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Calorie restriction increases cerebral mitochondrial respiratory capacity in a NO•-mediated mechanism: Impact on neuronal survival
Calorie restriction (CR) enhances animal life span and prevents age-related diseases, including neurological decline. Recent evidence suggests that a mechanism involved in CR-induced life-span extension is NO•-stimulated mitochondrial biogenesis. We examine here the effects of CR on brain mitochondr...
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Published in: | Free radical biology & medicine 2012-04, Vol.52 (7), p.1236-1241 |
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Main Authors: | , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Calorie restriction (CR) enhances animal life span and prevents age-related diseases, including neurological decline. Recent evidence suggests that a mechanism involved in CR-induced life-span extension is NO•-stimulated mitochondrial biogenesis. We examine here the effects of CR on brain mitochondrial content. CR increased eNOS and nNOS and the content of mitochondrial proteins (cytochrome c oxidase, citrate synthase, and mitofusin) in the brain. Furthermore, we established an in vitro system to study the neurological effects of CR using serum extracted from animals on this diet. In cultured neurons, CR serum enhanced nNOS expression and increased levels of nitrite (a NO• product). CR serum also enhanced the levels of cytochrome c oxidase and increased citrate synthase activity and respiratory rates in neurons. CR serum effects were inhibited by L-NAME and mimicked by the NO• donor SNAP. Furthermore, both CR sera and SNAP were capable of improving neuronal survival. Overall, our results indicate that CR increases mitochondrial biogenesis in a NO•-mediated manner, resulting in enhanced reserve respiratory capacity and improved survival in neurons.
► Calorie restriction (CR) increases eNOS, nNOS, and mitochondrial content in brain. ► Serum from CR animals increases nNOS and NO• in neuronal cultures. ► CR serum enhances mitochondrial biogenesis and respiratory rates in neurons. ► CR serum effects are inhibited by L-NAME and mimicked by the NO• donor SNAP. ► CR serum and SNAP increase neuronal survival. |
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ISSN: | 0891-5849 1873-4596 |
DOI: | 10.1016/j.freeradbiomed.2012.01.011 |