Mitochondrial transcription factor A binding to mitochondrial DNA during aging and calorie restriction.

According to the mitochondrial theory of aging mitochondria are involved with aging through endogenous production of oxidants. Recently it has become clear that in all species there is a marked decline in mitochondrial (mt) DNA, but the mechanisms are unknown. Calorie restriction (CR) is, so far, the only treatment shown to delay or avoid the onset of many age-related features in various species. Mitochondrial transcription factor A (TFAM) is a nuclear-encoded protein that plays a critical role in maintaining mtDNA structural integrity and functionality. Based on TFAM function in mtDNA maintenance and on the known accumulation of mtDNA oxidative DNA damage during aging we have tested whether the efficiency and/or the fidelity of TFAM binding to mtDNA changes with age in rat brain and liver tissues. We have measured TFAM binding to several functionally relevant mtDNA regions by mtDNA immunoprecipitation with TFAM policlonal antibody. We found tissue-specific changes in TFAM binding to mtDNA as a function of aging and CR treatment. These changes vary depending on the functional relevance of the DNA region bound, suggesting that TFAM functions in mtDNA maintenance processes (i.e. in replication and transcription) may be compromised during aging.