The National Institute on Aging has awarded $2.85 million in funding to a research team from the University of Tennessee Health Science Center (UTHSC) to study the role of mitochondria — cells’ powerhouses — in age-related diseases, such as Alzheimer’s.
The five-year funding will support a project called “The interaction effects of genetic variants, age, diet, sex and mitochondrial copy number on Alzheimer’s disease, aging-phenotypes and longevity.”
Mitochondria, the organelles that provide energy to cells, are important for the health and survival of cells, nerve cells (neurons) included. Mitochondrial damage is a hallmark of several neurodegenerative and aging-related diseases, such as Alzheimer’s.
People with higher numbers of mitochondria per cell are thought to have a longer lifespan, while those with fewer mitochondria are thought to be more prone to age-related diseases.
Mitochondria vary in number between different cell types and this variation depends on several factors, such as genetics, diet, and age. However, the link between the number of mitochondria and these factors remains unclear.
To address this, the project team will study how genetics, diet, and age can influence the number of mitochondria in a cell, and what the link is between the amount and different aging measures.
“We all want to live healthily for longer, and this project will help us understand why some of us do, while others do not,” David Ashbrook, PhD, assistant professor at UTHSC and the principal investigator on the study, said in a press release.
“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,” Ashbrook said.
The team will use a family of mice, the BXD family, for which there is a lot of genetic information. It consists of 140 strains of mice with those of same strain being genetically identical to each other. These strains share about half of their DNA with each other, making them genetic siblings.
Researchers are looking for gene variants, or changes in the DNA sequence, that may alter the number of mitochondria, and if these are related to Alzheimer’s disease.
They also want to understand whether changes in food intake can alter lifespan by changing mitochondria or if these changes affect other pathways and targets.
The study also seeks to identify which tissue is the most appropriate to measure mitochondrial number to predict healthy aging, or which tissues can be looked at to observe the first signs of unhealthy aging.
Importantly, the team intends to look for new targets that can be used to design new treatments for age-related diseases.
“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,” Ashbrook said.
Genetic information about this family, such as that linked to longevity and age-related memory decline, is stored on GeneNetwork, a free scientific web-based resource that helps researchers better understand what causes genes to influence health and disease.
“This allows us to link differences in genes with differences in any trait, such as memory or lifespan,” Ashbrook said.