Figure 2.
The mtDNA mutations accumulation and transcriptional dysregulation both contribute to the process of tissue-specific aging. As there is no synchronization between cell division and mtDNA replication, a mutated mtDNA of different tissue cells may be replicated many times and lead to accumulation of mtDNA mutations and impaired respiratory chain function. On the other side, there is a finely-tuned transcriptional network regulating mitochondrial biogenesis and function. PGC-1α can coactivate several important transcriptional factors such as NRF-1/-2, ERRα and PPARα. These factors play vital role in mitochondrial biogenesis and function. As the expression and regulation of these factors and the mtDNA mutation accumulation are all tissue-specific, there are tissue-specific physiological consequences when people age.