Science China Life Sciences

, Volume 58, Issue 5, pp 451–465 | Cite as

Artemisinin mimics calorie restriction to extend yeast lifespan via a dual-phase mode: a conclusion drawn from global transcriptome profiling

  • DaTing Wang
  • Ming Wu
  • SiMing Li
  • Qian Gao
  • QingPing Zeng
Open Access
Research Paper


Calorie restriction (CR) promotes longevity among distinct organisms from yeast to mammals. Although CR-prolonged lifespan is believed to associate with enhanced respiratory activity, it is apparently controversial for accelerated energy consumption regardless of insufficient nutrient intake. In reconciling the contradiction of less food supply versus much metabolite dispense, we revealed a CR-based mode of dual-phase responses that encompass a phase of mitochondrial enhancement (ME) and a phase of post-mitochondrial enhancement (PME), which can be distinguished by the expression patterns and activity dynamics of mitochondrial signatures. ME is characterized by global antioxidative activation, and PME is denoted by systemic metabolic modulation. CR-mediated aging-delaying effects are replicated by artesunate, a semi-synthetic derivative of the antimalarial artemisinin that can alkylate heme-containing proteins, suggesting artesunate-heme conjugation functionally resembles nitric oxide-heme interaction. A correlation of artesunate-heme conjugation with cytochrome c oxidase activation has been established from adduct formation and activity alteration. Exogenous hydrogen peroxide also mimics CR to trigger antioxidant responses, affect signaling cascades, and alter respiratory rhythms, implying hydrogen peroxide is engaged in lifespan extension. Conclusively, artesunate mimics CR-triggered nitric oxide and hydrogen peroxide to induce antioxidative networks for scavenging reactive oxygen species and mitigating oxidative stress, thereby directing metabolic conversion from anabolism to catabolism, maintaining essential metabolic functionality, and extending life expectancy in yeast.


calorie restriction nitric oxide artesunate hydrogen peroxide longevity Saccharomyces cerevisiae 

Supplementary material

11427_2014_4736_MOESM1_ESM.pdf (526 kb)
Supplementary material, approximately 525 KB.


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© The Author(s) 2015

This article is published under license to BioMed Central Ltd. Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

Authors and Affiliations

  • DaTing Wang
    • 1
  • Ming Wu
    • 2
  • SiMing Li
    • 3
  • Qian Gao
    • 1
  • QingPing Zeng
    • 1
  1. 1.Tropical Medicine InstituteGuangzhou University of Chinese MedicineGuangzhouChina
  2. 2.School of life ScienceSun Yat-sen UniversityGuangzhouChina
  3. 3.The Second Affiliated HospitalGuangzhou University of Chinese MedicineGuangzhouChina

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