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Mild mitochondrial uncoupling in mice affects energy metabolism, redox balance and longevity
Abstract
Summary: Caloric restriction is the most effective non‐genetic intervention to enhance lifespan known to date. A major research interest has been the development of therapeutic strategies capable of promoting the beneficial results of this dietary regimen. In this sense, we propose that compounds that decrease the efficiency of energy conversion, such as mitochondrial uncouplers, can be caloric restriction mimetics. Treatment of mice with low doses of the protonophore 2,4‐dinitrophenol promotes enhanced tissue respiratory rates, improved serological glucose, triglyceride and insulin levels, decrease of reactive oxygen species levels and tissue DNA and protein oxidation, as well as reduced body weight. Importantly, 2,4‐dinitrophenol‐treated animals also presented enhanced longevity. Our results demonstrate that mild mitochondrial uncoupling is a highly effective in vivo antioxidant strategy, and describe the first therapeutic intervention capable of effectively reproducing the physiological, metabolic and lifespan effects of caloric restriction in healthy mammals.
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“mitochondrial uncoupling, either genetically through the overexpression of the uncoupling protein UCP1 or by administration of the chemical uncoupler 2-4-dinitrophenol can increase lifespan in flies and mice”
From The Hallmarks of Aging (2013) · cites this paper as Caldeira da Silva et al., 2008
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Metadata
- Authors
- Caldeira da Silva, C. C., Cerqueira, F. M., Barbosa, L. F., Medeiros, M. H. G., & Kowaltowski, A. J.
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2008-07-10
- Volume
- 7
- Issue
- 4
- Pages
- 552-560
- ISSN
- 1474-9718
- 1474-9726
- Cited by
- 306
- References
- 11
- Language
- en
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