Figure 1. Schematic of effects of age and environmental toxicant exposures on mtDNA mutagenesis.

mtDNA mutations are thought to accumulation over time and contribute to healthy aging (green line). Exposure to exogenous stressors, such as environmental pollutants, may result in higher rates of mtDNA mutation accumulation (purple line). It is also hypothesized that many chemicals interfere with mtDNA replication, turnover, and organelle dynamics, potentially resulting in clonal expansion of existing mtDNA mutations, without increasing the rate of de novo mutation accumulation (blue line). Theoretically, if pathogenic mutations arise earlier or at great frequencies (or both; not shown), a threshold of tolerance (dashed line) of mtDNA mutations may be reached earlier in life, potentially resulting in premature aging phenotypes and accelerated onset of aging-related diseases such as neurodegeneration or cancer. It is likely that there will be high interindividual variation of the “threshold”, as shown in the shaded areas around the dashed line as some individuals are likely to be more sensitive and vulnerable, while others may be more tolerant to exposures and/or mtDNA mutation accumulation. Created with BioRender.com.