Targeted expression of the human uncoupling protein 2 (hUCP2) to adult neurons extends life span in the fly.

Authors: Fridell YW; Sánchez-Blanco A; Silvia BA; Helfand SL

Abstract: 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.

Keywords: Animals; Animals, Genetically Modified; Blotting, Western; DNA, Complementary/metabolism; Drosophila melanogaster; Female; Humans; Hydrogen Peroxide/chemistry; Ion Channels; Longevity; Male; Membrane Transport Proteins/*biosynthesis; Mitochondria/metabolism; Mitochondrial Proteins/*biosynthesis; Nervous System/*metabolism; Neurons/*metabolism; Oxidative Stress; Oxygen Consumption; Reactive Oxygen Species; Sex Factors; Time Factors
Journal: Cell metabolism
Volume: 1
Issue: 2
Pages: 145-52
Date: Aug. 2, 2005
PMID: 16054055
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Citation:

Fridell YW, Sánchez-Blanco A, Silvia BA, Helfand SL (2005) Targeted expression of the human uncoupling protein 2 (hUCP2) to adult neurons extends life span in the fly. Cell metabolism 1: 145-52.


Study Lifespan Factors:
  • UCP2 uncoupling protein 2 (mitochondrial, proton carrier)


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