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

Wang DT, He J, Wu M, Li SM, Gao Q, Zeng QP - PeerJ (2015)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Tropical Medicine Institute, Guangzhou University of Chinese Medicine , Guangzhou , China.

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.

No MeSH data available.


Related in: MedlinePlus

ART, SNP, ARG, or H2O2 mimics CR to increase the quantities of eNOS and COX4 in mouse skeletal muscle cells.(a) ELISA for eNOS measurement after treatment for different durations. (b) ELISA for COX4 measurement after treatment for different durations. 0 h represents AL; 3 m indicates CR for three months; and 1 h, 3 h, or 6 h means treatment for one hour, three hours, or six hours. ART (260 µM), SNP (67 µM), ARG (5.7 mM), or H2O2(200 µM) was injected into the mouse skeletal muscle in the dose of 50 µl volume/20 g body weight. The 1 h, 3 h, or 6 h group had only one injection, and the 3d group had three daily injections. The ages of mice used are two-month-old except for CR mice, which are four-month-old with one-month AL and three-month CR treatment. The significance of statistical difference between a treatment sample and the AL sample was represented by * P < 0.05; ** P < 0.01; *** P < 0.001(n = 3).
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fig-1: ART, SNP, ARG, or H2O2 mimics CR to increase the quantities of eNOS and COX4 in mouse skeletal muscle cells.(a) ELISA for eNOS measurement after treatment for different durations. (b) ELISA for COX4 measurement after treatment for different durations. 0 h represents AL; 3 m indicates CR for three months; and 1 h, 3 h, or 6 h means treatment for one hour, three hours, or six hours. ART (260 µM), SNP (67 µM), ARG (5.7 mM), or H2O2(200 µM) was injected into the mouse skeletal muscle in the dose of 50 µl volume/20 g body weight. The 1 h, 3 h, or 6 h group had only one injection, and the 3d group had three daily injections. The ages of mice used are two-month-old except for CR mice, which are four-month-old with one-month AL and three-month CR treatment. The significance of statistical difference between a treatment sample and the AL sample was represented by * P < 0.05; ** P < 0.01; *** P < 0.001(n = 3).

Mentions: Like CR exposure for as long as three months, treatment of mice by ART, SNP, ARG, or H2O2 for one, three, six hours, or three days allows the gradual increases of both eNOS quantities (Fig. 1A) and COX4 quantities (Fig. 1B). To reach a level of significant difference from the control (AL mice), ARG needs only one hour, H2O2 needs three hours, SNP needs six hours, and ART needs even three days. Among groups, ARG treatment exhibits the largest quantities of eNOS and COX4, even larger than those upon exposure to CR. Interestingly, H2O2 treatment also induces larger quantities of COX4 and equal quantities of eNOS as compared with NO generators.


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

Wang DT, He J, Wu M, Li SM, Gao Q, Zeng QP - PeerJ (2015)

ART, SNP, ARG, or H2O2 mimics CR to increase the quantities of eNOS and COX4 in mouse skeletal muscle cells.(a) ELISA for eNOS measurement after treatment for different durations. (b) ELISA for COX4 measurement after treatment for different durations. 0 h represents AL; 3 m indicates CR for three months; and 1 h, 3 h, or 6 h means treatment for one hour, three hours, or six hours. ART (260 µM), SNP (67 µM), ARG (5.7 mM), or H2O2(200 µM) was injected into the mouse skeletal muscle in the dose of 50 µl volume/20 g body weight. The 1 h, 3 h, or 6 h group had only one injection, and the 3d group had three daily injections. The ages of mice used are two-month-old except for CR mice, which are four-month-old with one-month AL and three-month CR treatment. The significance of statistical difference between a treatment sample and the AL sample was represented by * P < 0.05; ** P < 0.01; *** P < 0.001(n = 3).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4358698&req=5

fig-1: ART, SNP, ARG, or H2O2 mimics CR to increase the quantities of eNOS and COX4 in mouse skeletal muscle cells.(a) ELISA for eNOS measurement after treatment for different durations. (b) ELISA for COX4 measurement after treatment for different durations. 0 h represents AL; 3 m indicates CR for three months; and 1 h, 3 h, or 6 h means treatment for one hour, three hours, or six hours. ART (260 µM), SNP (67 µM), ARG (5.7 mM), or H2O2(200 µM) was injected into the mouse skeletal muscle in the dose of 50 µl volume/20 g body weight. The 1 h, 3 h, or 6 h group had only one injection, and the 3d group had three daily injections. The ages of mice used are two-month-old except for CR mice, which are four-month-old with one-month AL and three-month CR treatment. The significance of statistical difference between a treatment sample and the AL sample was represented by * P < 0.05; ** P < 0.01; *** P < 0.001(n = 3).
Mentions: Like CR exposure for as long as three months, treatment of mice by ART, SNP, ARG, or H2O2 for one, three, six hours, or three days allows the gradual increases of both eNOS quantities (Fig. 1A) and COX4 quantities (Fig. 1B). To reach a level of significant difference from the control (AL mice), ARG needs only one hour, H2O2 needs three hours, SNP needs six hours, and ART needs even three days. Among groups, ARG treatment exhibits the largest quantities of eNOS and COX4, even larger than those upon exposure to CR. Interestingly, H2O2 treatment also induces larger quantities of COX4 and equal quantities of eNOS as compared with NO generators.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Tropical Medicine Institute, Guangzhou University of Chinese Medicine , Guangzhou , China.

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.

No MeSH data available.


Related in: MedlinePlus