and effective therapeutic for human use.

According to Murach, their findings support the idea that exercise can act as a multivitamin. Along with medication and a healthy diet, he recommends regular exercise because "it is the most powerful drug we have" for improving health and, in some cases, extending life.