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Statin Treatment Increases Lifespan and Improves Cardiac Health in Drosophila by Decreasing Specific Protein Prenylation

Statins such as simvastatin are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and standard therapy for the prevention and treatment of cardiovascular diseases in mammals. Here we show that simvastatin significantly increased the mean and maximum lifespan of Drosophila melanoga...

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Autores principales: Spindler, Stephen R., Li, Rui, Dhahbi, Joseph M., Yamakawa, Amy, Mote, Patricia, Bodmer, Rolf, Ocorr, Karen, Williams, Renee T., Wang, Yinsheng, Ablao, Kenneth P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380867/
https://www.ncbi.nlm.nih.gov/pubmed/22737247
http://dx.doi.org/10.1371/journal.pone.0039581
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author Spindler, Stephen R.
Li, Rui
Dhahbi, Joseph M.
Yamakawa, Amy
Mote, Patricia
Bodmer, Rolf
Ocorr, Karen
Williams, Renee T.
Wang, Yinsheng
Ablao, Kenneth P.
author_facet Spindler, Stephen R.
Li, Rui
Dhahbi, Joseph M.
Yamakawa, Amy
Mote, Patricia
Bodmer, Rolf
Ocorr, Karen
Williams, Renee T.
Wang, Yinsheng
Ablao, Kenneth P.
author_sort Spindler, Stephen R.
collection PubMed
description Statins such as simvastatin are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and standard therapy for the prevention and treatment of cardiovascular diseases in mammals. Here we show that simvastatin significantly increased the mean and maximum lifespan of Drosophila melanogaster (Drosophila) and enhanced cardiac function in aging flies by significantly reducing heart arrhythmias and increasing the contraction proportion of the contraction/relaxation cycle. These results appeared independent of internal changes in ubiquinone or juvenile hormone levels. Rather, they appeared to involve decreased protein prenylation. Simvastatin decreased the membrane association (prenylation) of specific small Ras GTPases in mice. Both farnesyl (L744832) and type 1 geranylgeranyl transferase (GGTI-298) inhibitors increased Drosophila lifespan. These data are the most direct evidence to date that decreased protein prenylation can increase cardiac health and lifespan in any metazoan species, and may explain the pleiotropic (non-cholesterol related) health effects of statins.
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spelling pubmed-33808672012-06-26 Statin Treatment Increases Lifespan and Improves Cardiac Health in Drosophila by Decreasing Specific Protein Prenylation Spindler, Stephen R. Li, Rui Dhahbi, Joseph M. Yamakawa, Amy Mote, Patricia Bodmer, Rolf Ocorr, Karen Williams, Renee T. Wang, Yinsheng Ablao, Kenneth P. PLoS One Research Article Statins such as simvastatin are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and standard therapy for the prevention and treatment of cardiovascular diseases in mammals. Here we show that simvastatin significantly increased the mean and maximum lifespan of Drosophila melanogaster (Drosophila) and enhanced cardiac function in aging flies by significantly reducing heart arrhythmias and increasing the contraction proportion of the contraction/relaxation cycle. These results appeared independent of internal changes in ubiquinone or juvenile hormone levels. Rather, they appeared to involve decreased protein prenylation. Simvastatin decreased the membrane association (prenylation) of specific small Ras GTPases in mice. Both farnesyl (L744832) and type 1 geranylgeranyl transferase (GGTI-298) inhibitors increased Drosophila lifespan. These data are the most direct evidence to date that decreased protein prenylation can increase cardiac health and lifespan in any metazoan species, and may explain the pleiotropic (non-cholesterol related) health effects of statins. Public Library of Science 2012-06-21 /pmc/articles/PMC3380867/ /pubmed/22737247 http://dx.doi.org/10.1371/journal.pone.0039581 Text en Spindler et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Spindler, Stephen R.
Li, Rui
Dhahbi, Joseph M.
Yamakawa, Amy
Mote, Patricia
Bodmer, Rolf
Ocorr, Karen
Williams, Renee T.
Wang, Yinsheng
Ablao, Kenneth P.
Statin Treatment Increases Lifespan and Improves Cardiac Health in Drosophila by Decreasing Specific Protein Prenylation
title Statin Treatment Increases Lifespan and Improves Cardiac Health in Drosophila by Decreasing Specific Protein Prenylation
title_full Statin Treatment Increases Lifespan and Improves Cardiac Health in Drosophila by Decreasing Specific Protein Prenylation
title_fullStr Statin Treatment Increases Lifespan and Improves Cardiac Health in Drosophila by Decreasing Specific Protein Prenylation
title_full_unstemmed Statin Treatment Increases Lifespan and Improves Cardiac Health in Drosophila by Decreasing Specific Protein Prenylation
title_short Statin Treatment Increases Lifespan and Improves Cardiac Health in Drosophila by Decreasing Specific Protein Prenylation
title_sort statin treatment increases lifespan and improves cardiac health in drosophila by decreasing specific protein prenylation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380867/
https://www.ncbi.nlm.nih.gov/pubmed/22737247
http://dx.doi.org/10.1371/journal.pone.0039581
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