| The effect of dichloroacetate on health- and lifespan in C. elegans. | |
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MedLine Citation:
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PMID: 21153705 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Aging is associated with increased vulnerability to chronic, degenerative diseases and death. Strategies for promoting healthspan without necessarily affecting lifespan or aging rate have gained much interest. The mitochondrial free radical theory of aging suggests that mitochondria and, in particular, age-dependent mitochondrial decline play a central role in aging, making compounds that affect mitochondrial function a possible strategy for the modulation of healthspan and possibly the aging rate. Here we tested such a "metabolic tuning" approach in nematodes using the mitochondrial modulator dichloroacetate (DCA). We explored DCA as a proof-of-principle compound to alter mitochondrial parameters in wild-type animals and tested whether this approach is suitable for reducing reactive oxygen species (ROS) production and for improving organismal health- and lifespan. In parallel, we addressed the potential problem of operator bias by running both unblinded and blinded lifespan studies. We found that DCA treatment (1) increased ATP levels without elevating oxidative protein damage and (2) reduced ROS production in adult C. elegans. DCA treatment also significantly prolonged nematode health- and lifespan, but did not strongly impact mortality doubling time. Operator blinding resulted in considerably smaller lifespan-extending effects of DCA. Our data illustrate the promise of a "metabolic tuning" intervention strategy, emphasize the importance of mitochondria in nematode aging and highlight operator bias as a potential confounder in lifespan studies. |
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Authors:
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S Schaffer; J Gruber; L F Ng; S Fong; Y T Wong; S Y Tang; B Halliwell |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-12-14 |
Journal Detail:
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Title: Biogerontology Volume: 12 ISSN: 1573-6768 ISO Abbreviation: Biogerontology Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-05-18 Completed Date: 2011-09-01 Revised Date: 2013-04-24 |
Medline Journal Info:
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Nlm Unique ID: 100930043 Medline TA: Biogerontology Country: Netherlands |
Other Details:
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Languages: eng Pagination: 195-209 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, Centre for Life Sciences, National University of Singapore, Singapore. bchsebas@nus.edu.sg |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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metabolism Aging / physiology* Animals Caenorhabditis elegans / metabolism, physiology* DNA, Mitochondrial / metabolism Dichloroacetic Acid / pharmacology* Lipid Metabolism Locomotion Longevity / drug effects* Oxidative Stress Reactive Oxygen Species / metabolism |
| Chemical | |
Reg. No./Substance:
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0/DNA, Mitochondrial; 0/Reactive Oxygen Species; 56-65-5/Adenosine Triphosphate; 79-43-6/Dichloroacetic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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