A UTHSC research team has been awarded $2.85 million from the National Institute on Aging for a project that will deepen understanding of how mitochondria influence the aging process and age-related diseases.
David Ashbrook, PhD, assistant professor of Genetics, Genomics and Informatics, is the principal investigator on the study examining how sex, diet, age, and genetics influence the number of mitochondria per cell in different tissues, and how these relate to different aging measures. Stephen Alway, PhD, FACSM, dean of the College of Health Professions and professor in the Department of Physical Therapy, and the Department of Physiology, and Aman Bajwa, PhD, associate professor of Surgery in the College of Medicine, are co-investigators on the project.
Mitochondria, which provide energy to every cell of the body, are crucial to the aging process. While every cell contains many mitochondria, the number of copies within a cell is different in different organs and is influenced by things like genetics, diet and age. Evidence suggests people with a higher number of mitochondria per cell live longer and remain physically fit for longer, whereas those with a lower number of mitochondria are susceptible to many diseases of aging, such as Alzheimer’s disease. This project will study why there is a link, and how it works.
The team is using a family of mice, the BXD family, that have been used at UTHSC and around the world for over 40 years, and for which there is a huge amount of information. The BXD family are 140 strains of mice, in which every member of one strain is genetically identical to every other member of that strain (sharing all their DNA). Each strain is a genetic sibling to the other strains (sharing about half of their DNA). “This allows us to link differences in genes with differences in any trait, such as memory or lifespan,” Dr. Ashbrook said. “Because we can have many replicates of genetically identical individuals, we can put them in different environments and see how they differ – like giving one identical twin a high-fat diet and another identical twin a low-fat diet and seeing how it changes their weight.”
Many different measures for this family, including their longevity and memory decline that occurs with aging, have been stored in UTHSC’s GeneNetwork.org website.
Results from this new study will enable the team to answer questions, such as are there gene variants that change the number of mitochondria, and are these linked to Alzheimer’s disease? Do changes in diet change longevity via changing mitochondria, or by a different pathway? In which tissue should we measure the number of mitochondria to predict healthy aging? Which tissue gives the first warning signs of different aspects of unhealthy aging? Can we find new targets that could be used for new treatments?
“We all want to live healthily for longer, and this project will help us understand why some of us do, while others do not,” Dr. Ashbrook said. “It would not be possible without the excellent team we have put together across the Department of Genetics, Genomics and informatics, the Department of Surgery, and the College of Health Professions, as well as the long-term interest and support of the university.”
The project, titled “The interaction effects of genetic variants, age, diet, sex and mitochondrial copy number on Alzheimer’s disease, aging-phenotyes and longevity,” is funded for five years.