1. Aging Cell. 2008 Aug;7(4):552-60. doi: 10.1111/j.1474-9726.2008.00407.x. Epub
2008 Jul 10.

Mild mitochondrial uncoupling in mice affects energy metabolism, redox balance
and longevity.

Caldeira da Silva CC(1), Cerqueira FM, Barbosa LF, Medeiros MH, Kowaltowski AJ.

Author information: 
(1)Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo,
São Paulo, SP, Brazil.

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.

DOI: 10.1111/j.1474-9726.2008.00407.x 
PMID: 18505478  [Indexed for MEDLINE]