Targeted expression of the human uncoupling protein 2 (hUCP2) to adult neurons extends life span in the fly.
The oxidative stress hypothesis of aging predicts that a reduction in the generation of mitochondrial reactive oxygen species (ROS) will decrease oxidative damage and extend life span. Increasing mitochondrial proton leak-dependent state 4 respiration by increasing mitochondrial uncoupling is an intervention postulated to decrease mitochondrial ROS production. When human UCP2 (hUCP2) is targeted to the mitochondria of adult fly neurons, we find an increase in state 4 respiration, a decrease in ROS production, a decrease in oxidative damage, heightened resistance to the free radical generator paraquat, and an extension in life span without compromising fertility or physical activity. Our results demonstrate that neuronal-specific expression of hUCP2 in adult flies decreases cellular oxidative damage and is sufficient to extend life span.
Fridell
Yih-Woei C
YW
Department of Genetics and Developmental Biology, School of Medicine, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, Connecticut 06030, USA.
Sánchez-Blanco
Adolfo
A
Silvia
Brian A
BA
Helfand
Stephen L
SL
D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D018076:DNA, Complementary / Q000378:metabolism; D004331:Drosophila melanogaster; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D007473:Ion Channels; D008136:Longevity; D008297:Male; D026901:Membrane Transport Proteins / Q000096:biosynthesis*; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D009420:Nervous System / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D018384:Oxidative Stress; D010101:Oxygen Consumption; D017382:Reactive Oxygen Species; D012737:Sex Factors; D013997:Time Factors; D000071246:Uncoupling Protein 2
D018076:DNA, Complementary; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2; D006861:Hydrogen Peroxide