Calorie restriction mimetic treatments are those that recreate at least some part of the calorie restriction response. Calorie restriction with optimal nutrition alters near every measure of metabolism and slows near every measure of degenerative aging, producing improved short term metrics of health and extending longevity in those species where that has been evaluated. Thus there is a wide range of possible targets for calorie restriction mimetics, but this comes hand in hand with the continued challenge of identifying primary versus secondary mechanisms, and important versus unimportant mechanisms. One area gaining more attention of late involves the varied roles of nitric oxide in metabolism; having more of it in circulation seems like a good thing:
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.