Age‐related increase of reactive oxygen generation in the brains of mammals and birds: Is reactive oxygen a signaling molecule to determine the aging process and life span?

Since Harman proposed the “free‐radical theory of aging”, oxidative stress has been postulated to be a major causal factor of senescence. The accumulation of oxidative stress‐induced oxidatively modified macromolecules, including protein, DNA and lipid, were found in tissues during the aging process; however, it is not necessarily clear which factor is more critical, an increase in endogenous reactive oxygen and/or a decrease in anti‐oxidative defense, to the age‐related increase in oxidative damage. To clarify the increasing production of reactive oxygen with age, we examined reactive oxygen‐dependent chemiluminescent (CL) signals in ex vivo brain slices prepared from different‐aged animal brains during hypoxia–reoxygenation treatment using a novel photonic imaging method. The CL signal was intensified during reoxygenation. The signals in SAMP10 (short‐life strain) and SAMR1 (control) brain slices increased with aging. The slope of the increase of CL intensity with age in P10 was steeper than in R1. Age‐dependent increase of CL intensity was also observed in C57BL/6 mice, Wistar rats and pigeons; however, superoxide dismutase (SOD) activity in the brain did not change with age. These results suggest that reactive oxygen production itself increased with aging. The rate of age‐related increases of CL intensity was inversely related to the maximum lifespan of animals. We speculate that reactive oxygen might be a signaling molecule and its levels in tissue might determine the aging process and lifespan. Decelerating age‐related increases of reactive oxygen production are expected to be a potent strategy for anti‐aging interventions. Geriatr Gerontol Int 2010; 10 (Suppl. 1): S10–S24.