Figure 2. Schematic of effects of environmental toxicant exposures on mtDNA heteroplasmy in young versus old individuals or populations.

New evidence suggests mtDNA mutations undergo clonal expansion during aging. Theoretically, this results in more mutations at a higher frequency in aged versus young individuals. An old population also likely has a greater distribution in the frequency of mtDNA mutations compared to young populations. Exposure to stressors such as environmental pollutants may result in an increase in the rate of mutation accumulation or clonal expansion of existing variants, resulting in a shift and greater distribution of mtDNA heteroplasmy early in life, resulting in a premature “aged” mutational signature (green box) in individuals or a population with high exposures compared to low exposures. It is also likely that mtDNA mutation rates and heteroplasmy will vary when looking in within aged populations with variable environmental exposures. Those that have either endured a lifetime burden of exposures or recent exposure to chemicals may have greater accumulation of mtDNA mutations (i.e. more mutations within an individual, and more individuals with mtDNA mutations at higher frequencies), than healthy aged individuals and populations (blue box). Created with BioRender.com