Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals?

According to the free-radical theory, oxidizing species — including hydrogen peroxide (H 2 O 2 ) — are generated during aerobic respiration and cause molecular damage and ageing. However, recent evidence suggests that H 2 O 2 that is produced as a signalling molecule by a selected genetic programme regulates ageing. The reactive oxygen species that are generated by mitochondrial respiration, including hydrogen peroxide (H 2 O 2 ), are potent inducers of oxidative damage and mediators of ageing. It is not clear, however, whether oxidative stress is the result of a genetic programme or the by-product of physiological processes. Recent findings demonstrate that a fraction of mitochondrial H 2 O 2 , produced by a specialized enzyme as a signalling molecule in the pathway of apoptosis, induces intracellular oxidative stress and accelerates ageing. We propose that genes that control H 2 O 2 production are selected determinants of lifespan.