New Scholar Award in Aging
Yidong Bai, Ph.D.
University of Texas Health Science Center - San Antonio

Genetic and functional analysis of mitochondrial DNA mutations associated with aging.

The overall goal of this study is to isolate mitochondrial DNA (mtDNA) mutations associated with aging, to analyze the accumulation of the mutations during aging and to determine the genetic and functional consequences of the age-dependent mtDNA mutations in mouse. In mammalian cells, over 90% of oxygen is consumed by mitochondria, and up to 4% of the oxygen in the mitochondria is utilized to produce the by-product of oxidative phosphorylation, reactive oxygen species (ROS). ROS that escape antioxidant defense systems inflict damage on different cellular components. MtDNA, being close to the generation sites of ROS and with limited protective and repair systems, is assumed one of the primary targets for this oxidative destruction. If not repaired properly, the oxidative DNA damage could result in mutations. The mitochondrial theory of aging hypothesizes that accumulation of mtDNA mutations in somatic cells, due to the continuous attack by ROS, is responsible for compromising of mitochondrial functions including a decrease of the energy supply, which leads to the various phenotypes of aging.  

We plan to test this mitochondrial theory of aging by not only analyzing the accumulation of mtDNA mutation during aging, but, more importantly, studying the genetic and functional consequences of these mutations, and then further verifying these results with various aging-related transgenic mice. The particular hypothesis tested in this study is that mtDNA mutations accumulate with aging, and that these result in impaired mitochondrial functions. The success of the proposed study will help us to understand the effects of aging on mtDNA and the contribution of mitochondrial defects to the aging process.  

Contact Dr. Bai.