LAUSR

The free radical theory of aging, one of the nine suggested hallmarks of aging (López-Otín et al., 2016), implicates the gradual accumulation of oxidative cellular damage as a fundamental driver of cellular aging (Harman, 1956; Miquel et al., 1980). This theory has evolved over time to emphasize the role of free radical induced mitochondrial DNA (mtDNA) mutations and the accumulation of mtDNA deletions (Miquel et al., 1980; Cortopassi et al., 1992; Michikawa et al., 1999). Given the proximity of mtDNA to the electron transport chain, a primary producer of free radicals, it postulates that the mutations would promote mitochondrial dysfunction and concomitantly increase free radical production in a positive feedback loop. The observation of oxidative damage in the form of 7,8-dihydro-8-oxo-deoxyguanosine (8-oxodG) DNA oxidative lesions accumulating with age has been a cornerstone of the free radical theory of aging (Fraga et al., 1990).