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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

A hierarchical clustering illustration for the up/down-regulation of 84 ubiquitylation genes from RT-PCR array data.The red color represents up-regulation as compared with AL; and the green color represents down-regulation as compared with AL. The RT-PCR array was performed after daily injection for three days into mouse skeletal muscle by 260 µM ART, 67 µM SNP, 5.7 mM ARG in the dose of 50 µl volume/20 g body weight, or one injection by 200 µM H2O2(50 µl/20 g), and sampling after last injection for six hours. The ages of all mice used are four-month-old, among which CR mice have one-month AL and three-month CR treatment.
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fig-3: A hierarchical clustering illustration for the up/down-regulation of 84 ubiquitylation genes from RT-PCR array data.The red color represents up-regulation as compared with AL; and the green color represents down-regulation as compared with AL. The RT-PCR array was performed after daily injection for three days into mouse skeletal muscle by 260 µM ART, 67 µM SNP, 5.7 mM ARG in the dose of 50 µl volume/20 g body weight, or one injection by 200 µM H2O2(50 µl/20 g), and sampling after last injection for six hours. The ages of all mice used are four-month-old, among which CR mice have one-month AL and three-month CR treatment.

Mentions: To make sure the relevance of CR and mimetics to the ubiquitin-mediated proteolysis pathway (UMPP) that is involved in the auto-regulated degradation of proteins, we set out to investigate whether CR and mimetics would affect the expression of ubiquitylation pathway genes. From the transcript profiling of ubiquitylation genes among ART, SNP, ARG, H2O2, and CR groups, it was noted that all 84 ubiquitylation genes examined are mostly down-regulated (Fig. 3, and see also Tables S1–S5 for details).


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)

A hierarchical clustering illustration for the up/down-regulation of 84 ubiquitylation genes from RT-PCR array data.The red color represents up-regulation as compared with AL; and the green color represents down-regulation as compared with AL. The RT-PCR array was performed after daily injection for three days into mouse skeletal muscle by 260 µM ART, 67 µM SNP, 5.7 mM ARG in the dose of 50 µl volume/20 g body weight, or one injection by 200 µM H2O2(50 µl/20 g), and sampling after last injection for six hours. The ages of all mice used are four-month-old, among which CR mice have one-month AL and three-month CR treatment.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig-3: A hierarchical clustering illustration for the up/down-regulation of 84 ubiquitylation genes from RT-PCR array data.The red color represents up-regulation as compared with AL; and the green color represents down-regulation as compared with AL. The RT-PCR array was performed after daily injection for three days into mouse skeletal muscle by 260 µM ART, 67 µM SNP, 5.7 mM ARG in the dose of 50 µl volume/20 g body weight, or one injection by 200 µM H2O2(50 µl/20 g), and sampling after last injection for six hours. The ages of all mice used are four-month-old, among which CR mice have one-month AL and three-month CR treatment.
Mentions: To make sure the relevance of CR and mimetics to the ubiquitin-mediated proteolysis pathway (UMPP) that is involved in the auto-regulated degradation of proteins, we set out to investigate whether CR and mimetics would affect the expression of ubiquitylation pathway genes. From the transcript profiling of ubiquitylation genes among ART, SNP, ARG, H2O2, and CR groups, it was noted that all 84 ubiquitylation genes examined are mostly down-regulated (Fig. 3, and see also Tables S1–S5 for details).

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