Your muscles ensure your survival. Your heart beating, your blood pumping, your intestines digesting, all these unthinking acts are fulfilled through ceaseless muscle contractions. Were they to stop, so would you.
Of the three different muscle types in the human body—which include cardiac, smooth and skeletal—we consciously control only our skeletal muscles.
“Everything that allows you to stand up straight and move is a skeletal muscle,” said Arik Davidyan, ’14 B.S. in Exercise Biology and ’20 Ph.D. in Molecular, Cellular and Integrative Physiology. “Muscle is a very plastic tissue. It's changing very dramatically and very fast in many different ways and I think it's fascinating."
Integral to your body’s function, skeletal muscles decay with age, a natural process known as sarcopenia. Testosterone plays an important role in muscle mass maintenance, but the molecular minutiae of how these biological feats are achieved isn’t yet clear. Figuring this out could help researchers discover new ways to help our muscles age with grace.
While attending the UC Davis College of Biological Sciences, Davidyan investigated testosterone’s role in muscle mass gain, maintenance and decay, using mice as experimental models.
“How is testosterone doing what it’s doing?” he said, recalling the research curiosities foundational to his thesis work. “I wanted to see what was the importance of testosterone to the maintenance of muscle mass across the lifespan of the animal.”
Transferring to the Aggie life
Davidyan began Aggie life as a transfer student, studying for two years at Woodland Community College before enrolling at UC Davis in 2012. The campus shift wasn’t without its hurdles.
“It took me a while to figure out what was going on at a large university, so the first year, I was kind of trying to just get my bearings,” he said. “My second year, I became a lot more active.”
He got involved in research, joining the lab of former Professor of Neurobiology, Physiology and Behavior Sue Bodine, who later became his Ph.D. mentor, and sought internship experiences outside of the UC Davis campus. In 2014, he worked as a coroner’s office intern at the Yolo County Sheriff’s Office, where he collected evidence, photographed scenes and assisted with autopsies, among other duties. The experience bolstered his knowledge of human physiology, something that until that time was mostly informed by textbook illustrations.
As graduation neared, Davidyan considered the potential paths that lay before him. Medical school had always been a consideration, but his research experiences inspired a passion for physiology and foundational science. Already fond of the welcoming atmosphere of campus, he decided to double down on UC Davis, enrolling in the Molecular, Cellular and Integrative Physiology Graduate Group at the College of Biological Sciences.
How muscles age
Davidyan’s thesis research dove deep into the effects of aging on skeletal muscles. For years, he’d pored over physiological literature concerning testosterone’s role in skeletal muscle mass, and he thought something was off. Researchers had previously proposed that the decline of testosterone in males as they age led directly to muscle mass loss.
“This didn’t sit well with me when I read the literature for two reasons,” said Davidyan. “First, I thought, ‘Women lose muscle mass like men, but the amount of testosterone that women have in their bodies is much lower and as they get older it doesn’t change greatly.' This was one alarming thing. The other thing was that the loss of muscle mass starts to happen much, much sooner before the loss of testosterone starts to occur.”
According to research, after age 30, humans start to lose as much as three to five percent of muscle mass per decade, but a noticeable decline in male testosterone levels doesn’t occur until age 60, when about 20 percent of men are classified as having total testosterone levels below the normal range.
To satiate his curiosity, Davidyan investigated how testosterone and other growth stimuli affect cellular pathways related to muscle protein synthesis and degradation in mice, specifically studying the maintenance and decay of their leg muscles, including the tibias anterior, the gastrocnemius and quadriceps. Ultimately, he found that male mice treated solely with testosterone didn’t showcase any additional muscle growth when compared to the control group of mice. However, female mice treated with testosterone increased their muscle mass and roughly doubled their muscle growth following increased load treatment. The additional testosterone, Davidyan found, suppressed protein breakdown in the studied muscles in female mice, but it didn’t add to protein synthesis.
To uncover whether testosterone plays a role in age-related muscle loss, Davidyan castrated male mice between the ages of 1.5 months and 24 months. He then compared their succeeding muscular development after a month to control mice of the same age. Younger mice, still in the spurts of youthful growth, were adversely affected by the treatment, their muscles not growing as much as the control group’s. However, older castrated males’ muscles were no different than their control counterparts’.
“Even though I removed the testicles, which is where testosterone is being made, and I saw some decrease in the amount of circulating testosterone that these animals have in their blood, I did not see any effect whatsoever on their muscle mass,” said Davidyan.
According to Davidyan, this suggests that previous studies linking the loss of testosterone to sarcopenia may not be biologically accurate.
Davidyan is now a postdoctoral fellow at the Oklahoma Medical Research Foundation, where he investigates the role mitochondrial dysfunction plays in aging. With his OMRF research lab closed due to the coronavirus pandemic, he’s working on submitting his thesis research for publication.
Asked what advice he’d give to current Ph.D. students, Davidyan said to remember that “you’re developing not only as a scientist in your Ph.D., you're developing as a leader, as an educator, as a science communicator and as a mentor.”
“All of these aspects are really important to dedicate time to,” he said.