The accumulation of oxidative damage to biomolecules, such as DNA, is known to induce alterations in the cell's mechanisms and structure that might lead to the aging process. DNA mismatch repair system (MMR) corrects base mismatches generated during DNA replication that have escaped the proofreading process. In addition, antioxidant enzymes can reduce reactive oxygen species effects in order to protect cells from oxidizing damage. In order to determine the importance of these associated factors during the aging process, in this study, levels of MMR proteins MSH2 and MLH1, as well as microsatellite markers, were compared in liver, lung, and brain of juvenile, adult, and old, both female and male, individuals from two species of wild bats: the short-lived Myotis velifer and the longer lived Desmodus rotundus. Catalase, glutathione peroxidase, and superoxide dismutase were also analyzed to determine if the antioxidant protection correlates negatively with DNA damage. Antioxidant activities were higher in the longer lived D. rotundus than in M. velifer. Furthermore, old M. velifer but not old D. rotundus bats had reduced MMR levels and increased microsatellite instability. Therefore, although our results correlate the reduced MMR efficiency, the deficient antioxidant activity, and the increase in DNA damage with the aging process, this is not always true for all living organisms.