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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

Laser confocal microscopic phenotyping of coordinated down-regulation of BRCA1 with TERT in mouse skeletal muscles treated by ART, SNP, ARG, H2O2, or CR.Green fluorescence indicates BRCA1, red fluorescence indicates TERT, and blue fluorescence represents 4’,6-diamidino-2-phenylindole (DAPI)-staining nuclear DNA. For observation by a laser confocal microscope, samples were collected from the skeletal muscles of mice injected by 260 µM ART, 67 µM SNP, 5.7 mM ARG or 200 µM H2O2 (50 µl/20 g) for three times, in which the 2nd and the 3rd injections are on the 3rd and 5th day, respectively. The ages of AL and CR mimetic mice are two-month-old, but the ages of CR mice are five-month-old, including one-month AL treatment and four-month CR treatment.
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fig-5: Laser confocal microscopic phenotyping of coordinated down-regulation of BRCA1 with TERT in mouse skeletal muscles treated by ART, SNP, ARG, H2O2, or CR.Green fluorescence indicates BRCA1, red fluorescence indicates TERT, and blue fluorescence represents 4’,6-diamidino-2-phenylindole (DAPI)-staining nuclear DNA. For observation by a laser confocal microscope, samples were collected from the skeletal muscles of mice injected by 260 µM ART, 67 µM SNP, 5.7 mM ARG or 200 µM H2O2 (50 µl/20 g) for three times, in which the 2nd and the 3rd injections are on the 3rd and 5th day, respectively. The ages of AL and CR mimetic mice are two-month-old, but the ages of CR mice are five-month-old, including one-month AL treatment and four-month CR treatment.

Mentions: As described above, BRCA1 and TERT are down-regulated at the level of transcription (the mRNA level) (see Fig. 3 and Table 2). To ensure if BRCA1 and TERT are also down-regulated at the level of translation (the protein level), we tried to phenotyping the localization of BRCA1 and TERT in the skeletal muscle cells of AL, CR, and CR mimetics-treated mice. As a consequence, TERT was shown to co-exist with BRCA1 in overlapped nuclear locations, which can be clearly observed from the AL sample (Fig. 5), suggesting that TERT and BRCA1 may be interactive and cooperative. As to the dimmed BRCA1-TERT signals in ART, SNP, and ARG samples, they might represent the dual down-regulation of BRCA1 and TERT.


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)

Laser confocal microscopic phenotyping of coordinated down-regulation of BRCA1 with TERT in mouse skeletal muscles treated by ART, SNP, ARG, H2O2, or CR.Green fluorescence indicates BRCA1, red fluorescence indicates TERT, and blue fluorescence represents 4’,6-diamidino-2-phenylindole (DAPI)-staining nuclear DNA. For observation by a laser confocal microscope, samples were collected from the skeletal muscles of mice injected by 260 µM ART, 67 µM SNP, 5.7 mM ARG or 200 µM H2O2 (50 µl/20 g) for three times, in which the 2nd and the 3rd injections are on the 3rd and 5th day, respectively. The ages of AL and CR mimetic mice are two-month-old, but the ages of CR mice are five-month-old, including one-month AL treatment and four-month CR treatment.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig-5: Laser confocal microscopic phenotyping of coordinated down-regulation of BRCA1 with TERT in mouse skeletal muscles treated by ART, SNP, ARG, H2O2, or CR.Green fluorescence indicates BRCA1, red fluorescence indicates TERT, and blue fluorescence represents 4’,6-diamidino-2-phenylindole (DAPI)-staining nuclear DNA. For observation by a laser confocal microscope, samples were collected from the skeletal muscles of mice injected by 260 µM ART, 67 µM SNP, 5.7 mM ARG or 200 µM H2O2 (50 µl/20 g) for three times, in which the 2nd and the 3rd injections are on the 3rd and 5th day, respectively. The ages of AL and CR mimetic mice are two-month-old, but the ages of CR mice are five-month-old, including one-month AL treatment and four-month CR treatment.
Mentions: As described above, BRCA1 and TERT are down-regulated at the level of transcription (the mRNA level) (see Fig. 3 and Table 2). To ensure if BRCA1 and TERT are also down-regulated at the level of translation (the protein level), we tried to phenotyping the localization of BRCA1 and TERT in the skeletal muscle cells of AL, CR, and CR mimetics-treated mice. As a consequence, TERT was shown to co-exist with BRCA1 in overlapped nuclear locations, which can be clearly observed from the AL sample (Fig. 5), suggesting that TERT and BRCA1 may be interactive and cooperative. As to the dimmed BRCA1-TERT signals in ART, SNP, and ARG samples, they might represent the dual down-regulation of BRCA1 and TERT.

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