Calorie restriction is known to extend lifespan among organisms by a debating mechanism underlying
nitric oxide-driven mitochondrial biogenesis. We report here that
nitric oxide generators including
artemisinin,
sodium nitroprusside, and
L-arginine mimics calorie restriction and resembles
hydrogen peroxide to initiate the
nitric oxide signaling cascades and elicit the global antioxidative responses in mice. The large quantities of
antioxidant enzymes are correlated with the low levels of
reactive oxygen species, which allow the down-regulation of
tumor suppressors and accessory DNA repair partners, eventually leading to the compromise of telomere shortening. Accompanying with the up-regulation of signal transducers and respiratory chain signatures, mitochondrial biogenesis occurs with the elevation of
adenosine triphosphate levels upon exposure of mouse skeletal muscles to the mimetics of calorie restriction. In conclusion, calorie restriction-triggered
nitric oxide provides antioxidative protection and alleviates telomere attrition via mitochondrial biogenesis, thereby maintaining
chromosomal stability and integrity, which are the hallmarks of longevity.