Health and Human Sciences Assistant Professor Robert Musci is set to commence a six-month
collaborative research project titled “Investigating the Turnover Dynamics of mtDNA with Stable Isotop Deuterium Oxide” thanks to a $10,000 pilot grant awarded by the Oklahoma Nathan Shock Center on Aging, which is funded by the National Institute on Aging (NIA).
“I’m invested in improving the quality of life, especially as we age,” said Musci. “In the past two
decades, an explosion of interest has occurred in research focused on aging, ignited by the realization
that aging is a common risk factor for major diseases. I’m grateful to the Oklahoma Nathan Shock
Center and NIA, which focus on expanding the capacity and resource accessibility, such as state-of-
the-art lab equipment, for investigators at all levels to practice science. One reason my grant proposal
was selected was because of the promise it would bring to an institution like Loyola Marymount
University that focuses on undergraduate research.”
The research idea was born after a meeting with collaborators Benjamin Miller, Ph.D., of the Oklahoma Medical Research Foundation, who was Musci’s mentor throughout his graduate studies, and Jonathan Wanagat, M.D. Ph.D., of UCLA School of Medicine. Musci is also partnering with University of Wisconsin’s Adam Konopka, Ph.D.
The focus is on mitochondrial DNA (mtDNA), the circular chromosome found inside the cellular organelles that is the “blueprint” to construct mitochondria. Mitochondria are the site of the cell’s energy production (or powerhouse of the cell) and other metabolic functions.
“As blueprints to our mitochondria, mtDNA are important to our health,” said Musci. “When mtDNA accumulate mutations as we age, it’s as if our blueprints have smudges or errors that we can’t read. These mutations impair our ability to properly construct mitochondria. Consequently, our mitochondria accumulate defects, which impair cellular function.” These mtDNA mutations contribute to age-related diseases like cardiovascular disease, Alzheimer’s disease, and sarcopenia. Despite their importance to
people’s health, it is unclear how these mtDNA mutations occur. This project examines how the rate of mtDNA replication influences the mutation burden.
“The assumption is mtDNA turnover changes with age, which increases the mtDNA mutation burden,”
Musci said. “Investigating this phenomenon will help us understand the mechanisms underlying
mitochondrial dysfunction. Overall, this project will help us devise interventions to tackle age-related diseases.”
The research will be conducted in two phases. The first phase involves looking at ways to optimize the measurement of mtDNA turnover using less tissue, as well as trying frozen tissue samples. The second phase is to determine what happens to mtDNA turnover with exercise, which improves mitochondrial function and our health, and whether that increases or decreases mtDNA turnover.
This pilot research is a stepping stone to a larger future research project,” said Musci. “In broad terms, the goal of this project is to optimize our protocol measuring mtDNA turnover. If successful, this line of research will enable LMU students to engage in collaborative research efforts with labs around the world to understand the biology of aging.