Figure 1.

Schematic of plausible mechanisms of mutation expansion and development of mitochondrial deficiency in muscle fibers. Muscle fiber is represented by a short section shown at different time points. Brown represents normal fiber, and blue represents COX⁻ (cytochrome C oxidase-deficient) fiber. mtDNA molecules are represented by the small circles within the fiber section, with brown representing normal fiber and blue representing mutant fiber. The red burst denotes an initial mutational event. NRTIs could induce seed mutations that initiate expansions (a) or accelerate expansion of preexisting mutations (b). If expansion occurs rapidly, early mutations, if they exist, should be observable quickly (c) and COX⁻ fibers in the old originate from recent late mutations (d). If expansion is slow, only early mutations will have an effect on aging (e), not late mutations (f).