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Content Provider | World Health Organization (WHO)-Global Index Medicus |
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Author | Desquiret-dumas, Valérie Finley, Lydia W. S. Procaccio, Vincent Souza, Amanda Clish, Clary B. Arany, Zoltan Haigis, Marcia C. Lee, Jaewon Bullock, Kevin Rowe, Glenn C. |
Description | Author Affiliation: Finley LW ( Department of Cell Biology, Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, Boston, MA 02115, USA.); |
Abstract | Calorie restriction (CR) is a dietary intervention that extends lifespan and healthspan in a variety of organisms. CR improves mitochondrial energy production, fuel oxidation, and reactive oxygen species (ROS) scavenging in skeletal muscle and other tissues, and these processes are thought to be critical to the benefits of CR. PGC-1 is a transcriptional coactivator that regulates mitochondrial function and is induced by CR. Consequently, many of the mitochondrial and metabolic benefits of CR are attributed to increased PGC-1 activity. To test this model, we examined the metabolic and mitochondrial response to CR in mice lacking skeletal muscle PGC-1 (MKO). Surprisingly, MKO mice demonstrated a normal improvement in glucose homeostasis in response to CR, indicating that skeletal muscle PGC-1 is dispensable for the whole-body benefits of CR. In contrast, gene expression profiling and electron microscopy (EM) demonstrated that PGC-1 is required for the full CR-induced increases in mitochondrial gene expression and mitochondrial density in skeletal muscle. These results demonstrate that PGC-1 is a major regulator of the mitochondrial response to CR in skeletal muscle, but surprisingly show that neither PGC-1 nor mitochondrial biogenesis in skeletal muscle are required for the whole-body metabolic benefits of CR. |
ISSN | 00278424 |
e-ISSN | 10916490 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Issue Number | 8 |
Volume Number | 109 |
Language | English |
Publisher | National Academy of Sciences |
Publisher Date | 2012-02-01 |
Publisher Place | United States |
Access Restriction | Open |
Subject Keyword | Caloric Restriction Mitochondria Metabolism Muscle, Skeletal Trans-Activators Transcription, Genetic Animals Genes, Mitochondrial Genetics Homeostasis Metabolomics Mice Mice, Inbred C57BL Mice, Knockout Muscle Fibers, Skeletal Oxidation-Reduction Transcription Factors Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Multidisciplinary |
Content Type | Text |
Resource Type | Article |
Subject | Multidisciplinary |
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