DDS, 4,4′-diaminodiphenylsulfone, extends organismic lifespan
Edited by Paul Warren Sternberg, California Institute of Technology, Pasadena, CA, and approved October 4, 2010 (received for review April 15, 2010)
Abstract
DDS, 4,4′-diaminodiphenylsulfone, is the most common drug prescribed to treat Hansen disease patients. In addition to its antibacterial activity, DDS has been reported to be involved in other cellular processes that occur in eukaryotic cells. Because DDS treatment significantly enhances the antioxidant activity in humans, we examined its effect on lifespan extension. Here we show that DDS extends organismic lifespan using Caenorhabditis elegans as a model system. DDS treatment caused a delay in aging and decreased the levels of a mitochondrial complex. The oxygen consumption rate was also significantly lowered. Consistent with these data, paraquat treatment evoked less reactive oxygen species in DDS-treated worms, and these worms were less sensitive to paraquat. Interestingly enough, all of the molecular events caused by DDS treatment were consistently reproduced in mice treated with DDS for 3 mo and in the C2C12 muscle cell line. Structural prediction identified pyruvate kinase (PK) as a protein target of DDS. Indeed, DDS bound and inhibited PK in vitro and inhibited it in vivo, and a PK mutation conferred extended lifespan of C. elegans. Supplement of pyruvate to the media protected C2C12 cells from apoptosis caused by paraquat. Our findings establish the significance of DDS in lowering reactive oxygen species generation and extending the lifespan, which renders the rationale to examining the possible effect of DDS on human lifespan extension.
Acknowledgments
We thank the Caenorhabditis Genetics Center for the nematode strains and Dr. J. Yu for helpful discussion. This work is supported by the Aging and Apoptosis Research Center of the Korea Science and Engineering Foundation and the Ministry of Education, Science, and Technology, Korea Grant R11-2002-097-05001-1 and Seoul National University (to S.C.P.), by the Molecular Aging Research Center, Health Technology Planning and Evaluation Board, Korea, World Class Universities Program 305-20080089, and Korean Research Foundation Grant KRF-2008-005-J00201 (to J.L.).
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Published online: October 25, 2010
Published in issue: November 9, 2010
Acknowledgments
We thank the Caenorhabditis Genetics Center for the nematode strains and Dr. J. Yu for helpful discussion. This work is supported by the Aging and Apoptosis Research Center of the Korea Science and Engineering Foundation and the Ministry of Education, Science, and Technology, Korea Grant R11-2002-097-05001-1 and Seoul National University (to S.C.P.), by the Molecular Aging Research Center, Health Technology Planning and Evaluation Board, Korea, World Class Universities Program 305-20080089, and Korean Research Foundation Grant KRF-2008-005-J00201 (to J.L.).
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*This Direct Submission article had a prearranged editor.
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The authors declare no conflict of interest.
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DDS, 4,4′-diaminodiphenylsulfone, extends organismic lifespan, Proc. Natl. Acad. Sci. U.S.A.
107 (45) 19326-19331,
https://doi.org/10.1073/pnas.1005078107
(2010).
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