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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2012
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oai:doaj.org-article:d3ca8009de6843b5a3868d19b5cff6272021-11-18T07:14:43ZStatin treatment increases lifespan and improves cardiac health in Drosophila by decreasing specific protein prenylation.1932-620310.1371/journal.pone.0039581https://doaj.org/article/d3ca8009de6843b5a3868d19b5cff6272012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22737247/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Statins 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.Stephen R SpindlerRui LiJoseph M DhahbiAmy YamakawaPatricia MoteRolf BodmerKaren OcorrRenee T WilliamsYinsheng WangKenneth P AblaoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e39581 (2012) |
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Medicine R Science Q |
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Medicine R Science Q Stephen R Spindler Rui Li Joseph M Dhahbi Amy Yamakawa Patricia Mote Rolf Bodmer Karen Ocorr Renee T Williams Yinsheng Wang Kenneth P Ablao Statin treatment increases lifespan and improves cardiac health in Drosophila by decreasing specific protein prenylation. |
| 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. |
| format |
article |
| author |
Stephen R Spindler Rui Li Joseph M Dhahbi Amy Yamakawa Patricia Mote Rolf Bodmer Karen Ocorr Renee T Williams Yinsheng Wang Kenneth P Ablao |
| author_facet |
Stephen R Spindler Rui Li Joseph M Dhahbi Amy Yamakawa Patricia Mote Rolf Bodmer Karen Ocorr Renee T Williams Yinsheng Wang Kenneth P Ablao |
| author_sort |
Stephen R Spindler |
| title |
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_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_sort |
statin treatment increases lifespan and improves cardiac health in drosophila by decreasing specific protein prenylation. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/d3ca8009de6843b5a3868d19b5cff627 |
| work_keys_str_mv |
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| _version_ |
1718423759965126656 |