Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/75027
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dc.contributor.author | Civitarese, A. | - |
dc.contributor.author | Carling, S. | - |
dc.contributor.author | Heilbronn, L. | - |
dc.contributor.author | Hulver, M. | - |
dc.contributor.author | Deutsch, W. | - |
dc.contributor.author | Smith, S. | - |
dc.contributor.author | Ravussin, E. | - |
dc.contributor.editor | Barzilai, N. | - |
dc.date.issued | 2007 | - |
dc.identifier.citation | PLoS Medicine, 2007; 4(3):485-494 | - |
dc.identifier.issn | 1549-1277 | - |
dc.identifier.issn | 1549-1676 | - |
dc.identifier.uri | http://hdl.handle.net/2440/75027 | - |
dc.description | Extent: 10p. | - |
dc.description.abstract | Background: Caloric restriction without malnutrition extends life span in a range of organisms including insects and mammals and lowers free radical production by the mitochondria. However, the mechanism responsible for this adaptation are poorly understood. Methods and Findings: The current study was undertaken to examine muscle mitochondrial bioenergetics in response to caloric restriction alone or in combination with exercise in 36 young (36.8 ± 1.0 y), overweight (body mass index, 27.8 ± 0.7 kg/m2) individuals randomized into one of three groups for a 6-mo intervention: Control, 100% of energy requirements; CR, 25% caloric restriction; and CREX, caloric restriction with exercise (CREX), 12.5% CR + 12.5% increased energy expenditure (EE). In the controls, 24-h EE was unchanged, but in CR and CREX it was significantly reduced from baseline even after adjustment for the loss of metabolic mass (CR, −135 ± 42 kcal/d, p = 0.002 and CREX, −117 ± 52 kcal/d, p = 0.008). Participants in the CR and CREX groups had increased expression of genes encoding proteins involved in mitochondrial function such as PPARGC1A, TFAM, eNOS, SIRT1, and PARL (all, p < 0.05). In parallel, mitochondrial DNA content increased by 35% ± 5% in the CR group (p = 0.005) and 21% ± 4% in the CREX group (p < 0.004), with no change in the control group (2% ± 2%). However, the activity of key mitochondrial enzymes of the TCA (tricarboxylic acid) cycle (citrate synthase), beta-oxidation (beta-hydroxyacyl-CoA dehydrogenase), and electron transport chain (cytochrome C oxidase II) was unchanged. DNA damage was reduced from baseline in the CR (−0.56 ± 0.11 arbitrary units, p = 0.003) and CREX (−0.45 ± 0.12 arbitrary units, p = 0.011), but not in the controls. In primary cultures of human myotubes, a nitric oxide donor (mimicking eNOS signaling) induced mitochondrial biogenesis but failed to induce SIRT1 protein expression, suggesting that additional factors may regulate SIRT1 content during CR. Conclusions: The observed increase in muscle mitochondrial DNA in association with a decrease in whole body oxygen consumption and DNA damage suggests that caloric restriction improves mitochondrial function in young non-obese adults. | - |
dc.description.statementofresponsibility | Anthony E Civitarese, Stacy Carling, Leonie K Heilbronn, Mathew H Hulver, Barbara Ukropcova, Walter A Deutsch, Steven R Smith, and Eric Ravussin, for the CALERIE Pennington Team | - |
dc.language.iso | en | - |
dc.publisher | Public Library of Science | - |
dc.rights | © 2007 Civitarese et al. 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 credited. | - |
dc.source.uri | http://dx.doi.org/10.1371/journal.pmed.0040076 | - |
dc.subject | CALERIE Pennington Team | - |
dc.subject | Muscle, Skeletal | - |
dc.subject | Mitochondria, Muscle | - |
dc.subject | Humans | - |
dc.subject | DNA Damage | - |
dc.subject | Nitric Oxide | - |
dc.subject | Sirtuins | - |
dc.subject | Exercise | - |
dc.subject | Caloric Restriction | - |
dc.subject | Gene Expression Profiling | - |
dc.subject | Energy Metabolism | - |
dc.subject | Oxidative Stress | - |
dc.subject | Adult | - |
dc.subject | Middle Aged | - |
dc.subject | Female | - |
dc.subject | Male | - |
dc.subject | Overweight | - |
dc.subject | Adiponectin | - |
dc.subject | Membrane Potential, Mitochondrial | - |
dc.subject | Sirtuin 1 | - |
dc.title | Calorie restriction increases muscle mitochondrial biogenesis in healthy humans | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1371/journal.pmed.0040076 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Heilbronn, L. [0000-0003-2106-7303] | - |
Appears in Collections: | Aurora harvest Molecular and Biomedical Science publications |
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hdl_75027.pdf | Published version | 430.12 kB | Adobe PDF | View/Open |
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