Table 1.

Table summarizing the experimental evidence for and against the free radical theory of aging.

The Free Radical Theory (FRT) of Aging [8]
Supporting evidence	Conflicting evidence
Strong correlations between chronological age and levels of reactive oxygen species (ROS) generation and oxidative stress markers [48,49,50,51]	Lack of correlation between levels of ROS and longevity across various species [52,53,54]
Age-related accumulation of irreversible oxidation products in proteins or DNA [55,56,57,58,59] Increased DNA damage and lipid peroxidation products in aged vs. young organisms [58,59]	Mutant organisms associated with mitochondrial dysfunction have prolonged lifespan [60,61] Mitochondrial hormesis: relatively low levels of mitochondria-derived ROS improve systemic defense mechanisms and promote healthspan [62,63]
Age-related aggregation of mitochondrial damage may cause accumulated mutations in mitochondrial DNA [64] Biological ageing is associated with decreased expression of antioxidant and oxidoreductase enzymes [65] Gender divergence in mice during ageing associated with oxidative stress [66] Ageing is associated with decreased adaptive response to oxidative stress [67] Age-dependent diseases are frequently associated with increased oxidative stress [68]	Studies with antioxidant supplementation strategies typically do not enhance longevity and can sometimes reduce it [69] Genetic manipulation of antioxidant defense genes in mice does not affect lifespan [70,71] Some oxidative protein cysteine modifications may be important for promoting longevity and decrease with ageing [10] Hydrogen sulphide (H2S) may positively impact lifespan and ageing through S-sulfhydation (or persulfidation) [72]