The National Institutes of Health made an Independent Scientist Award of $713,000 to Kevin Murach, an assistant professor at the U of A in the College of Education and Health Professions. The five-year award is designed to augment a previous $2.5 million award made to Murach to study how exercise can mitigate the decline of tissue function with aging, with an emphasis on the role of a transcription factor known as MYC.

Among other things, the new award allows for a reduction in teaching load, enabling him to focus exclusively on his research and mentoring responsbilities. In essence, the award is a way for the NIH to protect their initial investment in Murach’s research by creating more time for him to focus on it, generating new experimental data for future grants that may not have otherwise been possible within the scope of the original award.

“The grant is really going to unlock the potential of my lab and allow us to do additional, really cutting-edge techniques applied to the original project,” Murach explained. “And it's going to be a really exciting opportunity for myself and for my lab to advance the science and to dive deeper into the biology of what we're studying.”

The award will also provide funds for travel, lodging, conference attendance and collaboration with Benjamin Miller, a researcher at the Oklahoma Medical Research Foundation based in Oklahoma City who oversees the aging and metabolism research program.

“Benjamin Miller is a juggernaut in the aging and muscle fields,” Murach said.
“He's the president of the American Aging Association, and he's a very, very accomplished researcher.”

Murach’s collaboration with Miller will investigate whether there is a causal relationship between exercise, MYC expression, DNA synthesis and muscle development. Murach will learn unique “tracer” approaches developed by Miller for studying how muscle regulates DNA content and protein homeostasis (i.e. “proteostasis”). These new technologies will deepen understanding into how exercise and MYC may promote healthy aging.

What is MYC?

Tissue function is known to decline with age, but exercise plays an important role in slowing the decline of skeletal muscle, the most voluminous tissue in the body. But the degree to which exercise mitigates that decline and the molecular mechanics of what is actually happening in the muscles when you exercise are not well understood.

A major focus of Murach’s research is the role of a transcription factor known as MYC (pronounced “mick”). This protein is one of the four Yamanaka factors (identified as OCT3/4, SOX2, KLF4 and MYC) that can revert highly specified cells (such as a skin cell) back to a stem cell, which is a younger and more adaptable state.  

In the correct dosages, inducing the Yamanaka factors throughout the body in rodents can ameliorate some hallmarks of aging in part by mimicking the adaptability that is common to more youthful cells. Of the four factors, MYC is the only one that can be induced by exercising skeletal muscle (as opposed to gene-editing to induce gene expression), but MYC also becomes less responsive to exercise with advancing age. 

Murach’s initial NIH grant focuses of the role MYC plays in the functional, metabolic, cellular and molecular plasticity of skeletal muscle throughout the entire lifespan. His case for the grant was that MYC induction in muscle would mimic functional and cellular aspects of exercise adaptation throughout the lifespan and amplify the effects of exercise training. Further, MYC could mediate youthfulness at several molecular levels, including biological aging determined by a DNA methylation “clock” age, which is a way of identifying cellular aging through known markers.  

Indeed, in a paper published last year, Murach and his colleagues determined that small doses of MYC alone can stimulate muscle growth without exercise.

This latest award will help Murach, in collaboration with Miller, to delve still deeper into the mysteries of MYC.

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