Artemisinin mimics calorie restriction to trigger mitochondrial biogenesis and compromise telomere shortening in mice

Abstract

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.

Insulin Does Not AugmentIn VitroTumor Growth Under A Hyperglycemia-Mimicking Milieu And In A Calorie Restriction-Resembling Manner

“…On the other hand, we noticed decrease in ROS and reduction in apoptosis of GH3 cells grown in a high-glucose medium supplemented with insulin, which was also observed in CR [32]. In our previous work, CR in yeast and mice was also found to diminish ROS burst, compromise telomere shortening, and promote lifespan extension [33,34]. It is well-known that resveratrol is an activator of SIRT, metformin is an activator of AMPK, and CR activates AMPK, SIRT1, and PGC-1α [35,36].…”

Type 2 diabetes mellitus, drug addiction, bipolar disorder and epilepsy display overlapping aetiopathogenic mechanisms: Implication for prevention and pharmacotherapy

“…Endothelial nitric oxide through boosting anti-oxidant mechanisms and decreasing brain excitability may occupy a central place in cardiometabolic and neuropsychiatric disorders Patel et al, 2000;Murashima et al, 2000;Ferraro and Sardo, 2004;Wang et al, 2014Wang et al, , 2015Oriaifo et al, 2015). It decreases lipid peroxidation while upregulating glutathione production and serotonin release.…”

“…These proteins exhibit a redox control of MMPs (Nelson and Melendez, 2004) and limiting ROS accumulation and the inflammatory state (Wang et al, 2015;Besse-Patin and Estall, 2014;Sitarc et al, 2014;Tedescoet al, 2008). A normally functioning mitochondrion helps to attenuate the effects of nutrient overload and hyperglycaemia (Aulston et al, 2013) on negatively impacting on insulin receptor substrate signalling to phosphatidylinositol 3, 4, 5-triphosphate (PIP3) (Figure 1).…”

“…AMPK acts as an important mediator of the beneficial effects of calorie restriction and metformin (Towler and Hardie, 2007), GLP-I agonists (Ben-Shlomo et al, 2011), artesunate (Wang et al, 2015;Tan et al, 2014), valproate (Avery and Bumpus, 2013) and cannabinoid CB2 agonists (Tedesco et al, 2010). AMPK exerts dual regulatory effects on the PI3K pathway, enhancing PIP3-Akt-eNOS signalling while inhibiting mTOR/S6K signalling which has negative effect on insulin signalling (Tao et al, 2010).…”

“…The calorie-memetics, metformin, cannabinoids and artesunate, stand to potentiate the effect of calorie-restriction (CR) in the management of epilepsy and AD where the activity of FOXO3a is reduced (Wang et al, 2015;Oriaifo, 2001;Penner et al, 2012;Qin et al, 2008). Calorie-restriction with weight loss inhibits drug relapse behaviour (Guccione et al, 2013).…”