Mitochondrial dysfunction may play an important role in the aging process and in age-associated neurodegenerative diseases. Dysfunction may be related to mtDNA damage and mitochondrial gene expression. The goal of this project is to determine the significance of mtDNA damage and mitochondrial gene expression in age-related neurodegenerative diseases and the importance of mitochondrial dysfunction in apoptotic cell death. Several brain regions in old rats exhibit higher levels of mtDNA deletions than in young rats. Old rats subjected to diet restriction have reduced levels of this deletion. Differentiation of neuronal cells with NGF leads to a down regulation of several mitochondrially encoded genes. Treatment of cells with mitochondrial toxins leads to either an apoptotic or necrotic cell death which is attenuated by NGF. These results suggest that mitochondrial dysfunction may play an important role in cell death in aging.
